In JoVE (4)

Other Publications (382)

Articles by Ke Li in JoVE

 JoVE Medicine

Quantitative Magnetic Resonance Imaging of Skeletal Muscle Disease

1Institute of Imaging Science, Vanderbilt University, 2Department of Radiology and Radiological Sciences, Vanderbilt University, 3Department of Biomedical Engineering, Vanderbilt University, 4Department of Molecular Physiology and Biophysics, Vanderbilt University, 5Department of Physical Medicine and Rehabilitation, Vanderbilt University, 6Department of Physics and Astronomy, Vanderbilt University

JoVE 52352

 JoVE Biology

Using Microfluidic Devices to Measure Lifespan and Cellular Phenotypes in Single Budding Yeast Cells

1The State Key Laboratory for Artificial Microstructures and Mesoscopic Physics, School of Physics, Peking University, 2Department of Biochemistry and Biophysics, University of California, San Francisco, 3Peking-Tsinghua Center for Life Sciences at Center for Quantitative Biology, Academy for Advanced Interdisciplinary Studies, Peking University

JoVE 55412

 JoVE Immunology and Infection

An All-on-chip Method for Rapid Neutrophil Chemotaxis Analysis Directly from a Drop of Blood

1Institute of Applied Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, 2University of Science and Technology of China, 3Department of Physics and Astronomy, University of Manitoba, 4Department of Biosystems Engineering, University of Manitoba, 5Seven Oaks General Hospital, 6Department of Immunology, University of Manitoba, 7Department of Biological Sciences, University of Manitoba

JoVE 55615

Other articles by Ke Li on PubMed

Interhemispheric Functional Connectivity and Its Relationships with Clinical Characteristics in Major Depressive Disorder: a Resting State FMRI Study

PloS One. 2013  |  Pubmed ID: 23555920

Abnormalities in large-scale, structural and functional brain connectivity have been increasingly reported in patients with major depressive disorder (MDD). However, MDD-related alterations in functional interaction between the cerebral hemispheres are still not well understood. Resting state fMRI, which reveals spontaneous neural fluctuations in blood oxygen level dependent signals, provides a means to detect interhemispheric functional coherence. We examined the resting state functional connectivity (RSFC) between the two hemispheres and its relationships with clinical characteristics in MDD patients using a recently proposed measurement named "voxel-mirrored homotopic connectivity (VMHC)".

Inhibitory Effect of IL-17 on Neural Stem Cell Proliferation and Neural Cell Differentiation

BMC Immunology. 2013  |  Pubmed ID: 23617463

IL-17, a Th17 cell-derived proinflammatory molecule, has been found to play an important role in the pathogenesis of autoimmune diseases, including multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). While IL-17 receptor (IL-17R) is expressed in many immune-related cells, microglia, and astrocytes, it is not known whether IL-17 exerts a direct effect on neural stem cells (NSCs) and oligodendrocytes, thus inducing inflammatory demyelination in the central nervous system.

Removal of Visual Feedback Lowers Structural Variability of Inter-digit Force Coordination During Sustained Precision Pinch

Neuroscience Letters. Jun, 2013  |  Pubmed ID: 23624025

This study examined the effects of visual feedback on inter-digit force coordination during a precision pinch. Sixteen healthy, right-handed subjects were instructed to pinch an instrumented apparatus for 1 min with a stable force output. Visual feedback was provided for the first 30s and withdrawn for the second 30s. Detrended fluctuation analysis (DFA) and detrended cross-correlation analysis (DCCA) methods were used to quantify the time-dependent structures of each digit's force and of the force correlation between the digits. After removing visual feedback, the DFA scaling exponent, αDFA, increased from 1.10±0.12 to 1.29±0.13 for the thumb and from 0.95±0.08 to 1.33±0.13 for the index finger (F1,95=372.47, p<0.001); the DCCA scaling exponent, αDCCA, increased from 1.00±0.08 to 1.33±0.13 (t95=20.33, p<0.001). Structural changes were observed beginning with the first 5s epoch after the removal of visual feedback. The results provide evidence that removing visual feedback lowers the structural variability of inter-digit force coordination. This change is reflected in the high-level control strategy, resulting in the two digits being more tightly coupled under somatosensory feedback without visual inputs.

Spatial Resolution Characterization of Differential Phase Contrast CT Systems Via Modulation Transfer Function (MTF) Measurements

Physics in Medicine and Biology. Jun, 2013  |  Pubmed ID: 23685949

By adding a Talbot-Lau interferometer to a conventional x-ray absorption computed tomography (CT) imaging system, both differential phase contrast (DPC) signal and absorption contrast signal can be simultaneously measured from the same set of CT measurements. The imaging performance of such multi-contrast x-ray CT imaging systems can be characterized with standard metrics such as noise variance, noise power spectrum, contrast-to-noise ratio, modulation transfer function (MTF), and task-based detectability index. Among these metrics, the measurement of the MTF can be challenging in DPC-CT systems due to several confounding factors such as phase wrapping and the difficulty of using fine wires as probes. To address these technical challenges, this paper discusses a viable and reliable method to experimentally measure the MTF of DPC-CT. It has been found that the spatial resolution of DPC-CT is degraded, when compared to that of the corresponding absorption CT, due to the presence of a source grating G0 in the Talbot-Lau interferometer. An effective MTF was introduced and experimentally estimated to describe the impact of the Talbot-Lau interferometer on the system MTF.

Reversal of Multidrug Resistance by Cisplatin-loaded Magnetic Fe3O4 Nanoparticles in A549/DDP Lung Cancer Cells in Vitro and in Vivo

International Journal of Nanomedicine. 2013  |  Pubmed ID: 23690684

The purpose of this study was to explore whether magnetic Fe(3)O(4) nanoparticles (Fe(3)O(4)-MNP) loaded with cisplatin (Fe(3)O(4)-MNP-DDP) can reverse DDP resistance in lung cancer cells and to investigate mechanisms of multidrug resistance in vitro and in vivo. MTT assay showed that DDP inhibited both A549 cells and DDP-resistant A549 cells in a time-dependent and dose-dependent manner, and that this inhibition was enhanced by Fe(3)O(4)-MNP. An increased rate of apoptosis was detected in the Fe(3)O(4)-MNP-DDP group compared with a control group and the Fe(3)O(4)-MNP group by flow cytometry, and typical morphologic features of apoptosis were confirmed by confocal microscopy. Accumulation of intracellular DDP in the Fe(3)O(4)-MNP-DDP group was greater than that in the DDP group by inductively coupled plasma mass spectrometry. Further, lower levels of multidrug resistance-associated protein-1, lung resistance-related protein, Akt, and Bad, and higher levels of caspase-3 genes and proteins, were demonstrated by reverse transcriptase polymerase chain reaction and Western blotting in the presence of Fe(3)O(4)-MNP-DDP. We also demonstrated that Fe(3)O(4)-MNP enhanced the effect of DDP on tumor growth in BALB/c nude mice bearing DDP-resistant human A549 xenografts by decreasing localization of lung resistance-related protein and Ki-67 immunoreactivity in cells. There were no apparent signs of toxicity in the animals. Overall, these findings suggest potential clinical application of Fe(3)O(4)-MNP-DDP to increase cytotoxicity in lung tumor xenografts.

A Chiral Ruthenium-monophosphine Catalyst for Asymmetric Addition of Arylboronic Acids to Aryl Aldehydes

The Journal of Organic Chemistry. Jun, 2013  |  Pubmed ID: 23705850

A novel ruthenium catalyst on the basis of a chiral monophosphorus ligand is efficient for the asymmetric addition of arylboronic acids to aryl aldehydes, providing a series of chiral diarylmethanols in excellent yields and enantioselectivities (up to 92% ee). Preliminary study has shown that this process is catalyzed by a Ru complex with a single monophosphorus ligand.

Abnormal Baseline Brain Activity in Non-depressed Parkinson's Disease and Depressed Parkinson's Disease: a Resting-state Functional Magnetic Resonance Imaging Study

PloS One. 2013  |  Pubmed ID: 23717467

Depression is the most common psychiatric disorder observed in Parkinson's disease (PD) patients, however the neural contribution to the high rate of depression in the PD group is still unclear. In this study, we used resting-state functional magnetic resonance imaging (fMRI) to investigate the underlying neural mechanisms of depression in PD patients. Twenty-one healthy individuals and thirty-three patients with idiopathic PD, seventeen of whom were diagnosed with major depressive disorder, were recruited. An analysis of amplitude of low-frequency fluctuations (ALFF) was performed on the whole brain of all subjects. Our results showed that depressed PD patients had significantly decreased ALFF in the dorsolateral prefrontal cortex (DLPFC), the ventromedial prefrontal cortex (vMPFC) and the rostral anterior cingulated cortex (rACC) compared with non-depressed PD patients. A significant positive correlation was found between Hamilton Depression Rating Scale (HDRS) and ALFF in the DLPFC. The findings of changed ALFF in these brain regions implied depression in PD patients may be associated with abnormal activities of prefrontal-limbic network.

Anaphylatoxins in Organ Transplantation

Seminars in Immunology. Feb, 2013  |  Pubmed ID: 23722015

C3a and C5a (also called anaphylatoxins) are inflammatory peptides generated during complement activation. They do not only play important roles in innate immunity through the initiation and regulation of inflammatory responses, but also significantly influence adaptive immune responses. Organ transplantation triggers an initial inflammatory response and subsequent to the specific immune response (also called the alloimmune response), both of which contribute to graft rejection. Emerging evidence suggests that anaphylatoxins, particularly C5a, are significantly involved in both inflammatory and alloimmune responses following organ transplantation, thus influencing graft outcome. This review will provide the information on our current understanding of the roles for anaphylatoxins in ischemia-reperfusion injury, graft rejection, and transplant tolerance, and the therapeutic potential of targeting anaphylatoxin receptors in organ transplantation.

Identification of Tubulin Beta Chain, Thymosin Beta-4-like Protein 3, and Cytochrome B-c₁ Complex Subunit 1 As Serological Diagnostic Biomarkers of Gastric Cancer

Clinical Biochemistry. Oct, 2013  |  Pubmed ID: 23747515

Despite major advances in its diagnosis and treatment, gastric cancer (GC) remains a major life-threatening disease. Treatment of the disease is further aggravated by the lack of diagnostic biomarkers that can aid in the early detection of GC and promote its favorable prognosis. The present work aims to identify novel diagnostic biomarkers for GC.

Endoscopic Retrograde Cholangiopancreatography Using a Dual-Lumen Endogastroscope for Patients with Billroth II Gastrectomy

Gastroenterology Research and Practice. 2013  |  Pubmed ID: 23781239

Objective. To evaluate the safety and efficacy of a dual-lumen forward-viewing endoscope for ERCP in patients with prior Billroth II gastrectomy. Methods. The records of 46 patients treated with ERCP by a dual-lumen forward-viewing endoscope after Billroth II gastrectomy from 2007 to 2012 were reviewed. Results. The success rate of selective cannulation was 82.6% (38/46). Of the 38 cases with successful selective cannulation, endoscopic sphincterotomy was achieved in 23 cases by placing the needle knife through the 2nd lumen, while endoscopic papillary balloon dilatation was conducted in the other 15 cases. Of the 8 failed cases of selective cannulation, 6 had failed afferent loop intubation, and 3 of these 6 patients had Braun's anastomosis. The safety and efficacy of catheter-assisted endoscopic sphincterotomy were increased by placing the needle knife through the 2nd lumen without altering the conventional endoscopic sphincterotomy procedure. Conclusions. A dual-lumen forward-viewing endoscope can be safely and effectively used to perform ERCP in patients with a Billroth II gastrectomy, except for patients with additional Braun's anastomosis.

Association of Epidermal Growth Factor and Epidermal Growth Factor Receptor Polymorphisms with the Risk of Hepatitis B Virus-related Hepatocellular Carcinoma in the Population of North China

Genetic Testing and Molecular Biomarkers. Aug, 2013  |  Pubmed ID: 23790025

Hepatocellular carcinoma (HCC) is a common solid malignant tumor occurring worldwide that leads to the third largest cause of death compared to other cancers. Genetic and environmental factors are involved in the pathogenesis of HCC. Epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) can stimulate the proliferation of epidermal and epithelial cells. The EGF signal pathway has a relationship with the growth of the embryo, tissue repairing, and tumorigenesis.

Sequential Fuzzy Diagnosis Method for Motor Roller Bearing in Variable Operating Conditions Based on Vibration Analysis

Sensors (Basel, Switzerland). 2013  |  Pubmed ID: 23793021

A novel intelligent fault diagnosis method for motor roller bearings which operate under unsteady rotating speed and load is proposed in this paper. The pseudo Wigner-Ville distribution (PWVD) and the relative crossing information (RCI) methods are used for extracting the feature spectra from the non-stationary vibration signal measured for condition diagnosis. The RCI is used to automatically extract the feature spectrum from the time-frequency distribution of the vibration signal. The extracted feature spectrum is instantaneous, and not correlated with the rotation speed and load. By using the ant colony optimization (ACO) clustering algorithm, the synthesizing symptom parameters (SSP) for condition diagnosis are obtained. The experimental results shows that the diagnostic sensitivity of the SSP is higher than original symptom parameter (SP), and the SSP can sensitively reflect the characteristics of the feature spectrum for precise condition diagnosis. Finally, a fuzzy diagnosis method based on sequential inference and possibility theory is also proposed, by which the conditions of the machine can be identified sequentially as well.

A Thermogenic Secondary Sexual Character in Male Sea Lamprey

The Journal of Experimental Biology. Jul, 2013  |  Pubmed ID: 23804672

Secondary sexual characters in animals are exaggerated ornaments or weapons for intrasexual competition. Unexpectedly, we found that a male secondary sexual character in sea lamprey (Petromyzon marinus) is a thermogenic adipose tissue that instantly increases its heat production during sexual encounters. This secondary sexual character, developed in front of the anterior dorsal fin of mature males, is a swollen dorsal ridge known as the 'rope' tissue. It contains nerve bundles, multivacuolar adipocytes and interstitial cells packed with small lipid droplets and mitochondria with dense and highly organized cristae. The fatty acid composition of the rope tissue is rich in unsaturated fatty acids. The cytochrome c oxidase activity is high but the ATP concentration is very low in the mitochondria of the rope tissue compared with those of the gill and muscle tissues. The rope tissue temperature immediately rose up to 0.3°C when the male encountered a conspecific. Mature males generated more heat in the rope and muscle tissues when presented with a mature female than when presented with a male (paired t-test, P<0.05). On average, the rope generated 0.027±0.013 W cm(-3) more heat than the muscle in 10 min. Transcriptome analyses revealed that genes involved in fat cell differentiation are upregulated whereas those involved in oxidative-phosphorylation-coupled ATP synthesis are downregulated in the rope tissue compared with the gill and muscle tissues. Sexually mature male sea lamprey possess the only known thermogenic secondary sexual character that shows differential heat generation toward individual conspecifics.

Occurrence and Distribution of Veterinary Antibiotics and Tetracycline Resistance Genes in Farmland Soils Around Swine Feedlots in Fujian Province, China

Environmental Science and Pollution Research International. Dec, 2013  |  Pubmed ID: 23812733

Six antibiotics, tetracyclines (TCs), and quinolones (QNs) in farmland soils from four coastal cities in Fujian Province of China were investigated. Oxytetracycline was most frequently detected, followed by enrofloxacin, ciprofloxacin, chlorotetracycline, ofloxacin, and tetracycline, with maximum concentrations of 613.2, 637.3, 237.3, 2668.9, 205.7, and 189.8 μg kg(-1), respectively. Samples from Putian City contained the highest maximum concentration of ∑TCs (3,064.2 μg kg(-1)), whereas those from Fuzhou City contained the highest maximum concentration of ∑QNs (897.8 μg kg(-1)). It is noteworthy that the ∑TCs and ∑QNs in 46.4 and 28.6 % of samples exceeded the ecotoxic effect trigger value (100 μg kg(-1)), respectively. The concentrations of these antibiotics and five tetracycline resistance genes in four soil plots at depth profiles were quantified thereafter. In most cases, both antibiotics and resistance genes decreased with the increase of depth. Some antibiotics can be detected at a depth of 60-80 cm where the abundance of tetO, tetM, and tetX reached up to 10(7) copies g(-1). Additionally, the sum of all tet genes (normalized to 16S rRNA genes) correlated with ∑TCs significantly (r=0.676). Our results suggest that resistance determinants can migrate to deeper soil layers and would probably contaminate groundwater by vertical transport.

Diagnostic Value of Transthoracic Echocardiography for Patent Foramen Ovale: a Meta-analysis

Ultrasound in Medicine & Biology. Oct, 2013  |  Pubmed ID: 23820251

As a non-invasive and convenient modality, transthoracic echocardiography (TTE) has been widely recommended for the diagnosis of patent foramen ovale (PFO). In this study our aim was to systematically review the diagnostic accuracy of TTE in detection of PFO. We conducted comprehensive searches in PubMed, Embase and the Cochrane Library to the end of September 1, 2012. Sixteen studies comprising 1831 patients were included in the meta-analysis. The quality of reported studies was modest. The summary sensitivity and specificity of TTE in diagnosis of PFO were 88% (95% confidence interval [CI], 79-94) and 97% (95% CI, 92-99), respectively. The positive likelihood ratio was 27.1 (95% CI, 11.2-65.1), and the negative likelihood ratio was 0.12 (95% CI, 0.07-0.22). The summary diagnostic odds ratio was 221 (95% CI, 95-518). Subgroup analyses suggested that age and initial disease may affect the accuracy of TTE in detection of PFO. The meta-analysis suggested that TTE is a test with high sensitivity and specificity in detection of PFO, but it may not be appropriate for screening for PFO in all patients, especially patients with a small right-left shunt.

Prevalence of 10 Human Polyomaviruses in Fecal Samples from Children with Acute Gastroenteritis: a Case-control Study

Journal of Clinical Microbiology. Sep, 2013  |  Pubmed ID: 23824769

We conducted a case-control study to explore the prevalence of 10 human polyomaviruses in fecal specimens from hospitalized children with diarrhea and asymptomatic control subjects by using multiplex PCR detected by matrix-assisted laser desorption ionization-time of flight mass spectrometry. The differences between cases and controls were not statistically significant.

Novel Prognostic Markers for Patients with Triple-negative Breast Cancer

Human Pathology. Oct, 2013  |  Pubmed ID: 23845466

Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by poor prognosis. Currently, no reliable markers have been identified as having a predictive role for the prognosis of TNBC patients. In this study, 119 breast cancer samples, including 31 TNBC and 89 non-TNBC subtypes, were collected. The protein levels of cleaved caspase-3 (CC3), aldehyde dehydrogenase 1 (ALDH1), cyclooxygenase-2, Ki-67, H2A histone family member X, and phosphorylated protein kinase B protein were measured by immunohistochemical staining. The percentage of positive CC3 (P = .017), ALDH1 (P = .015), Ki-67 (P = .001), and H2A histone family member X (P = .016) staining was significantly higher in TNBC than in non-TNBC cases. Positive CC3 and ALDH1 staining significantly correlated with poor prognosis of breast cancer, the TNBC subtype and non-TNBC subtype. Positive cyclooxygenase-2 expression significantly correlated with the survival of patients with TNBC. Multivariate analysis demonstrated that CC3 and ALDH1 are independent prognostic factors for BC and non-TNBC. ALDH1 is a prognostic marker for TNBC patients.

[Study on Multi-level Fractal Features Extraction Method of Breast Mass]

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi = Journal of Biomedical Engineering = Shengwu Yixue Gongchengxue Zazhi. Apr, 2013  |  Pubmed ID: 23858747

Breast mass is women's common disease, and it seriously affects the health of women. Accurate detection and location of the mass will greatly improve the precision of the diagnosis of the breast disease. Studies have shown that the organizational structure and surface roughness of the mass constitute the texture features of mass and it is an important basis for distinguishing the mass. In this paper, a multi-level fractal features extraction method is proposed, and, moreover, the fractal feature vector of the suspicious lesions has been established, thus realizing the feature extraction and analysis of the mammary gland. Finally, the result of classification with the support vector machine (SVM) was given. 110 mammograms are extracted and classified with an accuracy of 90%. The results showed that the multi-level fractal features extraction and classification methods proposed in this paper could improve the accuracy of mass detection and could be effective for the early diagnosis of the disease.

Rupatadine Protects Against Pulmonary Fibrosis by Attenuating PAF-mediated Senescence in Rodents

PloS One. 2013  |  Pubmed ID: 23869224

A similar immune response is implicated in the pathogenesis of pulmonary fibrosis and allergic disorders. We investigated the potential therapeutic efficacy and mechanism of rupatadine, a dual antagonist of histamine and platelet-activation factor (PAF), in bleomycin- (BLM-) and silica-induced pulmonary fibrosis. The indicated dosages of rupatadine were administered in rodents with bleomycin or silica-induced pulmonary fibrosis. The tissue injury, fibrosis, inflammatory cells and cytokines, and lung function were examined to evaluate the therapeutic efficacy of rupatadine. The anti-fibrosis effect of rupatadine was compared with an H1 or PAF receptor antagonist, and efforts were made to reveal rupatadine's anti-fibrotic mechanism. Rupatadine promoted the resolution of pulmonary inflammation and fibrosis in a dose-dependent manner, as indicated by the reductions in inflammation score, collagen deposition and epithelial-mesenchymal transformation, and infiltration or expression of inflammatory cells or cytokines in the fibrotic lung tissue. Thus, rupatadine treatment improved the declined lung function and significantly decreased animal death. Moreover, rupatadine was able not only to attenuate silica-induced silicosis but also to produce a superior therapeutic efficacy compared to pirfenidone, histamine H1 antagonist loratadine, or PAF antagonist CV-3988. The anti-fibrotic action of rupatadine might relate to its attenuation of BLM- or PAF-induced premature senescence because rupatadine treatment protected against the in vivo and in vitro activation of the p53/p21-dependent senescence pathway. Our studies indicate that rupatadine promotes the resolution of pulmonary inflammation and fibrosis by attenuating the PAF-mediated senescence response. Rupatadine holds promise as a novel drug to treat the devastating disease of pulmonary fibrosis.

Characterization of a Novel Bile Alcohol Sulfate Released by Sexually Mature Male Sea Lamprey (Petromyzon Marinus)

PloS One. 2013  |  Pubmed ID: 23874530

A sulphate-conjugated bile alcohol, 3,12-diketo-4,6-petromyzonene-24-sulfate (DKPES), was identified using bioassay-guided fractionation from water conditioned with sexually mature male sea lamprey (Petromyzon marinus). The structure and relative stereochemistry of DKPES was established using spectroscopic data. The electro-olfactogram (EOG) response threshold of DKPES was 10(-7) Molar (M) and that of 3-keto petromyzonol sulfate (3 KPZS; a known component of the male sea lamprey sex pheromone) was 10(-10) M. Behavioural studies indicated that DKPES can be detected at low concentrations by attracting sexually mature females to nests when combined with 3 KPZS. Nests baited with a mixture of DKPES and 3 KPZS (ratio 1∶29.8) attracted equal numbers of sexually mature females compared to an adjacent nest baited with 3 KPZS alone. When DKPES and 3 KPZS mixtures were applied at ratios of 2∶29.8 and 10∶29.8, the proportion of sexually mature females that entered baited nests increased to 73% and 70%, respectively. None of the sexually mature females released were attracted to nests baited with DKPES alone. These results indicated that DKPES is a component of the sex pheromone released by sexually mature male sea lamprey, and is the second biologically active compound identified from this pheromone. DKPES represents the first example that a minor component of a vertebrate pheromone can be combined with a major component to elicit critical sexual behaviors. DKPES holds considerable promise for increasing the effectiveness of pheromone-baited trapping as a means of sea lamprey control in the Laurentian Great Lakes.

[Establishment and Application of TLR2 Receptor-based Cell Screening Model]

Yao Xue Xue Bao = Acta Pharmaceutica Sinica. May, 2013  |  Pubmed ID: 23888692

TLR2 activity plays an important role in the pathogenesis of autoimmune diseases, tumor carcinogenesis and cardio-cerebrovascular diseases. To establish a TLR2 receptor-based cell screening model, NF-kappaB promoter-driven luciferase reporter plasmids were transfected into human embryonic kidney cells (HEK293) stably expressing human TLR2 and co-receptors CD14, TLR1 and TLR6. Single clones were then isolated and characterized. Using this screening system, a human TLR2-binding peptide C8 was obtained from the Ph.D.-7 Phage Display Peptide Library through biopanning and rapid analysis of selective interactive ligands (BRASIL). The binding characteristic of C8 with human TLR2 was evaluated by ELISA, flow cytometry and immunofluorescence. The NF-kappaB luciferase activity assay showed that C8 could activate the TLR2/TLR1 signaling pathway and induce the production of cytokines TNF-alpha and IL-6. In conclusion, the TLR2 receptor-based cell screening system is successfully established and a new TLR2-binding peptide is identified by using this system.

Proteome Changes in the Intestinal Mucosa of Broiler (Gallus Gallus) Activated by Probiotic Enterococcus Faecium

Journal of Proteomics. Oct, 2013  |  Pubmed ID: 23899589

Probiotics are supplemented to animal diet to support a well-balanced gut microbiota, finally contributing to improved health. The molecular mechanism of probiotics in animal intestine improvement is yet unclear. We investigated the production parameters, gut morphology and microbiota, and mucosal proteome of Arbor Acres broilers (Gallus gallus) supplemented with Enterococcus faecium by performing denaturing gradient gel electrophoresis, quantitative real-time PCR, two-dimensional fluorescence difference gel electrophoresis, and mass spectrometry. E. faecium supplementation promoted the development of immune organs and gut microvilli and enlarged the gut microbial diversity and population. However, it had no effects on daily weight gain and feed intake, and slightly enhanced feed conversion ratio. A total of 42 intestinal mucosal proteins were found to be differentially abundant. Four of them are related to intestinal structure and may extend the absorptive surface area. Of 17 differential proteins related to immune and antioxidant systems, only six are abundant in the broilers fed E. faecium, indicating that these chickens employ less nutrients and energy to deal with immune and antioxidant stresses. These findings have important implications for understanding the probiotic mechanisms of E. faecium on broiler intestine.

Heterotrophic Nitrification and Aerobic Denitrification by a Novel Halomonas Campisalis

Biotechnology Letters. Dec, 2013  |  Pubmed ID: 23907666

A novel halophilic strain that could carry out heterotrophic nitrification and aerobic denitrification was isolated and named as Halomonas campisalis ha3. It removed inorganic nitrogen compounds (e.g. NO3 (-), NO2 (-) and NH4 (+)) simultaneously, and grew well in the medium containing up to 20 % (w/v) NaCl. PCR revealed four genes in the genome of ha3 related to aerobic denitrification: napA, nirS, norB and nosZ. The optimal conditions for aerobic denitrification were pH 9.0, at 37 °C, with 4 % (w/v) NaCl and sodium succinate as carbon source. The nitrogen removal rate was 87.5 mg NO3 (-)-N l(-1 )h(-1). Therefore, this strain is a potential aerobic denitrifier for the treatment of saline wastewater.

Safety and Feasibility of Mapping and Stem Cell Delivery in the Presence of an Implanted Left Ventricular Assist Device: a Preclinical Investigation in Sheep

Texas Heart Institute Journal / from the Texas Heart Institute of St. Luke's Episcopal Hospital, Texas Children's Hospital. 2013  |  Pubmed ID: 23914010

The objective of this study was to determine the safety and feasibility of performing transendocardial electromechanical mapping and mesenchymal precursor stem cell injections after left ventricular assist device (LVAD) implantation in a sheep model of acute myocardial infarction. Six sheep were assigned to either an acute or chronic group. Then we created an acute myocardial infarction in each by occluding the distal left anterior descending coronary artery with a balloon for 90 minutes. All the sheep underwent LVAD implantation 30 days later. On the same day, sheep in the acute group underwent transendocardial cell injections and were euthanized. Sheep in the chronic group received cell injections 2 weeks after LVAD implantation and were euthanized 30 days later. The presence of the LVAD or the use of chest-closure wires did not interfere with electromechanical mapping. Furthermore, no adverse events were observed during electromechanical mapping or the stem cell injections. In all sheep, the LVAD flow rate was approximately 4 L/min during mapping and the injections, and no adjustments were required. Histologic analysis confirmed that the mesenchymal precursor stem cells were successfully delivered. No differences were observed between the acute and chronic groups. In conclusion, our study showed that transendocardial electromechanical mapping and stem cell injections are safe and feasible in the presence of an LVAD. Surgically implanted metal devices, including the LVAD, steel chest-closure wire, and skin staples, were compatible with the electromechanical mapping system.

Design and Synthesis of Novel 2'-hydroxy Group Substituted 2-pyridone Derivatives As Anticancer Agents

European Journal of Medicinal Chemistry. Sep, 2013  |  Pubmed ID: 23920246

We have synthesized a series of novel 2-pyridone derivatives with 1,2,3-triazole and evaluated their anti-tumor activities in vitro. The bioassays showed that the majority of the resultant compounds exerted inhibitory effects on six human cancer cell lines to various extents. In particular, compound 10k showed the best anti-tumor activities (IC50 values of A549, HeLa and SW480 cancer cell lines were 0.86 ± 0.17 μM, 0.54 ± 0.23 μM and 0.21 ± 0.13 μM, respectively).

Endovascular Management for Retreatment of Postsurgical Intracranial Aneurysms

Neuroradiology. Nov, 2013  |  Pubmed ID: 23949553

Incomplete surgical treatment of intracranial aneurysms and recurrent postsurgical aneurysms are associated with a risk of rebleeding, and additional treatment is generally recommended. Surgical retreatment may carry a risk of procedural complications due to technical difficulty. We present here our experience with the endovascular approach for the retreatment of intracranial aneurysms that were initially treated with open surgery.

Spindle and Kinetochore Associated Complex Subunit 1 Regulates the Proliferation of Oral Adenosquamous Carcinoma CAL-27 Cells in Vitro

Cancer Cell International. 2013  |  Pubmed ID: 23962337

The prognosis of oral squamous cell carcinoma is very poor due to local recurrence and metastasis. This study explores the molecular events involved in oral carcinoma with the goal of developing novel therapeutic strategies. The mitotic spindle is a complex mechanical apparatus required for the accurate segregation of sister chromosomes during mitosis. Spindle and kinetochore associated complex subunit 1 (SKA1) is a microtubule-binding subcomplex of the outer kinetochore that is essential for proper chromosome segregation. In recent years, much attention has been focused on determining how SKA proteins interact with each other, as well as their biological role in cancer cells. However, the precise role of SKA1 in oral carcinoma remains unknown.

Lentivirus-based RNA Silencing of Nemo-like Kinase (NLK) Inhibits the CAL 27 Human Adenosquamos Carcinoma Cells Proliferation and Blocks G0/G1 Phase to S Phase

International Journal of Medical Sciences. 2013  |  Pubmed ID: 23983589

The Nemo-like kinase (NLK) is a serine/threonine-protein kinase that involved in a number of signaling pathways regulating cell fate. Variation of NLK has been shown to be associated with the risk of cancer. However, the function of NLK in oral adenosquamous carcinoma cells line CAL-27 is unknown.

A Study on the Efficacy and Safety Assessment of Propionyl-L-carnitine Tablets in Treatment of Intermittent Claudication

Thrombosis Research. Oct, 2013  |  Pubmed ID: 23998557

This study investigated the efficacy, safety and tolerability of propionyl-L-carnitine (PLC) in patients with intermittent claudication in the Chinese population.

[Study on UPLC-UV-MS Fingerprints of Different Medicinal Parts of Poria Cocos]

Zhong Yao Cai = Zhongyaocai = Journal of Chinese Medicinal Materials. Mar, 2013  |  Pubmed ID: 24010317

To establish an analytical method for the fingerprint of triterpenoid constituents of Poria cocos by UPLC-UV-MS and compare the fingerprints of different medicinal parts of Poria cocos.

Chemical Approaches to Stem Cell Biology and Therapeutics

Cell Stem Cell. Sep, 2013  |  Pubmed ID: 24012368

Small molecules that modulate stem cell fate and function offer significant opportunities that will allow the full realization of the therapeutic potential of stem cells. Rational design and screening for small molecules have identified useful compounds to probe fundamental mechanisms of stem cell self-renewal, differentiation, and reprogramming and have facilitated the development of cell-based therapies and therapeutic drugs targeting endogenous stem and progenitor cells for repair and regeneration. Here, we will discuss recent scientific and therapeutic progress, as well as new perspectives and future challenges for using chemical approaches in stem cell biology and regenerative medicine.

[Survey of Aflatoxins Contamination of Foodstuffs and Edible Oil in Shenzhen]

Wei Sheng Yan Jiu = Journal of Hygiene Research. Jul, 2013  |  Pubmed ID: 24024374

To identify the aflatoxins contamination of foodstuffs and edible oil sold in Shenzhen.

VATS Right Middle Lobectomy

Journal of Thoracic Disease. Aug, 2013  |  Pubmed ID: 24040555

A 48-year-old patient was admitted due to space occupying lesion in the right middle lobe, which was found by her healthy examination 1 month ago. Preoperative examinations displayed that the cardiopulmonary functions of the patient was normal, and chest computer tomography (CT) showed lesion located in the peripheral lung, diameter of the lesion was 3 cm, there was evidence that lymph node was visible in the mediastinum and no metastasis. Video-assisted thoracic surgery (VATS) right middle lobectomy was preformed, and intraoperative frozen section ensures the diagnosis of adenocarcinoma.

Synthesis and Antimicrobial Activity of Polyhalobenzonitrile Quinazolin-4(3H)-one Derivatives

Bioorganic & Medicinal Chemistry Letters. Nov, 2013  |  Pubmed ID: 24044873

A novel series of polyhalobenzonitrile quinazolin-4(3H)-one derivatives were synthesized and characterized by NMR, IR, MS, and HRMS spectra. All of the newly prepared compounds were screened for antimicrobial activities against four strains of bacteria (Gram-positive bacterial: Staphylococcus aureus and Bacillus cereus; Gram-negative bacterial: Escherichia coli and Pseudomonas aeruginosa) and one strain of fungi (Candida albicans). Among the synthesized compounds, 5-(dimethylamino)-8-(2,4,5-trichloro-isophthalonitrile) quinazolin-4(3H)-one (7k) exhibited significant activity towards Gram-positive bacterial, Gram-negative bacterial, and the fungi strains. The MIC (0.8-3.3μg/mL) and MBC (2.6-7.8μg/mL) for this compound were close to those of nofloxacin, chlorothalonil, and fluconazole, making it the most potent antimicrobial agents in the series.

Construction of the Basic Skeleton of Ophiobolin A and Variecolin

Organic & Biomolecular Chemistry. Oct, 2013  |  Pubmed ID: 24096306

Ophiobolin and variecolin type sesterterpenoids belong to cyclooctane-containing natural products. Both sesterterpenoids have challenging structures and appealing biological activities. We envisioned that a key tandem ring closing metathesis of dienynes could provide the basic skeleton of ophiobolin A and variecolin. We report herein the detailed reactivities of the dienynes which furnished the 5-8-5 and 5-8-6-5 rings efficiently.

[Three-dimensional Finite Element Stress Analysis of Mandibular First Molar with Single and Combined Crowns After Separation Prosthodontic Therapy]

Shanghai Kou Qiang Yi Xue = Shanghai Journal of Stomatology. Aug, 2013  |  Pubmed ID: 24100896

To evaluate the influence of two kinds of fixed prosthesis on the stress of the mandibular first molar with separation prosthodontic therapy.

Clinical and Pathological Features and Surgical Treatment of Budd-Chiari Syndrome-associated Hepatocellular Carcinoma

Chinese Medical Journal. 2013  |  Pubmed ID: 24112155

Budd-Chiari syndrome (BCS) is characterized by liver sinusoidal congestion, ischemic liver cell damage, and liver portal hypertension caused by hepatic venous outflow constriction. The aim of this research was to investigate the clinicopathological features of BCS-associated hepatocellular carcinoma (HCC) and explore its surgical treatment and prognosis.

Proteomics Analysis of UV-irradiated Lonicera Japonica Thunb. with Bioactive Metabolites Enhancement

Proteomics. Dec, 2013  |  Pubmed ID: 24167072

A previous study showed that the contents of caffeoylquinic acids and iridoids, the major bioactive components in the postharvest Lonicera japonica Thunb., were induced by enhanced ultraviolet (UV)-A or UV-B irradiation. To clarify the UV-responsive key enzymes in the bioactive metabolites biosynthetic pathway and the related plant defense mechanism in L. japonica, 2DE in combination with MALDI-TOF/TOF MS was employed. Seventy-five out of 196 differential proteins were positively identified. Based on the functions, these proteins were grouped into nine categories, covering a wide range of molecular processes including the secondary metabolites (caffeoylquinic acids and iridoids) biosynthetic-related proteins, photosynthesis, carbohydrate and energy metabolism, stress, DNA, transport-related proteins, lipid metabolism, amino acid metabolism, cell wall. Of note is the increasing expression of 1-deoxy-d-xylulose 5-phosphate reductoisomerase and 5-enol-pyruvylshikimate-phosphate synthase, which was crucial to supply more precursor for the secondary metabolites including caffeoylquinic acids and iridoids. Thus, this study provides both the clues at the protein level for the increase of the two bioactive components upon UV irradiation and the profile of UV-responsive proteins in L. japonica.

Biosynthesis and Release of Pheromonal Bile Salts in Mature Male Sea Lamprey

BMC Biochemistry. 2013  |  Pubmed ID: 24188124

In vertebrates, bile salts are primarily synthesized in the liver and secreted into the intestine where they aid in absorption of dietary fats. Small amounts of bile salts that are not reabsorbed into enterohepatic circulation are excreted with waste. In sexually mature male sea lamprey (Petromyzon marinus L.) a bile salt is released in large amounts across gill epithelia into water where it functions as a pheromone. We postulate that the release of this pheromone is associated with a dramatic increase in its biosynthesis and transport to the gills upon sexual maturation.

Systematic Review and Meta-analysis of Tumor Biomarkers in Predicting Prognosis in Esophageal Cancer

BMC Cancer. 2013  |  Pubmed ID: 24206575

Esophageal cancer (EC) is a frequently occurring cancer with poor prognosis despite combined therapeutic strategies. Many biomarkers have been proposed as predictors of adverse events. We sought to assess the prognostic value of biomarkers in predicting the overall survival of esophageal cancer and to help guide personalized cancer treatment to give patients the best chance at remission.

[Lycopene Protects Against Hypoxia/reoxygenation-injury by Preventing Calpain Activation]

Zhonghua Xin Xue Guan Bing Za Zhi. Aug, 2013  |  Pubmed ID: 24225236

To investigate the possible mechanism of lycopene on protecting against hypoxia/reoxygenation (H/R)-injury.

Petromyzonin, a Hexahydrophenanthrene Sulfate Isolated from the Larval Sea Lamprey (Petromyzon Marinus L.)

Organic Letters. Dec, 2013  |  Pubmed ID: 24228814

A new hexahydrophenanthrene sulfate was identified from water conditioned with sea lamprey larvae ( Petromyzon marinus ) and named petromyzonin. Its structure was unequivocally elucidated on the basis of spectroscopic analyses including comparison with spectra of known compounds. The absolute configuration was determined by electronic circular dichroism. Petromyzonin may function as a chemical signal, as it elicited responses in electro-olfactogram recording with a dynamic concentration-response relationship and a detection threshold of 10(-11) M.

Directional Coordination of Thumb and Finger Forces During Precision Pinch

PloS One. 2013  |  Pubmed ID: 24236128

The human opposable thumb enables the hand to perform dexterous manipulation of objects, which requires well-coordinated digit force vectors. This study investigated the directional coordination of force vectors generated by the thumb and index finger during precision pinch. Fourteen right-handed, healthy subjects were instructed to exert pinch force on an externally stabilized apparatus with the pulps of the thumb and index finger. Subjects applied forces to follow a force-ramp profile that linearly increased from 0 to 12 N and then decreased to 0 N, at a rate of ± 3 N/s. Directional relationships between the thumb and index finger force vectors were quantified using the coordination angle (CA) between the force vectors. Individual force vectors were further analyzed according to their projection angles (PAs) with respect to the pinch surface planes and the shear angles (SAs) within those planes. Results demonstrated that fingertip force directions were dependent on pinch force magnitude, especially at forces below 2 N. Hysteresis was observed in the force-CA relationship for increasing and decreasing forces and fitted with exponential models. The fitted asymptotic values were 156.0 ± 6.6° and 150.8 ± 9.3° for increasing and decreasing force ramps, respectively. The PA of the thumb force vector deviated further from the direction perpendicular to the pinching surface planes than that of the index finger. The SA showed that the index finger force vector deviated in the ulnar-proximal direction, whereas the thumb switched its force between the ulnar-proximal and radial-proximal directions. The findings shed light on the effects of anatomical composition, biomechanical function, and neuromuscular control in coordinating digit forces during precision pinch, and provided insight into the magnitude-dependent force directional control which potentially affects a range of dexterous manipulations.

Intranasal Delivery of Neural Stem Cells: A CNS-specific, Non-invasive Cell-based Therapy for Experimental Autoimmune Encephalomyelitis

Journal of Clinical & Cellular Immunology. Jun, 2013  |  Pubmed ID: 24244890

The therapeutic potential of adult neural stem cells (aNSCs) has been shown in EAE, an animal model of MS, administered by either i.c.v. or i.v. injection. However, i.c.v. is an invasive approach, while the i.v. route of aNSCs is associated with a non-specific immune suppression in the periphery. Here we demonstrate that intranasal (i.n.) delivery of fluorescently labeled aNSCs resulted in their appearance in the olfactory bulb, cortex, hippocampus, striatum, brainstem, and spinal cord. These cells induce functional recovery from ongoing EAE similar to that achieved with i.v. injected aNSCs, with comparable anti-inflammatory and remeylination effects in CNS inflammatory foci. Importantly, unlike the peripheral immune suppression brought about by i.v. NSCs, intranasal delivery did not influence peripheral immune responses. We conclude that aNSCs can be reliably delivered to the CNS via the nasal route to induce functional recovery and confer immunomodulation and remyelination in EAE. Intranasal administration of NSCs provides a highly promising, noninvasive and CNS-specific alternative to current cell-based approaches in treating EAE.

The Analysis of Efficacy and Failure Factors of Uterine Artery Methotrexate Infusion and Embolization in Treatment of Cesarean Scar Pregnancy

TheScientificWorldJournal. 2013  |  Pubmed ID: 24282376

This study observes therapeutic efficacy of uterine artery embolization combined with MTX infusion which terminates cesarean scar pregnancy (CSP) and induces three factors which probably relate to failure.

Prognostic Value of Cancer Stem Cell Marker Aldehyde Dehydrogenase in Ovarian Cancer: a Meta-analysis

PloS One. 2013  |  Pubmed ID: 24282568

Aldehyde dehydrogenase (ALDH) has recently been reported as a marker of cancer stem-like cells in ovarian cancer. However, the prognostic role of ALDH in ovarian cancer still remains controversial. In this study, we aimed to evaluate the association between the expression of ALDH and the outcome of ovarian cancer patients by performing a meta-analysis.

Correlation Between Human Observer Performance and Model Observer Performance in Differential Phase Contrast CT

Medical Physics. Nov, 2013  |  Pubmed ID: 24320438

With the recently expanding interest and developments in x-ray differential phase contrast CT (DPC-CT), the evaluation of its task-specific detection performance and comparison with the corresponding absorption CT under a given radiation dose constraint become increasingly important. Mathematical model observers are often used to quantify the performance of imaging systems, but their correlations with actual human observers need to be confirmed for each new imaging method. This work is an investigation of the effects of stochastic DPC-CT noise on the correlation of detection performance between model and human observers with signal-known-exactly (SKE) detection tasks.

Study on the Absorbed Fingerprint-efficacy of Yuanhu Zhitong Tablet Based on Chemical Analysis, Vasorelaxation Evaluation and Data Mining

PloS One. 2013  |  Pubmed ID: 24339904

Yuanhu Zhitong Tablet (YZT) is an example of a typical and relatively simple clinical herb formula that is widely used in clinics. It is generally believed that YZT play a therapeutical effect in vivo by the synergism of multiple constituents. Thus, it is necessary to build the relationship between the absorbed fingerprints and bioactivity so as to ensure the quality, safety and efficacy. In this study, a new combinative method, an intestinal absorption test coupled with a vasorelaxation bioactivity experiment in vitro, was a simple, sensitive, and feasible technique to study on the absorbed fingerprint-efficacy of YZT based on chemical analysis, vasorelaxation evaluation and data mining. As part of this method, an everted intestinal sac method was performed to determine the intestinal absorption of YZT solutions. YZT were dissolved in solution (n = 12), and the portion of the solution that was absorbed into intestinal sacs was analyzed using rapid-resolution liquid chromatography coupled with quadruple time-of-flight mass spectrometry (RRLC-Q-TOF/MS). Semi-quantitative analysis indicated the presence of 34 compounds. The effect of the intestinally absorbed solution on vasorelaxation of rat aortic rings with endothelium attached was then evaluated in vitro. The results showed that samples grouped by HCA from chemical profiles have similar bioactivity while samples in different groups displayed very different. Moreover, it established a relationship between the absorbed fingerprints and their bioactivity to identify important components by grey relational analysis, which could predict bioactive values based on chemical profiles and provide an evidence for the quantification of multi-constituents.

Microbial Diversity and Succession in the Chinese Luzhou-Flavor Liquor Fermenting Cover Lees As Evaluated by SSU RRNA Profiles

Indian Journal of Microbiology. Dec, 2013  |  Pubmed ID: 24426146

The microbial diversity and the community succession in the fermenting cover lees of Chinese Luzhou-flavor liquor were investigated by small-subunit rRNA (SSU rRNA) culture independent method. All sequences retrieved from the 1, 7 and 60 days fermented cover lees were respectively assigned into the genera of Streptococcus, Acetobacter, Arthrobacter, Bacillus, Staphylococcus, Serratia, Nocardia, Methanoculleus, Clostridium, Aneurinibacillus, Corynebacterium, Lactobacillus, Microbacterium, Trichosporon, Saccharomycopsis, Sagenomella, Talaromyces, Eurotium, Issatchenkia, Zygosaccharomyces, Saccharomyces and TM7 phylum. The fungal Issatchenkia, Saccharomycopsis and Talaromyces and the bacteria Staphylococcus and Lactobacillus were most abundant in the 1 day fermented cover lees, the fungal Issatchenkia, Saccharomyces and Talaromyces and the bacteria Bacillus and Streptococcus were dominant in the 7 days cover lees, the archaea Methanoculleus and the fungal Eurotium and Talaromyces were prevalent in the 60 days cover lees. When the microbial community profiles in three samples were compared at species level, the prokaryotic community similarity coefficient was from 0.4042 to 0.5703 and descended to 0.2222, and that of eukaryotic community was from 0.3000 to 0.6000 and followed to 0.5215. These results suggested that microbial diversity variability and community succession have happened in the cover lees associated with fermentation proceeding and such variability and succession respond for the appearance of some unique flavor of Luzhou-flavor liquor.

Efficacy and Safety of Trastuzumab Added to Standard Treatments for HER2-positive Metastatic Breast Cancer Patients

Asian Pacific Journal of Cancer Prevention : APJCP. 2013  |  Pubmed ID: 24460260

Trastuzumab, an HER2-targeting agents, has shown efficacy in metastatic HER2-positive breast cancer patients. Single-agent clinical trials have evaluated therapeutic regimens using trastuzumab for metastatic breast cancer patients. The aim of our study is to evaluate the efficacy and safety of trastuzumab in combination with chemotherapy or hormone therapy in HER2-positive metastatic breast cancer patients.

[Study on Fingerprint of Shengxuening Tablets]

Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica. Oct, 2013  |  Pubmed ID: 24490562

To establish a method for studying fingerprint of Shengxuening tablets. With chlorin e6 as the reference substance, SHISEIDO Capcell-pak C18 (4.6 mm x 250 mm, 5 microm) analytical column was adopted and eluted with 0.2% formic acid ( containing 20 mmol x L(-1) TBAB) (A) and acetonitrile-methanol-acetone (50: 50: 5) (B). The detection wavelength was set 392 nm. The volume flow rate was 1.0 mL x min(-1). The temperature of column was 45 degrees C. Totally 10 common peaks were indicated on the HPLC fingerprint, with RSDs for variable retention values in common peaks below 0.50%. UPLC/DAD/Q-TOF-MS xevo G2 Q-TOF LC/MS was adopted to preliminarily indentify six chromatographic peaks. The main ingredient in Shengxuening tablets was ferrous derivative, which was mainly composed of Fe chlorin p6, Fe chlorin e6 and Fe isochlorin e4.

Targeting Acute Myeloid Leukemia with a Proapoptotic Peptide Conjugated to a Toll-like Receptor 2-mediated Cell-penetrating Peptide

International Journal of Cancer. Journal International Du Cancer. Feb, 2014  |  Pubmed ID: 23852533

Cell-penetrating peptides provide a unique platform to create a new generation of cancer therapeutics with enhanced efficacy and diminished toxicity. In our study, enhanced expression of toll-like receptor 2 (TLR2) was observed in acute myeloid leukemia (AML) cells. Screening of a phage display peptide library using Biopanning and Rapid Analysis of Selective Interactive Ligands (BRASIL) identified a TLR2-binding peptide motif, Pep2. We show that the TLR2-binding peptide motif targeted and penetrated into leukemia cells in a TLR2-dependent manner. Moreover, a synthetic, chimeric peptide composed of the TLR2-binding motif linked to a programmed cell death-inducing sequence, D(KLAKLAK)2, induced apoptosis in AML cells with high TLR2 expression (TLR2(high)) but not in chronic myeloid leukemia (CML) cells with low TLR2 expression (TLR2(low)). The antileukemia activity of this chimeric peptide was confirmed in leukemia patient samples and an animal model of myeloid leukemia, as the development of leukemia was significantly delayed in mice with TLR2(high) AML compared to TLR2(low) CML NOD/SCID mice. TUNEL assays on bone marrow tissue slices revealed that the chimerical peptide induced leukemia cell apoptosis in a TLR2-dependent manner. Together, our findings indicate that TLR2 is a potential therapeutic target for the prevention and treatment of AML, and the prototype, Pep2-D(KLAKLAK)2, is a promising drug candidate in this setting.

Upregulation of MiR-136 in Human Non-small Cell Lung Cancer Cells Promotes Erk1/2 Activation by Targeting PPP2R2A

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine. Jan, 2014  |  Pubmed ID: 23959478

MicroRNAs (miRNAs) have been integrated into cancer development and progression, because they repress translation of target genes which can be tumor suppressors and oncogenes. A number of miRNAs have been found to be closely related to human non-small cell lung cancer (NSCLC). However, the roles of miR-136 in NSCLC are still largely unknown. Here, we show that miR-136 is significantly upregulated in human NSCLC primary tumors and cell lines compared to their nontumor counterparts. Suppression of miR-136 expression in NSCLC cell line A549 inhibited both anchorage-dependent and anchorage-independent proliferation. Further studies showed that suppression of miR-136 expression attenuated phosphorylation of extracellular-signal-regulated kinase 1/2 (Erk1/2). We found that serine/threonine protein phosphatase 2A 55 kDa regulatory subunit B α isoform (PPP2R2A, also known as B55α) was a direct target of miR-136, and suppression of miR-136 expression led to a robust increase in both mRNA and protein levels of PPP2R2A. We found that miR-136 promoted phosphorylation of Erk1/2 through inhibition of PPP2R2A expression, and forced overexpression of PPP2R2A abrogated promotion of Erk1/2 phosphorylation by miR-136. Moreover, forced overexpression of PPP2R2A abrogated the promoting effect of miR-136 on cell growth and led to a reduced growth rate of NSCLC cells. Our findings indicate that miR-136 promotes Erk1/2 phosphorylation through targeting PPP2R2A in NSCLC cells and suggest that it may serve as a therapeutic target in NSCLC therapy.

Evolutionary Algorithms with Segment-based Search for Multiobjective Optimization Problems

IEEE Transactions on Cybernetics. Aug, 2014  |  Pubmed ID: 24132034

This paper proposes a variation operator, called segment-based search (SBS), to improve the performance of evolutionary algorithms on continuous multiobjective optimization problems. SBS divides the search space into many small segments according to the evolutionary information feedback from the set of current optimal solutions. Two operations, micro-jumping and macro-jumping, are implemented upon these segments in order to guide an efficient information exchange among "good" individuals. Moreover, the running of SBS is adaptive according to the current evolutionary status. SBS is activated only when the population evolves slowly, depending on general genetic operators (e.g., mutation and crossover). A comprehensive set of 36 test problems is employed for experimental verification. The influence of two algorithm settings (i.e., the dimensionality and boundary relaxation strategy) and two probability parameters in SBS (i.e., the SBS rate and micro-jumping proportion) are investigated in detail. Moreover, an empirical comparative study with three representative variation operators is carried out. Experimental results show that the incorporation of SBS into the optimization process can improve the performance of evolutionary algorithms for multiobjective optimization problems.

Effect of a Beating Process, As a Means of Reducing Salt Content in Chinese-style Meatballs (kung-wan): a Dynamic Rheological and Raman Spectroscopy Study

Meat Science. Feb, 2014  |  Pubmed ID: 24200556

Chopping and beating processes were used as meat-cutting methods in preparing kung-wan to produce low-salt products while retaining or improving the emulsion stability, sensory evaluation, and physico-chemical properties of the standard high-salt formulation. Increased salt content improved emulsion stability and dynamic rheology. However, 3% salt content decreased the overall acceptance of kung-wan. Compared with the chopping process, beating resulted in higher emulsion stability, overall acceptance, and β-sheet content (P<0.05). Additionally, the beating process formed more compact and continuous structures at the same salt content. Kung-wan produced by beating with 1% and 2% salt had similar emulsion stabilities, sensory evaluation, and secondary structures (P>0.05). Therefore, this process allows reduction of salt content, suggesting that the kung-wan produced in this manner is healthier and has better texture.

Influence of Timing Algorithm on Brachialankle Pulse Wave Velocity Measurement

Bio-medical Materials and Engineering. 2014  |  Pubmed ID: 24211905

The baPWV measurement is a non-invasive and convenient technique in an assessment of arterial stiffness. Despite its widespread application, the influence of different timing algorithms is still unclear. The present study was conducted to investigate the influence of six timing algorithms (MIN, MAX, D1, D2, MDP and INS) on the baPWV measurement and to evaluate the performance of them. Forty-five CAD patients and fifty-five healthy subjects were recruited in this study. A PVR acquisition apparatus was built up for baPWV measurement. The baPWV and other related parameters were calculated separately by the six timing algorithms. The influence and performance of the six algorithms was analyzed. The six timing algorithms generate significantly different baPWV values (left: F=29.036, P<0.001; right: F=40.076, P<0.001). In terms of reproducibility, the MAX has significantly higher CV value (≥ 18.6%) than the other methods, while the INS has the lowest CV value (≤ 2.7%). On the performance of classification, the INS produces the highest AUC values (left: 0.854; right: 0.872). The MIN and D2 also have a passable performance (AUC > 0.8). The choice of timing algorithm affects baPWV values and the quality of measurement. The INS method is recommended for baPWV measurement.

Exchange-mediated Contrast in CEST and Spin-lock Imaging

Magnetic Resonance Imaging. Jan, 2014  |  Pubmed ID: 24239335

Magnetic resonance images of biological media based on chemical exchange saturation transfer (CEST) show contrast that depends on chemical exchange between water and other protons. In addition, spin-lattice relaxation rates in the rotating frame (R1ρ) are also affected by exchange, especially at high fields, and can be exploited to provide novel, exchange-dependent contrast. Here, we evaluate and compare the factors that modulate the exchange contrast for these methods using simulations and experiments on simple, biologically relevant samples.

Difference in Cesium Accumulation Among Rice Cultivars Grown in the Paddy Field in Fukushima Prefecture in 2011 and 2012

Journal of Plant Research. 2014  |  Pubmed ID: 24338062

After the accident of the Fukushima 1 Nuclear Power Plant in March 2011, radioactive cesium was released and paddy fields in a wide area including Fukushima Prefecture were contaminated. To estimate the levels of radioactive Cs accumulation in rice produced in Fukushima, it is crucial to obtain the actual data of Cs accumulation levels in rice plants grown in the actual paddy field in Fukushima City. We herein conducted a two-year survey in 2011 and 2012 of radioactive and non-radioactive Cs accumulation in rice using a number of rice cultivars grown in the paddy field in Fukushima City. Our study demonstrated a substantial variation in Cs accumulation levels among the cultivars of rice.

Quantitative Magnetization Transfer Imaging of Rodent Glioma Using Selective Inversion Recovery

NMR in Biomedicine. Mar, 2014  |  Pubmed ID: 24338993

Magnetization transfer (MT) provides an indirect means to detect noninvasively variations in macromolecular contents in biological tissues, but, so far, there have been only a few quantitative MT (qMT) studies reported in cancer, all of which used off-resonance pulsed saturation methods. This article describes the first implementation of a different qMT approach, selective inversion recovery (SIR), for the characterization of tumor in vivo using a rodent glioma model. The SIR method is an on-resonance method capable of fitting qMT parameters and T1 relaxation time simultaneously without mapping B0 and B1 , which is very suitable for high-field qMT measurements because of the lower saturation absorption rate. The results show that the average pool size ratio (PSR, the macromolecular pool versus the free water pool) in rat 9 L glioma (5.7%) is significantly lower than that in normal rat gray matter (9.2%) and white matter (17.4%), which suggests that PSR is potentially a sensitive imaging biomarker for the assessment of brain tumor. Despite being less robust, the estimated MT exchange rates also show clear differences from normal tissues (19.7 Hz for tumors versus 14.8 and 10.2 Hz for gray and white mater, respectively). In addition, the influence of confounding effects, e.g. B1 inhomogeneity, on qMT parameter estimates is investigated with numerical simulations. These findings not only help to better understand the changes in the macromolecular contents of tumors, but are also important for the interpretation of other imaging contrasts, such as chemical exchange saturation transfer of tumors.

Penetrating Injury of the Vagina, Bladder and Omentum in a Woman with 5 Months Gestation: Case Report and Review of the Literature

International Urology and Nephrology. Jun, 2014  |  Pubmed ID: 24366762

Intra-peritoneal bladder and visceral injuries from impalement of the perineum in women are exceedingly rare. This kind of injury has not been previously reported in a pregnant woman. The evaluation and surgical management of a pregnant woman is a challenging surgical problem. Preoperative evaluation of the uterus and fetus is balanced with minimal use of radiographic studies. Multiple organs can be damaged with this type of injury, necessitating careful evaluation and operative planning. We report a rare case of transvaginal impalement injury with through-and-through bladder rupture and intra-peritoneal injury in a 5 months pregnant woman. We discuss diagnostic and management strategies and review the literature.

Grating-based Phase Contrast Tomosynthesis Imaging: Proof-of-concept Experimental Studies

Medical Physics. Jan, 2014  |  Pubmed ID: 24387511

This paper concerns the feasibility of x-ray differential phase contrast (DPC) tomosynthesis imaging using a grating-based DPC benchtop experimental system, which is equipped with a commercial digital flat-panel detector and a medical-grade rotating-anode x-ray tube. An extensive system characterization was performed to quantify its imaging performance.

Cytokine IL-6 is Required in Citrobacter Rodentium Infection-induced Intestinal Th17 Responses and Promotes IL-22 Expression in Inflammatory Bowel Disease

Molecular Medicine Reports. Mar, 2014  |  Pubmed ID: 24430732

Citrobacter rodentium (C. rodentium) infection is a widely used murine model to mimic human enteric bacteria infection and inflammatory bowel disease (IBD). In this model, interleukin (IL)‑17A plays critical roles in increasing chemokine and cytokine production in various tissues to recruit innate cells, including monocytes and neutrophils, to the local site of infection. However, the source of IL‑17A remains unclear, as the majority of cell types produce IL‑17A, including intestinal endothelium cells, innate immune cells and CD4+ T cells in disease development. In the current study, wild‑type B6 mice were treated with C. rodentium and the CD4+ Th17 cell subset was observed as being specifically increased in Peyer's patches (PP), but not in mesenteric draining lymph nodes. Furthermore, the research suggested that the differentiation and activation of Th17 cells in PP were dependent on the inflammatory cytokine IL‑6, as blocking IL‑6 signaling with neutralizing antibodies decreased Th17 cells and resulted in the mice being more susceptible to C. rodentium infection. These results confirmed that the Th17 cell subset was specifically activated in PP and demonstrated that IL‑6 is required in Th17 cell activation, which are important to the clinical treatment of IBD.

Small Molecules Facilitate the Reprogramming of Mouse Fibroblasts into Pancreatic Lineages

Cell Stem Cell. Feb, 2014  |  Pubmed ID: 24506886

Pancreatic β cells are of great interest for the treatment of type 1 diabetes. A number of strategies already exist for the generation of β cells, but a general approach for reprogramming nonendodermal cells into β cells could provide an attractive alternative in a variety of contexts. Here, we describe a stepwise method in which pluripotency reprogramming factors were transiently expressed in fibroblasts in conjunction with a unique combination of soluble molecules to generate definitive endoderm-like cells that did not pass through a pluripotent state. These endoderm-like cells were then directed toward pancreatic lineages using further combinations of small molecules in vitro. The resulting pancreatic progenitor-like cells could mature into cells of all three pancreatic lineages in vivo, including functional, insulin-secreting β-like cells that help to ameliorate hyperglycemia. Our findings may therefore provide a useful approach for generating large numbers of functional β cells for disease modeling and, ultimately, cell-based therapy.

Investigation of Inclusion Complex of Epothilone A with Cyclodextrins

Carbohydrate Polymers. Feb, 2014  |  Pubmed ID: 24507285

The inclusion complexation of Epothilone A with native cyclodextrin (β- or γ-CD) and its derivative hydroxypropyl-β-cyclodextrin (HPβCD) were prepared. Their behavior, characterization, and binding ability were investigated in both solution and the solid state by means of UV-vis, NMR, XRD, DSC and SEM. The results show that the water solubility and solution stability obviously increased in the inclusion complex with cyclodextrins. Meanwhile, the inclusion complexes still retained anticancer activity against A549 and MCF-7 cells, similar to free Epothilone A. This satisfactory water solubility, high solution stability, and high anticancer activity of the Epothilone A/CD complexes will be potentially useful as an anticancer therapy.

Spatiotemporal Independent Component Analysis Combine General Linear Model Applied to FMRI for Eliminating Neural Noise

Australasian Physical & Engineering Sciences in Medicine / Supported by the Australasian College of Physical Scientists in Medicine and the Australasian Association of Physical Sciences in Medicine. Mar, 2014  |  Pubmed ID: 24532392

Functional magnetic resonance imaging (fMRI) has recently become an effective means to explore the mechanism of functional rehabilitation in stroke patients. Neural noise is an inevitable structural noise, and is an important factor caused individual differences in fMRI data, therefore, eliminating the neural noise is being regarded as one of the task that cannot be ignored. In this paper, a new algorithm combines spatiotemporal independent component analysis and general linear model (GLM) is proposed to eliminate the effect caused by excess neural activity. This new algorithm simultaneously maximizes the independence over time and space in fMRI data for establishing the spatiotemporal balance. The new technique was applied to extract the active regions of ankle dorsiflexion during fMRI scanning process. Compared to results of GLM, the results of new combined algorithm is more reasonable with an 8% improvement in correlation coefficient. It confirmed that this new algorithm is effective in eliminating system noise and neural disturbance.

Adult Colonoscopy or Single-balloon Enteroscopy-assisted ERCP in Long-limb Surgical Bypass Patients

Clinics and Research in Hepatology and Gastroenterology. Sep, 2014  |  Pubmed ID: 24560303

The aim of this study was to evaluate the usefulness of adult colonoscopy or single-balloon enteroscopy (SBE)-assisted endoscopic retrograde cholangiopancreatography (ERCP) in long-limb surgical bypass patients.

Absorption Enhancement of Single Silicon Nanowire by Tailoring Rear Metallic Film for Photovoltaic Applications

Optics Letters. Feb, 2014  |  Pubmed ID: 24562214

In this work, single-nanowire solar cells (SCs) in lying configuration with a tunable rear metallic film are presented. Compared to the standalone silicon nanowire (SiNW), a significant/broadband enhancement in the overall optical absorption of the SiNW with rear metallic nanoconfiguration was observed. The optimized fraction, corresponding to the maximal ultimate photocurrent, of the SiNW surrounded by metallic film was achieved by properly engineering the SiNW radius and metallic film thickness. The considered configuration can be effectively extended to the alternative configuration with a SiNW partially embedded in a metallic substrate, where the ultimate photocurrent density of the 100 nm radius SiNW can be improved by 75.50% relative to that of the freestanding SiNW. Our simulations verify that it is a promising route for developing highly efficient single nanowire SCs.

Plasma Cell-free DNA for Predicting Outcomes of Patients with HBV-related Acute-on-chronic Liver Failure: a Pilot Study

Nan Fang Yi Ke Da Xue Xue Bao = Journal of Southern Medical University. Feb, 2014  |  Pubmed ID: 24589586

Cell-free DNA (cfDNA) was shown to be a prognostic marker for diverse pathological states in the Intense Care Unit, but little is known of the role of cfDNA in HBV-related acute-on-chronic liver failure (ACLF). We hypothesize that cfDNA can also be a promising prognostic as well as a diagnostic marker in patients with HBV-related ACLF.

4β-Hydroxycholesterol As an Endogenous Biomarker of CYP3A Activity in Cynomolgus Monkeys

Drug Metabolism and Disposition: the Biological Fate of Chemicals. May, 2014  |  Pubmed ID: 24595680

It has been proposed that in humans 4β-hydroxycholesterol is formed mainly by CYP3A-catalyzed metabolism of cholesterol and thus may serve as an endogenous marker for CYP3A activity. The cynomolgus monkey is widely used as one of the nonrodent preclinical safety species in pharmaceutical research. In the current study, the potential application of 4β-hydroxycholesterol as an endogenous biomarker of CYP3A in response to drug treatment was evaluated in cynomolgus monkeys. Following multiple oral administration of rifampicin (a known CYP3A inducer) at 15 mg/kg/d in cynomolgus monkeys, the mean serum 4β-hydroxycholesterol levels increased 4-fold from the baseline of 55.3 ± 21.7 to 221 ± 53.4 ng/ml. The mean concentration ratios of 4β-hydroxycholesterol to cholesterol increased 5-fold. The data suggest that 4β-hydroxycholesterol formation from cholesterol metabolism was induced by rifampicin treatment in monkeys. This observation correlated with the metabolism of midazolam (a probe substrate of CYP3A activity) monitored in the same study. The serum exposure (area under the curve) of midazolam was markedly decreased by ∼95%, confirming the induction of CYP3A catalytic activity by rifampicin treatment in monkeys. The formation of 4β-hydroxycholesterol from cholesterol was specifically mediated by recombinant cynomolgus CYP3A8 and CYP3A5. The Km values of CYP3A8 and CYP3A5 for 4β-hydroxycholesterol formation from cholesterol were 204 and 104 μM, respectively, and Vmax values were 0.600 and 0.310 pg/pmol/min, respectively. The results suggest that 4β-hydroxycholesterol can be used as an endogenous biomarker to identify strong CYP3A inducers in cynomolgus monkeys, which may help to evaluate drug-drug interaction potential of drug candidates in preclinical settings.

The Prognostic Value of CXCR4 in Ovarian Cancer: a Meta-analysis

PloS One. 2014  |  Pubmed ID: 24658065

Recent reports have shown that C-X-C chemokine receptor 4 (CXCR4) is expressed in ovarian cancer and plays an important role in metastasis. However, the prognostic value of CXCR4 in ovarian cancer remains controversial and has not been emphasized. The aim of this study is to evaluate the prognostic significance of CXCR4 in ovarian cancer by performing a meta-analysis.

Statistical Model Based Iterative Reconstruction (MBIR) in Clinical CT Systems: Experimental Assessment of Noise Performance

Medical Physics. Apr, 2014  |  Pubmed ID: 24694137

To reduce radiation dose in CT imaging, the statistical model based iterative reconstruction (MBIR) method has been introduced for clinical use. Based on the principle of MBIR and its nonlinear nature, the noise performance of MBIR is expected to be different from that of the well-understood filtered backprojection (FBP) reconstruction method. The purpose of this work is to experimentally assess the unique noise characteristics of MBIR using a state-of-the-art clinical CT system.

[The Etiology of Neurological Disorders in 1 188 Elder Patients with Neuroimaging at Geriatric Outpatient Clinic]

Zhonghua Nei Ke Za Zhi. Mar, 2014  |  Pubmed ID: 24767208

To investigate the etiology of neurological disorders in elderly at outpatient clinic.

Expression and Regulation of Complement Receptors by Human Natural Killer Cells

Immunobiology. Sep, 2014  |  Pubmed ID: 24775270

Integration of cellular and humoral arms of the innate immune response is fundamental to the development of powerful effector functions in host defence as well as aberrant immune responses. Here, we provide evidence in support of the relationship between complement activation and NK cell functional modulation. We demonstrate that human NK cells and both CD56(bright)CD16(-) and CD56(dim)CD16(+) populations express receptors known to detect the biologically active peptides C3a and C5a (i.e. C3aR, C5aR, C5L2) and the covalently-bound fragments C3b and metabolites iC3b and C3d which serve in immune adhesion (e.g. CR3, CR4). We also show that several pathogen- or tumour/inflammation-related stimuli differentially regulated those complement receptor expression. Furthermore, our results suggest that C3 fragments (C3a, iC3b) have a negative regulatory effect on IFN-γ production in NK cells. This work provides extensive information of human complement receptors relevant to the integrated actions of complement and NK cells which has been suggested by animal studies. The observations may act as a resource that allows further understanding and exploitation of role of complement in human health and immune mediated diseases.

Multi-parametric MRI Characterization of Inflammation in Murine Skeletal Muscle

NMR in Biomedicine. Jun, 2014  |  Pubmed ID: 24777935

Myopathies often display a common set of complex pathologies that include muscle weakness, inflammation, compromised membrane integrity, fat deposition, and fibrosis. Multi-parametric, quantitative, non-invasive imaging approaches may be able to resolve these individual pathological components. The goal of this study was to use multi-parametric MRI to investigate inflammation as an isolated pathological feature. Proton relaxation, diffusion tensor imaging (DTI), quantitative magnetization transfer (qMT-MRI), and dynamic contrast enhanced (DCE-MRI) parameters were calculated from data acquired in a single imaging session conducted 6-8 hours following the injection of λ-carrageenan, a local inflammatory agent. T2 increased in the inflamed muscle and transitioned to bi-exponential behavior. In diffusion measurements, all three eigenvalues and the apparent diffusion coefficient increased, but λ3 had the largest relative change. Analysis of the qMT data revealed that the T1 of the free pool and the observed T1 both increased in the inflamed tissue, while the ratio of exchanging spins in the solid pool to those in the free water pool (the pool size ratio) significantly decreased. DCE-MRI data also supported observations of an increase in extracellular volume. These findings enriched the understanding of the relation between multiple quantitative MRI parameters and an isolated inflammatory pathology, and may potentially be employed for other single or complex myopathy models.

Eye Development

Methods (San Diego, Calif.). Jun, 2014  |  Pubmed ID: 24784530

The eye has been one of the most intensively studied organs in Drosophila. The wealth of knowledge about its development, as well as the reagents that have been developed, and the fact that the eye is dispensable for survival, also make the eye suitable for genetic interaction studies and genetic screens. This article provides a brief overview of the methods developed to image and probe eye development at multiple developmental stages, including live imaging, immunostaining of fixed tissues, in situ hybridizations, and scanning electron microscopy and color photography of adult eyes. Also summarized are genetic approaches that can be performed in the eye, including mosaic analysis and conditional mutation, gene misexpression and knockdown, and forward genetic and modifier screens.

Optimization of Ultrasonic Extraction of Total Flavonoids from Tussilago Farfara L. Using Response Surface Methodology

Die Pharmazie. Apr, 2014  |  Pubmed ID: 24791598

In this work, ultrasound technology was used for the extraction of total flavonoids from Tussilago farfara L. Response surface methodology (RSM), based on a Box-Behnken design (BBD), was used to optimize the effects of processing parameters on total flavonoids yields. The parameters were ultrasonic frequency (X1), extraction time (X2) and ratio of liquid to solid (X3). The statistical analysis indicated that the parameters of ultrasonic power and ratio of liquid to solid, and the square effects among them had significant effects on the yield of flavonoids from Tussilago farfara L. The interaction between ultrasonic power and extraction time, and ultrasonic power and ratio of liquid to solid also caused significant effects on the yields. The optimum extraction conditions were determined as follows: ultrasonic power 420 W, extraction time 30 min, ratio of liquid to solid 25 mL/g. Under these conditions, the experimental yield 6.59 +/- 0.061% agreed closely with the predicted yield (6.64%).

Preclinical Pharmacokinetics and Disposition of a Novel Selective VEGFR Inhibitor Fruquintinib (HMPL-013) and the Prediction of Its Human Pharmacokinetics

Cancer Chemotherapy and Pharmacology. Jul, 2014  |  Pubmed ID: 24817647

This study evaluated the preclinical pharmacokinetics (PK) and disposition of fruquintinib (HMPL-013), a small molecule vascular endothelial growth factor receptors inhibitor.

Activation of Spinal Neuregulin 1-ErbB2 Signaling Pathway in a Rat Model of Cancer-induced Bone Pain

International Journal of Oncology. Jul, 2014  |  Pubmed ID: 24818668

Current therapies for cancer-induced bone pain (CIBP) are still limited. Until recently, the molecular mechanisms underlying the spinal cell-mediated CIBP remain largely unknown. To better understand the role of spinal cells in CIBP, we investigated the role of spinal neuregulin1 (NRG1)‑ErbB2 signaling pathway in CIBP. In this study, a rat model of CIBP was established by intra-tibia inoculation of Walker 256 mammary gland carcinoma cells. Tibia bone destruction was evaluated using various methods of Walker 256 inoculation, radiobioassay and histological analysis. Pain-like behavior including thermal hyperalgesia and mechanical allodynia were determined by measuring paw withdrawal latency (PWL) and mechanical paw withdrawal thresholds (PWT). The expression level of mRNA or protein of target genes was examined by quantitative reverse transcription-polymerase chain reaction (qPCR) and western blot analysis, respectively. Bone destruction, as well as thermal hyperalgesia and mechanical allodynia, were observed at the 6th day following Walker 256 inoculation. A time-dependent increase in the levels of NRG1, ErbB2 and p-ErbB2 could be detected within three weeks after tumor cell injection. ErbB2 signaling inactivation by PD168393 treatment significantly attenuated pain-like behavior, associated with inhibition of Akt-1 and p38MAPK activation. Administration of exogenous NRG1 provoked pain-like behavior in rats by induction of activation of ErbB2, Akt-1 and p38MAPK, which could be blocked by ErbB2 inhibitor. Our results indicate that activation of NRG1‑ErbB2 signaling pathway plays a critical role in the induction of CIBP. Akt-1 and p38MAPK may be potent players involved in the NRG1-ErbB2 pathway in CIBP.

Association of Two Polymorphisms Rs2910164 in MiRNA-146a and Rs3746444 in MiRNA-499 with Rheumatoid Arthritis: a Meta-analysis

Human Immunology. Jul, 2014  |  Pubmed ID: 24824381

It has been reported that two single nucleotide polymorphisms (SNPs) rs2910164 in miRNA-146a and rs3746444 in miRNA-499 might be associated with the susceptibility to rheumatoid arthritis (RA). Owing to mixed and inconclusive results, we conducted a meta-analysis to systematically summarize and clarify the association between the two SNPs and RA risk.

Alteration of Fractional Anisotropy and Mean Diffusivity in Glaucoma: Novel Results of a Meta-analysis of Diffusion Tensor Imaging Studies

PloS One. 2014  |  Pubmed ID: 24828063

We hypothesized that a meta-analysis of existing studies may help to reveal significant changes on diffusion tensor imaging (DTI) in patients with glaucoma. Therefore, a meta-analysis was utilized to investigate the possibility that DTI can detect white matter damage in patients with glaucoma.

Nonsteroidal Anti-inflammatory Drugs Versus Corticosteroid for Treatment of Shoulder Pain: a Systematic Review and Meta-analysis

Archives of Physical Medicine and Rehabilitation. Oct, 2014  |  Pubmed ID: 24841629

To compare the treatment efficacy between corticosteroid injection and nonsteroidal anti-inflammatory drugs (NSAIDs) for patients with shoulder pain.

Serum MicroRNA-21 As a Diagnostic Marker for Lung Carcinoma: a Systematic Review and Meta-analysis

PloS One. 2014  |  Pubmed ID: 24865991

MicroRNA-21 in serum is a promising marker for the diagnosis of lung carcinoma. A meta-analysis was performed to assess the diagnostic accuracy and clinical value of serum microRNA-21 in patients with lung carcinoma.

Overexpression of the Astrocyte Glutamate Transporter GLT1 Exacerbates Phrenic Motor Neuron Degeneration, Diaphragm Compromise, and Forelimb Motor Dysfunction Following Cervical Contusion Spinal Cord Injury

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. May, 2014  |  Pubmed ID: 24872566

A major portion of spinal cord injury (SCI) cases affect midcervical levels, the location of the phrenic motor neuron (PhMN) pool that innervates the diaphragm. While initial trauma is uncontrollable, a valuable opportunity exists in the hours to days following SCI for preventing PhMN loss and consequent respiratory dysfunction that occurs during secondary degeneration. One of the primary causes of secondary injury is excitotoxic cell death due to dysregulation of extracellular glutamate homeostasis. GLT1, mainly expressed by astrocytes, is responsible for the vast majority of functional uptake of extracellular glutamate in the CNS, particularly in spinal cord. We found that, in bacterial artificial chromosome-GLT1-enhanced green fluorescent protein reporter mice following unilateral midcervical (C4) contusion SCI, numbers of GLT1-expressing astrocytes in ventral horn and total intraspinal GLT1 protein expression were reduced soon after injury and the decrease persisted for ≥6 weeks. We used intraspinal delivery of adeno-associated virus type 8 (AAV8)-Gfa2 vector to rat cervical spinal cord ventral horn for targeting focal astrocyte GLT1 overexpression in areas of PhMN loss. Intraspinal delivery of AAV8-Gfa2-GLT1 resulted in transduction primarily of GFAP(+) astrocytes that persisted for ≥6 weeks postinjury, as well as increased intraspinal GLT1 protein expression. Surprisingly, we found that astrocyte-targeted GLT1 overexpression increased lesion size, PhMN loss, phrenic nerve axonal degeneration, and diaphragm neuromuscular junction denervation, and resulted in reduced functional diaphragm innervation as assessed by phrenic nerve-diaphragm compound muscle action potential recordings. These results demonstrate that GLT1 overexpression via intraspinal AAV-Gfa2-GLT1 delivery exacerbates neuronal damage and increases respiratory impairment following cervical SCI.

Comparative Study on Laparoscopic Sleeve Gastrectomy and Laparoscopic Gastric Bypass for Treatment of Morbid Obesity Patients

Hepato-gastroenterology. Mar-Apr, 2014  |  Pubmed ID: 24901132

Laparoscopic Roux-en-Y gastric bypass (LRYGB) is one of the most widely used bariatric procedures for the treatment of morbid obesity. Laparoscopic sleeve gastrectomy (LSG) is a relatively innovative procedure which has been increasingly accepted as a sole bariatric procedure in the Asian-Pacific region. This study aims to compare mid-term outcomes in morbid obesity patients undergoing LRYGB and LSG.

Management of Budd-Chiari: a Single-center Experience of 280 Cases

Hepato-gastroenterology. Mar-Apr, 2014  |  Pubmed ID: 24901162

Budd-Chiari syndrome (BCS) is a rare and life-threatening disorder secondary to hepatic venous outflow obstruction. How to manage this complex disease has haunted many surgeons. The aim of this study is to investigate the treatment of Budd-Chiari syndrome in our hospital.

Aging Influence on Gray Matter Structural Associations Within the Default Mode Network Utilizing Bayesian Network Modeling

Frontiers in Aging Neuroscience. 2014  |  Pubmed ID: 24910613

Recent neuroimaging studies have revealed normal aging-related alterations in functional and structural brain networks such as the default mode network (DMN). However, less is understood about specific brain structural dependencies or interactions between brain regions within the DMN in the normal aging process. In this study, using Bayesian network (BN) modeling, we analyzed gray matter volume data from 109 young and 82 old subjects to characterize the influence of aging on associations between core brain regions within the DMN. Furthermore, we investigated the discriminability of the aging-associated BN models for the young and old groups. Compared to their young counterparts, the old subjects showed significant reductions in connections from right inferior temporal cortex (ITC) to medial prefrontal cortex (mPFC), right hippocampus (HP) to right ITC, and mPFC to posterior cingulate cortex and increases in connections from left HP to mPFC and right inferior parietal cortex to right ITC. Moreover, the classification results showed that the aging-related BN models could predict group membership with 88.48% accuracy, 88.07% sensitivity, and 89.02% specificity. Our findings suggest that structural associations within the DMN may be affected by normal aging and provide crucial information about aging effects on brain structural networks.

Assessment of the Potential Diagnostic Value of Serum P53 Antibody for Cancer: a Meta-analysis

PloS One. 2014  |  Pubmed ID: 24911057

Mutant p53 protein over-expression has been reported to induce serum antibodies against p53. We assessed the diagnostic precision of serum p53 (s-p53) antibodies for diagnosis of cancer patients and compared the positive rates of the s-p53 antibody in different types of cancers.

Quantitative Evaluation and Visualization of Size Effect on Cellular Uptake of Gold Nanoparticles by Multiphoton Imaging-UV/Vis Spectroscopic Analysis

Journal of Biomedical Optics. 2014  |  Pubmed ID: 24927982

With ever-increasing applications of nanoscale materials in the biomedical field, the impact of nanoparticle size on cellular uptake efficiency, dynamics, and mechanism has attracted numerous interests but still leaves many open questions. A combined "multiphoton imaging-UV/Vis spectroscopic analysis" method was applied for the first time for quantitative visualization and evaluation of the cellular uptake process of different-sized (15-, 30-, 50-, and 80-nm) gold nanoparticles (AuNPs). Quantitative analysis of the size effect on cellular uptake behavior of AuNPs from a stack of three-dimensional multiphoton laser scanning microscopy images is obtained. The technique allows for differentiating AuNPs present in external and internal subcellular components, giving detailed information for elucidating cellular uptake dynamics without particle labeling. The data show that the internalization extent of AuNPs is highly dependent on particles' sizes and incubation time. Due to sedimentation, 50- and 80-nm AuNPs are taken up to a greater extent than 15- and 30-nm particles after exposure for 24 h. However, the smaller particles' uptake velocity is significantly faster in the first 10 h, indicating a disparity in uptake kinetics for different-sized AuNPs. The finding from this study will improve our understanding of the cellular uptake mechanisms of different-sized nanoparticles and has great implications in developing AuNP-based drug carriers with various sizes for different purposes.

Mining Gene Expression Data of Multiple Sclerosis

PloS One. 2014  |  Pubmed ID: 24932510

Microarray produces a large amount of gene expression data, containing various biological implications. The challenge is to detect a panel of discriminative genes associated with disease. This study proposed a robust classification model for gene selection using gene expression data, and performed an analysis to identify disease-related genes using multiple sclerosis as an example.

Effect of Beating Processing, As a Means of Reducing Salt Content in Frankfurters: a Physico-chemical and Raman Spectroscopic Study

Meat Science. Oct, 2014  |  Pubmed ID: 24960638

Structural changes, L(⁎)-value, cooking yield changes and textural properties of pork frankfurters containing 1% or 2% salt, produced by the two methods were studied by Raman spectroscopy and texture profile analysis. Increasing salt content from 1% to 2% increased the L(⁎)-value, cooking yield and hardness, and decreased (p<0.05) the C-H stretching and CH2 and CH3 bending vibrations, but did not affect the changes of secondary structures, tryptophan or tyrosine residues. Compared with the chopping, the beating increased L(⁎)-value, cooking yield and hardness of the frankfurters in both salt concentrations. It also resulted in an increase in β-sheets, accompanied by a significant (p<0.05) decrease in α-helix content, a greater exposure of tyrosine residues to the polar environment and a decrease in the CH stretching and CH2 and CH3 bending vibrations. The results showed that the beating process enabled lowering of the salt content while improving the L(⁎)-value, cooking yield and hardness of the frankfurters.

SENP2 Regulated the Stability of β-catenin Through WWOX in Hepatocellular Carcinoma Cell

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine. Oct, 2014  |  Pubmed ID: 24969559

SUMOylation and deSUMOylation are dynamic mechanisms regulating a spectrum of protein activities. The SUMO proteases (SENP) remove SUMO conjugate from proteins, and their expression is deregulated in cancers. SENP2 has been reported to play a critical role in the control of hepatocellular carcinoma (HCC) cell growth by modulating the stability of β-catenin. However, the underlying mechanism remains largely unknown. Here, we show that the WW domain-containing oxidoreductase (WWOX), a novel inhibitor of the Wnt/β-catenin pathway, is required for stabilization of β-catenin regulated by SENP2 in HCC cells. The transcriptional level of WWOX is tightly regulated by SENP2. Moreover, knockdown of WWOX by siRNA attuned SENP2-induced β-catenin degradation and decreased SENP2-mediated HCC cell proliferation arrest. Taken together, our data suggested that WWOX is a key downstream modulator of the SENP2 tumor suppressor function in HCC cell.

Grating Based X-ray Differential Phase Contrast Imaging Without Mechanical Phase Stepping

Optics Express. Jun, 2014  |  Pubmed ID: 24977522

Grating-based x-ray differential phase contrast imaging (DPCI) often uses a phase stepping procedure to acquire data that enables the extraction of phase information. This method prolongs the time needed for data acquisition by several times compared with conventional x-ray absorption image acquisitions. A novel analyzer grating design was developed in this work to eliminate the additional data acquisition time needed to perform phase stepping in DPCI. The new analyzer grating was fabricated such that the linear grating structures are shifted from one detector row to the next; the amount of the lateral shift was equal to a fraction of the x-ray diffraction fringe pattern. The x-ray data from several neighboring detector rows were then combined to extract differential phase information. Initial experimental results have demonstrated that the new analyzer grating enables accurate DPCI signal acquisition from a single x-ray exposure like conventional x-ray absorption imaging.

Statistical Model Based Iterative Reconstruction (MBIR) in Clinical CT Systems. Part II. Experimental Assessment of Spatial Resolution Performance

Medical Physics. Jul, 2014  |  Pubmed ID: 24989389

Statistical model based iterative reconstruction (MBIR) methods have been introduced to clinical CT systems and are being used in some clinical diagnostic applications. The purpose of this paper is to experimentally assess the unique spatial resolution characteristics of this nonlinear reconstruction method and identify its potential impact on the detectabilities and the associated radiation dose levels for specific imaging tasks.

In Vitro Antitumor Activity of Stellettin B, a Triterpene from Marine Sponge Jaspis Stellifera, on Human Glioblastoma Cancer SF295 Cells

Marine Drugs. Jul, 2014  |  Pubmed ID: 25028795

Stellettin B was isolated from marine sponge Jaspis stellifera. In vitro antitumor activities were investigated on 39 human cancer cell lines. Stellettin B exhibited highly potent inhibition against the growth of a human glioblastoma cell line SF295, with a GI50 of 0.01 μM. In contrast, stellettin B showed very weak inhibitory activity on normal cell lines including HMEC, RPTEC, NHBE and PrEC, with GI50s higher than 10 μM, suggesting its relatively selective cytotoxicity against human cancer cells compared to normal human cell lines. We then focused on the antitumor activity of this compound on SF295 cells. Flow cytometric analysis indicated that stellettin B induced apoptosis in SF295 cells in a concentration-dependent manner. Further study indicated that stellettin B increased the production of ROS, the activity of caspase 3/7, as well as the cleavage of PARP, each of which is known to be involved in apoptosis. To investigate the molecular mechanism for cell proliferation inhibition and apoptosis induction, effect on the phosphorylation of several signal proteins of PI3K/Akt and RAS/MAPK pathways was examined. Stellettin B inhibited the phosphorylation of Akt potently, with no activity on p-ERK and p-p38, suggesting that inhibition of PI3K/Akt pathway might be involved in the antiproliferative and apoptosis-inducing effect. However, homogenous time-resolved fluorescence (HTRF) assay indicated that stellettin B did not inhibit PI3K activity, suggesting that the direct target might be signal protein upstream of Akt pathway other than PI3K.

Multi-parametric MRI Characterization of Healthy Human Thigh Muscles at 3.0 T - Relaxation, Magnetization Transfer, Fat/water, and Diffusion Tensor Imaging

NMR in Biomedicine. Sep, 2014  |  Pubmed ID: 25066274

Muscle diseases commonly have clinical presentations of inflammation, fat infiltration, fibrosis, and atrophy. However, the results of existing laboratory tests and clinical presentations are not well correlated. Advanced quantitative MRI techniques may allow the assessment of myo-pathological changes in a sensitive and objective manner. To progress towards this goal, an array of quantitative MRI protocols was implemented for human thigh muscles; their reproducibility was assessed; and the statistical relationships among parameters were determined. These quantitative methods included fat/water imaging, multiple spin-echo T2 imaging (with and without fat signal suppression, FS), selective inversion recovery for T1 and quantitative magnetization transfer (qMT) imaging (with and without FS), and diffusion tensor imaging. Data were acquired at 3.0 T from nine healthy subjects. To assess the repeatability of each method, the subjects were re-imaged an average of 35 days later. Pre-testing lifestyle restrictions were applied to standardize physiological conditions across scans. Strong between-day intra-class correlations were observed in all quantitative indices except for the macromolecular-to-free water pool size ratio (PSR) with FS, a metric derived from qMT data. Two-way analysis of variance revealed no significant between-day differences in the mean values for any parameter estimate. The repeatability was further assessed with Bland-Altman plots, and low repeatability coefficients were obtained for all parameters. Among-muscle differences in the quantitative MRI indices and inter-class correlations among the parameters were identified. There were inverse relationships between fractional anisotropy (FA) and the second eigenvalue, the third eigenvalue, and the standard deviation of the first eigenvector. The FA was positively related to the PSR, while the other diffusion indices were inversely related to the PSR. These findings support the use of these T1 , T2 , fat/water, and DTI protocols for characterizing skeletal muscle using MRI. Moreover, the data support the existence of a common biophysical mechanism, water content, as a source of variation in these parameters.

Ritonavir-induced Hepatotoxicity and Ultrastructural Changes of Hepatocytes

Ultrastructural Pathology. Oct, 2014  |  Pubmed ID: 25079492

To investigate the effect of ritonavir on hepatocyte proliferation, we detected the change of cleaved caspase-3 expression level in the hepatocytes. Furthermore, the morphological and ultrastructural changes of hepatocytes derived from RTV-treated mice have been observed. The results showed that ritonavir can evidently inhibit hepatocyte proliferation and increase cleaved caspase-3 expression level. Under the electron microscope, chromatin margination, mitochondrial cristae disappearance, karyopyknosis and cytoplasmic vacuolization can be observed in the hepatocytes of mice treated with ritonavir. In conclusion, the mechanism of ritonavir's hepatotoxicity is that it induces apoptosis of hepatocytes via the caspase-cascade system.

Primary Neuronal-astrocytic Co-culture Platform for Neurotoxicity Assessment of Di-(2-ethylhexyl) Phthalate

Journal of Environmental Sciences (China). May, 2014  |  Pubmed ID: 25079645

Plastics such as polyvinyl chlorides (PVC) are widely used in many indoor constructed environments; however, their unbound chemicals, such as di-(2-ethylhexyl) phthalates (DEHP), can leach into the surrounding environment. This study focused on DEHP's effect on the central nervous system by determining the precise DEHP content in mice brain tissue after exposure to the chemical, to evaluate the specific exposure range. Primary neuronal-astrocyte co-culture systems were used as in vitro models for chemical hazard identification of DEHP. Oxidative stress was hypothesized as a probable mechanism involved, and therefore the total reactive oxygen species (ROS) concentration was determined as a biomarker of oxidative stress. In addition, NeuriteTracer, a neurite tracing plugin with ImageJ, was used to develop an assay for neurotoxicity to provide quantitative measurements of neurological parameters, such as neuronal number, neuron count and neurite length, all of which could indicate neurotoxic effects. The results showed that with 1 nmol/L DEHP exposure, there was a significant increase in ROS concentrations, indicating that the neuronal-astrocyte cultures were injured due to exposure to DEHP. In response, astrocyte proliferation (gliosis) was initiated, serving as a mechanism to maintain a homeostatic environment for neurons and protect neurons from toxic chemicals. There is a need to assess the cumulative effects of DEHP in animals to evaluate the possible uptake and effects on the human neuronal system from exposure to DEHP in the indoor environment.

Effects of Doctor-patient Communication on Quality of Life Among Breast Cancer Patients in Southern China

Asian Pacific Journal of Cancer Prevention : APJCP. 2014  |  Pubmed ID: 25081679

This study aimed to determine effects of doctor-patient communication on the quality of life among breast cancer survivors in 16 communities in southern China.

Maximal Privacy Without Coherence

Physical Review Letters. Jul, 2014  |  Pubmed ID: 25083622

Privacy is a fundamental feature of quantum mechanics. A coherently transmitted quantum state is inherently private. Remarkably, coherent quantum communication is not a prerequisite for privacy: there are quantum channels that are too noisy to transmit any quantum information reliably that can nevertheless send private classical information. Here, we ask how much private classical information a channel can transmit if it has little quantum capacity. We present a class of channels N(d) with input dimension d(2), quantum capacity Q(N(d)) ≤ 1, and private capacity P(N(d)) = log d. These channels asymptotically saturate an interesting inequality P(N) ≤ (1/2)[log d(A) + Q(N)] for any channel N with input dimension d(A) and capture the essence of privacy stripped of the confounding influence of coherence.

Multiplex PCR/mass Spectrometry Screening of Biological Carcinogenic Agents in Human Mammary Tumors

Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. Oct, 2014  |  Pubmed ID: 25088618

While many studies have suggested a possible link between breast cancer pathogenesis and infection by viruses, the role of viruses in breast carcinogenesis remains controversial.

A Systematic Review and Meta-analysis of Diagnostic and Prognostic Serum Biomarkers of Colorectal Cancer

PloS One. 2014  |  Pubmed ID: 25105762

Our systematic review summarizes the evidence concerning the accuracy of serum diagnostic and prognostic tests for colorectal cancer (CRC).

Design and Implementation of Hybrid CORDIC Algorithm Based on Phase Rotation Estimation for NCO

TheScientificWorldJournal. 2014  |  Pubmed ID: 25110750

The numerical controlled oscillator has wide application in radar, digital receiver, and software radio system. Firstly, this paper introduces the traditional CORDIC algorithm. Then in order to improve computing speed and save resources, this paper proposes a kind of hybrid CORDIC algorithm based on phase rotation estimation applied in numerical controlled oscillator (NCO). Through estimating the direction of part phase rotation, the algorithm reduces part phase rotation and add-subtract unit, so that it decreases delay. Furthermore, the paper simulates and implements the numerical controlled oscillator by Quartus II software and Modelsim software. Finally, simulation results indicate that the improvement over traditional CORDIC algorithm is achieved in terms of ease of computation, resource utilization, and computing speed/delay while maintaining the precision. It is suitable for high speed and precision digital modulation and demodulation.

Preparation, Characterisation and Bioactivity Evaluation of the Inclusion Complex Formed Between Picoplatin and γ-cyclodextrin

Carbohydrate Research. Sep, 2014  |  Pubmed ID: 25119104

The inclusion complex of picoplatin with γ-cyclodextrin (γ-CD) was prepared and characterised by different analytical methods, including NMR, FTIR, TGA, phase solubility as well as SEM. All of these approaches indicated that picoplatin was able to form an inclusion complex with γ-CD, and that the picoplatin/γ-CD inclusion compounds exhibited different spectroscopic features and properties from free picoplatin. The stoichiometry of the complex was 1:1; the pyridine group of picoplatin was deeply inserted into the cavity of γ-CD and the amine platinum group of picoplatin was near the narrower rim of γ-CD. The calculated apparent stability constant of the complex was 10,318M(-1). Moreover, the water solubility of picoplatin was significantly improved, according to phase-solubility studies. The complex maintained its anticancer activity, as shown by an in vitro cell-survival assay on A549 and MCF-7 cancer cell lines. All of these results showed that inclusion complexation may be a promising strategy to design a novel formulation of picoplatin as an anticancer therapy.

Immunohistochemical Toolkit for Tracking and Quantifying Xenotransplanted Human Stem Cells

Regenerative Medicine. 2014  |  Pubmed ID: 25159062

Biomarker-based tracking of human stem cells xenotransplanted into animal models is crucial for studying their fate in the field of cell therapy or tumor xenografting.

Intermittent Hypothermia is Neuroprotective in an in Vitro Model of Ischemic Stroke

International Journal of Biological Sciences. 2014  |  Pubmed ID: 25170301

To investigate whether the intermittent hypothermia (IH) protects neurons against ischemic insult and the potential molecular targets using an in vitro ischemic model of oxygen glucose deprivation (OGD).

Nutrient Release, Recovery and Removal from Waste Sludge of a Biological Nutrient Removal System

Environmental Technology. Nov-Dec, 2014  |  Pubmed ID: 25176308

The uncontrolled release of nutrients from waste sludge results in nitrogen and phosphorus overloading in wastewater treatment plants when supernatant is returned to the inlet. A controlled release, recovery and removal of nutrient from the waste sludge of a Biological Nutrient Removal system (BNR) are investigated. Results showed that the supernatant was of high mineral salt, high electrical conductivity and poor biodegradability, in addition to high nitrogen and phosphorus concentrations after the waste sludge was hydrolysed through sodium dodecyl sulphate addition. Subsequently, over 91.8% of phosphorus and 10.5% of nitrogen in the supernatants were extracted by the crystallization method under the conditions of 9.5 pH and 400 rpm. The precipitate was mainly struvite according to X-ray diffraction and morphological examination. A multistage anoxic-oxic Moving Bed Biofilm Reactor (MBBR) was then adopted to remove the residual carbon, nitrogen and phosphorus in the supernatant. The MBBR exhibited good performance in simultaneously removing carbon, nitrogen and phosphorus under a short aeration time, which accounted for 31.25% of a cycle. Fluorescence in situ hybridization analysis demonstrated that nitrifiers presented mainly in floc, although higher extracellular polymeric substance content, especially DNA, appeared in the biofilm. Thus, a combination of hydrolysis and precipitation, followed by the MBBR, can complete the nutrient release from the waste sludge of a BNR system, recovers nutrients from the hydrolysed liquor and removes nutrients from leftovers effectively.

HPS6 Interacts with Dynactin P150Glued to Mediate Retrograde Trafficking and Maturation of Lysosomes

Journal of Cell Science. Nov, 2014  |  Pubmed ID: 25189619

Hermansky-Pudlak syndrome 6 protein (HPS6) has originally been identified as a subunit of the BLOC-2 protein complex that is involved in the biogenesis of lysosome-related organelles. Here, we demonstrate that HPS6 directly interacts with the dynactin p150(Glued) subunit of the dynein-dynactin motor complex and acts as cargo adaptor for the retrograde motor to mediate the transport of lysosomes from the cell periphery to the perinuclear region. Small interfering RNA (siRNA)-mediated knockdown of HPS6 in HeLa cells not only partially blocks centripetal movement of lysosomes but also causes delay in lysosome-mediated protein degradation. Moreover, lysosomal acidification and degradative capacity, as well as fusion between late endosomes and/or multivesicular bodies and lysosomes are also impaired when HPS6 is depleted, suggesting that perinuclear positioning mediated by the dynein-dynactin motor complex is required for lysosome maturation and activity. Our results have uncovered a so-far-unknown specific role for HPS6 in the spatial distribution of the lysosomal compartment.

A Dedicated High-resolution PET Imager for Plant Sciences

Physics in Medicine and Biology. Oct, 2014  |  Pubmed ID: 25190198

PET provides an in vivo molecular and functional imaging capability that could be valuable for studying the interaction of plants in changing environments at the whole-plant level. We have developed a dedicated plant PET imager housed in a plant growth chamber (PGC), which provides a fully controlled environment. The system currently contains two types of scintillation detector modules from commercial small animal PET scanners: 84 microPET® detectors, which are made with scintillation crystal arrays of 2.2 mm(3) × 2.2 mm(3) × 10 mm(3) crystals to provide a large detection area; and 32 Inveon™ detectors, which are made with scintillation crystal arrays of 1.5 mm(3) × 1.5 mm(3) × 10 mm(3) crystals to provide higher spatial resolution. The detector modules are configured to form two half-rings, which provide a 15 cm-diameter trans-axial field of view (FOV) for dynamic tomographic imaging of small plants. Alternatively, the Inveon detectors can be reconfigured to form quarter-rings, which provide a 25 cm FOV using step-and-shoot motion. The imager contains two linear stages that move detectors vertically at different heights for multisection scanning, and two rotation stages to collect coincidence events from all angles when using the step-and-shoot acquisition. The detector modules and mechanical components of the imager are housed inside a PGC that regulates the environmental parameters. The system has a typical energy resolution of 15% for the Inveon detectors and 24% for the microPET detectors, timing resolution of 1.8 ns, and sensitivity of 1.3%, 1.4% and 3.0% measured at the center of the FOV, 5 cm off to the larger half-ring and 5 cm off to the smaller half-ring, respectively (with a 350-650 keV energy window and 3.1 ns timing window). The system's spatial resolution is capable of resolving rod sources of 1.25 mm diameter spaced 2.5 mm apart (center to center) using the ML-EM reconstruction algorithm. Preliminary imaging experiments using soybean and wild type and mutant maize labeled with (11)CO2 produced high-quality dynamic PET images that reveal the translocation and distribution patterns of photoassimilates. This system can be used to provide an in vivo molecular and functional imaging capability for plant research.

Nodal Involvement by Marginal Zone B-cell Lymphoma Harboring T(14;22)(q32;q11) Involving Immunoglobulin Heavy Chain and Light Chain Lambda As the Sole Karyotypically Recognizable Abnormality in a Patient with Systemic Lupus Erythematosus

International Journal of Clinical and Experimental Pathology. 2014  |  Pubmed ID: 25197401

Recurrent non-random balanced chromosomal translocation, usually involving the immunoglobulin heavy chain (IgH) gene or an immunoglobulin light chain gene and a proto-oncogene, which results in the overexpression of the latter under the control of an enhancer or promoter of the former, is a hallmark of many types of non-Hodgkin lymphoma (NHL) of B-cell origin. However, translocations between IgH and the immunoglobulin (Ig) light chain lambda gene (IgL), namely, a t(14;22)(q32;q11), have rarely been described in B-cell NHL. Herein we report the first case of marginal zone B-cell lymphoma harboring a t(14;22)(q32;q11) as its sole genetic abnormality in a patient with a 12-year history of systemic lupus erythematosus (SLE). Other interesting findings of this case include: 1) the neoplastic B-cells lack expression of both surface and cytoplasmic Ig light chain as revealed by flow cytometry and 2) monoclonal rearrangement of Ig light chain kappa (IgK) only due to k-deleting element (kde) recombination event. This case illustrates the necessity of utilizing a multi-modality approach in the diagnosis of B-cell NHL.

[Dietary Exposure Assessment of Aflatoxin of Foodstuff and Edible Oil from Shenzhen Residents]

Wei Sheng Yan Jiu = Journal of Hygiene Research. Jul, 2014  |  Pubmed ID: 25199295

To assess the dietary exposure aflatoxin B1 and total aflatoxins of foodstuff and edible oil in Shenzhen residents.

[Autophagy in Ageing and Ageing-related Diseases]

Yao Xue Xue Bao = Acta Pharmaceutica Sinica. Jun, 2014  |  Pubmed ID: 25212019

Autophagy is an important homeostatic cellular recycling mechanism responsible for degrading injured or dysfunctional cellular organelles and proteins in all living cells. Aging is a universal phenomenon characterized by progressive deterioration of cells and organs due to accumulation of macromolecular and organelle damage. Growing evidences indicate that the rate of autophagosome formation and maturation and the efficiency of autophagosome/lysosome fusion decline with age. Dysfunctional autophagy has also been observed in age-related diseases. Autophagy disruption resulted accumulation of mutated or misfolded proteins is the essential feature of neurodegenerative disorders. However, in cancers, fibroproliferative diseases or cardiovascular diseases, autophagy can play either a protective or destructive role in different types of disease, and even in different stages of the same disease. The review will discuss the cellular and molecular mechanisms of autophagy and its important role in the pathogenesis of aging and age-related diseases, and the ongoing drug discovery strategies for therapeutic intervention.

Phase I and Phase II Reductive Metabolism Simulation of Nitro Aromatic Xenobiotics with Electrochemistry Coupled with High Resolution Mass Spectrometry

Analytical and Bioanalytical Chemistry. Nov, 2014  |  Pubmed ID: 25234306

Electrochemistry combined with (liquid chromatography) high resolution mass spectrometry was used to simulate the general reductive metabolism of three biologically important nitro aromatic molecules: 3-trifluoromethyl-4-nitrophenol (TFM), niclosamide, and nilutamide. TFM is a pesticide used in the Laurential Great Lakes while niclosamide and nilutamide are used in cancer therapy. At first, a flow-through electrochemical cell was directly connected to a high resolution mass spectrometer to evaluate the ability of electrochemistry to produce the main reduction metabolites of nitro aromatic, nitroso, hydroxylamine, and amine functional groups. Electrochemical experiments were then carried out at a constant potential of -2.5 V before analysis of the reduction products by LC-HRMS, which confirmed the presence of the nitroso, hydroxylamine, and amine species as well as dimers. Dimer identification illustrates the reactivity of the nitroso species with amine and hydroxylamine species. To investigate xenobiotic metabolism, the reactivity of nitroso species to biomolecules was also examined. Binding of the nitroso metabolite to glutathione was demonstrated by the observation of adducts by LC-ESI(+)-HRMS and the characteristics of their MSMS fragmentation. In conclusion, electrochemistry produces the main reductive metabolites of nitro aromatics and supports the observation of nitroso reactivity through dimer or glutathione adduct formation.

Glypican-4 is Increased in Human Subjects with Impaired Glucose Tolerance and Decreased in Patients with Newly Diagnosed Type 2 Diabetes

Acta Diabetologica. Dec, 2014  |  Pubmed ID: 25240528

Glypican-4 (GPC-4) has been identified as a novel adipokine capable of enhancing insulin signaling. A significant association between circulating GPC-4 levels and nonalcoholic fatty liver disease and cardiometabolic risk factors has been found in women.

Therapeutically Targeting Astrocytes with Stem and Progenitor Cell Transplantation Following Traumatic Spinal Cord Injury

Brain Research. Sep, 2014  |  Pubmed ID: 25251595

Replacement of lost and/or dysfunctional astrocytes via multipotent neural stem cell (NSC) and lineage-restricted neural progenitor cell (NPC) transplantation is a promising therapeutic approach for traumatic spinal cord injury (SCI). Cell transplantation in general offers the potential to replace central nervous system (CNS) cell types, achieve remyelination, deliver missing gene products, promote and guide axonal growth, modulate the host immune response, deliver neuroprotective factors, and provide a cellular substrate for bridging the lesion site, amongst other possible benefits. A host of cell types that differ in their developmental stage, CNS region and species of derivation, as well as in their phenotypic potential, have been tested in a variety of SCI animal models. Historically in the SCI field, most pre-clinical NSC and NPC transplantation studies have focused on neuronal and oligodendrocyte replacement. However, much less attention has been geared towards targeting astroglial dysfunction in the inured spinal cord, despite the integral roles played by astrocytes in both normal CNS function and in the diseased nervous system. Despite the relative lack of studies, cell transplantation-based targeting of astrocytes dates back to some of the earliest transplant studies in SCI animal models. In this review, we will describe the history of work involving cell transplantation for targeting astrocytes in models of SCI. We will also touch on the current state of affairs in the field, as well as on important future directions as we move forward in trying to develop this approach into a viable strategy for SCI patients. Practical issues such as timing of delivery, route of transplantation and immunesuppression needs are beyond the scope of this review. This article is part of a Special Issue entitled SI: Spinal cord injury.

Proteomic Study of Sporadic Inclusion Body Myositis

Proteome Science. 2014  |  Pubmed ID: 25253997

Sporadic inclusion body myositis (s-IBM) is the most commonly occurring acquired inflammatory myopathy in elderly people (>45 years); however, pathogenic mechanisms are poorly understood and diagnostic tools are limited. In view of this, new therapeutic and diagnostic molecular markers for s-IBM need to be identified.

Characterizing Structural Association Alterations Within Brain Networks in Normal Aging Using Gaussian Bayesian Networks

Frontiers in Computational Neuroscience. 2014  |  Pubmed ID: 25324771

Recent multivariate neuroimaging studies have revealed aging-related alterations in brain structural networks. However, the sensory/motor networks such as the auditory, visual and motor networks, have obtained much less attention in normal aging research. In this study, we used Gaussian Bayesian networks (BN), an approach investigating possible inter-regional directed relationship, to characterize aging effects on structural associations between core brain regions within each of these structural sensory/motor networks using volumetric MRI data. We then further examined the discriminability of BN models for the young (N = 109; mean age =22.73 years, range 20-28) and old (N = 82; mean age =74.37 years, range 60-90) groups. The results of the BN modeling demonstrated that structural associations exist between two homotopic brain regions from the left and right hemispheres in each of the three networks. In particular, compared with the young group, the old group had significant connection reductions in each of the three networks and lesser connection numbers in the visual network. Moreover, it was found that the aging-related BN models could distinguish the young and old individuals with 90.05, 73.82, and 88.48% accuracy for the auditory, visual, and motor networks, respectively. Our findings suggest that BN models can be used to investigate the normal aging process with reliable statistical power. Moreover, these differences in structural inter-regional interactions may help elucidate the neuronal mechanism of anatomical changes in normal aging.

Structural Covariance Networks Across Healthy Young Adults and Their Consistency

Journal of Magnetic Resonance Imaging : JMRI. Oct, 2014  |  Pubmed ID: 25327998

To investigate structural covariance networks (SCNs) as measured by regional gray matter volumes with structural magnetic resonance imaging (MRI) from healthy young adults, and to examine their consistency and stability.

Spatial Distribution of Microbial Communities Associated with Dune Landform in the Gurbantunggut Desert, China

Journal of Microbiology (Seoul, Korea). Nov, 2014  |  Pubmed ID: 25359267

The microbial community compositions and potential ammonia oxidation in the topsoil at different positions of sand dune (stoss slope, crest, lee slope, and interdune) from the Gurbantunggut Desert, the largest semi-fixed desert in China, were investigated using several molecular methods. Actinobacteria and Proteobacteria (especially Alphaproteobacteria) were commonly the dominant taxa across all soil samples. Bacterial communities were similar in soils collected from the stoss slopes and interdunes (HC-BSCs, biological soil crusts with a high abundance of cyanobacteria), containing more abundant cyanobacterial populations (16.9-24.5%) than those (0.2-0.7% of Cyanobacteria) in the crests and lee slopes (LC-BSCs, biological soil crusts with a low abundance of cyanobacteria). The Cyanobacteria were mainly composed of Microcoleus spp., and quantitative PCR analysis revealed that 16S rRNA gene copy numbers of Cyanobacteria (especially genus Microcoleus) were at least two orders of magnitude higher in HC-BSCs than in LC-BSCs. Heterotrophic Geodermatophilus spp. frequently occurred in HC-BSCs (2.5-8.0%), whereas genera Arthrobacter, Bacillus, and Segetibacter were significantly abundant in LC-BSC communities. By comparison, the desert archaeal communities were less complex, and were dominated by Nitrososphaera spp. The amoA gene abundance of ammonia-oxidizing archaea (AOA) was higher than that of ammonia-oxidizing bacteria (AOB) in all soil samples, particularly in the interdunal soils (10(6)-10(8) archaeal amoA gene copies per gram dry soil), indicating that AOA possibly dominate the ammonia oxidation at the interdunes.

Enhanced Photoabsorption in Front-tapered Single-nanowire Solar Cells

Optics Letters. Oct, 2014  |  Pubmed ID: 25360977

Vertically aligned single-nanowire is verified to be a unique building block to realize the high-efficiency solar cell beyond Schockley-Queisser limit. We proposed a front-tapered vertically aligned single-nanowire solar cell (V-SNSC) and investigated numerically the possibility of this configuration to improve the photoabsorption efficiency compared to the conventional designs, by using 2.5D full-wave finite-element method. The influences of the feature sizes of aspect ratio, bottom radius, and nanowire length on the light-trapping properties were explored; the detailed field distribution and carrier generation rate were revealed as well based on the theory of dielectric resonant antenna, in order to elucidate the underlying physical mechanism. Results showed that, compared with the cylindrical counterparts, the absorption capability of V-SNSCs could be greatly enhanced by using a front-tapered configuration with less material utilized, and that such a positive effect can be further strengthened by increasing the nanowire length. The proposed configuration provides a promising approach to engineer the photoabsorption in the photovoltaic and other optoelectronic devices.

Recent Developments in the Use of Intralesional Injections Keloid Treatment

Archives of Plastic Surgery. Nov, 2014  |  Pubmed ID: 25396172

Keloid scars are often considered aesthetically unattractive and frustrating problems that occur following injuries. They cause functional and cosmetic deformities, displeasure, itching, pain, and psychological stress and possibly affect joint movement. The combination of these factors ultimately results in a compromised quality of life and diminished functional performance. Various methods have been implemented to improve keloid scars using both surgical and non-surgical approaches. However, it has proven to be a challenge to identify a universal treatment that can deliver optimal results for all types of scars. Through a PubMed search, we explored most of the literature that is available about the intralesional injection treatment of hypertrophic scars and keloids and highlights both current (corticosteroid, 5-fluorouracil, bleomycin, interferon, cryotherapy and verapamil) and future treatments (interleukin-10 and botulinum toxin type A). The reference lists of retrieved articles were also analysed. Information was gathered about the mechanism of each injection treatment, its benefits and associated adverse reactions, and possible strategies to address adverse reactions to provide reliable guidelines for determining the optimal treatment for particular types of keloid scars. This article will benefit practitioners by outlining evidence-based treatment strategies using intralesional injections for patients with hypertrophic scars and keloids.

Selective Photodynamic Inactivation of Bacterial Cells over Mammalian Cells by New Triarylmethanes

Langmuir : the ACS Journal of Surfaces and Colloids. Dec, 2014  |  Pubmed ID: 25419964

Three new triarylmethane dyes (TAMs), MPCV, DPCV, and AEV, were synthesized and their photodynamic inactivation abilities against E. coli and human pulmonary carcinoma A549 cells were compared to two commercial TAMs, CV and EV. The enhanced hydrophilicity of MPCV and AEV decreases their cellular uptake to A549 cells dramatically. However, their binding affinity toward E. coli cells are comparable to that of CV and EV by virtue of the improved electrostatic attraction with highly negatively charged E. coli outer membranes. MPCV and AEV were also found to generate hydroxyl radicals more efficiently upon irradiation than CV and EV. Consequently, MPCV and AEV exhibited markedly improved photodynamic inactivation of E. coli cells but remarkably diminished photodynamic inactivation of A549 cells than CV and EV. The photodynamic inactivation ability of DPCV was much lower than that of CV due to its high propensity for bleaching in neutral aqueous solution. Our work demonstrates that the introduction of protonatable groups in a proper manner into the structures of TAMs may lead to selective binding and photodynamic inactivation toward bacterial cells over mammalian cells. This strategy may be extended to other types of photodynamic antimicrobial chemotherapy (PACT) agents to improve their clinical potential.

Optimization of the Design of Pre-signal System Using Improved Cellular Automaton

Computational Intelligence and Neuroscience. 2014  |  Pubmed ID: 25435871

The pre-signal system can improve the efficiency of intersection approach under rational design. One of the main obstacles in optimizing the design of pre-signal system is that driving behaviors in the sorting area cannot be well evaluated. The NaSch model was modified by considering slow probability, turning-deceleration rules, and lane changing rules. It was calibrated with field observed data to explore the interactions among design parameters. The simulation results of the proposed model indicate that the length of sorting area, traffic demand, signal timing, and lane allocation are the most important influence factors. The recommendations of these design parameters are demonstrated. The findings of this paper can be foundations for the design of pre-signal system and show promising improvement in traffic mobility.

[Study on Neurofeedback System Based on Electroencephalogram Signals]

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi = Journal of Biomedical Engineering = Shengwu Yixue Gongchengxue Zazhi. Aug, 2014  |  Pubmed ID: 25464809

Neurofeedback, as an alternative treatment method of behavioral medicine, is a technique which translates the electroencephalogram (EEG) signals to styles as sounds or animation to help people understand their own physical status and learn to enhance or suppress certain EEG signals to regulate their own brain functions after several repeated trainings. This paper develops a neurofeedback system on the foundation of brain-computer interface technique. The EEG features are extracted through real-time signal process and then translated to feedback information. Two feedback screens are designed for relaxation training and attention training individually. The veracity and feasibility of the neurofeedback system are validated through system simulation and preliminary experiment.

Olfactory Deprivation Hastens Alzheimer-Like Pathologies in a Human Tau-Overexpressed Mouse Model Via Activation of Cdk5

Molecular Neurobiology. Dec, 2014  |  Pubmed ID: 25465240

Olfactory dysfunction is a recognized risk factor for the pathogenesis of Alzheimer's disease (AD), while the mechanisms are still not clear. Here, we applied bilateral olfactory bulbectomy (OBX), an olfactory deprivation surgery to cause permanent anosmia, in human tau-overexpressed mice (htau mice) to investigate changes of AD-like pathologies including aggregation of abnormally phosphorylated tau and cholinergic neuron loss. We found that tau phosphorylation in hippocampus was increased at Thr-205, Ser-214, Thr-231, and Ser-396 after OBX. OBX also increased the level of sarkosyl-insoluble Tau at those epitopes and accelerated accumulation of somatodendritic tau. Moreover, OBX resulted in the elevation of calpain activity accompanied by an increased expression of the cyclin-dependent kinase 5 (cdk5) neuronal activators, p35 and p25, in hippocampus. Furthermore, OBX induces the loss of the cholinergic neurons in medial septal. Administration of cdk5 pharmacological inhibitor roscovitine into lateral ventricles suppressed tau hyperphosphorylation and mislocalization and restored the cholinergic neuron loss. These findings suggest that olfactory deprivation by OBX hastens tau pathology and cholinergic system impairment in htau mice possibly via activation of cdk5.

Anatomical Background Noise Power Spectrum in Differential Phase Contrast and Dark Field Contrast Mammograms

Medical Physics. Dec, 2014  |  Pubmed ID: 25471946

In x-ray absorption mammography, it has been found that the anatomical background noise can be characterized by a power law dependence on the spatial frequency, NPSa(f) ≈ αf(-β). In this letter, the authors present the first experimental results of the corresponding exponents, β, for differential phase contrast (βDPC) and dark field contrast (βDF) mammography.

Spindle Cell Metaplastic Carcinoma of Breast: A Clinicopathological and Immunohistochemical Analysis

Asia-Pacific Journal of Clinical Oncology. Dec, 2014  |  Pubmed ID: 25483573

To better characterize spindle cell metaplastic carcinoma (SpCMC) of breast, a rare variant of breast cancer that has been classified under the broad rubric of metaplastic carcinoma.

Interrelationship-Based Selection for Decomposition Multiobjective Optimization

IEEE Transactions on Cybernetics. Dec, 2014  |  Pubmed ID: 25494518

Multiobjective evolutionary algorithm based on decomposition (MOEA/D), which bridges the traditional optimization techniques and population-based methods, has become an increasingly popular framework for evolutionary multiobjective optimization. It decomposes a multiobjective optimization problem (MOP) into a number of optimization subproblems. Each subproblem is handled by an agent in a collaborative manner. The selection of MOEA/D is a process of choosing solutions by agents. In particular, each agent has two requirements on its selected solution: one is the convergence toward the efficient front, the other is the distinction with the other agents' choices. This paper suggests addressing these two requirements by defining mutual-preferences between subproblems and solutions. Afterwards, a simple yet effective method is proposed to build an interrelationship between subproblems and solutions, based on their mutual-preferences. At each generation, this interrelationship is used as a guideline to select the elite solutions to survive as the next parents. By considering the mutual-preferences between subproblems and solutions (i.e., the two requirements of each agent), the selection operator is able to balance the convergence and diversity of the search process. Comprehensive experiments are conducted on several MOP test instances with complicated Pareto sets. Empirical results demonstrate the effectiveness and competitiveness of our proposed algorithm.

Enhanced in Vivo Delivery of 5-fluorouracil by Ethosomal Gels in Rabbit Ear Hypertrophic Scar Model

International Journal of Molecular Sciences. 2014  |  Pubmed ID: 25501333

Applying Ethosomal Gels (EGs) in transdermal drug delivery systems has evoked considerable interest because of their good water-solubility and biocompatibility. However, there has not been an explicit description of applying EGs as a vehicle for hypertrophic scars treatment. Here, a novel transdermal EGs loaded with 5-fluorouracil (5-FU EGs) was successfully prepared and characterized. The stability assay in vitro revealed that 5-FU EGs stored for a period of 30 days at 4 ± 1 °C had a better size stability than that at 25 ± 1 °C. Furthermore, using confocal laser scanning microscopy, EGs labeled with Rhodamine 6 G penetrated into the deep dermis of the hypertrophic scar within 24 h in the rabbit ear hypertrophic model suggested that the EGs were an optional delivery carrier through scar tissues. In addition, the value of the Scar Elevation Index (SEI) of 5-FU EGs group in the rabbit ear scar model was lower than that of 5-FU Phosphate Buffered Saline gel and Control groups. To conclude, these results suggest that EGs delivery system loaded 5-fluorouracil is a perfect candidate drug for hypertrophic scars therapy in future.

[Study on Neurofeedback System Based on Electroencephalogram Signals]

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. Aug, 2014  |  Pubmed ID: 25508440

Neurofeedback, as an alternative treatment method of behavioral medicine, is a technique which translates the electroencephalogram (EEG) signals to styles as sounds or animation to help people understand their own physical status and learn to enhance or suppress certain EEG signals to regulate their own brain functions after several repeated trainings. This paper develops a neurofeedback system on the foundation of brain-computer interface technique. The EEG features are extracted through real-time signal process and then translated to feedback information. Two feedback screens are designed for relaxation training and attention training individually. The veracity and feasibility of the neurofeedback system are validated through system simulation and preliminary experiment. Key words: neurofeedback; electroencephalogram; feature extraction; brain-computer interface

Time Trends of Nasopharyngeal Carcinoma in Urban Guangzhou over a 12-year Period (2000-2011): Declines in Both Incidence and Mortality

Asian Pacific Journal of Cancer Prevention : APJCP. 2014  |  Pubmed ID: 25520125

Nasopharyngeal carcinoma (NPC) is an uncommon disease in most countries but occurs with much greater frequency in southern China. This study aimed to examine the secular trends of NPC in urban Guangzhou over the time period of 2000-2011 using data from the Guangzhou Cancer Registry. Age-adjusted annual incidence rates of NPC were calculated by the direct method using the WHO World Standard Population (1960) as the reference. The average annual percentage change (AAPC) was used as an estimate of the trend. A total of 7,532 new cases of NPC and 3,449 related deaths were registered. In both genders, the peak incidence occurred in the 50- to 59-year age group, and this age distribution pattern remained similar throughout. The AAPC in NPC incidence rates was -3.26% (95% CI: -5.4%--1.1) for males and -5.74% (95% CI: -8.9%--2.5) for females, resulting in a total decrease of 39.3% (from 22.14 to 13.44 per 100,000 population) for males and 48.6% (from 10.1 to 5.18 per 100,000 population) for females over this 12-year period. The AAPCs in NPC mortality rates were -4.62% (95%CI: -3.5%--5.7) for males and -6.75% (95% CI: -5.2%--8.3) for females, resulting in a total decrease of -46.1% (from 12.1 to 6.54 per 100,000 population) for males and 51.7% (from 4.14 to 2.00 per 100,000 population) for females. The age-adjusted incidence and mortality rates of NPC declined during 2000-2011 in urban Guangzhou but remained high. Future efforts to improve prevention, early detection and treatment strategies are needed.

Proteome Changes Underpin Improved Meat Quality and Yield of Chickens (Gallus Gallus) Fed the Probiotic Enterococcus Faecium

BMC Genomics. 2014  |  Pubmed ID: 25532559

Supplementation of broiler chicken diets with probiotics may improve carcass characteristics and meat quality. However, the underlying molecular mechanism remains unclear. In the present study, 2D-DIGE-based proteomics was employed to investigate the proteome changes associated with improved carcass traits and meat quality of Arbor Acres broilers (Gallus gallus) fed the probiotic Enterococcus faecium.

Synthesis and In-Vitro Cytotoxicity of (E)-N,2,3-Triarylacrylamide Derivatives As Analogs of Combretastatin A-4

Medicinal Chemistry (Shariqah (United Arab Emirates)). Dec, 2014  |  Pubmed ID: 25541746

A new series of (E)-N,2,3-triarylacrylamide derivatives were designed and synthesized as potent anticancer agents. Cytotoxicity of the 26 target compounds was evaluated in vitro against six cancer cell lines (HCT116, A549, MDA-MB-468, HepG2, SKNMC and SK-OV-3) by Sulforhodamine B colorimetric assay. The most promising compound, 4h, was as potent as the reference drug cisplatin (DDP). Preliminary structure-activity relationship (SAR) data provided guidance for further design and discovery of (E)-N,2,3-triarylacrylamide scaffold anticancer agents.

Inhibiting Drug Efflux Transporters Improves Efficacy of ALS Therapeutics

Annals of Clinical and Translational Neurology. Dec, 2014  |  Pubmed ID: 25574474

Research identified promising therapeutics in cell models of Amyotrophic Lateral Sclerosis (ALS), but there is limited progress translating effective treatments to animal models and patients, and ALS remains a disease with no effective treatment. One explanation stems from an acquired pharmacoresistance driven by the drug efflux transporters P-glycoprotein (P-gp) and breast cancer-resistant protein (BCRP), which we have shown are selectively upregulated at the blood-brain and spinal cord barrier (BBB/BSCB) in ALS mice and patients. Pharmacoresistance is well appreciated in other brain diseases, but overlooked in ALS despite many failures in clinical trials.

[Effects of Noxious Coldness and Non-noxious Warmth on the Magnitude of Cerebral Cortex Activation During Intraoral Stimulation with Water]

Hua Xi Kou Qiang Yi Xue Za Zhi = Huaxi Kouqiang Yixue Zazhi = West China Journal of Stomatology. Dec, 2014  |  Pubmed ID: 25665418

We used functional magnetic resonance imaging (fMRI) to explore the effects of noxious coldness and non-noxious warmth on the magnitude of cerebral cortex activation during intraoral stimulation with water.

Serum Peptidome Patterns of Hepatocellular Carcinoma Based on Magnetic Bead Separation and Mass Spectrometry Analysis

The Turkish Journal of Gastroenterology : the Official Journal of Turkish Society of Gastroenterology. Dec, 2014  |  Pubmed ID: 25910294

The only hope for a cure from hepatocellular carcinoma (HCC) rests on early diagnosis. The present study aims to determine serum peptidome patterns for early diagnosis of HCC.

Carpal Tunnel Syndrome Impairs Sustained Precision Pinch Performance

Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. Jan, 2015  |  Pubmed ID: 24877682

The purpose of this study was to investigate effects of carpal tunnel syndrome (CTS) on digit force control during a sustained precision pinch.

Community Succession of Bacteria and Eukaryotes in Dune Ecosystems of Gurbantünggüt Desert, Northwest China

Extremophiles : Life Under Extreme Conditions. Jan, 2015  |  Pubmed ID: 25253412

Pyrosequencing and quantitative polymerase chain reaction of small subunit rRNA genes were used to provide a comprehensive examination of bacterial, cyanobacterial, and eukaryotic communities in the biological soil crusts (BSCs) of Gurbantünggüt Desert sand dunes (China). Three succession stages were recognized based on the analyses of eukaryotic communities: a late succession stage of BSCs in a swale with eukaryotes mainly related to the Bryophyta clade, an initial succession stage in a slope with barely any eukaryotic phototrophic microorganisms detected, and an intermediate succession type detected from both the swale and slope BSCs dominated by the phylum Chlorophyta. Moreover, the cyanobacterial community dominated all of the BSCs (48.2-69.5% of the total bacteria) and differed among the three succession stages: sequences related to Microcoleus steenstrupii and the genus Scytonema were abundant in the later succession stage, whereas both the initial and intermediate stages were dominated by Microcoleus vaginatus. Compared with swales, BSCs from slopes are exposed to a harsher environment, e.g., higher irradiance and lower water availability, and thus may be restricted from developing to a higher succession stage. Other disturbances such as wind and grazing may explain the different succession stages observed in swales or slopes. However, no clear differences were detected from non-phototrophic bacterial communities of the three succession stages, and sequences related to Alphaproteobacteria and Actinobacteria were most abundant in all the BSCs. The closest matches for the most frequent non-phototrophic bacterial genera were mainly derived from harsh environments, indicating the robustness of these genera.

The Effects of Antidepressant Treatment on Resting-state Functional Brain Networks in Patients with Major Depressive Disorder

Human Brain Mapping. Feb, 2015  |  Pubmed ID: 25332057

Although most knowledge regarding antidepressant effects is at the receptor level, the neurophysiological correlates of these neurochemical changes remain poorly understood. Such an understanding could benefit from elucidation of antidepressant effects at the level of neural circuits, which would be crucial in identifying biomarkers for monitoring treatment efficacy of antidepressants. In this study, we recruited 20 first-episode drug-naive major depressive disorder (MDD) patients and performed resting-state functional magnetic resonance imaging (MRI) scans before and after 8 weeks of treatment with a selective serotonin reuptake inhibitor-escitalopram. Twenty healthy controls (HCs) were also scanned twice with an 8-week interval. Whole-brain connectivity was analyzed using a graph-theory approach-functional connectivity strength (FCS). The analysis of covariance of FCS was used to determine treatment-related changes. We observed significant group-by-time interaction on FCS in the bilateral dorsomedial prefrontal cortex and bilateral hippocampi. Post hoc analyses revealed that the FCS values in the bilateral dorsomedial prefrontal cortex were significantly higher in the MDD patients compared to HCs at baseline and were significantly reduced after treatment; conversely, the FCS values in the bilateral hippocampi were significantly lower in the patients at baseline and were significantly increased after treatment. Importantly, FCS reduction in the dorsomedial prefrontal cortex was significantly correlated with symptomatic improvement. Together, these findings provided evidence that this commonly used antidepressant can selectively modulate the intrinsic network connectivity associated with the medial prefrontal-limbic system, thus significantly adding to our understanding of antidepressant effects at a circuit level and suggesting potential imaging-based biomarkers for treatment evaluation in MDD.

Robinetinidol-flavone Attenuates Cholesterol Synthesis in Hepatoma Cells Via Inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A Reductase

Molecular Medicine Reports. Jan, 2015  |  Pubmed ID: 25339541

Robinetinidol-(4β,2')-tetrahydroxy-flavone (RBF) is an oligomeric condensed polyphenol that has been shown to exhibit anti-obesity effects in mice. However, little is know regarding its effect on cholesterol synthesis. The present study therefore aimed to investigate the effect of RBF on cholesterol synthesis. It was determined that RBF decreased serum total cholesterol and low density lipoprotein cholesterol in rats by 25.9 and 50.8%, respectively (P<0.001). These results strengthen evidence for the hypothesis that RBF exerts anti-atherogenic effects in vivo. Furthermore, RBF decreased cholesterol synthesis by 72%, when measured using a 3 h period of radiolabeled acetate incorporation into cholesterol, but not when using radiolabelled mevalonate, suggesting that RBF-mediated inhibition occurred largely at or above the level of 3-hydroxy-3-methylglutaryl-coenzymeA (HMG-CoA) reductase. The mechanism by which RBF inactivates HMG-CoA reductase may be attributed to the induction of phosphorylation of adenosine monophosphate (AMP)-kinase, since these results showed that RBF increased phosphorylation of AMP-kinase and HMG-CoA reductase by 2.1- and 3.2-fold, respectively, within 30 min of addition. These results suggest that RBF may be a potential therapeutic agent for hypercholesteremia.

Assessing the Complexity of Short-term Heartbeat Interval Series by Distribution Entropy

Medical & Biological Engineering & Computing. Jan, 2015  |  Pubmed ID: 25351477

Complexity of heartbeat interval series is typically measured by entropy. Recent studies have found that sample entropy (SampEn) or fuzzy entropy (FuzzyEn) quantifies essentially the randomness, which may not be uniformly identical to complexity. Additionally, these entropy measures are heavily dependent on the predetermined parameters and confined to data length. Aiming at improving the robustness of complexity assessment for short-term RR interval series, this study developed a novel measure--distribution entropy (DistEn). The DistEn took full advantage of the inherent information underlying the vector-to-vector distances in the state space by probability density estimation. Performances of DistEn were examined by theoretical data and experimental short-term RR interval series. Results showed that DistEn correctly ranked the complexity of simulated chaotic series and Gaussian noise series. The DistEn had relatively lower sensitivity to the predetermined parameters and showed stability even for quantifying the complexity of extremely short series. Analysis further showed that the DistEn indicated the loss of complexity in both healthy aging and heart failure patients (both p < 0.01), whereas neither the SampEn nor the FuzzyEn achieved comparable results (all p ≥ 0.05). This study suggested that the DistEn would be a promising measure for prompt clinical examination of cardiovascular function.

Fractional Anisotropy Alterations in Individuals Born Preterm: a Diffusion Tensor Imaging Meta-analysis

Developmental Medicine and Child Neurology. Apr, 2015  |  Pubmed ID: 25358534

This meta-analysis explored cerebral microstructural changes in individuals born preterm using fractional anisotropy from diffusion tensor imaging.

T-cell-associated Cellular Immunotherapy for Lung Cancer

Journal of Cancer Research and Clinical Oncology. Jul, 2015  |  Pubmed ID: 25381064

The aim of the present study was to discuss recent findings on the role of T cells in lung cancer to provide information on their potential application, especially in cellular immunotherapy.

Composite Peptide-based Vaccines for Cancer Immunotherapy (Review)

International Journal of Molecular Medicine. Jan, 2015  |  Pubmed ID: 25395173

The use of peptide-based vaccines as therapeutics aims to elicit immune responses through antigenic epitopes derived from tumor antigens. Peptide-based vaccines are easily synthesized and chemically stable entities, and of note, they are absent of oncogenic potential. However, their application is more complicated as the success of an effective peptide-based vaccine is determined by numerous parameters. The success thus far has been limited by the choice of tumor antigenic peptides, poor immunogenicity and incorporation of strategies to reverse cancer-mediated immune suppression. In the present review, an overview of the mechanisms of peptide-based vaccines is provided and antigenic peptides are categorized with respect to their tissue distribution in order to determine their usefulness as targets. Furthermore, certain approaches are proposed that induce and maintain T cells for immunotherapy. The recent progress indicates that peptide-based vaccines are preferential for targeted therapy in cancer patients.

DNA Photocleavage in Anaerobic Conditions by a Ru(ii) Complex: a New Mechanism

Chemical Communications (Cambridge, England). Jan, 2015  |  Pubmed ID: 25406916

[Ru(bpy)2(py-SO3)](+) (bpy = 2,2'-bipyridine and py-SO3 = pyridine-2-sulfonate) was found to undergo py-SO3 dissociation upon visible light irradiation (≥470 nm) via Ru-O homolysis, producing reactive free radical species, and is thus able to not only photobind but also photocleave DNA in hypoxic conditions.

Upper Gastrointestinal Hemorrhage Due to a Fistula Between the Splenic Vein and Main Pancreatic Duct: A Rare Case

Journal of Digestive Diseases. Apr, 2015  |  Pubmed ID: 25420959

High Circulating CD39(+) Regulatory T Cells Predict Poor Survival for Sepsis Patients

International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases. Jan, 2015  |  Pubmed ID: 25461658

Sepsis encompasses two phases, the 'hyper'-reactive phase and the 'hypo'-reactive phase. The initial inflammatory stage is quickly counterbalanced by an anti-inflammatory response, which compromises the immune system, leading to immune suppression. Regulatory T cells (Tregs) have been implicated in the pathogenesis of sepsis by inducing immunosuppression; however, the role of CD39(+) Tregs in the process of sepsis is uncertain. This study investigated the dynamic levels of CD39(+) Tregs and their phenotypic change in sepsis.

Mulberry-like Dual-drug Complicated Nanocarriers Assembled with Apogossypolone Amphiphilic Starch Micelles and Doxorubicin Hyaluronic Acid Nanoparticles for Tumor Combination and Targeted Therapy

Biomaterials. Jan, 2015  |  Pubmed ID: 25477180

A comprehensive strategy for the preparation of mulberry-like dual-drug complicated nanocarriers (MLDC NCs) with high drug loading and adjustable dual-drug ratio was developed. First, apogossypolone (ApoG2) amphiphilic starch micelles (AASt MCs) were prepared by self-assembly process, and doxorubicin (DOX) hyaluronic acid nanoparticles (DHA NPs) were prepared by DOX absorption with excess HA by electrostatic absorption. MLDC NCs were obtained by adsorption of 8-9 DHA NPs around one AASt MC via electrostatic interaction. UV-visible and fluorescence spectrophotometers were used to measure the entrapment efficiency and loading efficiency of the two drugs. Transmission electron microscope and dynamic light scattering method were used to observe the size distribution and morphology of the particles. The tumor-targeting feature caused by HA-receptor mediation was confirmed by in vitro cell uptake and in vivo near-infrared fluorescence imaging. MLDC NCs were found to possess a mulberry-like shape with a dynamic size of 83.1 ± 6.6 nm. The final encapsulation efficiencies of ApoG2 and DOX in MLDC NCs were 94 ± 1.7% and 87 ± 5.8% with respect to drug-loading capacities of 13.3 ± 1.2% and 13.1 ± 3.7%, respectively. Almost no ApoG2 release was found within 80 h and less than 30% of DOX was released into the outer phase even after 72 h. In vivo fluorescence imaging revealed that MLDC NCs had highly efficient targeting and accumulation at the tumor in vivo and was maintained for 96 h after being injected intravenously in mice. Low LD50 for the two drugs in MLDC NCs was found after acute toxicity test. One-fifth normal dosage of the two drugs in MLDC NCs exhibited significantly higher anti-tumor efficiency in reducing tumor size compared with free drugs combination or single drug-loaded nanoparticles individually, indicating that the mulberry-like dual-drug nanoplatform has a great potential in tumor therapy.

Activation of Endogenous Anti-inflammatory Mediator Cyclic AMP Attenuates Acute Pyelonephritis in Mice Induced by Uropathogenic Escherichia Coli

The American Journal of Pathology. Feb, 2015  |  Pubmed ID: 25478807

The pathogenesis of pyelonephritis caused by uropathogenic Escherichia coli (UPEC) is not well understood. Here, we show that besides UPEC virulence, the severity of the host innate immune response and invasion of renal epithelial cells are important pathogenic factors. Activation of endogenous anti-inflammatory mediator cAMP significantly attenuated acute pyelonephritis in mice induced by UPEC. Administration of forskolin (a potent elevator of intracellular cAMP) reduced kidney infection (ie, bacterial load, tissue destruction); this was associated with attenuated local inflammation, as evidenced by the reduction of renal production of proinflammatory mediators, renal infiltration of inflammatory cells, and renal myeloperoxidase activity. In primary cell culture systems, forskolin not only down-regulated UPEC-stimulated production of proinflammatory mediators by renal tubular epithelial cells and inflammatory cells (eg, monocyte/macrophages) but also reduced bacterial internalization by renal tubular epithelial cells. Our findings clearly indicate that activation of endogenous anti-inflammatory mediator cAMP is beneficial for controlling UPEC-mediated acute pyelonephritis in mice. The beneficial effect can be explained at least in part by limiting excessive inflammatory responses through acting on both renal tubular epithelial cells and inflammatory cells and by inhibiting bacteria invasion of renal tubular epithelial cells.

Effective Expansion of Forkhead Box P3⁺ Regulatory T Cells Via Early Secreted Antigenic Target 6 and Antigen 85 Complex B from Mycobacterium Tuberculosis

Molecular Medicine Reports. Apr, 2015  |  Pubmed ID: 25483347

The expansion of CD4+ CD25+ forkhead box (FOX)P3+ regulatory T (Treg) cells has been observed in patients with Mycobacterium (M.) tuberculosis; however, the mechanism of expansion remains to be elucidated. The aim of the present study was to examine the role of the early secreted antigenic target 6(ESAT‑6) and antigen 85 complex B (Ag85B) from M. tuberculosis on Treg cell expansion. To investigate the sensitivity of peripheral blood cultures to the M. tuberculosis ESAT‑6 and Ag85B antigens, the proportion of circulating CD4+ CD25+ FOXP3+ Treg cells was determined using flow cytometry and the levels of FOXP3 mRNA were determined using reverse transcription quantitative polymerase chain reaction. The mRNA levels of FOXP3 and the proportion of circulating CD4+ CD25+ FOXP3+ Treg cells were increased in multiplicitous drug‑resistant tuberculosis patients compared with those in healthy controls and patients with latent tuberculosis (TB) infection (LTBI) (P<0.001). The mycobacterial antigens ESAT‑6 and Ag85B increased the expansion of the CD4+ CD25+ FOXP3+ Treg cells and the mRNA levels of FOXP3 in healthy controls and LTBI patients compared with the effect of Bacillus Calmette‑Guerin (P<0.05). Additionally, the mRNA levels of FOXP3 were elevated in the LTBI patients following stimulations with the mycobacterial antigens (P=0.012). Therefore, the M. tuberculosis antigens ESAT‑6 and Ag85B induced CD4+ CD25+ FOXP3+ Treg‑cell expansion, particularly in patients with LTBI. These findings indicated that CD4+ CD25+ FOXP3+ Treg cells may have a primary role in the failure of the host immune system to eradicate M. tuberculosis.

Vitamin and Multiple-vitamin Supplement Intake and Incidence of Colorectal Cancer: a Meta-analysis of Cohort Studies

Medical Oncology (Northwood, London, England). Jan, 2015  |  Pubmed ID: 25491145

This paper systematically evaluated the association of intake of different vitamins and multiple-vitamin supplements and the incidence of colorectal cancer. Relevant studies were identified in MEDLINE via PubMed (published up to April 2014). We extracted data from articles on vitamins A, C, D, E, B9 (folate), B2, B3, B6, and B12 and multiple-vitamin supplements. We used multivariable-adjusted relative risks (RRs) and a random-effects model for analysis and random effects. With heterogeneity, we looked for the source of heterogeneity or performed sensitivity and stratified analyses. We found 47 articles meeting the inclusion criteria. The multivariable-adjusted RR for pooled studies for the association between the highest versus lowest vitamin B9 (folate) intake and colorectal cancer was 0.88 [95 % confidence interval (95 % CI) 0.81-0.95]. Vitamin D was 0.87 (95 % CI 0.77-0.99); vitamin B6, 0.88 (95 % CI 0.79-0.99); vitamin B2, 0.86 (95 % CI, 0.76-0.97); vitamin A, 0.87 (95 % CI, 0.75-1.03); vitamin C, 0.92 (95 % CI, 0.80-1.06); vitamin E, 0.94 (95 % CI, 0.82-1.07); vitamin B12, 1.10 (95 % CI, 0.92-1.32); vitamin B3, 1.18 (95 % CI, 0.76-1.84). Vitamin B9 (folate), D, B6, and B2 intake was inversely associated with risk of colorectal cancer, but further study is needed. Our study featured unacceptable heterogeneity for studies of multiple-vitamin supplements, so findings were inconclusive.

Transplantation of Glial Progenitors That Overexpress Glutamate Transporter GLT1 Preserves Diaphragm Function Following Cervical SCI

Molecular Therapy : the Journal of the American Society of Gene Therapy. Mar, 2015  |  Pubmed ID: 25492561

Approximately half of traumatic spinal cord injury (SCI) cases affect cervical regions, resulting in chronic respiratory compromise. The majority of these injuries affect midcervical levels, the location of phrenic motor neurons (PMNs) that innervate the diaphragm. A valuable opportunity exists following SCI for preventing PMN loss that occurs during secondary degeneration. One of the primary causes of secondary injury is excitotoxicity due to dysregulation of extracellular glutamate homeostasis. Astrocytes express glutamate transporter 1 (GLT1), which is responsible for the majority of CNS glutamate clearance. Given our observations of GLT1 dysfunction post-SCI, we evaluated intraspinal transplantation of Glial-Restricted Precursors (GRPs)--a class of lineage-restricted astrocyte progenitors--into ventral horn following cervical hemicontusion as a novel strategy for reconstituting GLT1 function, preventing excitotoxicity and protecting PMNs in the acutely injured spinal cord. We find that unmodified transplants express low levels of GLT1 in the injured spinal cord. To enhance their therapeutic properties, we engineered GRPs with AAV8 to overexpress GLT1 only in astrocytes using the GFA2 promoter, resulting in significantly increased GLT1 protein expression and functional glutamate uptake following astrocyte differentiation in vitro and after transplantation into C4 hemicontusion. Compared to medium-only control and unmodified GRPs, GLT1-overexpressing transplants reduced lesion size, diaphragm denervation and diaphragm dysfunction. Our findings demonstrate transplantation-based replacement of astrocyte GLT1 is a promising approach for SCI.

Performance of Vertical Up-flow Constructed Wetlands on Swine Wastewater Containing Tetracyclines and Tet Genes

Water Research. Mar, 2015  |  Pubmed ID: 25528541

Antibiotics and antibiotic resistance genes (ARGs) pollution in animal feeding farms received more public attention recently. Livestock wastewater contains large quantities of antibiotics and ARGs even after traditional lagoon treatment. In this study, the performance of vertical up-flow constructed wetlands (VUF-CWs) on swine wastewater containing tetracycline compounds (TCs) and tet genes was evaluated based on three aspects, TCs and tet genes removal efficiencies, residual TCs and tet genes in soils and plants, and the effect of TCs accumulation on nutrients removal and tet genes development. High removal efficiencies (69.0-99.9%) were achieved for oxytetracycline (OTC), tetracycline (TC) and chlortetracycline (CTC) with or without OTC spiked in the influent additionally. TCs concentrations in surface soils increased at first two sampling periods and then decreased after plants were harvested. Satisfactory nutrients removal efficiencies were also obtained, but TN and NH4-N removal efficiencies were significantly negative correlated with total concentration of TCs (∑TCs) in the soils (p < 0.01). The absolute abundances of all the target genes (tetO, tetM, tetW, tetA, tetX and intI1) were greatly reduced with their log units ranging from 0.26 to 3.3. However, the relative abundances of tetO, tetM and tetX in some effluent samples were significantly higher than those in the influent (p < 0.05). The relative abundances of tet genes except for tetO were significantly correlated with ∑TCs in the soils (p < 0.05). In summary, the proposed VUF-CWs are effective alternative for the removal of TCs and tet genes. But it is of great importance to prevent large accumulation of TCs in the soils.

(+)- and (-)-petromyroxols: Antipodal Tetrahydrofurandiols from Larval Sea Lamprey (Petromyzon Marinus L.) That Elicit Enantioselective Olfactory Responses

Organic Letters. Jan, 2015  |  Pubmed ID: 25534255

(+)- and (-)-petromyroxol [(+)-1 and (-)-1, respectively], two novel tetrahydrofuran (THF)-diol fatty acid enantiomers, were isolated from water conditioned with larval sea lamprey. We herein describe their isolation and subsequent resolution using chiral chromatography. The absolute configuration of each enantiomer was determined by a combination of Mosher ester analysis and comparison with related natural and synthetic products. Electro-olfactogram (EOG) assays indicated that (+)-petromyroxol (1) possesses potent olfactory activity for sea lamprey.

Excessive Fatal Injury Among Migrant Children in China: Inequities in Safety

Injury Prevention : Journal of the International Society for Child and Adolescent Injury Prevention. Jan, 2015  |  Pubmed ID: 25568288

The wide variability in economic development levels among different regions in China results in the migration of millions of households to more developed areas. Death records from 2008 to 2012 of children aged 0-17 years old from the vital surveillance system of Guangzhou were used to determine if death rates were different for resident and migrant children. A total of 1358 injury-related deaths were identified with rates rising slightly from 2008 to 2012 both in resident and migrant populations. The total crude incidence rate of injury death was significantly higher among migrant households (29.50/100 000) compared with resident households (8.42/100 000). The adjusted rate in migrant households was 3.50 (95% CI 3.14 to 3.89) times higher than in resident households. Drowning and traffic crashes represented the most common causes of death and residences were the most frequent site of injury-related death for both groups of children. Migrant children were at a significantly higher risk of injury-related mortality compared with local resident children.

Nucleolar Stress and Impaired Stress Granule Formation Contribute to C9orf72 RAN Translation-induced Cytotoxicity

Human Molecular Genetics. May, 2015  |  Pubmed ID: 25575510

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are the two common neurodegenerative diseases that have been associated with the GGGGCC·GGCCCC repeat RNA expansion in a noncoding region of C9orf72. It has been previously reported that unconventional repeat-associated non-ATG (RAN) translation of GGGGCC·GGCCCC repeats produces five types of dipeptide-repeat proteins (referred to as RAN proteins): poly-glycine-alanine (GA), poly-glycine-proline (GP), poly-glycine-arginine (GR), poly-proline-arginine (PR) and poly-proline-alanine (PA). Although protein aggregates of RAN proteins have been found in patients, it is unclear whether RAN protein aggregation induces neurotoxicity. In the present study, we aimed to understand the biological properties of all five types of RAN proteins. Surprisingly, our results showed that none of these RAN proteins was aggregate-prone in our cellular model and that the turnover of these RAN proteins was not affected by the ubiquitin-proteasome system or autophagy. Moreover, poly-GR and poly-PR, but not poly-GA, poly-GP or poly-PA, localized to the nucleolus and induced the translocation of the key nucleolar component nucleophosmin, leading to nucleolar stress and cell death. This poly-GR- and poly-PR-mediated defect in nucleolar function was associated with the suppression of ribosomal RNA synthesis and the impairment of stress granule formation. Taken together, the results of the present study suggest a simple model of the molecular mechanisms underlying RAN translation-mediated cytotoxicity in C9orf72-linked ALS/FTD in which nucleolar stress, but not protein aggregation, is the primary contributor to C9orf72-linked neurodegeneration.

A Variant of CLEC16A Gene Confers Protection for Vogt-Koyanagi-Harada Syndrome but Not for Behcet's Disease in a Chinese Han Population

Experimental Eye Research. Mar, 2015  |  Pubmed ID: 25576669

Vogt-Koyanagi-Harada (VKH) syndrome and Behcet's disease (BD) are two common form of uveitis in China. The aim of this study was to investigate the association of C-type lectin domain family 16, member A (CLEC16A) gene polymorphisms with Vogt-Koyanagi-Harada syndrome and Behcet's disease in a Chinese Han population. A two-stage association study was carried out in 988 VKH syndrome patients,400 BD patients and 976 healthy controls. Eight single nucleotide polymorphisms of CLEC16A gene were determined with the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The data were analyzed by χ(2) test or Fisher's exact test and corrected for multiple comparisons by the Bonferroni method. The first stage study showed that the frequency of the A allele of rs6498169 was significantly decreased in VKH syndrome patients (Pc = 1.1 × 10(-2), OR = 0.7, 95%CI = 0.6-0.9). No significant association was observed in the other 7 SNPs between VKH syndrome patients and controls. No association was found with BD for the 8 SNPs tested. We further confirmed the association of single nucleotide polymorphism rs6498169 with VKH syndrome in another cohort. Consistent with the first stage study, the combined study showed significantly lower frequencies of the AA genotype and the A allele of rs6498169 in VKH syndrome patients (Pc = 3.5 × 10(-4), OR = 0.6, 95%CI = 0.5-0.7; Pc = 8.2 × 10(-4), OR = 0.8, 95%CI = 0.7-0.9, respectively). In conclusion, the study suggested that a CLEC16A polymorphism may be protective against VKH syndrome in a Chinese Han population.

The Combustion Behavior of Large Scale Lithium Titanate Battery

Scientific Reports. 2015  |  Pubmed ID: 25586064

Safety problem is always a big obstacle for lithium battery marching to large scale application. However, the knowledge on the battery combustion behavior is limited. To investigate the combustion behavior of large scale lithium battery, three 50 Ah Li(Ni(x)Co(y)Mn(z))O2/Li(4)Ti(5)O(12) batteries under different state of charge (SOC) were heated to fire. The flame size variation is depicted to analyze the combustion behavior directly. The mass loss rate, temperature and heat release rate are used to analyze the combustion behavior in reaction way deeply. Based on the phenomenon, the combustion process is divided into three basic stages, even more complicated at higher SOC with sudden smoke flow ejected. The reason is that a phase change occurs in Li(Ni(x)Co(y)Mn(z))O2 material from layer structure to spinel structure. The critical temperatures of ignition are at 112-121 °C on anode tab and 139 to 147 °C on upper surface for all cells. But the heating time and combustion time become shorter with the ascending of SOC. The results indicate that the battery fire hazard increases with the SOC. It is analyzed that the internal short and the Li(+) distribution are the main causes that lead to the difference.

An UPLC-MS/MS Method for Quantitative Profiling of Bile Acids in Sea Lamprey Plasma and Tissues

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. Feb, 2015  |  Pubmed ID: 25589257

Bile acids (BAs) have recently gained more attention because of their diverse roles from digestion to signaling. Simultaneous analyses of various BAs in biological samples are challenging due to their structural similarity, relatively low concentrations, and the presence of isomeric forms. In this study, we report a simple and sensitive UPLC-MS/MS method for simultaneous quantifications of 13 BAs including four unique sea lamprey BAs in sea lamprey plasma, liver, intestine, and gills. A straightforward protein precipitation (PPT) method was used to extract BAs from the biological samples. Separation of all target analytes was achieved on a reverse-phase UPLC column in 15min, and detection was carried out on MS/MS with ESI in the negative ionization mode. This method was validated regarding its linearity, limits of detection (LOD), recovery, matrix effect, reproducibility, accuracy and precision. Significant improvements compared to previous LC-MS/MS methods were observed as a result of the application of UPLC and extensive optimization of experimental conditions. The method showed excellent linearity with high regression coefficients (>0.99) over a range of 0.5-1000ng/mL and LODs ranged from 0.009 to 0.11ng/mL. The applications of the developed method demonstrated that it simultaneously determined all target BAs in different biological sample matrices with excellent sensitivity, selectivity and reproducibility.

Lottery Spending: a Non-parametric Analysis

PloS One. 2015  |  Pubmed ID: 25642699

We analyze the spending of individuals in the United States on lottery tickets in an average month, as reported in surveys. We view these surveys as sampling from an unknown distribution, and we use non-parametric methods to compare properties of this distribution for various demographic groups, as well as claims that some properties of this distribution are constant across surveys. We find that the observed higher spending by Hispanic lottery players can be attributed to differences in education levels, and we dispute previous claims that the top 10% of lottery players consistently account for 50% of lottery sales.

Protective Effect of Sodium Nitroprusside on the Rat Small Intestine Transplanted Mucosa

Biochemistry Research International. 2015  |  Pubmed ID: 25650248

The intestinal mucosal epithelium is extremely susceptible to even brief periods of ischemia. Mucosal barrier damage, which is associated with ischemia/reperfusion (I/R) injury and consequently bacterial translocation, remains a major obstacle for clinically successful small bowel transplantation (SBT). Previous studies have demonstrated a protective effect of nitric oxide (NO) on other transplanted organs and NO mediated intestinal protection has also been reported in vitro. The aim of this study was to evaluate the effect of sodium nitroprusside (SNP), NO donor, on graft mucosal histology and molecular markers of function after SBT in rats. We used SNP in different period of heterotopic SBT rats. The groups consisted of SBT, pre-SNP group, and post-SNP group. Interestingly, the pre-SNP graft samples exhibited less damage compared to the SBT and post-SNP samples. In addition, mucosal samples from the pre-SNP group showed higher Na(+)-K(+)-ATPase activity and higher levels of laminin expression compared to the SBT and post-SNP samples. The findings of the present study reveal that SNP given before graft ischemia/reperfusion injury has a protective effect on mucosal histology and molecular markers of function in the transplanted small intestine.

Covered Stents for the Endovascular Treatment of a Direct Carotid Cavernous Fistula : Single Center Experiences with 10 Cases

Journal of Korean Neurosurgical Society. Jan, 2015  |  Pubmed ID: 25674338

Covered stent has been recently reported as an effective alternative treatment for direct carotid cavernous fistulas (DCCFs). The purpose of this study is to describe our experiences with the treatment of DCCF with covered stents and to evaluate whether a covered stent has a potential to be used as the first choice in selected cases.

Potential Quality Evaluation Method for Radix Astragali Based on Sweetness Indicators

Molecules (Basel, Switzerland). 2015  |  Pubmed ID: 25689640

Sweetness is a traditional sensory indicator used to evaluate the quality of the popular Chinese herb Radix Astragali (RA). RA roots with strong sweetness are considered to be of good quality. However, neither a thorough analysis of the component(s) contributing to RA sweetness, nor a scientific investigation of the reliability of this indicator has been conducted to date. In this study, seven kinds of sweetness components were identified in RA and a quality evaluation method based on these components was established and used to characterize the quality of 48 RA samples. The sweetness evaluation method of RA was first built based on the sweetness components, and a comprehensive evaluation index commonly used in quality control of RA was also derived, which was based on the contents of four indicators (astragaloside IV, calycosin glucoside, polysaccharides and extracts). After evaluating the correlation of these indexes the results showed that the level of sweetness exhibited a strong positive correlation with the proposed comprehensive index. Our results indicate that sweetness is one of the most important quality attributes of RA and thus provide a scientific basis for the utility of the sweetness indicator in quality assessment of this Chinese herb.

Diagnostic Value of Multiple Tumor Markers for Patients with Esophageal Carcinoma

PloS One. 2015  |  Pubmed ID: 25693076

Various studies assessing the diagnostic value of serum tumor markers in patients with esophageal cancer remain controversial. This study aims to comprehensively and quantitatively summarize the potential diagnostic value of 5 serum tumour markers in esophageal cancer.

First-line Gemcitabine and Oxaliplatin (GEMOX) Plus Sorafenib, Followed by Sorafenib As Maintenance Therapy, for Patients with Advanced Hepatocellular Carcinoma: a Preliminary Study

International Journal of Clinical Oncology. Feb, 2015  |  Pubmed ID: 25712158

Because of the poor prognosis of unresectable or metastatic hepatocellular carcinoma there is a need for effective systemic therapy. The purpose of this study was to assess the efficacy and safety of gemcitabine and oxaliplatin (GEMOX) combined with sorafenib, as first-line therapy, followed by sorafenib as maintenance therapy for patients with advanced hepatocellular carcinoma (HCC).

Enhanced Neuroactivation During Working Memory Task in Postmenopausal Women Receiving Hormone Therapy: A Coordinate-Based Meta-Analysis

Frontiers in Human Neuroscience. 2015  |  Pubmed ID: 25717297

Hormone therapy (HT) has long been thought beneficial for controlling menopausal symptoms and human cognition. Studies have suggested that HT has a positive association with working memory, but no consistent relationship between HT and neural activity has been shown in any cognitive domain. The purpose of this meta-analysis was to assess the convergence of findings from published randomized control trials studies that examined brain activation changes in postmenopausal women.

Complement 5a Receptor-mediated Neutrophil Dysfunction is Associated with a Poor Outcome in Sepsis

Cellular & Molecular Immunology. Mar, 2015  |  Pubmed ID: 25726869

Complement 5a (C5a) has been implicated in the pathogenesis of sepsis by inducing the functional impairment of neutrophils; however, the utility of C5a receptors (C5aRs; C5aR and C5L2) as biomarkers for the management of sepsis is uncertain. This study investigated the dynamic expression of C5aR and C5L2 on neutrophils and their effects on neutrophil function. We found that sepsis patients displayed low expression levels of C5aR and C5L2 on neutrophils compared to healthy and systemic inflammatory response syndrome (SIRS) subjects, and this expression pattern was correlated with disease severity. Additionally, the expression levels of C5aR and C5L2 were associated with the survival of sepsis patients. In vitro, the addition of C5a significantly reduced C5aR and C5L2 expression levels and IL-8 production in neutrophils from sepsis patients. Those findings suggest that the reduced expression of C5aRs was associated with the functional impairment of neutrophils and a poor prognosis for sepsis patients. Overall, these findings may help establish C5aRs expression levels as early markers to predict the severity of sepsis.Cellular & Molecular Immunology advance online publication, 2 March 2015; doi:10.1038/cmi.2014.136.

A Quantitative Assay for Reductive Metabolism of a Pesticide in Fish Using Electrochemistry Coupled with Liquid Chromatography Tandem Mass Spectrometry

Environmental Science & Technology. Apr, 2015  |  Pubmed ID: 25730707

This is the first study to use electrochemistry to generate a nitro reduction metabolite as a standard for a liquid chromatography-mass spectrometry-based quantitative assay. This approach is further used to quantify 3-trifluoromethyl-4-nitrophenol (TFM) reductive metabolism. TFM is a widely used pesticide for the population control of sea lamprey (Petromyzon marinus), an invasive species of the Laurentian Great Lakes. Three animal models, sea lamprey, lake sturgeon (Acipenser fulvescens), and rainbow trout (Oncorhynchus mykiss), were selected to evaluate TFM reductive metabolism because they have been known to show differential susceptibilities to TFM toxicity. Amino-TFM (aTFM; 3-trifluoromethyl-4-aminophenol) was the only reductive metabolite identified through liquid chromatography-high-resolution mass spectrometry screening of liver extracts incubated with TFM and was targeted for electrochemical synthesis. After synthesis and purification, aTFM was used to develop a quantitative assay of the reductive metabolism of TFM through liquid chromatography and tandem mass spectrometry. The concentrations of aTFM were measured from TFM-treated cellular fractions, including cytosolic, nuclear, membrane, and mitochondrial protein extracts. Sea lamprey extracts produced the highest concentrations (500 ng/mL) of aTFM. In addition, sea lamprey and sturgeon cytosolic extracts showed concentrations of aTFM substantially higher than thoose of rainbow trout. However, other fractions of lake sturgeon extracts tend to show aTFM concentrations similar to those of rainbow trout but not with sea lamprey. These data suggest that the level of reductive metabolism of TFM may be associated with the sensitivities of the animals to this particular pesticide.

Using a Sequence of Estrogen Response Elements As a DNA Aptamer for Estrogen Receptors in Vitro

Nucleic Acid Therapeutics. Jun, 2015  |  Pubmed ID: 25734367

Estrogen receptors (ERs) are overexpressed in approximately 70% of breast cancer cases, and they play an important role in tumorigenesis. ERs are strong predictive factors for measuring responses to hormonal therapies. Aptamers are short and single stranded oligonucleotides that are able to recognize target molecules with high affinity. In the present study, we selected and synthesized an oligonucleotide, which has a similar sequence to estrogen response element in the Xenopus Vitellogenin A2 gene. The synthesized oligonucleotide was evaluated by using immunostaining of paraffin-embedded breast cancer tissues and treating MCF-7 human mammary carcinoma cell line in vitro. We found that the synthesized oligonucleotide had a high binding affinity to ER similar to estradiol. Using a specific anti-ER antibody as a standard control, we showed that the synthesized oligonucleotide specifically recognized and immunostained tumor cells of breast cancer without cross-reaction with normal tissues. The overall agreement of ER detection between the anti-ER antibody and the ER aptamer was 97.1% (kappa value=0.943; 95% CI=0.879-1.006; p<0.002). Similar to tamoxifen or fulvestrant, the oligonucleotide also had an inhibitory effect on cell proliferation of MCF-7 cell line in a dose- and time-dependent fashion but had no cytotoxic effect on human normal mammary epithelial cells. Therefore, the synthesized oligonucleotide may be used as an aptamer for immunostaining of paraffin-embedded tissue sections for breast cancer diagnosis, as well as a potential ER antagonist in the treatment of breast cancer.

Vitamin B2 Intake and the Risk of Colorectal Cancer: a Meta-analysis of Observational Studies

Asian Pacific Journal of Cancer Prevention : APJCP. 2015  |  Pubmed ID: 25735381

A systematic review and meta-analysis of observational studies evaluated the association of intake of vitamin B2 with the incidence of colorectal cancer.

Efficient Asymmetric Transfer Hydrogenation of Ketones in Ethanol with Chiral Iridium Complexes of SpiroPAP Ligands As Catalysts

Chemical Communications (Cambridge, England). Apr, 2015  |  Pubmed ID: 25743888

Highly efficient iridium catalyzed asymmetric transfer hydrogenation of simple ketones with ethanol as a hydrogen donor has been developed. By using chiral spiro iridium catalysts (S)- a series of alkyl aryl ketones were hydrogenated to chiral alcohols with up to 98% ee.

T-box Transcription Factor Brachyury in Lung Cancer Cells Inhibits Macrophage Infiltration by Suppressing CCL2 and CCL4 Chemokines

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine. Mar, 2015  |  Pubmed ID: 25744730

Both intra-tumor macrophage and T-box transcription factor Brachyury (T) have been proved to play important roles in tumor progression and metastasis. However, it is still unknown whether T could regulate the infiltration of macrophages. Here, we report that the Brachyury expression in human lung tumors was inversely correlated with the infiltration of macrophages. Brachyury suppressed the capability of human lung cancer cells to attract macrophages. Using PCR array, we found that Brachyury inhibited expression of several chemokines, including CCL2, CCL4, and CXCL10. Accordingly, knockdown of CCL2 and CCL4 in lung cancer cells suppressed macrophage invasion under coculture conditions. Furthermore, we found that Brachyury expression was inversely correlated with CCL2 and CCL4 expression in human lung tumors. Taken together, our findings shed light on the novel role of Brachyury in regulation of macrophage infiltration.

Independent Component Analysis-based Identification of Covariance Patterns of Microstructural White Matter Damage in Alzheimer's Disease

PloS One. 2015  |  Pubmed ID: 25775003

The existing DTI studies have suggested that white matter damage constitutes an important part of the neurodegenerative changes in Alzheimer's disease (AD). The present study aimed to identify the regional covariance patterns of microstructural white matter changes associated with AD. In this study, we applied a multivariate analysis approach, independent component analysis (ICA), to identify covariance patterns of microstructural white matter damage based on fractional anisotropy (FA) skeletonised images from DTI data in 39 AD patients and 41 healthy controls (HCs) from the Alzheimer's Disease Neuroimaging Initiative database. The multivariate ICA decomposed the subject-dimension concatenated FA data into a mixing coefficient matrix and a source matrix. Twenty-eight independent components (ICs) were extracted, and a two sample t-test on each column of the corresponding mixing coefficient matrix revealed significant AD/HC differences in ICA weights for 7 ICs. The covariant FA changes primarily involved the bilateral corona radiata, the superior longitudinal fasciculus, the cingulum, the hippocampal commissure, and the corpus callosum in AD patients compared to HCs. Our findings identified covariant white matter damage associated with AD based on DTI in combination with multivariate ICA, potentially expanding our understanding of the neuropathological mechanisms of AD.

Associations Between Polymorphisms in the IL-4 and IL-4 Receptor Genes and Urinary Carcinomas: a Meta-analysis

International Journal of Clinical and Experimental Medicine. 2015  |  Pubmed ID: 25785117

To evaluate the association between polymorphisms of interleukin-4 (IL-4) and IL-4 receptor (IL-4R) genes and risk of renal cell cancer (RCC), bladder cancer (BC), and prostate cancer (PC) based on meta-analysis. PubMed, Web of Science and SpecilalSCI(TM) were searched for studies published up to May 2014 that reported the association between IL-4 or IL-4R and RCC, BC or PC risk. Odds ratio (OR)/Hazard ratio (HR) and 95% confidence interval (CI) were analyzed to evaluate the association. Meta-analysis showed that the IL-4R polymorphism rs1805010 was associated with increased RCC risk (CC/CT vs. TT: OR=1.266, 95% CI 1.09-1.472, P=0.002). The IL-4 haplotypes, IL4-589T and IL4-33T, were associated with higher survival rate of the patients comparted with the haplotype IL-4-589C-33C (P<0.05). The IL-4 polymorphism rs2243250 was associated with an increased risk of developing multiple BCs (OR=2.52, P=0.033). The IL-4 polymorphisms rs2243228, rs2243250, and rs22272480 were significantly associated with PC risk (rs2243228 CC vs.

Transurethral Endoscopic Treatment of Seminal Vesicle Cysts (report of Seven Cases)

International Urology and Nephrology. May, 2015  |  Pubmed ID: 25794499

Seminal vesicle cysts are a rare disorder of the male reproductive system. The goal of this report was to summarize the radiological manifestations and transurethral endoscopic treatment of large seminal vesicle cysts.

Silencing IFN-γ Binding/Signaling in Astrocytes Versus Microglia Leads to Opposite Effects on Central Nervous System Autoimmunity

Journal of Immunology (Baltimore, Md. : 1950). May, 2015  |  Pubmed ID: 25795755

IFN-γ, the hallmark cytokine of Th1 cells, plays an important role in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Thus far, the role of IFN-γ in EAE has been largely studied through its effects on immune cells, whereas much less is known about its effects on CNS cells, especially in vivo. In this study, we dissected the in vivo effects and mechanisms of IFN-γ binding/signaling in astrocytes and microglia, and found that IFN-γ signaling in these cell types has opposite effects in EAE pathogenesis. Silencing IFN-γ binding/signaling in astrocytes alleviated EAE, whereas in microglia, and likely in some infiltrating macrophages, it increased disease severity. Silencing IFN-γ signaling in astrocytes resulted in diminished expression of chemokines and fewer inflammatory cells infiltrating into the CNS, whereas blocking IFN-γ binding/signaling in microglia, probably infiltrating macrophages as well, increased disease severity through augmented activation and proliferation of microglia. Further, blocking IFN-γ binding/signaling in astrocytes alleviated both Th1- and Th17-mediated adoptive EAE, indicating an important role for IFN-γ signaling in astrocytes in autoimmune CNS inflammation. Thus, our study defines novel mechanisms of action of IFN-γ in EAE pathogenesis, and also highlights an opportunity for development of multiple sclerosis therapies directed at CNS cells.

Iso-petromyroxols: Novel Dihydroxylated Tetrahydrofuran Enantiomers from Sea Lamprey (Petromyzon Marinus)

Molecules (Basel, Switzerland). 2015  |  Pubmed ID: 25806547

An enantiomeric pair of new fatty acid-derived hydroxylated tetrahydrofurans, here named iso-petromyroxols, were isolated from sea lamprey larvae-conditioned water. The relative configuration of iso-petromyroxol was elucidated with 1D and 2D NMR spectroscopic analyses. The ratio of enantiomers (er) in the natural sample was measured by chiral-HPLC-MS/MS to be ca. 3:1 of (-)- to (+)-antipodes.

[Tsc1 Promoter Methylation Rate, MTOR Expression in Food-induced Obese Rat Hypothalamus]

Sichuan Da Xue Xue Bao. Yi Xue Ban = Journal of Sichuan University. Medical Science Edition. Jan, 2015  |  Pubmed ID: 25807795

To investigate the methylation rate of tuberous sclerosis complex 1 (Tsc1) promoter and expression of mammalian target of rapamycin (mTOR) in food-induced rat hypothalamus.

Differential Roles of PIN1 and PIN2 in Root Meristem Maintenance Under Low-B Conditions in Arabidopsis Thaliana

Plant & Cell Physiology. Mar, 2015  |  Pubmed ID: 25814435

Boron (B) is an essential element for plants; its deficiency causes rapid cessation of root elongation. In addition, B influences auxin accumulation in plants. To assess the importance of auxin transport in B-dependent root elongation, Arabidopsis thaliana pin1-pin4 mutants were grown under low-B conditions. Among them, only the pin2/eir1-1 mutant showed a significantly shorter root under low-B conditions than under control conditions. Moreover, the root meristem size of pin2/eir1-1 was reduced under low-B conditions. Among the PIN-FORMED (PIN) family, PIN1 and PIN2 are important for root meristem growth/maintenance under normal conditions. To investigate the differential response of pin1 and pin2 mutants under low-B conditions, the effect of low-B on PIN1-green fluorescent protein (GFP) and PIN2-GFP accumulation and localization was examined. Low-B did not affect PIN2-GFP, while it reduced the accumulation of PIN1-GFP. Moreover, no signal from DII-VENUS, an auxin sensor, was detected under the low-B condition in the stele of wild-type root meristems. Taken together, these results indicate that under low-B conditions PIN1 is down-regulated and PIN2 plays an important role in root meristem maintenance.

GLT1 Overexpression in SOD1(G93A) Mouse Cervical Spinal Cord Does Not Preserve Diaphragm Function or Extend Disease

Neurobiology of Disease. Jun, 2015  |  Pubmed ID: 25818008

Amyotrophic lateral sclerosis (ALS) is characterized by relatively rapid degeneration of both upper and lower motor neurons, with death normally occurring 2-5years following diagnosis primarily due to respiratory paralysis resulting from phrenic motor neuron (PhMN) loss and consequent diaphragm denervation. In ALS, cellular abnormalities are not limited to MNs. For example, decreased levels and aberrant functioning of the major central nervous system (CNS) glutamate transporter, GLT1, occur in spinal cord and motor cortex astrocytes of both humans with ALS and in SOD1(G93A) rodents, a widely studied ALS animal model. This results in dysregulation of extracellular glutamate homeostasis and consequent glutamate excitotoxicity, a primary mechanism responsible for MN loss in ALS animal models and in the human disease. Given these observations of GLT1 dysfunction in areas of MN loss, as well as the importance of testing therapeutic strategies for preserving PhMNs in ALS, we evaluated intraspinal delivery of an adeno-associated virus type 8 (AAV8)-Gfa2 vector to the cervical spinal cord ventral horn of SOD1(G93A) ALS mice for focally restoring intraspinal GLT1 expression. AAV8 was specifically injected into the ventral horn bilaterally throughout the cervical enlargement at 110days of age, a clinically-relevant time point coinciding with phenotypic/symptomatic disease onset. Intraspinal delivery of AAV8-Gfa2-GLT1 resulted in robust transduction primarily of GFAP(+) astrocytes that persisted until disease endstage, as well as a 2-3-fold increase in total intraspinal GLT1 protein expression in the ventral horn. Despite this robust level of astrocyte transduction and GLT1 elevation, GLT1 overexpression did not protect PhMNs, preserve histological PhMN innervation of the diaphragm NMJ, or prevent decline in diaphragmatic respiratory function as assessed by phrenic nerve-diaphragm compound muscle action potential (CMAP) recordings compared to control AAV8-Gfa2-eGFP injected mice. In addition, AAV-Gfa2-GLT1 did not delay forelimb disease onset, extend disease duration (i.e. time from either forelimb or hindlimb disease onsets to endstage) or prolong overall animal survival. These findings suggest that focal restoration of GLT1 expression in astrocytes of the cervical spinal cord using AAV delivery is not an effective therapy for ALS.

Endoscopic Enucleation Versus Open Prostatectomy for Treating Large Benign Prostatic Hyperplasia: a Meta-analysis of Randomized Controlled Trials

PloS One. 2015  |  Pubmed ID: 25826453

To evaluate the overall efficacy and safety of endoscopic enucleation of the prostate (EP) vs open prostatectomy (OP) for large benign prostatic hyperplasia (BPH).

Tuning Zinc Coordination Architectures by Benzenedicarboxylate Position Isomers and Bis(triazole)

Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy. Mar, 2015  |  Pubmed ID: 25827762

Three position isomers 1,2-, 1,3-, 1,4-benzenedicarboxylate and 1,4-bis(1,2,4-triazol-4-yl)benzene were used to assembly zinc(II) coordination polymers {[Zn2(btx)0.5(1,2-bdc)2(H2O)]·H2O}n (1), {[Zn(btx)(1,3-bdc)]·2H2O·(DMF)}n (2) and {[Zn(btx)(1,4-bdc)]·3H2O}n (3). 1 is a (3,4,4,4)-connected two-dimensional network with point symbol (4(2)·6)(4(4)·6(2))(4(3)·6(2)·8)(4(2)·6·10(3)). 2 shows a two-dimensional (4,4) network. 3 exhibits a 5-fold interpenetrated three-dimensional diamondoid network. The structural versatility shows that the structures of coordination polymers can be tuned by the position isomers ligands. The luminescence and thermal stability were investigated.

A Rapid Approach for Quantitative Magnetization Transfer Imaging in Thigh Muscles Using the Pulsed Saturation Method

Magnetic Resonance Imaging. Apr, 2015  |  Pubmed ID: 25839394

Quantitative magnetization transfer (qMT) imaging in skeletal muscle may be confounded by intramuscular adipose components, low signal-to-noise ratios (SNRs), and voluntary and involuntary motion artifacts. Collectively, these issues could create bias and error in parameter fitting. In this study, technical considerations related to these factors were systematically investigated, and solutions were proposed. First, numerical simulations indicate that the presence of an additional fat component significantly underestimates the pool size ratio (F). Therefore, fat-signal suppression (or water-selective excitation) is recommended for qMT imaging of skeletal muscle. Second, to minimize the effect of motion and muscle contraction artifacts in datasets collected with a conventional 14-point sampling scheme, a rapid two-parameter model was adapted from previous studies in the brain and spinal cord. The consecutive pair of sampling points with highest accuracy and precision for estimating F was determined with numerical simulations. Its performance with respect to SNR and incorrect parameter assumptions was systematically evaluated. QMT data fitting was performed in healthy control subjects and polymyositis patients, using both the two- and five-parameter models. The experimental results were consistent with the predictions from the numerical simulations. These data support the use of the two-parameter modeling approach for qMT imaging of skeletal muscle as a means to reduce total imaging time and/or permit additional signal averaging.

Comparison of Two Different Astragali Radix by a (1)H NMR-Based Metabolomic Approach

Journal of Proteome Research. May, 2015  |  Pubmed ID: 25844502

Astragali Radix (AR) is a commonly used herbal drug in traditional chinese medicine and is widely used for the treatment of diabetes, cardiovascular diseases, nephropathy, and neuropathy. The main source of AR in China is the dried root of Astragalus membranaceus var. mongholicus (Bge.) Hsiao, and both cultivated and wild ARs are used clinically. A systematic comparison of cultivated AR (GS-AR) and wild AR (SX-AR) should be performed to ensure the clinical efficacy and safety. In this study, the chemical composition of the two different ARs, which were collected in the Shanxi (wild) and Gansu (cultivated) provinces, were compared by NMR-based metabolic fingerprint coupled with multivariate analysis. The SX-AR- and GS-AR-induced metabolic changes in the endogenous metabolites in mice were also compared. The results showed that SX-AR and GS-AR differed significantly not only in the primary metabolites but also in the secondary metabolites. However, alterations among the endogenous metabolites in the serum, lung, liver, and spleen were relatively small. This study provided a novel and valuable method for the evaluation of the consistency and diversity of herbal drugs, and further studies should be conducted on the difference in polysaccharides as well as the biological effects between the two kinds of AR.

A Bivalent Cationic Dye Enabling Selective Photo-inactivation Against Gram-negative Bacteria

Chemical Communications (Cambridge, England). Apr, 2015  |  Pubmed ID: 25857842

A piperazine-modified Crystal Violet was found to be able to selectively inactivate Gram-negative bacteria upon visible light irradiation but left Gram-positive bacteria less damaged, which can serve as a blueprint for the development of novel narrow-spectrum agents to replenish the current arsenal of photodynamic antimicrobial chemotherapy (PACT).

The Prevalence of STL Polyomavirus in Stool Samples from Chinese Children

Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology. May, 2015  |  Pubmed ID: 25866330

Over the past 7 years, eleven novel human polyomaviruses (HPyVs) have been identified. The frequent discovery of human polyomaviruses (HPyVs) in the gastrointestinal tract and stool samples suggests a potential involvement in gastroenteritis.

Coordination of Digit Force Variability During Dominant and Non-dominant Sustained Precision Pinch

Experimental Brain Research. Apr, 2015  |  Pubmed ID: 25869742

This study examined the effects of handedness on the inter-digit coordination of force variability with and without concurrent visual feedback during sustained precision pinch. Twenty-four right-handed subjects were instructed to pinch an instrumented apparatus with their dominant and non-dominant hands, separately. During the pinch, the subjects were required to maintain a stable force output at 5 N for 1 min. Visual feedback was given for the first 30 s and removed for the second 30 s. Coefficient of variation and detrended fluctuation analysis were employed to examine the amount and structural variability of the thumb and index finger forces. Similarly, correlation coefficient and detrended cross-correlation analysis were applied to quantify the inter-digit correlation of force amount and structural variability. Results showed that, compared to the non-dominant hand, the dominant hand had higher inter-digit difference in the amount of digit force variability. Without visual feedback, the dominant hand exhibited lower digit force structural variability but higher inter-digit force structural correlation than the non-dominant hand. These results implied that the dominant hand would be more independent, less flexible and with lower dynamic degrees of freedom than the non-dominant hand in coordination of the thumb and index finger forces during sustained precision pinch. The effects of handedness on inter-digit force coordination were dependent on sensory condition, which shed light on higher-level sensorimotor mechanisms that may be responsible for the asymmetries in coordination of digit force variability.

[Correlation Between Minimal Apparent Diffusion Coefficient and Expression of Ki-67 in Glioma]

Zhonghua Yi Xue Za Zhi. Jan, 2015  |  Pubmed ID: 25876807

To explore the correlation between minimal apparent diffusion coefficient (minADC) and expression of Ki-67 in glioma.

Manipulation of Prostate Cancer Metastasis by Locus-specific Modification of the CRMP4 Promoter Region Using Chimeric TALE DNA Methyltransferase and Demethylase

Oncotarget. Apr, 2015  |  Pubmed ID: 25888628

Prostate cancer is the most commonly diagnosed non-cutaneous cancer and one of the leading causes of cancer death for North American men. Whereas localized prostate cancer can be cured, there is currently no cure for metastatic prostate cancer. Here we report a novel approach that utilizes designed chimeric transcription activator-like effectors (dTALEs) to control prostate cancer metastasis. Transfection of dTALEs of DNA methyltransferase or demethylase induced artificial, yet active locus-specific CpG and subsequent histone modifications. These manipulations markedly altered expression of endogenous CRMP4, a metastasis suppressor gene. Remarkably, locus-specific CpG demethylation of the CRMP4 promoter in metastatic PC3 cells abolished metastasis, whereas locus-specific CpG methylation of the promoter in non-metastatic 22Rv1 cells induced metastasis. CRMP4-mediated metastasis suppression was found to require activation of Akt/Rac1 signaling and down-regulation of MMP-9 expression. This proof-of-concept study with dTALEs for locus-specific epigenomic manipulation validates the selected CpG methylation of CRMP4 gene as an independent biomarker for diagnosis and prognosis of prostate cancer metastasis and opens up a novel avenue for mechanistic research on cancer biology.

Effect of Ultrasound Treatment on Functional Properties of Reduced-salt Chicken Breast Meat Batter

Journal of Food Science and Technology. May, 2015  |  Pubmed ID: 25892760

The effect of ultrasound treatments (40 kHz, 300 W) for different times (10, 20, 30 and 40 min) combined with different salt contents (1.0 %, 1.5 % and 2.0 %) on gel properties and water holding capacity (WHC) of chicken breast meat batter were investigated. Results showed salt level significantly (p < 0.05) affected the texture, storage modulus (G'), loss modulus (G″), cooking loss and WHC. Ultrasound treatments for 10 min and 20 min improved the texture and WHC, and had higher G' values. Compared with the controls (2 % salt), ultrasound treatment for 20 min with reduced-salt (1.5 %) had not significant effect (p > 0.05) on texture, cooking loss or WHC. However, longer ultrasound (40 min) treatment resulted in a decrease in hardness, G' value and WHC. Microstructural analysis revealed that gels treated with ultrasound for 20 min had a compact structure whereas those treated for 40 min contained more protein aggregations and more cavities. Low-field nuclear magnetic resonance (LF-NMR) indicated that ultrasound treatment for 20 min lowered the values of spin-spin relaxation time (T2) and increased the proportion of myofibillar water. Overall, high power ultrasound technology is a promising process which can improve the gelation properties and thereby allowing for a partial reduction in the salt levels in chicken meat gels.

Synthesis of Fluoren-9-ones and Ladder-Type Oligo-p-phenylene Cores Via Pd-Catalyzed Carbonylative Multiple C-C Bond Formation

Organic Letters. May, 2015  |  Pubmed ID: 25895161

A new route to various substituted fluoren-9-ones has been developed via an efficient Pd-catalyzed carbonylative multiple C-C bond formation. Under a CO atmosphere, using commercially available aryl halides and arylboronic acids as substrates, this three-component reaction proceeded smoothly in moderate to excellent yields with good functional-group compatibility. The mechanistic investigations suggested a sequential process for the reaction that forms o-bromobiaryls in the first stage followed by a cyclocarbonylation reaction. This chemistry has been successfully extended to construct ladder-type oligo-p-phenylene cores.

Sub-milliSievert (sub-mSv) CT Colonography: a Prospective Comparison of Image Quality and Polyp Conspicuity at Reduced-dose Versus Standard-dose Imaging

European Radiology. Apr, 2015  |  Pubmed ID: 25903700

To prospectively compare reduced-dose (RD) CT colonography (CTC) with standard-dose (SD) imaging using several reconstruction algorithms.

REGγ is Critical for Skin Carcinogenesis by Modulating the Wnt/β-catenin Pathway

Nature Communications. 2015  |  Pubmed ID: 25908095

Here we report that mice deficient for the proteasome activator, REGγ, exhibit a marked resistance to TPA (12-O-tetradecanoyl-phorbol-13-acetate)-induced keratinocyte proliferation, epidermal hyperplasia and onset of papillomas compared with wild-type counterparts. Interestingly, a massive increase of REGγ in skin tissues or cells resulting from TPA induces activation of p38 mitogen-activated protein kinase (MAPK/p38). Blocking p38 MAPK activation prevents REGγ elevation in HaCaT cells with TPA treatment. AP-1, the downstream effector of MAPK/p38, directly binds to the REGγ promoter and activates its transcription in response to TPA stimulation. Furthermore, we find that REGγ activates Wnt/β-catenin signalling by degrading GSK-3β in vitro and in cells, increasing levels of CyclinD1 and c-Myc, the downstream targets of β-catenin. Conversely, MAPK/p38 inactivation or REGγ deletion prevents the increase of cyclinD1 and c-Myc by TPA. This study demonstrates that REGγ acts in skin tumorigenesis mediating MAPK/p38 activation of the Wnt/β-catenin pathway.

The Microstructural Correlates of T1 in White Matter

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Apr, 2015  |  Pubmed ID: 25920491

Several studies have shown strong correlations between myelin content and T1 within the brain, and have even suggested that T1 can be used to estimate myelin content. However, other micro-anatomical features such as compartment size are known to affect longitudinal relaxation rates, similar to compartment size effects in porous media.

Recent Advances and Applications of Experimental Technologies in Marine Natural Product Research

Marine Drugs. 2015  |  Pubmed ID: 25939037

Marine natural products are a rich source of novel and biologically active compounds. The number of identified marine natural compounds has grown 20% over the last five years from 2009 to 2013. Several challenges, including sample collection and structure elucidation, have limited the development of this research field. Nonetheless, new approaches, such as sampling strategies for organisms from extreme ocean environments, nanoscale NMR and computational chemistry for structural determination, are now available to overcome the barriers. In this review, we highlight the experimental technology innovations in the field of marine natural products, which in our view will lead to the development of many new drugs in the future.

Repair of Urethral Defects with Polylactid Acid Fibrous Membrane Seeded with Adipose-derived Stem Cells in a Rabbit Model

Connective Tissue Research. May, 2015  |  Pubmed ID: 25943462

The aim of this study is to evaluate the capacity of polylactid acid (PLA) fibrous membrane seeded with allogeneic rabbit adipose tissue-derived stem cells (ADSCs) to repair urethral defects in a rabbit model.

Quantum De Finetti Theorem Under Fully-One-Way Adaptive Measurements

Physical Review Letters. Apr, 2015  |  Pubmed ID: 25955040

We prove a version of the quantum de Finetti theorem: permutation-invariant quantum states are well approximated as a probabilistic mixture of multifold product states. The approximation is measured by distinguishability under measurements that are implementable by fully-one-way local operations and classical communication (LOCC). Our result strengthens Brandão and Harrow's de Finetti theorem where a kind of partially-one-way LOCC measurements was used for measuring the approximation, with essentially the same error bound. As main applications, we show (i) a quasipolynomial-time algorithm which detects multipartite entanglement with an amount larger than an arbitrarily small constant (measured with a variant of the relative entropy of entanglement), and (ii) a proof that in quantum Merlin-Arthur proof systems, polynomially many provers are not more powerful than a single prover when the verifier is restricted to one-way LOCC operations.

Peptide Nucleic Acid Fluorescence In-situ Hybridization for Identification of Vibrio Spp. in Aquatic Products and Environments

International Journal of Food Microbiology. Apr, 2015  |  Pubmed ID: 25955286

A peptide nucleic acid fluorescence in situ hybridization (PNA-FISH) method was developed for specific detection of the Vibrio genus. In silico analysis by BLAST and ProbeCheck showed that the designed PNA probe targeting the 16S rRNAs was suitable for specific identification of Vibrio. Specificity and sensitivity of the probe Vib-16S-1 were experimentally verified by its reactivity against 18 strains of 9 Vibrio species and 14 non-Vibrio strains of 14 representative species. The PNA-FISH assay was able to identify 47 Vibrio positive samples from selectively enriched cultures of 510 samples of aquatic products and environments, comparable with the results obtained by biochemical identification and real-time PCR. We conclude that PNA-FISH can be an alternative method for rapid identification of Vibrio species in a broad spectrum of seafood or related samples.

Longitudinal Assessment of Spinal Cord Injuries in Nonhuman Primates with Quantitative Magnetization Transfer

Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. May, 2015  |  Pubmed ID: 25960050

This study aimed to evaluate the reproducibility and specificity of quantitative magnetization transfer (qMT) imaging for monitoring spinal cord injuries (SCIs).

Expression of Selenoprotein Genes Is Affected by Obesity of Pigs Fed a High-Fat Diet

The Journal of Nutrition. May, 2015  |  Pubmed ID: 25972525

Relations of the 25 mammalian selenoprotein genes with obesity and the associated inflammation remain unclear.

Efficacy and Safety of HER2-Targeted Agents for Breast Cancer with HER2-Overexpression: A Network Meta-Analysis

PloS One. 2015  |  Pubmed ID: 25993646

Clinical trials of human epidermal growth factor receptor 2 (HER2)-targeted agents added to standard treatment have been efficacious for HER2-positive (HER2+) advanced breast cancer. To our knowledge, no meta-analysis has evaluated HER2-targeted therapy including trastuzumab emtansine (T-DM1) and pertuzumab for HER2-positive breast caner and ranked the targeted treatments. We performed a network meta-analysis of both direct and indirect comparisons to evaluate the effect of adding HER2-targeted agents to standard treatment and examined side effects.

A Comparison Study of Aliphatic and Aromatic Structure Directing Agents Influencing the Crystal and Electronic Structures, and Properties of Iodoplumbate Hybrids: Water Induced Structure Conversion and Visible Light Photocatalytic Properties

Dalton Transactions (Cambridge, England : 2003). Jul, 2015  |  Pubmed ID: 26000877

The introduction of the aliphatic amines en (ethylenediamine), aep (N-(2-aminoethyl)piperazine) and tepa (tetraethylenepentamine), and the aromatic species 2,2'-bipy (2,2'-bipyridine) and dpe (1,2-di(4-pyridyl)ethylene) as structure directing agents (SDAs) into inorganic iodoplumbates affords six hybrids, namely [(Hen)4(H2.5O)2I](PbI6) (1), Cs2n[Pb3I8(en)2]n (2), (H3tepa)n(PbI5)n (3), (H2aep)n(PbI4)n (4), (Et22,2'-bipy)n(Pb2I6)n (5) and (Et2dpe)n(Pb2I6)n (6). 1 contains a discrete octahedral (PbI6)(4-) anion generated under the direction of a novel co-template, [(Hen)4(H2.5O)2I](4+). 2 contains inorganic Cs(+) ions and a novel hybrid anionic layer [Pb3I8(en)2]n(2n-) that has never been encountered in iodoplumbate hybrids. 3 features a zigzag (PbI5)(3-) chain with the charge being compensated by a triprotonated tepa cation. 4 is composed of perovskite sheets of lead(ii) octahedra and aep cations that are generated from tepa via an unprecedented in situ ligand reaction. Both 5 and 6 have (Pb2I6)n(2n-) chains and represent the first example of introducing a 2,2'-bipy or dpe derivative cation in iodoplumbate hybrids, respectively. The comparative study reveals that aliphatic amines and aromatic species contribute differently to the crystal and electronic structures, and the properties of the hybrids. Importantly, 1-4 exhibit interesting water induced structure conversions, while 5 and 6 can be used as heterogeneous photocatalysts for dye wastewater treatment under visible light irradiation.

HPV Type 16 Infection Switches Keratinocytes from Apoptotic to Proliferative Fate Under TWEAK/Fn14 Interaction

The Journal of Investigative Dermatology. Oct, 2015  |  Pubmed ID: 26016896

Previously, tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) had been known to be an inducer of apoptosis of keratinocytes by engaging the Fn14 receptor. However, the high-risk human papillomavirus (HPV) infection confers a proliferation advantage on keratinocytes that may consequently harbor tumorigenicity. This study was designed to investigate the cross-talk in keratinocytes between TWEAK/Fn14 signaling and HPV type 16 infection, which may cooperate in regulating cell-cycle progression. TWEAK and Fn14 expression was determined in anogenital warts and normal skin. Both primary keratinocytes and HaCaT cells were transfected with HPV16 E6/E7 genes. The results showed that Fn14 is highly expressed upon HPV16 transfection and accompanied by an increase in Ras GTPase activity and TNF-receptor-associated factor 2 (TRAF2) expression. Moreover, the E6/E7-transfected keratinocytes exhibit a shift of TNF receptor profile from type 1 to type 2 and weakened apoptotic response to TNF-α stimuli, when compared with the normal control. Surprisingly, significant increase in proliferation but not apoptosis was seen in E6/E7-positive keratinocytes, as TWEAK was additionally supplemented. In conclusion, the HPV16 infection in keratinocytes causes a switch of apoptotic to proliferative fate under TWEAK/Fn14 interaction, possibly by favoring Ras and TRAF2 activation and modulating TNF receptor expression.

[Therapeutic Effect of Heating and Bandage Treatment for Chronic Lymphedema of Extremities Accompanied with Erysipelas: a Report of 80 Cases]

Zhonghua Zheng Xing Wai Ke Za Zhi = Zhonghua Zhengxing Waike Zazhi = Chinese Journal of Plastic Surgery. Jan, 2015  |  Pubmed ID: 26027323

To investigate the therapeutic effect of heating and bandage treatment for chronic lymphedema of extremities accompanied with erysipelas.

Diagnostic Value of Transthoracic Echocardiography in Patients with Coarctation of Aorta: The Chinese Experience in 53 Patients Studied Between 2008 and 2012 in One Major Medical Center

PloS One. 2015  |  Pubmed ID: 26030197

Although aortography is well known as the "gold standard" for the diagnosis of coarctation of aorta (CoA), the method is invasive, expensive and not readily accepted by some patients. Ultrasound diagnosis for CoA is non-invasive, inexpensive, readily accepted by every patient, and can be repeated as frequently as necessary. The purpose of this presentation is to evaluate the applicability of transthoracic echocardiography for the diagnosis of CoA. The echocardiographic appearances of 53 patients with CoA who had undergone surgery during a 5-year period from January 2008 to October 2012 were analyzed retrospectively, and the results were compared with findings at surgery. Fifty-three patients with CoA include six with isolated CoA and 47 of CoA associated with other cardiac anomalies. Of the 53 operated patients, 48 were correctly diagnosed preoperatively by echocardiography, while two were misdiagnosed as interrupted aortic arch and the diagnosis were missed in three other patients. Thus the diagnostic accuracy rate was 90.6%, and the misdiagnosis rate was 9.4%. Preoperative echocardiographic evaluation offers very satisfactory anatomic assessment in most patients with CoA. It makes preoperative angiography unnecessary. Thus transthoracic echocardiography should be the first-line method for the diagnosis of coarctation of the aorta.

TKTL1 Expression and Its Downregulation is Implicated in Cell Proliferation Inhibition and Cell Cycle Arrest in Esophageal Squamous Cell Carcinoma

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine. Nov, 2015  |  Pubmed ID: 26032094

It is well known that tumor cells mainly depend on the nonoxidative pathway of the pentose phosphate pathway (PPP), and transketolase-like 1 (TKTL1), a kind of crucial metabolism enzyme, participates in the regulation of PPP; notably, overwhelming evidence has demonstrated that TKTL1 plays pivotal roles in the development and progression of multiple tumors. However, there were no reports about the role of TKTL1 in esophageal squamous cell carcinoma (ESCC). Here, we investigated TKTL1 expression and preliminarily elucidated its underlying biological functions in ESCC. We found that TKTL1 exhibited the high expression in ESCC tissues and cells, and the survival rate of patients with negative TKTL1 expression was significantly higher than that of patients with positive TKTL1 staining (P < 0.05). Additionally, significant correlations of TKTL1 expression with histologic grade, clinical stage, and lymph node metastasis were found (P < 0.05). Subsequently, TKTL1 small interfering RNA (siRNA) significantly reduced TKTL1 messenger RNA (mRNA), and protein levels companied with the marked reduce of total transketolase activity but did not affect TKT and TKTL1 mRNA level. More importantly, TKTL1 siRNA obviously induced cell cycle arrest in G0/G1 phase and suppressed cell proliferation in vitro and in vivo coupled with the reduced cyclin D1 and cdk4 levels as well as decrease of Ki-67 proliferation index in EC1 cells. Taken altogether, our results suggest that TKTL1 as a key prognostic factor may be a novel target for therapy of the patients with ESCC.

Synthesis of Oxazoles by Silver Catalysed Oxidative Decarboxylation-cyclization of α-oxocarboxylates and Isocyanides

Chemical Communications (Cambridge, England). Jul, 2015  |  Pubmed ID: 26038311

A silver catalysed synthesis of oxazoles by the oxidative decarboxylation-cyclization of α-oxocarboxylates and isocyanides was developed. This method provided a novel strategy to construct oxazole rings compared to traditional methods. Mechanistic investigations such as operando IR, EPR and radical inhibition experiments were carefully done and confirmed the acyl cation and Ag(II) as the intermediates in this transformation, and the involvement of a radical decarboxylative process.

Biochemical Characterization of Three Distinct Polygalacturonases from Neosartorya Fischeri P1

Food Chemistry. Dec, 2015  |  Pubmed ID: 26041232

Polygalacturonase is one of the most important industrial pectinases. To enrich the genetic resources and develop new enzyme candidates, three polygalacturonase genes (Nfpg I-III) of glycosyl hydrolase family 28 were cloned from Neosartorya fischeri P1 and functionally expressed in Pichia pastoris. The purified recombinant proteins exhibited some distinguished properties. In comparison with other counterparts, NfPG I showed the highest specific activity (40, 123 U/mg), NfPG II had the highest temperature optimum (65 °C), and the pH optimum of NfPG III was the lowest (3.5). The orders of their thermostability and resistance to chemicals tested were NfPG II>NfPG III>NfPG I and NfPG II>NfPG I>NfPG III, respectively. Combinations of these enzymes showed better performance than individuals in the processing and clarification of apple and strawberry juice. These results suggest that N. fischeri polygalacturonases have great application potentials in the food industry for juice production.

Association of Single Nucleotide Polymorphisms of DNA Repair Gene and Susceptibility to Pancreatic Cancer

International Journal of Clinical and Experimental Pathology. 2015  |  Pubmed ID: 26045837

We conducted a case-control study to assess the XRCC4 genes polymorphism and development of pancreatic cancer. A case-control study including 248 cases and 496 controls was conducted in a Chinese population. Genotypes of XRCC4 rs2075685, rs10040363, rs963248 and rs1805377 were determined using Polymerase Chain Reaction combined with a restriction fragment length polymorphism (PCR-RFLP) assay (Applied Biosystems, Foster City, CA, USA). Pancreatic cancer cases were more likely to have a history of diabetes, a higher BMI, family history of cancer and a habit of alcohol drinking when compared with control. Conditional logistic regression analysis showed that individuals carrying TT genotype of XRCC4 rs2075685 was associated with increased risk of pancreatic cancer when compared with GG genotype, and the OR (95% CI) was 1.62 (1.04-2.52). Individuals with GT+TT genotype of XRCC4 rs2075685 were significantly associated with increased risk of pancreatic cancer in those with ever tobacco smoking habit, and the OR (95% CI) was 1.77 (1.07-2.98). In conclusion, our results suggest that XRCC4 rs2075685 polymorphism plays an important role in the risk of pancreatic cancer in a Chinese population, especially in tobacco smokers.

A Novel Azopyridine-based Ru(II) Complex with GSH-responsive DNA Photobinding Ability

Chemical Communications (Cambridge, England). Jul, 2015  |  Pubmed ID: 26051473

A novel azopyridine-based Ru(II) complex [Ru(bpy)2(L1)2](2+) (bpy = 2,2'-bipyridine, L1 = 4,4'-azopyridine) was designed and synthesized as a potential glutathione (GSH)-responsive photoactivated chemotherapy (PACT) agent, the DNA covalent binding capability of which can only be activated after GSH reduction and visible light irradiation.

A Pheromone Outweighs Temperature in Influencing Migration of Sea Lamprey

Royal Society Open Science. May, 2015  |  Pubmed ID: 26064660

Organisms continuously acquire and process information from surrounding cues. While some cues complement one another in delivering more reliable information, others may provide conflicting information. How organisms extract and use reliable information from a multitude of cues is largely unknown. We examined movement decisions of sea lampreys (Petromyzon marinus L.) exposed to a conspecific and an environmental cue during pre-spawning migration. Specifically, we predicted that the mature male-released sex pheromone 3-keto petromyzonol sulfate (3kPZS) will outweigh the locomotor inhibiting effects of cold stream temperature (less than 15°C). Using large-scale stream bioassays, we found that 3kPZS elicits an increase (more than 40%) in upstream movement of pre-spawning lampreys when the water temperatures were below 15°C. Both warming temperatures and conspecific cues increase upstream movement when the water temperature rose above 15°C. These patterns define an interaction between abiotic and conspecific cues in modulating animal decision-making, providing an example of the hierarchy of contradictory information.

A Novel Strategy to Improve the Therapeutic Efficacy of Gemcitabine for Non-Small Cell Lung Cancer by the Tumor-Penetrating Peptide IRGD

PloS One. 2015  |  Pubmed ID: 26066322

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, comprising approximately 75-80% of all lung cancers. Gemcitabine is an approved chemotherapy drug for NSCLC. The objective of this study was to develop a novel strategy to improve the therapeutic efficacy of Gemcitabine for NSCLC by the co-administered iRGD peptide. We showed that the rates of positive expression of αvβ3, αvβ5 and NRP-1 in the A549 cell line were 68.5%, 35.3% and 94.5%, respectively. The amount of Evans Blue accumulated in the tumor of Evans Blue+iRGD group was 2.5 times that of Evans Blue group. The rates of growth inhibition of the tumors of the iRGD group, the Gemcitabine group and the Gemcitabine+iRGD group were 8%, 59.8% and 86.9%, respectively. The results of mechanism studies showed that PCNA expression in the Gemcitabine+iRGD group decreased 71.5% compared with that in Gemcitabine group. The rate of apoptosis in the Gemcitabine+iRGD group was 2.2 time that of the Gemcitabine group. Therefore, the tumor-penetrating Peptide iRGD can enhance the tumor-penetrating ability and therapeutic efficacy of Gemcitabine in the A549 xenograft. The combined application of Gemcitabine with iRGD may be a novel strategy to enhance the clinical therapeutic efficacy of Gemcitabine in patients with NSCLC.

Long-term Outcome of Transcatheter Arterial Chemoembolization After Radiofrequency Ablation As a Combined Therapy for Chinese Patients with Hepatocellular Carcinoma

Current Medical Research and Opinion. Aug, 2015  |  Pubmed ID: 26067770

This study was undertaken to assess the long-term outcome of transcatheter arterial chemoembolization (TACE) after radiofrequency ablation (RFA) combined with a combined therapy for Chinese patients with intermediate (stage B) hepatocellular carcinoma (HCC) of single block type, and evaluate the survival rate for 1, 3, 5, and 7 years.

Highly Enantioselective Asymmetric Transfer Hydrogenation (ATH) of α-phthalimide Ketones

Organic & Biomolecular Chemistry. Jul, 2015  |  Pubmed ID: 26068194

A mild catalyst system for the synthesis of chiral amino alcohols via asymmetric transfer hydrogenation (ATH) of α-phthalimide ketones has been developed by using a chiral Ru-TsDPEN complex as the catalyst in DMF/MeOH at 40 °C. The reaction exhibits high reaction activity and excellent enantioselectivity where up to 96% yield and 99% ee of the product were obtained.

[Time Trends of the Incidence of Thyroid Cancer in Urban Guangzhou, 2000-2011]

Zhonghua Yu Fang Yi Xue Za Zhi [Chinese Journal of Preventive Medicine]. Feb, 2015  |  Pubmed ID: 26081399

To investigate the incidence and trends of thyroid cancer in urban areas of Guangzhou, 2000-2011.

A Compact High Resolution Flat Panel PET Detector Based on the New 4-side Buttable MPPC for Biomedical Applications

Nuclear Instruments & Methods in Physics Research. Section A, Accelerators, Spectrometers, Detectors and Associated Equipment. Sep, 2015  |  Pubmed ID: 26085702

Compact high-resolution panel detectors using virtual pinhole (VP) PET geometry can be inserted into existing clinical or pre-clinical PET systems to improve regional spatial resolution and sensitivity. Here we describe a compact panel PET detector built using the new Though Silicon Via (TSV) multi-pixel photon counters (MPPC) detector. This insert provides high spatial resolution and good timing performance for multiple bio-medical applications. Because the TSV MPPC design eliminates wire bonding and has a package dimension which is very close to the MPPC's active area, it is 4-side buttable. The custom designed MPPC array (based on Hamamatsu S12641-PA-50(x)) used in the prototype is composed of 4 × 4 TSV-MPPC cells with a 4.46 mm pitch in both directions. The detector module has 16 × 16 lutetium yttrium oxyorthosilicate (LYSO) crystal array, with each crystal measuring 0.92 × 0.92 × 3 mm(3) with 1.0 mm pitch. The outer diameter of the detector block is 16.8 × 16.8 mm(2). Thirty-two such blocks will be arranged in a 4 × 8 array with 1 mm gaps to form a panel detector with detection area around 7 cm × 14 cm in the full-size detector. The flood histogram acquired with Ge-68 source showed excellent crystal separation capability with all 256 crystals clearly resolved. The detector module's mean, standard deviation, minimum (best) and maximum (worst) energy resolution were 10.19%, +/-0.68%, 8.36% and 13.45% FWHM, respectively. The measured coincidence time resolution between the block detector and a fast reference detector (around 200 ps single photon timing resolution) was 0.95 ns. When tested with Siemens Cardinal electronics the performance of the detector blocks remain consistent. These results demonstrate that the TSV-MPPC is a promising photon sensor for use in a flat panel PET insert composed of many high resolution compact detector modules.

Two Novel BODIPY-Ru(ii) Arene Dyads Enabling Effective Photo-inactivation Against Cancer Cells

Dalton Transactions (Cambridge, England : 2003). Jul, 2015  |  Pubmed ID: 26087131

BODIPY (boron dipyrromethene) derivatives and Ru(ii) complexes are two types of functional compounds that have found wide applications in the fields of biology and medicine. We herein synthesized two new Ru(ii) arene complexes based on an iodized BODIPY-containing pyridine (py-I-BODIPY) ligand, [(p-cym)Ru(bpy)(py-I-BODIPY)](2+) (2) and [(p-cym)Ru(2-pydaT)(py-I-BODIPY)](2+) (3), where p-cym = para-cymene, bpy = 2,2'-bipyridine, and 2-pydaT = 2,4-diamino-6-(2-pyridyl)-1,3,5-triazine. The photophysical, photochemical and photobiological properties of 2 and 3 were compared with that of [(p-cym)Ru(bpy)(py-BODIPY)](2+) (1). While 1 undergoes efficient monodentate ligand dissociation upon visible light irradiation and therefore may photobind DNA as a potential photoactivated chemotherapy (PACT) agent, 2 and 3 can generate (1)O2 effectively and thus may serve as photosensitizers in photodynamic therapy (PDT). In electrophoresis experiments, 2 and 3 are even able to retard the mobility of plasmid DNA in the dark at high concentrations. More importantly, the cytotoxicities of 2 and 3 against human ovarian adenocarcinoma SKOV3 cells are enhanced about ten times under irradiation, leading to cytotoxicities more than one order of magnitude higher than that of cisplatin, demonstrating an efficient hybridization of the iodized BODIPY chromophore and the Ru(ii) arene complex.

Trends in the Levels of Serum Lipids and Lipoproteins and the Prevalence of Dyslipidemia in Adults with Newly Diagnosed Type 2 Diabetes in the Southwest Chinese Han Population During 2003-2012

International Journal of Endocrinology. 2015  |  Pubmed ID: 26089896

Objective. To determine the trends of serum lipid levels and dyslipidemia in adults newly diagnosed with type 2 diabetes mellitus during 2003-2012 in Southwest China. Methods. Serum lipid measurements of 994 adults were obtained from 5 independent, cross-sectional studies (2003-2004, 2005-2006, 2007-2008, 2009-2010, and 2011-2012). The main outcome measures were mean serum total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels; body mass index; hemoglobin A1C level; and the percentages of patients with dyslipidemia, hypertension, coronary heart disease, and cerebrovascular disease. Results. The mean total cholesterol and low-density lipoprotein cholesterol levels increased from 4.92 ± 1.15 to 5.30 ± 1.17 mmol/L (P = 0.039) and 2.72 ± 0.83 to 3.11 ± 1.09 mmol/L (P = 0.004), respectively, and the mean HDL cholesterol level declined from 1.22 ± 0.30 to 1.06 ± 0.24 mmol/L (P < 0.001). The percentages of patients with dyslipidemia increased gradually. The incidence of coronary heart and cerebrovascular diseases increased from 8.2% to 19.1% and 6.6% to 15.3%, respectively (P < 0.05). Conclusion. Unfavorable upward trends were observed in serum lipid levels and the prevalence of dyslipidemia, coronary heart disease, and cerebrovascular disease in adults newly diagnosed with type 2 diabetes mellitus in Southwest China during 2003-2012.

PD150606 Protects Against Ischemia/reperfusion Injury by Preventing μ-calpain-induced Mitochondrial Apoptosis

Archives of Biochemistry and Biophysics. Nov, 2015  |  Pubmed ID: 26091952

Calpain plays an important role in myocardial ischemia/reperfusion (I/R) injury. PD150606, a nonpeptide, cell-permeable and noncompetitive calpain inhibitor, has been shown to have protective properties in ischemic disease. The aims of the present study were to investigate whether PD150606 could alleviate myocardial I/R injury and to examine the possible mechanisms involved. The I/R model was established in vivo in C57BL/6 mice and in vitro using neonatal mouse cardiomyocytes, respectively. To evaluate the protective effects of PD150606 on I/R injury, we measured the myocardial infarct area, apoptosis, and expression of cleaved caspase-3. We also investigated the underlying mechanisms by examining mitochondrial function as reflected by the ATP concentration, translocation of cytochrome c, dynamics of mPTP opening, and membrane potential (ΔΨm), coupled with calpain activity. Pretreatment with PD150606 significantly reduced the infarct area and apoptosis caused by I/R. PD150606 pretreatment also reduced mitochondrial dysfunction by inhibiting calpain activation. Moreover, we found that μ-calpain is the main contributor to I/R-induced calpain activation. Knockdown of μ-calpain with siRNA significantly reversed calpain activation, mitochondrial dysfunction, and cardiomyocyte apoptosis caused by I/R in vitro. Our results suggest that PD150606 may protect against I/R injury via preventing μ-calpain-induced mitochondrial apoptosis.

Crystal Structure of Human Stearoyl-coenzyme A Desaturase in Complex with Substrate

Nature Structural & Molecular Biology. Jul, 2015  |  Pubmed ID: 26098317

Stearoyl-coenzyme A desaturase-1 (SCD1) has an important role in lipid metabolism, and SCD1 inhibitors are potential therapeutic agents for the treatment of metabolic diseases and cancers. Here we report the 3.25-Å crystal structure of human SCD1 in complex with its substrate, stearoyl-coenzyme A, which defines the new SCD1 dimetal catalytic center and reveals the determinants of substrate binding to provide insights into the catalytic mechanism of desaturation of the stearoyl moiety. The structure also provides a mechanism for localization of SCD1 in the endoplasmic reticulum: human SCD1 folds around a tight hydrophobic core formed from four long α-helices that presumably function as an anchor spanning the endoplasmic reticulum membrane. Furthermore, our results provide a framework for the rational design of pharmacological inhibitors targeting the SCD1 enzyme.

Elevated Serum Levels of NSE and S-100β Correlate with Increased Risk of Acute Cerebral Infarction in Asian Populations

Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. Jun, 2015  |  Pubmed ID: 26124190

We investigated the clinical value of serum levels of neuron-specific enolase (NSE) and human soluble protein-100β (S-100β) in acute cerebral infarction (ACI) patients.

Analysis of Short-term Heart Rate and Diastolic Period Variability Using a Refined Fuzzy Entropy Method

Biomedical Engineering Online. Jul, 2015  |  Pubmed ID: 26126807

Heart rate variability (HRV) has been widely used in the non-invasive evaluation of cardiovascular function. Recent studies have also attached great importance to the cardiac diastolic period variability (DPV) examination. Short-term variability measurement (e.g., 5 min) has drawn increasing attention in clinical practice, since it is able to provide almost immediate measurement results and enables the real-time monitoring of cardiovascular function. However, it is still a contemporary challenge to robustly estimate the HRV and DPV parameters based on short-term recordings.

Multiple Hyperplastic Nodular Lesions of the Liver in the Budd-Chari Syndrome: a Case Report and Review of Published Reports

Annals of Saudi Medicine. Jan-Feb, 2015  |  Pubmed ID: 26142943

The Budd-Chari syndrome (BCS) is a group of disorders of hepatic vein outflow at various levels from the hepatic veins to inferior vena cave. We describe a 49-year-old man with multiple intrahepatic lesions who had been diagnosed with the BCS. The inferior vena cavography showed hepatic vein occlusion and long-range obstruction of inferior vena cava. The biopsy proved to be hyperplastic nodules, also called large regenerative nodules (LRNs). Both benign regenerative nodules and hepatocellular carcinoma (HCC) appear in patients with BCC; however, published reports about the diagnosis and differential diagnosis are limited. The incidence of HCC in patients with BCS varies greatly depending on geography. This case illustrates that benign nodules can arise in BCS patients. We reviewed published reports and speculated that medical procedures leading to portal perfusion decrease may be associated with the development of these hyperplastic nodules.

Clinicopathologic Features of Sporadic Inclusion Body Myositis in China

Neurologia I Neurochirurgia Polska. 2015  |  Pubmed ID: 26188941

This study is to investigate the clinical and pathologic features of sporadic inclusion body myositis (sIBM) in China. We retrospectively evaluated the clinical and pathological features of consecutive patients in our department between January 1986 to May 2012. Total 28 cases of sIBM (20 males, 8 females, mean age was 56.93±8.79) were obtained by review of all 4099 muscle biopsy reports. The proportion of sIBM was 0.68% (28/4099) in China. Muscle weakness of quadriceps appeared 100% in 28 cases, while conspicuous atrophy of quadriceps appeared only in five cases (17.86%). Creatase values of 28 patients with sIBM were normal or mildly elevated. Muscle biopsies showed that atrophic fibers resembled more frequent in small angular and irregular shape (82.14%), less common in small round shape (17.86%). Rimmed vacuoles resembled crack (67.86%) and round (32.14%) shape. Mononuclear cell invasion into necrotic muscle fibers (35.71%) was more frequent than non-necrotic muscle fibers (7.14%). sIBM was still a rare disease in China compared to other countries. There were some certain specific pathological characteristics existed in Chinese sIBM patients.

Isolation and Antitumor Efficacy Evaluation of a Polysaccharide from Nostoc Commune Vauch

Food & Function. Sep, 2015  |  Pubmed ID: 26201366

Nostoc commune Vauch. has been traditionally used as a healthy food and medicine for centuries especially in China. It has been demonstrated that the polysaccharides isolated from Nostoc commune Vauch. exhibit strong antimicrobial and antioxidant activities. However, little is known about their anticancer activities and the underlying mechanisms of action. Herein, we report the isolation of a polysaccharide from Nostoc commune Vauch. (NVPS), and its physicochemical properties were analyzed. In an attempt to demonstrate the potential application of NVPS in tumor chemotherapy, the in vitro antitumor activity was determined. NVPS significantly suppressed the growth and proliferation of MCF-7 and DLD1 cells. The molecular mechanism underlying this in vitro antitumor efficacy was elucidated, and the results indicated that NVPS simultaneously triggered intrinsic, extrinsic and endoplasmic reticulum stress (ERS)-mediated apoptotic signaling pathways. Collectively, these findings demonstrate that NVPS could be used as a novel promising source of natural antitumor agents.

Microstructures and Functional Groups of Nannochloropsis Sp. Cells with Arsenic Adsorption and Lipid Accumulation

Bioresource Technology. Oct, 2015  |  Pubmed ID: 26210144

The pore structures and surface morphological characteristics of Nannochloropsis sp. cells with arsenic adsorption were initially investigated by N2-adsorption analysis and scanning electronic microscopy. Functional groups of cells were analysed by Fourier-transform infrared spectrometry and X-ray photoelectron spectroscopy. Total surface area of microalgal cells increased from 0.54 m(2)/g to 1.80 m(2)/g upon arsenic adsorption. The external cell surface area increased. More wrinkles and measles-like granules formed on the surfaces as a result of arsenic toxicity. Arsenic ions blocked cell pores and decreased the average pore diameter and total pore volume. Ether cross-linked structures in the algaenan layer of cell walls were disrupted as the percentage of C-O functional groups decreased. These functional groups underwent complexation reactions with arsenic ions. Accumulation of polyunsaturated fatty acids decreased because of oxidative stresses induced by arsenic. The increase in generation of short-chain saturated fatty acids was favourable for the production of quality biodiesel.

Human IPS Cell-derived Astrocyte Transplants Preserve Respiratory Function After Spinal Cord Injury

Experimental Neurology. Sep, 2015  |  Pubmed ID: 26216662

Transplantation-based replacement of lost and/or dysfunctional astrocytes is a promising therapy for spinal cord injury (SCI) that has not been extensively explored, despite the integral roles played by astrocytes in the central nervous system (CNS). Induced pluripotent stem (iPS) cells are a clinically-relevant source of pluripotent cells that both avoid ethical issues of embryonic stem cells and allow for homogeneous derivation of mature cell types in large quantities, potentially in an autologous fashion. Despite their promise, the iPS cell field is in its infancy with respect to evaluating in vivo graft integration and therapeutic efficacy in SCI models. Astrocytes express the major glutamate transporter, GLT1, which is responsible for the vast majority of glutamate uptake in spinal cord. Following SCI, compromised GLT1 expression/function can increase susceptibility to excitotoxicity. We therefore evaluated intraspinal transplantation of human iPS cell-derived astrocytes (hIPSAs) following cervical contusion SCI as a novel strategy for reconstituting GLT1 expression and for protecting diaphragmatic respiratory neural circuitry. Transplant-derived cells showed robust long-term survival post-injection and efficiently differentiated into astrocytes in injured spinal cord of both immunesuppressed mice and rats. However, the majority of transplant-derived astrocytes did not express high levels of GLT1, particularly at early times post-injection. To enhance their ability to modulate extracellular glutamate levels, we engineered hIPSAs with lentivirus to constitutively express GLT1. Overexpression significantly increased GLT1 protein and functional GLT1-mediated glutamate uptake levels in hIPSAs both in vitro and in vivo post-transplantation. Compared to human fibroblast control and unmodified hIPSA transplantation, GLT1-overexpressing hIPSAs reduced (1) lesion size within the injured cervical spinal cord, (2) morphological denervation by respiratory phrenic motor neurons at the diaphragm neuromuscular junction, and (3) functional diaphragm denervation as measured by recording of spontaneous EMGs and evoked compound muscle action potentials. Our findings demonstrate that hiPSA transplantation is a therapeutically-powerful approach for SCI.

Local Activity and Causal Connectivity in Children with Benign Epilepsy with Centrotemporal Spikes

PloS One. 2015  |  Pubmed ID: 26225427

The aim of the current study was to localize the epileptic focus and characterize its causal relation with other brain regions, to understand the cognitive deficits in children with benign childhood epilepsy with centrotemporal spikes (BECTS). Resting-state functional magnetic resonance imaging (fMRI) was performed in 37 children with BECTS and 25 children matched for age, sex and educational achievement. We identified the potential epileptogenic zone (EZ) by comparing the amplitude of low frequency fluctuation (ALFF) of spontaneous blood oxygenation level dependent fMRI signals between the groups. Granger causality analysis was applied to explore the causal effect between EZ and the whole brain. Compared with controls, children with BECTS had significantly increased ALFF in the right postcentral gyrus and bilateral calcarine, and decreased ALFF in the left anterior cingulate cortex, bilateral putaman/caudate, and left cerebellum. ALFF values in the putaman/caudate were positively correlated with verbal IQ scores in patients. The ALFF values in cerebellum and performance IQ scores were negatively correlated in patients. These results suggest that ALFF disturbances in the putaman/caudate and cerebellum play an important role in BECTS cognitive dysfunction. Compared with controls, the patients showed increased driving effect from the EZ to the right medial frontal cortex and posterior cingulate cortex and decreased causal effects from the EZ to left inferior frontal gyrus. The causal effect of the left inferior frontal gyrus negatively correlated with disease duration, which suggests a relation between the epileptiform activity and language impairment. All together, these findings provide additional insight into the neurophysiological mechanisms of epilepitogenisis and cognitive dysfunction associated with BECTS.

A Generalized Reconstruction Framework for Unconventional PET Systems

Medical Physics. Aug, 2015  |  Pubmed ID: 26233187

Quantitative estimation of the radionuclide activity concentration in positron emission tomography (PET) requires precise modeling of PET physics. The authors are focused on designing unconventional PET geometries for specific applications. This work reports the creation of a generalized reconstruction framework, capable of reconstructing tomographic PET data for systems that use right cuboidal detector elements positioned at arbitrary geometry using a regular Cartesian grid of image voxels.

Localization of Transcranial Targets for Photoacoustic-Guided Endonasal Surgeries

Photoacoustics. Jun, 2015  |  Pubmed ID: 26236644

Neurosurgeries to remove pituitary tumors using the endonasal, transsphenoidal approach often incur the risk of patient death caused by injury to the carotid arteries hidden by surrounding sphenoid bone. To avoid this risk, we propose intraoperative photoacoustic vessel visualization with an optical fiber attached to the surgical tool and an external ultrasound transducer placed on the temple. Vessel detection accuracy is limited by acoustic propagation properties, which were investigated with k-Wave simulations. In a two-layer model of temporal bone (3200 m/s sound speed, 1-4 mm thickness) and surrounding tissues, the localization error was ≤2 mm in the tranducer's axial dimension, while temporal bone curvature further degraded target localization. Phantom experiments revealed that multiple image targets (e.g. sphenoid bone and vessels) can be visualized, particularly with coherence-based beamforming, to determine tool-to-vessel proximity despite expected localization errors. In addition, the potential flexibility of the fiber position relative to the transducer and vessel was elucidated.

Incidence Trends and Age Distribution of Colorectal Cancer by Subsite in Guangzhou, 2000-2011

Chinese Journal of Cancer. Aug, 2015  |  Pubmed ID: 26245843

Colorectal cancer (CRC) is the third most common cancer in China. The incidence of CRC has been increasing in recent years. The aim of this study was to explore the incidence trends and the age distribution of CRC by subsite in Guangzhou between 2000 and 2011.

Compression Therapy in the Prevention of Postthrombotic Syndrome: A Systematic Review and Meta-Analysis

Medicine. Aug, 2015  |  Pubmed ID: 26252318

Although compression therapy has been widely used after deep vein thrombosis (DVT), its efficacy in prevention of postthrombotic syndrome (PTS) remains disputable. We aimed to update the meta-analysis to comprehensively evaluate the effect of compression therapy on the prevention of PTS in adult patients after DVT.PubMed, Embase, and Cochrane library databases were systematically searched. Randomized controlled trials (RCTs) evaluating the preventive effect of compression therapy on PTS in adult patients after DVT were included. The primary outcome was the incidence of PTS. All meta-analyses were performed using random-effects models regardless of the heterogeneity. Subgroup and sensitivity analysis were also performed to examine the robustness of the pooled effects according to our predesigned plan. Potential publication bias was assessed.Eight RCTs with 1598 patients were included. Overall, compression therapy could significantly reduce the incidence of PTS (estimate 0.68, 95% confidence interval [CI] 0.52-0.90; P = 0.007). However, it was only associated with a reduction in the incidence of mild/moderate PTS (relative risk [RR] 0.66, 95% CI 0.46-0.93; P = 0.019) but not in the incidence of severe PTS (RR 0.64, 95% CI 0.27-1.50; P = 0.31). Additionally, compression therapy failed to reduce the incidence of recurrent venous thromboembolism (RR 0.91, 95% CI 0.65-1.27; P = 0.58), the incidence of ulceration (RR 0.74, 95% CI 0.36-1.53; P = 0.42), or mortality (RR 0.99, 95% CI 0.72-1.37; P = 0.96). No publication bias was observed.Current evidence still supports compression therapy to be a clinical practice for prophylaxis of PTS in adult patients after DVT. However, our findings should be cautiously interpreted because of heterogeneity and hence more large-scale and well-designed RCTs are still warranted.

Quantification of 15 Bile Acids in Lake Charr Feces by Ultra-high Performance Liquid Chromatography-tandem Mass Spectrometry

Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. Sep, 2015  |  Pubmed ID: 26253808

Many fishes are hypothesized to use bile acids (BAs) as chemical cues, yet quantification of BAs in biological samples and the required methods remain limited. Here, we present an UHPLC-MS/MS method for simultaneous, sensitive, and rapid quantification of 15 BAs, including free, taurine, and glycine conjugated BAs, and application of the method to fecal samples from lake charr (Salvelinus namaycush). The analytes were separated on a C18 column with acetonitrile-water (containing 7.5mM ammonium acetate and 0.1% formic acid) as mobile phase at a flow rate of 0.25mL/min for 12min. BAs were monitored with a negative electrospray triple quadrupole mass spectrometer (Xevo TQ-S™). Calibration curves of 15 BAs were linear over the concentration range of 1.00-5,000ng/mL. Validation revealed that the method was specific, accurate, and precise. The method was applied to quantitative analysis of feces extract of fry lake charr and the food they were eating. The concentrations of analytes CA, TCDCA, TCA, and CDCA were 242.3, 81.2, 60.7, and 36.2ng/mg, respectively. However, other taurine conjugated BAs, TUDCA, TDCA, and THDCA, were not detected in feces of lake charr. Interestingly, TCA and TCDCA were detected at high concentrations in food pellets, at 71.9 and 38.2ng/mg, respectively. Application of the method to feces samples from lake charr supported a role of BAs as chemical cues, and will enhance further investigation of BAs as chemical cues in other fish species.

Ultralow Friction of Steel Surfaces Using a 1,3-Diketone Lubricant in the Thin Film Lubrication Regime

Langmuir : the ACS Journal of Surfaces and Colloids. Oct, 2015  |  Pubmed ID: 26267214

Ultralow friction (coefficient of friction μ ≈ 0.005) is observed when two steel surfaces are brought into sliding contact in the presence of a particular 1,3-diketone lubricant (1-(4-ethyl phenyl) nonane-1,3-dione). We investigate the friction process of such a system both experimentally and theoretically and show that the superlubricity is caused by a novel, unique mechanism: The formation of iron-1,3-diketonato complexes during frictional contact leads to a self-limiting, tribochemical polishing process while at the same time a self-assembled monolayer of the diketone is formed on the employed steel surfaces. This polishing process reduces the contact pressure and at the same time leads to formation of a boundary lubricant layer. During sliding the system transits from the original boundary lubrication regime toward hydrodynamic lubrication. Conductivity measurements across the friction gap during sliding show that the lubricant layer present in the gap between the two shearing surfaces is a only few 10 nanometers thick, so that the molecules experience under typical sliding conditions shear rates of a few 10(6) s(-1). Simulations show that under such strong shear the molecules become strongly oriented in the friction gap and the effective viscosity in sliding direction is significantly reduced so that the system is in the thin film lubrication regime and superlubricity is observed. The results of the experiments suggest that such diketones are promising lubricants to achieve a decrease of energy loss and frictional damage in steel based mechanical devices.

TRB3 Links Insulin/IGF to Tumour Promotion by Interacting with P62 and Impeding Autophagic/proteasomal Degradations

Nature Communications. Aug, 2015  |  Pubmed ID: 26268733

High insulin/IGF is a biologic link between diabetes and cancers, but the underlying molecular mechanism remains unclear. Here we report a previously unrecognized tumour-promoting mechanism for stress protein TRB3, which mediates a reciprocal antagonism between autophagic and proteasomal degradation systems and connects insulin/IGF to malignant promotion. We find that several human cancers express higher TRB3 and phosphorylated insulin receptor substrate 1, which correlates negatively with patient's prognosis. TRB3 depletion protects against tumour-promoting actions of insulin/IGF and attenuates tumour initiation, growth and metastasis in mice. TRB3 interacts with autophagic receptor p62 and hinders p62 binding to LC3 and ubiquitinated substrates, which causes p62 deposition and suppresses autophagic/proteasomal degradation. Several tumour-promoting factors accumulate in cancer cells to support tumour metabolism, proliferation, invasion and metastasis. Interrupting TRB3/p62 interaction produces potent antitumour efficacies against tumour growth and metastasis. Our study opens possibility of targeting this interaction as a potential novel strategy against cancers with diabetes.

Effect of Simulated Microgravity on Human Brain Gray Matter and White Matter--Evidence from MRI

PloS One. 2015  |  Pubmed ID: 26270525

There is limited and inconclusive evidence that space environment, especially microgravity condition, may affect microstructure of human brain. This experiment hypothesized that there would be modifications in gray matter (GM) and white matter (WM) of the brain due to microgravity.

Distribution and Effect of Steroidal Saponin Derivative WRC3 in B16 Melanoma Cells

Molecular Medicine Reports. Oct, 2015  |  Pubmed ID: 26299565

Steroidal saponins have recently attracted attention due to their structural diversity and significant biological activities, including anti‑hyperlipidemic, antibacterial, anti‑inflammatory, immunomodulatory and anti‑HIV activities. In the present study, it was demonstrated that WRC3, a novel saponin derivative, can inhibit B16 cancer cells by inducing apoptotic cell death with an IC50 value of 12.09 µM. The inhibitory effect of WRC3 on B16 cells appears to occur in a time‑ and concentration‑dependent manner. The fluorescence distribution observed by confocal microscopy revealed that WRC3 entered cells and acted in the cytoplasm without causing genetic toxicity. Following administration of WRC3 (2.5, 5.0 and 7.5 g/kg body weight) once a day for 7 days, no obvious abnormalities were observed in the organs of the mice as demonstrated by hematoxylin and eosin staining. Compared with the normal control group, aspartate transaminase (AST), alanine transaminase (ALT), creatine and urea levels in the serum of mice treated with WRC3 (2.5‑7.5 µM) remained unchanged. In conclusion, it was demonstrated that WRC3 can induce cancer cell death without causing genetic toxicity, hepatotoxicity or nephrotoxicity.

The TRIB3-SQSTM1 Interaction Mediates Metabolic Stress-promoted Tumorigenesis and Progression Via Suppressing Autophagic and Proteasomal Degradation

Autophagy. 2015  |  Pubmed ID: 26301314

Cancer and diabetes are 2 multifactorial chronic diseases with tremendous impact on health worldwide. Metabolic risk factors play a critical role in fueling a wide range of cancers, but with undefined mechanisms. We recently reported that TRIB3, a stress-induced protein, mediates a reciprocal antagonism between autophagic and proteasomal degradation systems and connects insulin-IGF1 to malignant promotion. We found that several human cancer tissues express higher TRIB3 and phosphorylated IRS1 (insulin receptor substrate 1), which correlates negatively with patient prognosis. Silencing of TRIB3 not only restores insulin-IGF1-suppressed autophagic flux, but also attenuates tumor growth and metastasis. TRIB3 physically interacts with the autophagic receptor SQSTM1, and this interaction hinders the binding of SQSTM1 to LC3 and ubiquitinated proteins, leading to SQSTM1 accumulation and clearance inhibition of ubiquitinated proteins. Interrupting the TRIB3-SQSTM1 interaction with an α-helical peptide derived from SQSTM1 attenuates tumor growth and metastasis through activating autophagic flux. Our findings indicate that TRIB3 links insulin-IGF1 to cancer development and progression through interacting with SQSTM1. Thus, interrupting the TRIB3-SQSTM1 interaction may provide a potential strategy against cancers in patients with diabetes.

The Diagnostic Value of Transthoracic Echocardiography for Eosinophilic Myocarditis: A Single Center Experience from China

International Journal of Cardiology. Dec, 2015  |  Pubmed ID: 26301679

The aim of this study is to explore the value of transthoracic echocardiography in the diagnosis of eosinophilic myocarditis. The echocardiographic characteristics of nine patients with eosinophilic myocarditis in our hospital between January 2004 and January 2012 were retrospectively reviewed. In our study, four of the nine patients were diagnosed to have small pericardial effusion. The obliteration of the apical cavity was observed in five of the nine patients. There were six patients with both mitral and tricuspid regurgitation, one patient with only mitral regurgitation, and one patient with only tricuspid regurgitation. Transthoracic echocardiography showed that the diameters of the left and right atria were both increased in eight of the nine patients. The diameter of the left ventricle was increased in five patients, and the right ventricular diameter was increased in four patients. The left ventricular ejection fraction was decreased in two of the nine patients. Five of the nine patients had pulmonary hypertension, and one patient had severe pulmonary hypertension. Transthoracic echocardiography is the primary method for the diagnosis of eosinophilic myocarditis and is also useful in follow-up of the disease.

Anticipatory Pleasure Predicts Effective Connectivity in the Mesolimbic System

Frontiers in Behavioral Neuroscience. 2015  |  Pubmed ID: 26321934

Convergent evidence suggests the important role of the mesolimbic pathway in anticipating monetary rewards. However, the underlying mechanism of how the sub-regions interact with each other is still not clearly understood. Using dynamic causal modeling, we constructed a reward-related network for anticipating monetary reward using the Monetary Incentive Delay Task. Twenty-six healthy adolescents (Female/Male = 11/15; age = 18.69 ± 1.35 years; education = 12 ± 1.58 years) participated in the present study. The best-fit network involved the right substantia nigra/ventral tegmental area (SN/VTA), the right nucleus accumbens (NAcc) and the right thalamus, which were all activated during anticipation of monetary gain and loss. The SN/VTA directly activates the NAcc and the thalamus. More importantly, monetary gain modulated the connectivity from the SN/VTA to the NAcc and this was significantly correlated with subjective anticipatory pleasure (r = 0.649, p < 0.001). Our findings suggest that activity in the mesolimbic pathway during the anticipation of monetary reward could to some extent be predicted by subjective anticipatory pleasure.

Statistical Model Based Iterative Reconstruction in Clinical CT Systems. Part III. Task-based KV/mAs Optimization for Radiation Dose Reduction

Medical Physics. Sep, 2015  |  Pubmed ID: 26328971

For a given imaging task and patient size, the optimal selection of x-ray tube potential (kV) and tube current-rotation time product (mAs) is pivotal in achieving the maximal radiation dose reduction while maintaining the needed diagnostic performance. Although contrast-to-noise (CNR)-based strategies can be used to optimize kV/mAs for computed tomography (CT) imaging systems employing the linear filtered backprojection (FBP) reconstruction method, a more general framework needs to be developed for systems using the nonlinear statistical model-based iterative reconstruction (MBIR) method. The purpose of this paper is to present such a unified framework for the optimization of kV/mAs selection for both FBP- and MBIR-based CT systems.

[Fibroblast Growth Factor-1 Inhibits Wnt/β-catenin Pathway During Adipogenesis]

Zhong Nan Da Xue Xue Bao. Yi Xue Ban = Journal of Central South University. Medical Sciences. Aug, 2015  |  Pubmed ID: 26333491

To determine the time course and potential mechanism of fibroblast growth factor-1 (FGF-1) in the regulation of adipogenesis.

Interhemispheric Connectivity in Drug-Naive Benign Childhood Epilepsy With Centrotemporal Spikes: Combining Function and Diffusion MRI

Medicine. Sep, 2015  |  Pubmed ID: 26376406

Decreased intelligence quotients (IQ) have been consistently reported in drug-naive benign childhood epilepsy with centrotemporal spikes (BECTS). We aimed to identify the neurophysiological basis of IQ deficits by studying interhemispheric and anatomical functional connectivity in BECTS patients. Resting-state functional and structural magnetic resonance images were acquired in 32 children with BECTS and 25 healthy controls. The IQ was estimated using Wechsler Intelligence Scale for Children China-Revised. The functional connectivity between bilateral homotopic voxels was calculated and compared between groups. Homotopic regions showing abnormal functional connectivity in patients were adopted as regions of interest for analysis by diffusion-tensor imaging tractography. The fractional anisotropy, fiber length, and fiber number were compared between groups. Abnormal homotopic connectivities were correlated with IQ in BECTS patients. Compared with control subjects, patients showed decreased IQ, and decreased voxel-mirrored homotopic connectivity (VMHC) in the bilateral frontal lobule and cerebellum. The performance and full scale IQ significantly increased with the VMHC strength of the middle frontal gyrus (MFG) in controls but not in BECTS patients. A significant negative correlation was observed between VMHC in the premotor cortex and disease duration. Microstructural features within white matter tracts connecting functionally abnormal regions did not reveal any differences between groups. This study provides preliminary evidence for the disrupted functional cooperation between hemispheres in children with BECTS. The findings suggest that the hyposynchrony between the bilateral MFG may be involved in the decreased IQ of BECTS patients.

Identification of Cultured and Natural Astragalus Root Based on Monosaccharide Mapping

Molecules (Basel, Switzerland). Sep, 2015  |  Pubmed ID: 26378510

As the main substances responsible for immunomodulatory activity, saccharides can be used as quality indicators for Astragalus root (RA). Saccharide content is commonly determined by ultraviolet spectroscopy, which lacks species specificity and has not been applied in the Chinese Pharmacopoeia. Monosaccharide mapping based on trifluoroacetic acid (TFA) hydrolysis can be used for quantitative analysis of saccharide compositions. In addition, species specificity can be evaluated by analysis of the mapping characteristics. In this study, monosaccharide mapping of soluble saccharides in the cytoplasm and polysaccharides in the cell wall of 24 batches of RA samples with different growth patterns were obtained based on TFA hydrolysis followed by gas chromatography-mass spectrometry. Results indicated that the mapping and the molar ratios of saccharide compositions of the cultured and natural RA samples were different for both cytoplasm and cell wall. For example, the molar ratio of mannose and arabinose was more than 3.5:1 in cytoplasm in cultured RA, whereas the ratio was less than 3.5:1 in natural RA. This research not only lays a foundation for screening indicators for RA, but also provided new ways of evaluating the quality of Chinese medicinal materials in which saccharides are the main bioactive substances.

Correction of Data Truncation Artifacts in Differential Phase Contrast (DPC) Tomosynthesis Imaging

Physics in Medicine and Biology. Oct, 2015  |  Pubmed ID: 26394181

The use of grating based Talbot-Lau interferometry permits the acquisition of differential phase contrast (DPC) imaging with a conventional medical x-ray source and detector. However, due to the limited area of the gratings, limited area of the detector, or both, data truncation image artifacts are often observed in tomographic DPC acquisitions and reconstructions, such as tomosynthesis (limited-angle tomography). When data are truncated in the conventional x-ray absorption tomosynthesis imaging, a variety of methods have been developed to mitigate the truncation artifacts. However, the same strategies used to mitigate absorption truncation artifacts do not yield satisfactory reconstruction results in DPC tomosynthesis reconstruction. In this work,several new methods have been proposed to mitigate data truncation artifacts in a DPC tomosynthesis system. The proposed methods have been validated using experimental data of a mammography accreditation phantom, a bovine udder, as well as several human cadaver breast specimens using a bench-top DPC imaging system at our facility.

A Study of the Post-Op Lymphedema of Prefabricated Flaps and Its Prognosis

Plastic and Reconstructive Surgery. Oct, 2015  |  Pubmed ID: 26397625

Nasobiliary Tube Placement: How to Accomplish Oral-to-nasal Transfer

Endoscopy. 2015  |  Pubmed ID: 26397849

Non-functional Parathyroid Carcinoma: a Case Report and Review of the Literature

Cancer Biology & Therapy. 2015  |  Pubmed ID: 26408508

Non-functional parathyroid carcinoma is an exceedingly rare disease with 31 reported cases since 1909. Because of the scarce number of cases of non-functional parathyroid carcinoma, there are no evidence-based recommendations for its optimal treatment. Surgery, including en bloc resection of the carcinoma, ipsilateral thyroid lobe and isthmus together with a neck dissection only in case of lymph node involvement, is the main treatment for non-functioning parathyroid carcinoma. The patient usually has a poorer prognosis because of detection at advanced stages, the relative ineffectiveness of adjuvant treatment modalities and the lack of adequate parameters for clinical follow-up. In this report, we present a case of non-functional parathyroid carcinoma at our institution, and we review the previous literature to discuss the latest advances in the diagnosis and treatment of this rare disease.

Influence of Radiation Dose and Reconstruction Algorithm in MDCT Assessment of Airway Wall Thickness: A Phantom Study

Medical Physics. Oct, 2015  |  Pubmed ID: 26429266

Wall thickness (WT) is an airway feature of great interest for the assessment of morphological changes in the lung parenchyma. Multidetector computed tomography (MDCT) has recently been used to evaluate airway WT, but the potential risk of radiation-induced carcinogenesis-particularly in younger patients-might limit a wider use of this imaging method in clinical practice. The recent commercial implementation of the statistical model-based iterative reconstruction (MBIR) algorithm, instead of the conventional filtered back projection (FBP) algorithm, has enabled considerable radiation dose reduction in many other clinical applications of MDCT. The purpose of this work was to study the impact of radiation dose and MBIR in the MDCT assessment of airway WT.

Structures and Multiple Properties of Two Polar Metal-organic Frameworks Based on Achiral N,O-coordinated Ligands: Toward Multifunctional Materials

Dalton Transactions (Cambridge, England : 2003). Nov, 2015  |  Pubmed ID: 26465876

Two novel metal-organic frameworks (MOFs) [Cd3(padc)(Hpadc)(H2padc)(H2O)]n·nH2O (1, H3padc = pyrazole-3,5-dicarboxylic acid) and [Co4(pidc)2(Hpidc)4(H2O)3]n·12nH2O (2, H2pidc = pyridine-2,5-dicarboxylic acid), that both crystallize in polar space groups, were solvothermally synthesized by using achiral N,O-coordinated ligands. Compound 1 consists of trinuclear Cd(II)-based units that are further bridged by the backbone of H3padc ligands to form a three-dimensional (3-D) (4,6)-connected fsc topology network, while compound 2 features two types of double-helical tubes with different chiralities connecting with each other alternatively to construct a typical 2-D (3,6)-connected kgd topology network. Importantly, 1 exhibits combined properties of photoluminescence (PL) and second harmonic generation (SHG), and represents the first noncentrosymmetric H3padc-based MOF that was obtained without any ancillary ligands. While 2 shows strong antiferromagnetic interactions between paramagnetic Co(II) centers, and the aqueous solution of 2 exhibits effective homogeneous photocatalysis properties under visible irradiation. Further, the mechanisms of the physical properties of 1 and 2 are discussed in detail.

R1 Correction in Amide Proton Transfer Imaging: Indication of the Influence of Transcytolemmal Water Exchange on CEST Measurements

NMR in Biomedicine. Dec, 2015  |  Pubmed ID: 26466161

Amide proton transfer (APT) imaging may potentially detect mobile proteins/peptides non-invasively in vivo, but its specificity may be reduced by contamination from other confounding effects such as asymmetry of non-specific magnetization transfer (MT) effects and spin-lattice relaxation with rate R1 (=1/T1). Previously reported spillover, MT and R1 correction methods were based on a two-pool model, in which the existence of multiple water compartments with heterogeneous relaxation properties in real tissues was ignored. Such simple models may not adequately represent real tissues, and thus such corrections may be unreliable. The current study investigated the effectiveness and accuracy of correcting for R1 in APT imaging via simulations and in vivo experiments using tumor-bearing rats subjected to serial injections of Gd-DTPA that produced different tissue R1 values in regions of blood-brain-barrier breakdown. The results suggest that conventional measurements of APT contrast (such as APT* and MTRasym ) may be significantly contaminated by R1 variations, while the R1 -corrected metric AREX* was found to be relatively unaffected by R1 changes over a broad range (0.4-1 Hz). Our results confirm the importance of correcting for spin-lattice relaxation effects in quantitative APT imaging, and demonstrate the reliability of using the observed tissue R1 for corrections to obtain more specific and accurate measurements of APT contrast in vivo. The results also indicate that, due to relatively fast transcytolemmal water exchange, the influence of intra- and extracellular water compartments on CEST measurements with seconds long saturation time may be ignored in tumors.

Atg5-independent Autophagy Regulates Mitochondrial Clearance and is Essential for IPSC Reprogramming

Nature Cell Biology. Nov, 2015  |  Pubmed ID: 26502054

Successful generation of induced pluripotent stem cells entails a major metabolic switch from mitochondrial oxidative phosphorylation to glycolysis during the reprogramming process. The mechanism of this metabolic reprogramming, however, remains elusive. Here, our results suggest that an Atg5-independent autophagic process mediates mitochondrial clearance, a characteristic event involved in the metabolic switch. We found that blocking such autophagy, but not canonical autophagy, inhibits mitochondrial clearance, in turn, preventing iPSC induction. Furthermore, AMPK seems to be upstream of this autophagic pathway and can be targeted by small molecules to modulate mitochondrial clearance during metabolic reprogramming. Our work not only reveals that the Atg5-independent autophagy is crucial for establishing pluripotency, but it also suggests that iPSC generation and tumorigenesis share a similar metabolic switch.

A Spacecraft Electrical Characteristics Multi-Label Classification Method Based on Off-Line FCM Clustering and On-Line WPSVM

PloS One. 2015  |  Pubmed ID: 26544549

This paper proposes a novel multi-label classification method for resolving the spacecraft electrical characteristics problems which involve many unlabeled test data processing, high-dimensional features, long computing time and identification of slow rate. Firstly, both the fuzzy c-means (FCM) offline clustering and the principal component feature extraction algorithms are applied for the feature selection process. Secondly, the approximate weighted proximal support vector machine (WPSVM) online classification algorithms is used to reduce the feature dimension and further improve the rate of recognition for electrical characteristics spacecraft. Finally, the data capture contribution method by using thresholds is proposed to guarantee the validity and consistency of the data selection. The experimental results indicate that the method proposed can obtain better data features of the spacecraft electrical characteristics, improve the accuracy of identification and shorten the computing time effectively.

Distinguishing Bipolar and Major Depressive Disorders by Brain Structural Morphometry: a Pilot Study

BMC Psychiatry. Nov, 2015  |  Pubmed ID: 26590556

The clinical presentation of common symptoms during depressive episodes in bipolar disorder (BD) and major depressive disorder (MDD) poses challenges for accurate diagnosis. Disorder-specific neuroanatomical features may aid the development of reliable discrimination between these two clinical conditions.

Association of Single Nucleotide Polymorphisms of DNA Repair Genes in NER Pathway and Susceptibility to Pancreatic Cancer

International Journal of Clinical and Experimental Pathology. 2015  |  Pubmed ID: 26617894

In our study, we conducted a case-control study to investigate the association of ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, XPA, XPC and DDB2 gene polymorphisms in the risk of pancreatic cancer. Between May 2012 and May 2014, a total of 246 patients with who were newly diagnosed with histopathologically confirmed primary pancreatic cancer and 246 controls were selected into our study. Genotyping of ERCC1 rs3212986 and rs11615, ERCC2 rs13181, ERCC3 rs4150441, ERCC4 rs6498486, ERCC5 rs873601, XPA rs2808668, XPC rs2228000, XPC rs2228001 and DDB2 rs2029298 were analyzed using polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By conditional logistic regression analysis, individuals carrying with TT genotype of ERCC1 rs3212986 and GG genotype of ERCC2 rs13181 were associated with increased risk of pancreatic cancer when compared with wide-type genotype, and the adjusted ORs (95% CI) were 2.40 (1.29-4.52) and 2.27 (1.26-4.15), respectively. We found that individuals carrying with GT+TT genotype of ERCC1 rs3212986 and TG+GG genotype of ERCC2 rs1318 gene polymorphisms were correlated with higher risk of pancreatic cancer in smokers when compared with non-smokers, and the adjusted ORs (95% CI) were 1.89 (1.05-3.40) and 1.88 (1.06-3.34), respectively. In conclusion, our study suggests that ERCC1 rs3212986 and ERCC2 rs1318 gene polymorphisms contribute to the development of pancreatic cancer, especially in smokers.

MiR-185 Acts As a Tumor Suppressor by Targeting AKT1 in Non-small Cell Lung Cancer Cells

International Journal of Clinical and Experimental Pathology. 2015  |  Pubmed ID: 26617940

Increasing evidence has shown that microRNAs play critical roles in the initiation and progression of non-small cell lung cancer (NSCLC). miR-185 is deregulated in various cancers, whereas its functional mechanism in NSCLC is still unclear. Here, we confirmed that the expression of miR-185 was significantly down-regulated in NSCLC tissues and cell lines. miR-185 over-expression caused significant suppression of in vitro cell proliferation, migration and invasion, and in vivo tumor growth. We subsequently identified that AKT1 was a target gene of miR-185. Re-expression of AKT1 could partially rescue the inhibitory effects of miR-185 on the capacity of NSCLC cell proliferation and motility. Collectively, we conclude that miR-185 has a critical function by blocking AKT1 in NSCLC cells, and it may be a novel therapeutic agent for miRNA based NSCLC therapy.

Hsp90 and Hepatobiliary Transformation During Sea Lamprey Metamorphosis

BMC Developmental Biology. Dec, 2015  |  Pubmed ID: 26627605

Biliary atresia (BA) is a human infant disease with inflammatory fibrous obstructions in the bile ducts and is the most common cause for pediatric liver transplantation. In contrast, the sea lamprey undergoes developmental BA with transient cholestasis and fibrosis during metamorphosis, but emerges as a fecund adult. Therefore, sea lamprey liver metamorphosis may serve as an etiological model for human BA and provide pivotal information for hepatobiliary transformation and possible therapeutics.

Occurrence and Profiles of the Artificial Endocrine Disruptor Bisphenol A and Natural Endocrine Disruptor Phytoestrogens in Urine from Children in China

International Journal of Environmental Research and Public Health. Nov, 2015  |  Pubmed ID: 26633438

Exposure to artificial or natural endocrine disruptors, such as bisphenol A (BPA) and phytoestrogens has been demonstrated to have health effects, especially in children. Biomonitoring of BPA and phytoestrogens in human urine can be used to assess the intake levels of these compounds.

[Effects of JAZF1 Overexpression on Proinflammatory Cytokines in Hepatocytes Induced by Palmitic Acid]

Zhonghua Gan Zang Bing Za Zhi = Zhonghua Ganzangbing Zazhi = Chinese Journal of Hepatology. Dec, 2015  |  Pubmed ID: 26739470

To investigate the effects of JAZF1 overexpression on the pro-inflammatory cytokines in hepatic steatosis.


Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi = Zhongguo Xiufu Chongjian Waike Zazhi = Chinese Journal of Reparative and Reconstructive Surgery. Oct, 2015  |  Pubmed ID: 26749723

To evaluate the inflammatory markers in patients with ankylosing spondylitis (AS) or non-inflammatory diseases undergoing total hip arthroplasty (THA) and to ascertain the variation trend of perioperative inflammatory markers and the influence of inflammation markers after THA.

[Effect of Different Nitrogen Forms and Ratio on Growth and Active Ingredient Content of Platycodon Grandiflorum]

Zhongguo Zhong Yao Za Zhi = Zhongguo Zhongyao Zazhi = China Journal of Chinese Materia Medica. Oct, 2015  |  Pubmed ID: 26975097

To providing evidence about nitrogen adequate application of Platycodon grandiflorum, the pot culture experiment was conducted to study the effect of nitrogen on the growth, physiological metabolism and the quality of P. grandiflorum. The activity of NR, GS and SOD, POD and CAT were determined. And the nitrate and ammonium nitrogen content, photosynthetic characteristics, active components of P. grandiflorum were determined. The results showed that the nitrate nitrogen content and P. biomass reached its maximum value, when NH4(+)-N/NO3(-) -N was 0: 100, the activity of NR. The activity of GS was the highest at the NH4(+) -N/NO3(-) -N ratio of 25:75 and ammonium nitrogen content was the highest at 75:25. The activity of SOD decreased and then increased with the increasing of NO3(-) -N. At the NH4(+) -N/NO3(-) -N ratio of 25: 75, the activity of CAT had its maximum value and the content of MDA had the minimum value. At the same time, the content of platycodon D was the highest at this treatment. The studies had shown that different nitrogen forms and ratio had a significant effect on the characteristics of photosynthetic physiology, nitrogen metabolism and resistance adjustment, growth and the quality of P. grandiflorum. The NH4(+) -N/NO3(-) -N ratio of 25: 75 was a suitable ratio of nitrogen forms for the growth of P. Grandiflorum and accumulating the content of platycodon D.

Association Between the LIG1 Polymorphisms and Lung Cancer Risk: A Meta-analysis of Case-Control Studies

Cell Biochemistry and Biophysics. Nov, 2015  |  Pubmed ID: 27352326

Non-homologous end joining (NHEJ) is one of the pathways used to repair the DNA double-strand breaks. A number of genes involved in NHEJ have been implicated as lung cancer susceptibility genes such as the LIG1. However, some studies have generated conflicting results. The aim of this review and meta-analysis was to investigate the association between the LIG1 gene polymorphism and lung cancer risk. Studies focusing on the relationship between the LIG1 gene polymorphisms and susceptibility to lung cancer were selected from several electronic databases, with the last search up to October 25, 2014. Data were extracted by two independent reviewers, and the meta-analysis was performed with STATA version 12.0 software, calculating odds ratios (ORs) with 95 % confidence intervals (95 % CIs). According to the inclusion criteria, we included ten studies with a total of 4012 lung cancer cases and 5629 healthy controls in the meta-analysis. The results showed that the rs156641 polymorphism was significantly associated with lung cancer risk (dominant model: OR 0.694, 95 % CI 0.549-0.878; homozygote model: OR 0.677, 95 % CI 0.526-0.871; heterozygote model: OR 0.712, 95 % CI 0.556-0.913; additive model: OR 0.859, 95 % CI 0.767-0.962), whereas no association was found between rs3730931/rs439132/rs20579 polymorphisms and lung cancer. Our meta-analysis suggested that the rs156641 polymorphism in the LIG1 gene might be associated with an increased risk of lung cancer.

Preparation, Characterisation and Antitumour Activity of β-, γ- and HP-β-cyclodextrin Inclusion Complexes of Oxaliplatin

Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy. Jan, 2016  |  Pubmed ID: 26254603

Three water-soluble oxaliplatin complexes were prepared by inclusion complexation with β-cyclodextrin (β-CD), γ-CD and HP-β-CD. The structures of oxaliplatin/CDs were confirmed by NMR, FTIR, TGA, XRD as well as SEM analysis. The results show that the water solubility of oxaliplatin was increased in the complex with CDs in 1:1 stoichiometry inclusion modes, and the cyclohexane ring of oxaliplatin molecule was deeply inserted into the cavity of CDs. Moreover, the stoichiometry was established by a Job plot and the water stability constant (Kc) of oxaliplatin/CDs was calculated by phase solubility studies, all results show that the oxaliplatin/β-CD complex is more stable than free oxaliplatin, oxaliplatin/HP-β-CD and oxaliplatin/γ-CD. Meanwhile, the inclusion complexes displayed almost twice as high cytotoxicity compared to free oxaliplatin against HCT116 and MCF-7 cells. This satisfactory water solubility and higher cytotoxic activity of the oxaliplatin/CD complexes will potentially be useful for their application in anti-tumour therapy.

Distinct Processing of Social and Monetary Rewards in Late Adolescents with Trait Anhedonia

Neuropsychology. Mar, 2016  |  Pubmed ID: 26280299

Anticipatory and consummatory dissociation of hedonic experience may manifest as trait anhedonia in healthy and clinical populations. It is still unclear whether the underlying neural mechanisms of the monetary-based and affect-based incentive delay paradigms are distinct from each other. The present study aimed to examine the similarities and differences between the Affect Incentive Delay (AID) and the Monetary Incentive Delay (MID) imaging paradigms in relation to brain activations.

Influence of Water Compartmentation and Heterogeneous Relaxation on Quantitative Magnetization Transfer Imaging in Rodent Brain Tumors

Magnetic Resonance in Medicine. Aug, 2016  |  Pubmed ID: 26375875

The goal of this study was to investigate the influence of water compartmentation and heterogeneous relaxation properties on quantitative magnetization transfer (qMT) imaging in tissues, and in particular whether a two-pool model is sufficient to describe qMT data in brain tumors.

Cnga2 Knockout Mice Display Alzheimer's-Like Behavior Abnormities and Pathological Changes

Molecular Neurobiology. Sep, 2016  |  Pubmed ID: 26377105

Olfactory dysfunction is recognized as a potential risk factor for Alzheimer's disease (AD). We have reported previously that olfactory deprivation by olfactory bulbectomy (OBX) induced Alzheimer's-like pathological changes and behavioral abnormalities. However, the acute OBX model undergoes surgical-induced brain parenchyma loss and unexpected massive hemorrhage so that it cannot fully mimic the progressive olfactory loss and neurodegeneration in AD. Here, we employed the mice loss of cyclic nucleotide-gated channel alpha 2 (Cnga2) which is critical for olfactory sensory transduction, to investigate the role of olfactory dysfunction in AD pathological process. We found that impaired learning and memory abilities, loss of dendrite spines, as well as decrement of synaptic proteins were displayed in Cnga2 knockout mice. Moreover, Aβ overproduction, tau hyperphosphorylation, and somatodendritic translocation were also found in Cnga2 knockout mice. Our findings suggest that progressive olfactory loss leads to Alzheimer's-like behavior abnormities and pathological changes.

Human Papillomavirus and Polyomavirus Coinfections Among Chinese Men Who Have Sex with Men

The Journal of Infection. Jan, 2016  |  Pubmed ID: 26416469

Transcription Factors WRKY70 and WRKY11 Served As Regulators in Rhizobacterium Bacillus Cereus AR156-induced Systemic Resistance to Pseudomonas Syringae Pv. Tomato DC3000 in Arabidopsis

Journal of Experimental Botany. Jan, 2016  |  Pubmed ID: 26433201

The activation of both the SA and JA/ETsignalling pathways may lead to more efficient general and broad resistance to Pst DC3000 by non-pathogenic rhizobacteria. However, the mechanisms that govern this simultaneous activation are unclear. Using Arabidopsis as a model system, two transcription factors, WRKY11 and WRKY70, were identified as important regulators involved in Induced Systemic Resistance (ISR) triggered by Bacillus cereus AR156. The results revealed that AR156 treatment significantly stimulated the transcription of WRKY70, but suppressed that of WRKY11 in Arabidopsis leaves. Furthermore, they were shown to be required for AR156 enhancing the activation of cellular defence responses and the transcription level of the plant defence response gene. Overexpression of the two transcription factors in Arabidopsis also showed that they were essential for AR156 to elicit ISR. AR156-triggered ISR was completely abolished in the double mutant of the two transcription factors, but still partially retained in the single mutants, indicating that the regulation of the two transcription factors depend on two different pathways. The target genes of the two transcription factors and epistasis analysis suggested that WRKY11 regulated AR156-triggered ISR through activating the JA signalling pathway, and WRKY70 regulated the ISR through activating the SA signalling pathway. In addition, both WRKY11 and WRKY70 modulated AR156-triggered ISR in a NPR1-dependent manner. In conclusion, WRKY11 and WRKY70 played an important role in regulating the signalling transduction pathways involved in AR156-triggered ISR. This study is the first to illustrate the mechanism by which a single rhizobacterium elicits ISR by simultaneously activating both the SA and JA/ET signalling pathways.

Prior Image Constrained Compressed Sensing Metal Artifact Reduction (PICCS-MAR): 2D and 3D Image Quality Improvement with Hip Prostheses at CT Colonography

European Radiology. Jul, 2016  |  Pubmed ID: 26521266

To assess the effect of the prior-image-constrained-compressed-sensing-based metal-artefact-reduction (PICCS-MAR) algorithm on streak artefact reduction and 2D and 3D-image quality improvement in patients with total hip arthroplasty (THA) undergoing CT colonography (CTC).

Effects of Sitagliptin on Circulating Zinc-α2-glycoprotein Levels in Newly Diagnosed Type 2 Diabetes Patients: a Randomized Trial

European Journal of Endocrinology. Feb, 2016  |  Pubmed ID: 26546612

Zinc-α2-glycoprotein (ZAG) has recently been characterized as a potent metabolic regulator. However, the effects of anti-diabetic agents on circulating ZAG levels in humans remain largely unknown. To explore the possible mechanisms by which the dipeptidyl peptidase-IV (DPP-IV) inhibitor improves insulin resistance, we investigated the effect of sitagliptin, a DPP-IV inhibitor, on circulating cytokine levels in newly diagnosed type 2 diabetes (nT2DM) patients.

Free-Standing Conducting Polymer Films for High-Performance Energy Devices

Angewandte Chemie (International Ed. in English). Jan, 2016  |  Pubmed ID: 26630234

Thick, uniform, easily processed, highly conductive polymer films are desirable as electrodes for solar cells as well as polymer capacitors. Here, a novel scalable strategy is developed to prepare highly conductive thick poly(3,4-ethylenedioxythiophene):polystyrene sulfonate (HCT-PEDOT:PSS) films with layered structure that display a conductivity of 1400 S cm(-1) and a low sheet resistance of 0.59 ohm sq(-1). Organic solar cells with laminated HCT-PEDOT:PSS exhibit a performance comparable to the reference devices with vacuum-deposited Ag top electrodes. More importantly, the HCT-PEDOT:PSS film delivers a specific capacitance of 120 F g(-1) at a current density of 0.4 A g(-1). All-solid-state flexible symmetric supercapacitors with the HCT-PEDOT:PSS films display a high volumetric energy density of 6.80 mWh cm(-3) at a power density of 100 mW cm(-3) and 3.15 mWh cm(-3) at a very high power density of 16160 mW cm(-3) that outperforms previous reported solid-state supercapacitors based on PEDOT materials.

Resolvin D1 Attenuates CCl4-induced Acute Liver Injury Involving Up-regulation of HO-1 in Mice

Immunopharmacology and Immunotoxicology. 2016  |  Pubmed ID: 26630551

Acute hepatic failure involves in excessive oxidative stress and inflammatory responses, leading to a high mortality due to lacking effective therapy. Resolvin D1 (RvD1), an endogenous lipid mediator derived from polyunsaturated fatty acids, has been shown anti-inflammatory and anti-oxidative actions, however, whether RvD1 has protective effects on hepatic failure remains elusive. In this study, the roles and molecular mechanisms of RvD1 were explored in carbon tetrachloride (CCl4)-induced acute liver injury. Our results showed that RvD1 protected mice against CCl4-induced hepatic damage, as evaluated by reduced aminotransferase activities and malondialdehyde content, elevated glutathione and superoxide dismutase activities, and alleviated hepatic pathological damage. Moreover, RvD1 significantly attenuated serum tumor necrosis factor-α and interleukin-6 levels as well as hepatic myeloperoxidase activity, whereas enhanced serum IL-10 level in CCl4-administered mice. Further, RvD1 markedly up-regulated the expression and activity of heme oxygenase-1 (HO-1). However, inhibition of HO-1 activity reversed the protective effects of RvD1 on CCl4-induced liver injury. These results suggest that RvD1 could effectively prevent CCl4-induced liver injury by inhibition of oxidative stress and inflammation, and the underlying mechanism may be related to up-regulation of HO-1.

Acid-Promoted Cross-Dehydrative Aromatization for the Synthesis of Tetraaryl-Substituted Pyrroles

Organic Letters. Jan, 2016  |  Pubmed ID: 26683651

Tetraaryl-substituted pyrroles are one important class of luminophores. In this work, an acid-promoted cross-dehydrative aromatization between benzoin and deoxybenzion was developed. This transformation provides an efficient and straightforward path for the synthesis of various aryl group substituted tetraarylpyrroles. Good to excellent yields were obtained through the easy operation with acetic acid and ammonium acetate.

In vivo HMRS and Lipidomic Profiling Reveals Comprehensive Changes of Hippocampal Metabolism During Aging in Mice

Biochemical and Biophysical Research Communications. Jan, 2016  |  Pubmed ID: 26707637

Aging is characterized by various cellular changes in the brain. Hippocampus is important for systemic aging and lifespan control. There is still a lack of comprehensive overview of metabolic changes in hippocampus during aging. In this study, we first created an accelerated brain aging mice model through the chronic administration of d-galactose. We then performed a multiplatform metabolomic profiling of mice hippocampus using the combination of in vivo 9.4 T HMRS and in vitro LC-MS/MS based lipidomics. We found N-acetylaspartic acid (NAA), gama-aminobutyric acid (GABA), glutamate/glutamine, taurine, choline, sphingolipids (SMs), phosphatidylethanolamines (PEs), phosphatidylinositols (PIs), phosphatidylglycerols (PGs) and phosphatidylserines (PSs), all of them decreasing with the aging process in mice hippocampus. The changes of sphingolipids and phospholipids were not limited to one single class or molecular species. In contrast, we found the significant accumulation of lactate, myoinositol and phosphatidylcholines (PCs) along with aging in hippocampus. SM (d18:1/20:2), PE (36:2), PG (34:1), PI (36:4), PS (18:0/20:4) and PC (36:0) have the most significant changes along with aging. Network analysis revealed the striking loss of biochemical connectivity and interactions between hippocampal metabolites with aging. The correlation pattern between metabolites in hippocampus could function as biomarkers for aging or diagnosis of aging-related diseases.

Chemical Derivatization of Neurosteroids for Their Trace Determination in Sea Lamprey by UPLC-MS/MS

Talanta. 2016  |  Pubmed ID: 26717848

This article describes the development and validation of a sensitive and robust method for the determination of neurosteroids in sea lamprey, an ancestral animal in vertebrate evolution. Chemical derivatization was used to enhance the detection of neurosteroids containing ketone function by ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Iminooxy derivatives of 12 oxosteroids and three internal standards were monitored by positive electrospray tandem mass spectrometry using the neutral loss of sulfate. Limit of quantification, extraction recovery and matrix effect were first evaluated and SPE using C18 sorbent was selected after comparison with liquid/liquid extraction and protein precipitation. Matrix effect ranged from 89.6% to 113.1% in plasma and from 79.8% to 100.0% in the brain. Recovery values ranged from 80.0% to 103.8% in plasma and from 86.3% to 107.9% in the brain. Chromatographic separation was achieved by reverse phase chromatography (2.1mm×100mm, 1.7µm particle size, C18) with a binary gradient between methanol and 0.1% formic acid in water. Limit of quantification ranged from 5 to 10pg/mL and was up to 80 times lower than those for non-derivatized steroids. Accuracy and precision parameters were determined and inter- and intra-day at three concentrations: 50, 500 and 5000pg/mL. This method was applied to analyze real samples. progesterone (P), pregnenolone (P5), 7-hydroxy-pregnenolpne (7P5), 17-hydroxy-pregnenolpne (17P5)dehydroepiandrosterone (DHEA), androstenedienone (A4), testosterone (T), dihydrotestosterone (DHT), allopregnanolone (THP), 11-hydroxy-androstenedienone (11A4) and 11-Deoxycortisol (S) were measured in sea lamprey brain and plasma matrixes.

A Method for Establishing a Patient-derived Xenograft Model to Explore New Therapeutic Strategies for Esophageal Squamous Cell Carcinoma

Oncology Reports. Feb, 2016  |  Pubmed ID: 26718633

Esophageal squamous cell carcinoma (ESCC) is the predominant histological type of esophageal carcinoma in China. The overall 5-year survival rate of ESCC patients is in the low range of 15-25%. One important reason for the poor prognosis is that the underlying molecular mechanisms are unclear. Furthermore, the development of effective therapeutic strategies to improve patient outcome is needed. Animal models can be beneficial to analyze the molecular mechanisms as well as specific clinical therapeutic strategies for esophageal cancer. In recent years, patient-derived xenografts (PDXs) have been widely used in numerous types of cancers to investigate the basic mechanisms and to conduct preclinical research. Accumulating evidence indicates that the PDX model is an important tool for basic and clinical research. Herein, we successfully established 14 ESCC PDXs. These PDX models preserved the patient pathological characteristics and effectively reflected the patient biological heterogeneity. Cancers exhibit diverse growth rates and tumor texture, even more, they have different signaling pathways. The PDX model is a superior strategy for understanding the underlying molecular mechanisms of ESCC and for screening new therapeutic strategies for ESCC patients.

Enhancing Growth Rate and Lipid Yield of Chlorella with Nuclear Irradiation Under High Salt and CO2 Stress

Bioresource Technology. Mar, 2016  |  Pubmed ID: 26724554

In order to produce biodiesel from microalgae cultured with abundant seawater, Chlorella sp. was mutated with (137)Se-γ ray irradiation and domesticated with f/2 seawater culture medium (salinity=3 wt.%) under 15 vol.% CO2 stress. Biomass yield of the mutant increased by 25% compared with wild species and lipid content increased to 54.9%. When nitrogen and phosphorus concentrations in the initial substrate increased, the increased propagation speed of the mutant resulted in decreased cell diameter by 26.6% and decreased cell wall thickness by 69.7%. The dramatically increased biomass yield of the mutant with sufficient initial substrate and relative nitrogen starvation in the later growth period with continuous 15 vol.% CO2 led to an increased lipid yield of 1.0 g/L. The long-chain unsaturated fatty acids increased, whereas short-chain saturated fatty acids decreased.

Molecular Identification of Tobacco Leaf Curl Disease in Sichuan Province of China

Virology Journal. Jan, 2016  |  Pubmed ID: 26738931

Tobacco leaf curl disease (TLCD) is caused by begomoviruses in Geminiviridae, and infected plants exhibit leaf thickening, downward leaf curling, vein swelling as well as stunting symptoms. It is one of the economically important diseases in tropical and subtropical tobacco-growing areas. Seven monopartite begomoviruses have been identified causing TLCD in China.

Detection of Coupling in Short Physiological Series by a Joint Distribution Entropy Method

IEEE Transactions on Bio-medical Engineering. Nov, 2016  |  Pubmed ID: 26760967

In this study, we developed a joint distribution entropy (JDistEn) method to robustly estimate the coupling in short physiological series.

Intelligent Condition Diagnosis Method Based on Adaptive Statistic Test Filter and Diagnostic Bayesian Network

Sensors (Basel, Switzerland). Jan, 2016  |  Pubmed ID: 26761006

A new fault diagnosis method for rotating machinery based on adaptive statistic test filter (ASTF) and Diagnostic Bayesian Network (DBN) is presented in this paper. ASTF is proposed to obtain weak fault features under background noise, ASTF is based on statistic hypothesis testing in the frequency domain to evaluate similarity between reference signal (noise signal) and original signal, and remove the component of high similarity. The optimal level of significance α is obtained using particle swarm optimization (PSO). To evaluate the performance of the ASTF, evaluation factor Ipq is also defined. In addition, a simulation experiment is designed to verify the effectiveness and robustness of ASTF. A sensitive evaluation method using principal component analysis (PCA) is proposed to evaluate the sensitiveness of symptom parameters (SPs) for condition diagnosis. By this way, the good SPs that have high sensitiveness for condition diagnosis can be selected. A three-layer DBN is developed to identify condition of rotation machinery based on the Bayesian Belief Network (BBN) theory. Condition diagnosis experiment for rolling element bearings demonstrates the effectiveness of the proposed method.

Hybrid Vesicles with Alterable Fully Covered Armors of Nanoparticles: Fabrication, Catalysis, and Surface-Enhanced Raman Scattering

Langmuir : the ACS Journal of Surfaces and Colloids. Feb, 2016  |  Pubmed ID: 26766236

This work reports on the facile preparation of hybrid polymer vesicles with alterable armors of metal nanoparticles by using a novel hyperbranched polymer vesicle as the templates. The vesicles were prepared through the aqueous self-assembly of a hyperbranched multiarm copolymers with many tertiary amino groups on the surface, which can electrostatically complexed or coordinated with metal ions like AuCl4(-), PtCl6(2-), and Ag(+) ions. Subsequently, the vesicles coated with metal ions can be in situ reduced into metal nanoparticles, through which a series of surface-engineered vesicles (Au@vesicles, Ag@vesicles, Pt@vesicles) with an advantage of fully covered metal nanoparticles on the surface could be readily prepared. The morphologies, structures, and formation mechanism of the as-prepared hybrid vesicles were carefully characterized, and the obtained hybrid vesicles also showed great potentials in catalysis and surface-enhanced Raman scattering (SERS) applications.

Enhancing the Growth Rate and Astaxanthin Yield of Haematococcus Pluvialis by Nuclear Irradiation and High Concentration of Carbon Dioxide Stress

Bioresource Technology. Mar, 2016  |  Pubmed ID: 26773378

Unicellular green microalgae Haematococcus pluvialis was mutated with (60)Co-γ irradiation to promote growth rate and increase astaxanthin yield under high concentration of CO2 stress. The average specific growth rate of H. pluvialis mutated with 4000 Gy γ-ray irradiation was increased by 15% compared with the original strain with air aeration. The mutant grew best with 6% CO2 (the maximum specific growth rate was 0.60/d) when it was cultured with high concentrations of CO2 (2-10%). The peak biomass productivity (0.16 g/L/d) of the mutant cultured with 6% CO2 was 82% higher than that of the mutant with air. The astaxanthin yield and lipid content of the mutant induced with 6% CO2 and high light (108 μmol photons m(-2) s(-1)) increased to 46.0mg/L and 45.9%, which were 2.4 and 1.3 times higher than those of the wild-type strain, respectively.

Hollow Cobalt-Based Bimetallic Sulfide Polyhedra for Efficient All-pH-Value Electrochemical and Photocatalytic Hydrogen Evolution

Journal of the American Chemical Society. Feb, 2016  |  Pubmed ID: 26777119

The development of highly active, universal, and stable inexpensive electrocatalysts/cocatalysts for hydrogen evolution reaction (HER) by morphology and structure modulations remains a great challenge. Herein, a simple self-template strategy was developed to synthesize hollow Co-based bimetallic sulfide (MxCo3-xS4, M = Zn, Ni, and Cu) polyhedra with superior HER activity and stability. Homogenous bimetallic metal-organic frameworks are transformed to hollow bimetallic sulfides by solvothermal sulfidation and thermal annealing. Electrochemical measurements and density functional theory computations show that the combination of hollow structure and homoincorporation of a second metal significantly enhances the HER activity of Co3S4. Specifically, the homogeneous doping in Co3S4 lattice optimizes the Gibbs free energy for H* adsorption and improves the electrical conductivity. Impressively, hollow Zn0.30Co2.70S4 exhibits electrocatalytic HER activity better than most of the reported nobel-metal-free electrocatalysts over a wide pH range, with overpotentials of 80, 90, and 85 mV at 10 mA cm(-2) and 129, 144, and 136 mV at 100 mA cm(-2) in 0.5 M H2SO4, 0.1 M phosphate buffer, and 1 M KOH, respectively. It also exhibits photocatalytic HER activity comparable to that of Pt cocatalyst when working with organic photosensitizer (Eosin Y) or semiconductors (TiO2 and C3N4). Furthermore, this catalyst shows excellent stability in the electrochemical and photocatalytic reactions. The strategy developed here, i.e., homogeneous doping and self-templated hollow structure, provides a way to synthesize transition metal sulfides for catalysis and energy conversion.

Frequency-dependent Changes in Amplitude of Low-frequency Oscillations in Depression: A Resting-state FMRI Study

Neuroscience Letters. Feb, 2016  |  Pubmed ID: 26797652

We conducted this fMRI study to examine whether the alterations in amplitudes of low-frequency oscillation (LFO) of major depressive disorder (MDD) patients were frequency dependent.

Guidelines for the Use and Interpretation of Assays for Monitoring Autophagy (3rd Edition)

Autophagy. Jan, 2016  |  Pubmed ID: 26799652

Multilayer Coating of Tetrandrine-loaded PLGA Nanoparticles: Effect of Surface Charges on Cellular Uptake Rate and Drug Release Profile

Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban. Feb, 2016  |  Pubmed ID: 26838734

The effect of surface charges on the cellular uptake rate and drug release profile of tetrandrine-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (TPNs) was studied. Stabilizer-free nanoprecipitation method was used in this study for the synthesis of TPNs. A typical layer-by-layer approach was applied for multi-coating particles' surface with use of poly(styrene sulfonate) sodium salt (PSS) as anionic layer and poly(allylamine hydrochloride) (PAH) as cationic layer. The modified TPNs were characterized by different physicochemical techniques such as Zeta sizer, scanning electron microscopy and transmission electron microscopy. The drug loading efficiency, release profile and cellular uptake rate were evaluated by high performance liquid chromatography and confocal laser scanning microscopy, respectively. The resultant PSS/PAH/PSS/PAH/TPNs (4 layers) exhibited spherical-shaped morphology with the average size of 160.3±5.165 nm and zeta potential of-57.8 mV. The encapsulation efficiency and drug loading efficiency were 57.88% and 1.73%, respectively. Multi-layer coating of polymeric materials with different charges on particles' surface could dramatically influence the drug release profile of TPNs (4 layers vs. 3 layers). In addition, variable layers of surface coating could also greatly affect the cellular uptake rate of TPNs in A549 cells within 8 h. Overall, by coating particles' surface with those different charged polymers, precise control of drug release as well as cellular uptake rate can be achieved simultaneously. Thus, this approach provides a new strategy for controllable drug delivery.

Can Conclusions Drawn from Phantom-based Image Noise Assessments Be Generalized to in Vivo Studies for the Nonlinear Model-based Iterative Reconstruction Method?

Medical Physics. Feb, 2016  |  Pubmed ID: 26843232

Phantom-based objective image quality assessment methods are widely used in the medical physics community. For a filtered backprojection (FBP) reconstruction-based linear or quasilinear imaging system, the use of this methodology is well justified. Many key image quality metrics acquired with phantom studies can be directly applied to in vivo human subject studies. Recently, a variety of image quality metrics have been investigated for model-based iterative image reconstruction (MBIR) methods and several novel characteristics have been discovered in phantom studies. However, the following question remains unanswered: can certain results obtained from phantom studies be generalized to in vivo animal studies and human subject studies? The purpose of this paper is to address this question.

Differentiation of Pluripotent Stem Cells for Regenerative Medicine

Biochemical and Biophysical Research Communications. Feb, 2016  |  Pubmed ID: 26851367

A long-standing goal in regenerative medicine is to obtain scalable functional cells on demand to replenish cells lost in various conditions, including relevant diseases, injuries, and aging. As an unlimited cell source, pluripotent stem cells (PSCs) are invaluable for regenerative medicine, because they have the potential to give rise to any cell type in an organism. For therapeutic purposes, it is important to develop specific approach to directing PSC differentiation towards desired cell types efficiently. Through directed differentiation, PSCs could give rise to scalable, clinically relevant cells for in vivo transplantation, as well as for studying diseases in vitro and discovering drugs to treat them. Over the past few years, significant progress has been made in directing differentiation of PSCs into a variety of cell types. In this review, we discuss recent progress in directed differentiation of PSCs, clinical translation of PSC-based cell replacement therapies, and remaining challenges.

Mixtures of Two Bile Alcohol Sulfates Function As a Proximity Pheromone in Sea Lamprey

PloS One. 2016  |  Pubmed ID: 26885832

Unique mixtures of pheromone components are commonly identified in insects, and have been shown to increase attractiveness towards conspecifics when reconstructed at the natural ratio released by the signaler. In previous field studies of pheromones that attract female sea lamprey (Petromyzon marinus, L.), putative components of the male-released mating pheromone included the newly described bile alcohol 3,12-diketo-4,6-petromyzonene-24-sulfate (DkPES) and the well characterized 3-keto petromyzonol sulfate (3kPZS). Here, we show chemical evidence that unequivocally confirms the elucidated structure of DkPES, electrophysiological evidence that each component is independently detected by the olfactory epithelium, and behavioral evidence that mature female sea lamprey prefer artificial nests activated with a mixture that reconstructs the male-released component ratio of 30:1 (3kPZS:DkPES, molar:molar). In addition, we characterize search behavior (sinuosity of swim paths) of females approaching ratio treatment sources. These results suggest unique pheromone ratios may underlie reproductive isolating mechanisms in vertebrates, as well as provide utility in pheromone-integrated control of invasive sea lamprey in the Great Lakes.

Overcoming Chemo/radio-resistance of Pancreatic Cancer by Inhibiting STAT3 Signaling

Oncotarget. Mar, 2016  |  Pubmed ID: 26887043

Chemo/radio-therapy resistance to the deadly pancreatic cancer is mainly due to the failure to kill pancreatic cancer stem cells (CSCs). Signal transducer and activator of transcription 3 (STAT3) is activated in pancreatic CSCs and, therefore, may be a valid target for overcoming therapeutic resistance. Here we investigated the potential of STAT3 inhibition in sensitizing pancreatic cancer to chemo/radio-therapy. We found that the levels of nuclear pSTAT3 in pancreatic cancer correlated with advanced tumor grade and poor patient outcome. Liposomal delivery of a STAT3 inhibitor FLLL32 (Lip-FLLL32) inhibited STAT3 phosphorylation and STAT3 target genes in pancreatic cancer cells and tumors. Consequently, Lip-FLLL32 suppressed pancreatic cancer cell growth, and exhibited synergetic effects with gemcitabine and radiation treatment in vitro and in vivo. Furthermore, Lip-FLLL32 reduced ALDH1-positive CSC population and modulated several potential stem cell markers. These results demonstrate that Lip-FLLL32 suppresses pancreatic tumor growth and sensitizes pancreatic cancer cells to radiotherapy through inhibition of CSCs in a STAT3-dependent manner. By targeting pancreatic CSCs, Lip-FLLL32 provides a novel strategy for pancreatic cancer therapy via overcoming radioresistance.

Effects of Mechanical Stresses on Sperm Function and Fertilization Rate in Mice

Systems Biology in Reproductive Medicine. 2016  |  Pubmed ID: 26889695

In this study, we investigated whether any of the observed changes in mouse sperm function tests secondary to mechanical stresses (centrifugation and pipetting) correlate with sperm fertilization ability. Chinese Kunming mice were used as sperm and oocyte donors. Sperm samples were allocated evenly into centrifugation, pipette, and control groups. Sperm plasma membrane integrity (PMI), mitochondrial membrane permeability (MMP), baseline and stimulated intracellular ROS, and sperm fertilization ability were measured by hypo-osmotic swelling, flow cytometry, and fertilization tests. Parallel studies were conducted and all tests were repeated six times. Our results showed that after centrifugation, the progressive motility, average path velocity, and overall sperm motility and PMI decreased significantly (p < 0.05). In addition, the MMP level decreased significantly in viable sperm when the centrifugation condition reached 1,400 g × 15 minutes (p < 0.05). When pipetting was performed two or more times, progressive motility, average path velocity, and overall sperm motility decreased significantly (p < 0.05); when it was performed four or more times, sperm membrane integrity and intracellular basal ROS level of viable sperm was also significantly decreased (p < 0.05). In conclusion, various mechanical stresses seem to affect sperm function, however this does not appear to alter fertilization rate. Laboratory handling steps should be minimized to avoid unnecessary mechanical stresses being applied to sperm samples.

Overexpression of Cdc20 in Clinically Localized Prostate Cancer: Relation to High Gleason Score and Biochemical Recurrence After Laparoscopic Radical Prostatectomy

Cancer Biomarkers : Section A of Disease Markers. 2016  |  Pubmed ID: 26889981

This study was aimed to explore Cdc20 expression and its correlation with clinicopathological characteristics and biochemical recurrence (BCR) after laparoscopic radical prostatectomy (LRP) in clinically localized prostate cancer (PCa).

Platinum-zoledronate Complex Blocks Gastric Cancer Cell Proliferation by Inducing Cell Cycle Arrest and Apoptosis

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine. Aug, 2016  |  Pubmed ID: 26891667

A series of novel dinuclear platinum complexes based on the bisphosphonate ligands have been synthesized and characterized in our recent study. For the purpose of discovering the pharmacology and action mechanisms of this kind of compounds, the most potent compound [Pt(en)]2ZL was selected for systematic investigation. In the present study, the inhibition effect on the human gastric cancer cell lines SGC7901 and action mechanism of [Pt(en)]2ZL were investigated. The traditional 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2-tetrazolium bromide (MTT) assay and colony formation assay were carried out to study the effect of [Pt(en)]2ZL on the cell viability and proliferation capacity, respectively. The senescence-associated β-galactosidase staining and immunofluorescence staining were also performed to assess the cell senescence and microtubule polymerization. Fluorescence staining and flow cytometry (FCM) were used to monitor the cell cycle distribution and apoptosis, and Western blot analysis was applied to examine the expression of several apoptosis-related proteins. The results demonstrated that [Pt(en)]2ZL exhibited remarkable cytotoxicity and anti-proliferative effects on the SGC7901 cells in a dose- and time-dependent manner, and it also induced cell senescence and abnormal microtubule assembly. The cell apoptosis and cell cycle arrest induced by [Pt(en)]2ZL were also observed with the fluorescence staining and FCM. The expressions of cell cycle regulators (p53, p21, cyclin D1, cyclin E, and cyclin-dependent kinase (CDK)2) and apoptosis-related proteins (Bcl-2, Bax, caspase-3, poly ADP ribose polymerase (PARP), and survivin) were regulated by the treatment of [Pt(en)]2ZL, resulting in the cell cycle arrest and apoptosis. Therefore, [Pt(en)]2ZL exerted anti-tumor effect on the gastric cancer via inducing cell cycle arrest at G1/S phase and apoptosis.

Efficacy and Safety of Chronomodulated Chemotherapy for Patients with Metastatic Colorectal Cancer: a Systematic Review and Meta-analysis

Asia-Pacific Journal of Clinical Oncology. Feb, 2016  |  Pubmed ID: 26892158

Chronomodulated chemotherapy has been reported to be superior to conventional chemotherapy, but the results from randomized controlled trials (RCTs) are inconsistent. We performed a meta-analysis to summarize the efficacy and safety of chronomodulated chemotherapy for patients with metastatic colorectal cancer.

A Room Temperature Approach for the Fabrication of Aligned TiO₂ Nanotube Arrays on Transparent Conductive Substrates

Chemical Communications (Cambridge, England). Mar, 2016  |  Pubmed ID: 26892268

A novel solution approach is reported for the fabrication of TiO₂ nanotube arrays on transparent conductive substrates via in situ conversion from nanowires. The as-prepared nanotube arrays not only demonstrate a larger surface area in comparison with the primary NWs, but also longer charge carrier lifetime than that of randomly packed nanoparticle films.

The REGγ-proteasome Forms a Regulatory Circuit with IκBɛ and NFκB in Experimental Colitis

Nature Communications. Feb, 2016  |  Pubmed ID: 26899380

Increasing incidence of inflammatory bowel disorders demands a better understanding of the molecular mechanisms underlying its multifactorial aetiology. Here we demonstrate that mice deficient for REGγ, a proteasome activator, show significantly attenuated intestinal inflammation and colitis-associated cancer in dextran sodium sulfate model. Bone marrow transplantation experiments suggest that REGγ's function in non-haematopoietic cells primarily contributes to the phenotype. Elevated expression of REGγ exacerbates local inflammation and promotes a reciprocal regulatory loop with NFκB involving ubiquitin-independent degradation of IκBɛ. Additional deletion of IκBɛ restored colitis phenotypes and inflammatory gene expression in REGγ-deficient mice. In sum, this study identifies REGγ-mediated control of IκBɛ as a molecular mechanism that contributes to NFκB activation and promotes bowel inflammation and associated tumour formation in response to chronic injury.

Effects of Chestnut Tannins on the Meat Quality, Welfare, and Antioxidant Status of Heat-stressed Lambs

Meat Science. Jun, 2016  |  Pubmed ID: 26914512

A study was conducted to evaluate the effects of chestnut tannins (CT) on the meat quality, welfare and antioxidant status of heat-stressed lambs. Lambs in one group were raised at 20°C and fed a basal diet (N), and three other groups (32°C) were fed a basal diet with 0 (CT0), 5 (CT5), and 10 g (CT10) of CT/kg. Addition of CT increased the b* and L* values of meat and superoxide dismutase and glutathione peroxidase activity in the serum and liver of heat-stressed lambs. The malondialdehyde concentration in meat, serum, and liver of heat-stressed lambs was decreased by dietary CT supplementation. Lambs in the CT0 group had higher cortisol, T3, and T4 levels, creatine kinase activity, white blood cell count, neutrophil count, neutrophil:lymphocyte ratio and a lower lymphocyte count than that in the N and CT10 groups. In conclusion, the addition of CT improved meat quality, certain stress parameters, and the antioxidant status of heat-stressed lambs.

Preparation and Biological Evaluation of Two Novel Platinum(II) Complexes Based on the Ligands of Dipicolyamine Bisphosphonate Esters

Molecules (Basel, Switzerland). Feb, 2016  |  Pubmed ID: 26927037

Two new platinum(II)-based complexes bearing a bone-targeting group were synthesized and characterized. They both have excellent affinity for hydroxyapatite (HA), which is abundant in human bone tissues. Their antitumor activities against five human cancer cell lines (U2OS, A549, HCT116, MDA-MB-231 and HepG2) were evaluated and compared with cisplatin (CDDP). Though the antitumor efficacies of new complexes are lower than that of CDDP, they show higher selectivity against the HepG2 hepatoma cell line than the L02 normal liver cell line. Morphology studies exhibited typical characteristics of cell apoptosis and the cell cycle distribution analysis indicated that the complexes can inhibit cancer cells by inducing cell cycle arrest at the G2/M phase, a similar mechanism of action to CDDP.

Mucin 1 and Poly I:C Activates Dendritic Cells and Effectively Eradicates Pituitary Tumors As a Prophylactic Vaccine

Molecular Medicine Reports. Apr, 2016  |  Pubmed ID: 26935338

Pituitary tumors are the most common type of cancer within the central nervous system. In the present study, the expression levels of mucin 1 (Muc1) were examined in invasive and non‑invasive pituitary tumor samples, and the results of immunohistochemical staining and Western blot analysis demonstrated marked positive expression of Muc1. In addition, Muc1 + polyinosinic:polycytidylic acid (poly I:C) was found to stimulate the expression levels of the surface molecules cluster of differentiation (CD)40, CD83 and CD80, and HLA‑DRm and decreased the expression of CD14 in the dendritic cells, determined using fluorescence‑activated cell sorting. The secretions of interleukin (IL)‑6, tumor necrosis factor‑α and IL‑1β cytokines were also significantly induced, in a dose‑dependent manner. In in vivo experiments, a higher percentage of CD3+CD4+ T lymphocytes was detected, and the levels of interferon‑γ and IL‑2 in the splenocytes were also upregulated. Furthermore, the combination treatment of Muc1 with poly I:C increased anti‑Muc1 IgM and anti‑Muc1 IgG titers, and altered the balance of IgG2a and IgG1, all of which increased the T helper (Th)1 polarized immune response. Thus, the tumor antigen, Muc1, with poly I:C may produce potent protective effects, which polarize immune responses towards Th1, and elicit antitumor immunity to inhibit the progression of pituitary tumors.

Expandable Cardiovascular Progenitor Cells Reprogrammed from Fibroblasts

Cell Stem Cell. Mar, 2016  |  Pubmed ID: 26942852

Stem cell-based approaches to cardiac regeneration are increasingly viable strategies for treating heart failure. Generating abundant and functional autologous cells for transplantation in such a setting, however, remains a significant challenge. Here, we isolated a cell population with extensive proliferation capacity and restricted cardiovascular differentiation potentials during cardiac transdifferentiation of mouse fibroblasts. These induced expandable cardiovascular progenitor cells (ieCPCs) proliferated extensively for more than 18 passages in chemically defined conditions, with 10(5) starting fibroblasts robustly producing 10(16) ieCPCs. ieCPCs expressed cardiac signature genes and readily differentiated into functional cardiomyocytes (CMs), endothelial cells (ECs), and smooth muscle cells (SMCs) in vitro, even after long-term expansion. When transplanted into mouse hearts following myocardial infarction, ieCPCs spontaneously differentiated into CMs, ECs, and SMCs and improved cardiac function for up to 12 weeks after transplantation. Thus, ieCPCs are a powerful system to study cardiovascular specification and provide strategies for regenerative medicine in the heart.

Sequential Co-delivery of MiR-21 Inhibitor Followed by Burst Release Doxorubicin Using NIR-responsive Hollow Gold Nanoparticle to Enhance Anticancer Efficacy

Journal of Controlled Release : Official Journal of the Controlled Release Society. Apr, 2016  |  Pubmed ID: 26956593

Previous literature and our study showed the delivery sequence of microRNA inhibitor and chemotherapeutic compounds achieve distinct therapeutic anticancer efficacy. Yet, it is challenging to use nanoparticle to achieve sequential drug delivery. In the current study, we designed sequential co-delivery system using a near-infrared-radiation (NIR) responsive hollow gold nanoparticle (HGNPs) to achieve sequential release of microRNA inhibitor (miR-21i)/doxirubicin(Dox) in order to achieve synergistic efficacy. PAMAM modified HGNPs was used to encapsulate miR-21i and Dox. Upon entering tumor cells, miRNA-21i was released first to sensitize the cancer cells, the subsequent burst release of Dox was achieved by NIR triggered collapse of HGNPs. This sequential delivery of miRNA-21i and Dox produced a synergistic apoptotic response, thereby enhancing anticancer efficacy by 8-fold and increasing anti-cancer stem cell activity by 50-fold. The sequential delivery of miR-21i and Dox using HGNPs under NIR after intravenous administration showed high tumor accumulation and significantly improved efficacy, which was 4-fold compared to free Dox group. These data suggested that the sequential co-delivery of miR-21i followed by burst release Dox using NIR-responsive HGNPs sensitized cancer cells to chemotherapeutic compound, which provided a novel concept for co-delivery miRNA inhibitors and chemotherapeutic compounds to enhance their efficacy.

Synthesis of Chiral 1,4-Benzodioxanes and Chromans by Enantioselective Palladium-Catalyzed Alkene Aryloxyarylation Reactions

Angewandte Chemie (International Ed. in English). Apr, 2016  |  Pubmed ID: 26990370

A highly enantioselective alkene aryloxyarylation led to the high-yielding formation of a series of 1,4-benzodioxanes, 1,4-benzooxazines, and chromans containing quaternary stereocenters with excellent enantioselectivity. The sterically bulky and conformationally well defined chiral monophosphorus ligand L4 or L5 was responsible for the high reactivity and enantioselectivity of these transformations. The application of this method to the synthesis of the chiral chroman backbone of α-tocopherol was demonstrated.

Application of Liquid Chromatography-tandem Mass Spectrometry in Quantitative Bioanalyses of Organic Molecules in Aquatic Environment and Organisms

Environmental Science and Pollution Research International. May, 2016  |  Pubmed ID: 26996906

Analytical methods using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for the simultaneous determination of metabolites or contaminants (or both) in various tissues of aquatic organisms and in the aquatic environment have received increasing attention in the last few years. This review discusses the findings relevant to such procedures published between 2005 and 2015. The aim is to evaluate the advantages, restrictions, and performances of the procedures from sample preparation to mass spectrometry measurement. To support these discussions, a general knowledge on LC-MS/MS is also provided.

The Real Role of Pseudokinase: Linking Diabetes to Cancers

Cancer Medicine. Jul, 2016  |  Pubmed ID: 27038142

A recent paper in Nature Communications shows that pseudokinase TRIB3 has a critical role in the development of diabetes-related cancers via interacting with SQSTM1, a selective autophagy receptor. Interrupting the TRIB3-SQSTM1 interaction using an α-helix peptide shows a significant antitumor effect both in normal and diabetic mice. This work provides a potential strategy against cancers in patients with diabetes.

A High-yield Synthesis of [m]biphenyl-extended Pillar[n]arenes for an Efficient Selective Inclusion of Toluene and M-xylene in the Solid State

Chemical Communications (Cambridge, England). Apr, 2016  |  Pubmed ID: 27045359

[m]Bp-ExPn with a rigid and nanometer-sized cavity, as an extended version of pillar[n]arene by replacing 1,4-dimethoxybenzene monomers with biphenyl entities, was synthesized for the first time. Intriguingly, toluene and m-xylene can be stably included within the cavity of [2]Bp-ExP6, which endows these newly developed synthetic receptors with great potential in the purification of petrochemicals.

Analysis of Tumor-infiltrating Gamma Delta T Cells in Rectal Cancer

World Journal of Gastroenterology. Apr, 2016  |  Pubmed ID: 27053849

To investigate the regulatory effect of Vδ1 T cells and the antitumor activity of Vδ2 T cells in rectal cancer.

A Simultaneous Beta and Coincidence-gamma Imaging System for Plant Leaves

Physics in Medicine and Biology. May, 2016  |  Pubmed ID: 27065022

Positron emitting isotopes, such as (11)C, (13)N, and (18)F, can be used to label molecules. The tracers, such as (11)CO2, are delivered to plants to study their biological processes, particularly metabolism and photosynthesis, which may contribute to the development of plants that have a higher yield of crops and biomass. Measurements and resulting images from PET scanners are not quantitative in young plant structures or in plant leaves due to poor positron annihilation in thin objects. To address this problem we have designed, assembled, modeled, and tested a nuclear imaging system (simultaneous beta-gamma imager). The imager can simultaneously detect positrons ([Formula: see text]) and coincidence-gamma rays (γ). The imaging system employs two planar detectors; one is a regular gamma detector which has a LYSO crystal array, and the other is a phoswich detector which has an additional BC-404 plastic scintillator for beta detection. A forward model for positrons is proposed along with a joint image reconstruction formulation to utilize the beta and coincidence-gamma measurements for estimating radioactivity distribution in plant leaves. The joint reconstruction algorithm first reconstructs beta and gamma images independently to estimate the thickness component of the beta forward model and afterward jointly estimates the radioactivity distribution in the object. We have validated the physics model and reconstruction framework through a phantom imaging study and imaging a tomato leaf that has absorbed (11)CO2. The results demonstrate that the simultaneously acquired beta and coincidence-gamma data, combined with our proposed joint reconstruction algorithm, improved the quantitative accuracy of estimating radioactivity distribution in thin objects such as leaves. We used the structural similarity (SSIM) index for comparing the leaf images from the simultaneous beta-gamma imager with the ground truth image. The jointly reconstructed images yield SSIM indices of 0.69 and 0.63, whereas the separately reconstructed beta alone and gamma alone images had indices of 0.33 and 0.52, respectively.

Fast and Simplified Mapping of Mean Axon Diameter Using Temporal Diffusion Spectroscopy

NMR in Biomedicine. Apr, 2016  |  Pubmed ID: 27077155

Mapping axon diameter is of interest for the potential diagnosis and monitoring of various neuronal pathologies. Advanced diffusion-weighted MRI methods have been developed to measure mean axon diameters non-invasively, but suffer major drawbacks that prevent their direct translation into clinical practice, such as complex non-linear data fitting and, more importantly, long scanning times that are usually not tolerable for most human subjects. In the current study, temporal diffusion spectroscopy using oscillating diffusion gradients was used to measure mean axon diameters with high sensitivity to small axons in the central nervous system. Axon diameters have been found to be correlated with a novel metric, DDR⊥ (the rate of dispersion of the perpendicular diffusion coefficient with gradient frequency), which is a model-free quantity that does not require complex data analyses and can be obtained from two diffusion coefficient measurements in clinically relevant times with conventional MRI machines. A comprehensive investigation including computer simulations and animal experiments ex vivo showed that measurements of DDR⊥ agree closely with histological data. In humans in vivo, DDR⊥ was also found to correlate well with reported mean axon diameters in human corpus callosum, and the total scan time was only about 8 min. In conclusion, DDR⊥ may have potential to serve as a fast, simple and model-free approach to map the mean axon diameter of white matter in clinics for assessing axon diameter changes.

Collectin-11 Detects Stress-induced L-fucose Pattern to Trigger Renal Epithelial Injury

The Journal of Clinical Investigation. May, 2016  |  Pubmed ID: 27088797

Physiochemical stress induces tissue injury as a result of the detection of abnormal molecular patterns by sensory molecules of the innate immune system. Here, we have described how the recently discovered C-type lectin collectin-11 (CL-11, also known as CL-K1 and encoded by COLEC11) recognizes an abnormal pattern of L-fucose on postischemic renal tubule cells and activates a destructive inflammatory response. We found that intrarenal expression of CL-11 rapidly increases in the postischemic period and colocalizes with complement deposited along the basolateral surface of the proximal renal tubule in association with L-fucose, the potential binding ligand for CL-11. Mice with either generalized or kidney-specific deficiency of CL-11 were strongly protected against loss of renal function and tubule injury due to reduced complement deposition. Ex vivo renal tubule cells showed a marked capacity for CL-11 binding that was induced by cell stress under hypoxic or hypothermic conditions and prevented by specific removal of L-fucose. Further analysis revealed that cell-bound CL-11 required the lectin complement pathway-associated protease MASP-2 to trigger complement deposition. Given these results, we conclude that lectin complement pathway activation triggered by ligand-CL-11 interaction in postischemic tissue is a potent source of acute kidney injury and is amenable to sugar-specific blockade.

DNA Photocleavage by Non-innocent Ligand-Based Ru(II) Complexes

Inorganic Chemistry. May, 2016  |  Pubmed ID: 27101335

In this work, we demonstrate for the first time that [Ru(bpy)2(R-OQN)](+) complexes (bpy = 2,2'-bipyridine, R-OQN = 5-chloro-8-oxyquinolate or 5-bromo-8-oxyquinolate) are able to generate hydroxyl radicals and cleave DNA effectively upon visible light irradiation. The potent electron-donating ability of the R-OQN-based non-innocent ligands gives the complexes a high reducing capability, favoring the generation of superoxide anion radicals from which hydroxyl radicals may be generated. More interestingly, halogen substitution plays an important role. When the 5-Cl- or 5-Br-8-oxyquinolate ligand is replaced by 8-oxyquinolate or 5-CH3-8-oxyquinolate, the corresponding complexes lose their hydroxyl radical-generation and DNA photocleavage abilities. These findings open new applications for the non-innocent ligand-based Ru(II) complexes in the fields of biology and medicine, such as in photodynamic therapy (PDT).

Pharmacological Reprogramming of Fibroblasts into Neural Stem Cells by Signaling-Directed Transcriptional Activation

Cell Stem Cell. May, 2016  |  Pubmed ID: 27133794

Cellular reprogramming using chemically defined conditions, without genetic manipulation, is a promising approach for generating clinically relevant cell types for regenerative medicine and drug discovery. However, small-molecule approaches for inducing lineage-specific stem cells from somatic cells across lineage boundaries have been challenging. Here, we report highly efficient reprogramming of mouse fibroblasts into induced neural stem cell-like cells (ciNSLCs) using a cocktail of nine components (M9). The resulting ciNSLCs closely resemble primary neural stem cells molecularly and functionally. Transcriptome analysis revealed that M9 induces a gradual and specific conversion of fibroblasts toward a neural fate. During reprogramming specific transcription factors such as Elk1 and Gli2 that are downstream of M9-induced signaling pathways bind and activate endogenous master neural genes to specify neural identity. Our study provides an effective chemical approach for generating neural stem cells from mouse fibroblasts and reveals mechanistic insights into underlying reprogramming processes.

Optimizing Gas Transfer to Improve Growth Rate of Haematococcus Pluvialis in a Raceway Pond with Chute and Oscillating Baffles

Bioresource Technology. Aug, 2016  |  Pubmed ID: 27140817

Up-down chute and oscillating (UCO) baffles were used to generate vortex and oscillating flow field to improve growth rate of Haematococcus pluvialis in a raceway pond. Effects of gas flow rate, solution velocity, and solution depth on solution mass transfer coefficient and mixing time were evaluated using online pH and dissolved oxygen probes. Mass transfer coefficient increased by 1.3 times and mixing time decreased by 33% when UCO baffles were used in the H. pluvialis solution, resulting in an 18% increase in biomass yield with 2% CO2. The H. pluvialis biomass yield further increased to 1.5g/L, and astaxanthin composition accumulated to 29.7mg/L under relatively higher light intensity and salinity.

Hi-Res Scan Mode in Clinical MDCT Systems: Experimental Assessment of Spatial Resolution Performance

Medical Physics. May, 2016  |  Pubmed ID: 27147351

The introduction of a High-Resolution (Hi-Res) scan mode and another associated option that combines Hi-Res mode with the so-called High Definition (HD) reconstruction kernels (referred to as a Hi-Res/HD mode in this paper) in some multi-detector CT (MDCT) systems offers new opportunities to increase spatial resolution for some clinical applications that demand high spatial resolution. The purpose of this work was to quantify the in-plane spatial resolution along both the radial direction and tangential direction for the Hi-Res and Hi-Res/HD scan modes at different off-center positions.

Protein-Framed Multi-Porphyrin Micelles for a Hybrid Natural-Artificial Light-Harvesting Nanosystem

Angewandte Chemie (International Ed. in English). Jul, 2016  |  Pubmed ID: 27187799

A micelle-like hybrid natural-artificial light-harvesting nanosystem was prepared through protein-framed electrostatic self-assembly of phycocyanin and a four-armed porphyrin star polymer. The nanosystem has a special structure of pomegranate-like unimolecular micelle aggregate with one phycocyanin acceptor in the center and multiple porphyrin donors in the shell. It can inhibit donor self-quenching effectively and display efficient transfer of excitation energy (about 80.1 %) in water. Furthermore, the number of donors contributing to a single acceptor could reach as high as about 179 in this nanosystem.

Structure of Human GIVD Cytosolic Phospholipase A2 Reveals Insights into Substrate Recognition

Journal of Molecular Biology. Jul, 2016  |  Pubmed ID: 27220631

Cytosolic phospholipases A2 (cPLA2s) consist of a family of calcium-sensitive enzymes that function to generate lipid second messengers through hydrolysis of membrane-associated glycerophospholipids. The GIVD cPLA2 (cPLA2δ) is a potential drug target for developing a selective therapeutic agent for the treatment of psoriasis. Here, we present two X-ray structures of human cPLA2δ, capturing an apo state, and in complex with a substrate-like inhibitor. Comparison of the apo and inhibitor-bound structures reveals conformational changes in a flexible cap that allows the substrate to access the relatively buried active site, providing new insight into the mechanism for substrate recognition. The cPLA2δ structure reveals an unexpected second C2 domain that was previously unrecognized from sequence alignments, placing cPLA2δ into the class of membrane-associated proteins that contain a tandem pair of C2 domains. Furthermore, our structures elucidate novel inter-domain interactions and define three potential calcium-binding sites that are likely important for regulation and activation of enzymatic activity. These findings provide novel insights into the molecular mechanisms governing cPLA2's function in signal transduction.

NAMPT Knockdown Attenuates Atherosclerosis and Promotes Reverse Cholesterol Transport in ApoE KO Mice with High-fat-induced Insulin Resistance

Scientific Reports. May, 2016  |  Pubmed ID: 27229177

NAMPT has been suggested association with atherosclerosis and insulin resistance. However, the impact of NAMPT on atherosclerosis remained unknown. Therefore, the objective of this study was to use a NAMPT loss-of-function approach to investigate the effect of NAMPT on atherosclerosis in hypercholesterolemic mice. We demonstrated that a specific NAMPT knockdown increased plasma HDL-C levels, reduced the plaque area of the total aorta en face and the cross-sectional aortic sinus, decreased macrophage number and apoptosis, and promoted RCT in HFD-fed ApoE KO mice. These changes were accompanied by increased PPARα, LXRα, ABCA1 and ABCG1 expressions in the liver. NAMPT knockdown also facilitated cholesterol efflux in RAW264.7 cells. We further investigated the effect of NAMPT knockdown on the PPARα-LXRα pathway of cholesterol metabolism with MK886 (a selective inhibitor of PPARα) in RAW264.7 macrophages. MK886 abolished the ability of NAMPT knockdown to decrease intracellular cholesterol levels to enhance the rate of (3)H-cholesterol efflux and to increase ABCA1/G1 and LXRα expressions in RAW264.7 macrophages. Our observations demonstrate that NAMPT knockdown exerted antiatherogenic effects by promoting cholesterol efflux and macrophage RCT through the PPARα- LXRα- ABCA1/G1pathway in vitro and in vivo.

Gradient Domestication of Haematococcus Pluvialis Mutant with 15% CO2 to Promote Biomass Growth and Astaxanthin Yield

Bioresource Technology. Sep, 2016  |  Pubmed ID: 27259189

In order to increase biomass yield and reduce culture cost of Haematococcus pluvialis with flue gas from coal-fired power plants, a screened mutant by nuclear irradiation was gradually domesticated with 15% CO2 to promote biomass dry weight and astaxanthin yield. The biomass yield of mutant after 10 generations of 15% CO2 domestication increased to 1.3 times as that with air. With the optimization of nitrogen and phosphorus concentration, the biomass dry weight was further increased by 62%. The astaxanthin yield induced with 15% CO2 and high light of 135 μmol photons m(-2) s(-1) increased to 87.4mg/L, which was 6 times higher than that induced with high light in air.

Study of Single Nucleotide Polymorphisms of FBW7 and Its Substrate Genes Revealed a Predictive Factor for Paclitaxel Plus Cisplatin Chemotherapy in Chinese Patients with Advanced Esophageal Squamous Cell Carcinoma

Oncotarget. Jul, 2016  |  Pubmed ID: 27259248

Paclitaxel plays a major role in the treatment of advanced esophageal squamous cell carcinoma. However, there is no biomarker that could be used to predict the clinical response of paclitaxel. This work was conducted to investigate the association of genetic polymorphisms in FBW7 and its substrate genes and the clinical response of paclitaxel. Patients with advanced esophageal squamous cell carcinoma were treated with paclitaxel 175 mg/m2 over 3 hours day 1 and cisplatin 75 mg/m2 day 1, every 3 weeks. The genotypes of 11 FBW7 and its substrate gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Statistical analysis revealed that patients with mTOR rs1057079 AG (ORadjusted: 4.59; 95% CI: 1.78-11.86) genotype had significant correlation with the clinical response of paclitaxel when compared with AA genotype after adjustment for sex, age, and chemotherapy cycle. The median progression-free survival (PFS) of patients with advanced ESCC who received paclitaxel plus cisplatin (TP) as first-line treatment is 14.3 months (95% CI: 9.0-19.60 months). The median PFS (mPFS) of AG genotypes and AA genotypes in mTOR rs1057079 were 17.31 months (95% CI: 15.9-18.67 months) and 9.8 months (95% CI: 8.58-11.02 months) (p=0.019), respectively.

Heating and Compression Bandage Treatment Is Effective for Chronic Lymphedema with Dermatolymphangioadenitis-A Case-Controlled Study

Lymphatic Research and Biology. Jun, 2016  |  Pubmed ID: 27267348

To investigate the therapeutic effect of far infrared rays and compression bandaging in the treatment of chronic lymphedema with dermatolymphangioadenitis (DLA).

Phenotypic and Signaling Consequences of a Novel Aberrantly Spliced Transcript FGF Receptor-3 in Hepatocellular Carcinoma

Cancer Research. Jul, 2016  |  Pubmed ID: 27267910

Fibroblast growth factor receptor 3 (FGFR3) plays important roles in cell proliferation, differentiation, and angiogenesis. FGFR3 is abnormally upregulated in hepatocellular carcinoma (HCC), where it correlates positively with clinicopathologic index, HCC differentiation, and advanced nuclear grade. In this study, we describe an aberrantly spliced transcript of FGFR3, termed FGFR3Δ7-9, was identified as a high frequency even in HCC. FGFR3Δ7-9 lacks exons encoding the immunoglobulin-like III domain and promoted the proliferation, migration, and metastasis of HCC cells both in vitro and in vivo Coimmunoprecipation and surface plasmon resonance assays demonstrated that the binding affinity of the aberrant FGFR3Δ7-9 receptor to FGFs was significantly higher than wild-type FGFR3IIIc Furthermore, FGFR3Δ7-9 could be self-activated by homodimerization and autophosphorylation even in the absence of ligand. Finally, FGFR3Δ7-9 more potently induced phosphorylation of the ERK and AKT kinases, leading to abnormal downstream signaling through the ERK and PI3K/AKT/mTOR pathways. FGFR3Δ7-9 also upregulated the metastasis-associated molecules Snail, MMP-9, and downregulated E-cadherin, which associated directly with FGFR3Δ7-9 Thus, as a ligand-dependent or -independent receptor, FGFR3Δ7-9 exerted multiple potent oncogenic functions in HCC cells, including proliferation, migration, and lung metastatic capacity. Overall, FGFR3 mRNA missplicing in HCC contributes significantly to its malignant character, with implications for therapeutic targeting. Cancer Res; 76(14); 4205-15. ©2016 AACR.

A Low-Cost and Fast Real-Time PCR System Based on Capillary Convection

Journal of Laboratory Automation. Jun, 2016  |  Pubmed ID: 27272156

A low-cost and fast real-time PCR system in a pseudo-isothermal manner with disposable capillary tubes based on thermal convection for point-of-care diagnostics is developed and tested. Once stable temperature gradient along the capillary tube has been established, a continuous circulatory flow or thermal convection inside the capillary tube will repeatedly transport PCR reagents through temperature zones associated with the DNA denaturing, annealing, and extension stages of the reaction. To establish stable temperature gradient along the capillary tube, a dual-temperature heating strategy with top and bottom heaters is adopted here. A thermal waveguide is adopted for precise maintenance of the temperature of the top heater. An optimized optical network is developed for monitoring up to eight amplification units for real-time fluorescence detection. The system performance was demonstrated with repeatable detection of influenza A (H1N1) virus nucleic acid targets with a limit of detection of 1.0 TCID50/mL within 30 min.

Risk Factors for Acute Kidney Injury After Cardiovascular Surgery: Evidence from 2,157 Cases and 49,777 Controls - A Meta-Analysis

Cardiorenal Medicine. May, 2016  |  Pubmed ID: 27275160

Cardiovascular surgery-associated acute kidney injury (AKI-CS) contributes to mortality and morbidity. However, risk factors accelerating its development are unclear. We identified risk factors for AKI-CS in patients with cardiopulmonary bypass in the hospital surgical intensive care unit to predict and minimize renal complication in future cardiac surgery.

Adaptive and Acquired Resistance to EGFR Inhibitors Converge on the MAPK Pathway

Theranostics. 2016  |  Pubmed ID: 27279914

Both adaptive and acquired resistance significantly limits the efficacy of the epidermal growth factor receptor (EGFR) kinase inhibitors. However, the distinct or common mechanisms of adaptive and acquired resistance have not been fully characterized. Here, through systematic modeling of erlotinib resistance in lung cancer, we found that feedback reactivation of MAPK signaling following erlotinib treatment, which was dependent on the MET receptor, contributed to the adaptive resistance of EGFR inhibitors. Interestingly, acquired resistance to erlotinib was also associated with the MAPK pathway activation as a result of CRAF or NRAS amplification. Consequently, combined inhibition of EGFR and MAPK impeded the development of both adaptive and acquired resistance. These observations demonstrate that adaptive and acquired resistance to EGFR inhibitors can converge on the same pathway and credential cotargeting EGFR and MAPK as a promising therapeutic approach in EGFR mutant tumors.

A Phase I Study of Safety and Pharmacokinetics of Fruquintinib, a Novel Selective Inhibitor of Vascular Endothelial Growth Factor Receptor-1, -2, and -3 Tyrosine Kinases in Chinese Patients with Advanced Solid Tumors

Cancer Chemotherapy and Pharmacology. Aug, 2016  |  Pubmed ID: 27299749

Fruquintinib (HMPL-013) is a novel oral small molecule compound that selectively inhibits vascular endothelial growth factor receptors-1, -2, and -3 with potent inhibitory effects on multiple human tumor xenografts. This first-in-human study was conducted to assess the maximum tolerated dose and dose-limiting toxicities, safety and tolerability, pharmacokinetics, and preliminary anti-tumor activity of fruquintinib.

Corticothalamic Network Dysfunction and Behavioral Deficits in a Mouse Model of Alzheimer's Disease

Neurobiology of Aging. Aug, 2016  |  Pubmed ID: 27318137

Alzheimer's disease is associated with cognitive decline and seizures. Growing evidence indicates that seizures contribute to cognitive deficits early in disease, but how they develop and impact cognition are unclear. To investigate potential mechanisms, we studied a mouse model that overexpresses mutant human amyloid precursor protein with high levels of amyloid beta (Aβ). These mice develop generalized epileptiform activity, including nonconvulsive seizures, consistent with alterations in corticothalamic network activity. Amyloid precursor protein mice exhibited reduced activity marker expression in the reticular thalamic nucleus, a key inhibitory regulatory nucleus, and increased activity marker expression in downstream thalamic relay targets that project to cortex and limbic structures. Slice recordings revealed impaired cortical inputs to the reticular thalamic nucleus that may contribute to corticothalamic dysfunction. These results are consistent with our findings of impaired sleep maintenance in amyloid precursor protein mice. Finally, the severity of sleep impairments predicted the severity of deficits in Morris water maze, suggesting corticothalamic dysfunction may relate to hippocampal dysfunction, and may be a pathophysiological mechanism underlying multiple behavioral and cognitive alterations in Alzheimer's disease.

Reversible Immortalization Enables Seamless Transdifferentiation of Primary Fibroblasts into Other Lineage Cells

Stem Cells and Development. Aug, 2016  |  Pubmed ID: 27328768

Fibroblasts can be transdifferentiated directly into other somatic cells such as cardiomyocytes, hematopoietic cells, and neurons. An advantage of somatic cell differentiation without first generating induced pluripotent stem cells (iPSCs) is that it avoids contamination of the differentiated cells with residual iPSCs, which may cause teratoma. However, since primary fibroblasts from biopsy undergo senescence during repeated culture, it may be difficult to grow transdifferentiated cells in sufficient numbers for future therapeutic purposes. To circumvent this problem, we reversibly immortalized primary fibroblasts by using the piggyBac transposon to deliver the human telomerase reverse transcriptase (hTERT) gene hTERT plus SV40 Large T. Both approaches enabled fibroblasts to grow continuously without senescence, and neither caused teratoma formation in immunodeficient mice. However, fibroblasts immortalized with hTERT plus SV40 large T antigen accumulated chromosomal rearrangements, whereas fibroblasts immortalized with hTERT retained the normal karyotype. To transdifferentiate hTERT-immortalized fibroblasts into other somatic lineage cells, we transiently transfected them with episomal OCT4 and cultured them under neural cell growth condition with transposase to remove the transposon. Tripotent neural progenitor cells were seamlessly and efficiently generated. Thus, reversible immortalization of primary fibroblasts with hTERT will allow potential autologous cell-based therapeutics that bypass and simulate iPSC generation.

Sesamin Protects Against Renal Ischemia Reperfusion Injury by Promoting CD39-adenosine-A2AR Signal Pathway in Mice

American Journal of Translational Research. 2016  |  Pubmed ID: 27347331

Ischemia reperfusion injury (IRI) is a leading cause of acute kidney injury with high morbidity and mortality due to limited therapy. Here, we examine whether sesamin attenuates renal IRI in an animal model and explore the underlying mechanisms. Male mice were subjected to right renal ischemia for 30 min followed by reperfusion for 24 h with sesamin (100 mg/kg) during which the left kidney was removed. Renal damage and function were assessed subsequently. The results showed that sesamin reduced kidney ischemia reperfusion injury, as assessed by decreased serum creatinine (Scr) and Blood urea nitrogen (BUN), alleviated tubular damage and apoptosis. In addition, sesamin inhibited neutrophils infiltration and pro-inflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β production in IR-preformed kidney. Notably, sesamin promoted the expression of CD39, A2A adenosine receptor (A2AAR), and A2BAR mRNA and protein as well as adenosine production. Furthermore, CD39 inhibitor or A2AR antagonist abolished partly the protection of sesamin in kidney IRI. In conclusion, sesamin could effectively protect kidney from IRI by inhibiting inflammatory responses, which might be associated with promoting the adenosine-CD39-A2AR signaling pathway.

Noninvasive Cardiac Quantum Spectrum Technology Effectively Detects Myocardial Ischemia

Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. Jun, 2016  |  Pubmed ID: 27351755

BACKGROUND A standard resting electrocardiogram (ECG) shows limited sensitivity and specificity for the detection of coronary artery disease (CAD). Several analytic methods exist to enhance the sensitivity and specificity of resting ECG for diagnosis of CAD. We compared a new computer-enhanced, resting ECG analysis device, the cardiac quantum spectrum (CQS) technique, with coronary angiography in the detection of CAD. MATERIAL AND METHODS A consecutive sample of 93 patients with a history of suspected CAD scheduled for coronary angiography was evaluated with CQS before coronary angiography. The sensitivity and specificity of CQS and standard 12-lead ECG for detecting hemodynamically relevant coronary stenosis were compared, using coronary angiography as the reference standard. Kappa analysis was performed to assess the agreement between CQS severity scores and the level of stenosis determined by coronary angiography. RESULTS The CQS system identified 78 of 82 patients with hemodynamically relevant stenosis (sensitivity, 95.1%; specificity, 63.6%; accuracy, 91.4%; positive predictive value, 95.1%; negative predictive value, 63.6%). Sensitivity and accuracy were much higher for CQS analysis than for the standard ECG. The Kappa value, assessing the level of agreement between CQS and coronary angiography, was 0.376 (P<0.001). CONCLUSIONS CQS analysis of resting ECG data detects hemodynamically relevant CAD with high sensitivity and specificity.

The Complement Factor 5a Receptor 1 Has a Pathogenic Role in Chronic Inflammation and Renal Fibrosis in a Murine Model of Chronic Pyelonephritis

Kidney International. Sep, 2016  |  Pubmed ID: 27370410

Complement factor 5a (C5a) interaction with its receptor (C5aR1) contributes to the pathogenesis of inflammatory diseases, including acute kidney injury. However, its role in chronic inflammation, particularly in pathogen-associated disorders, is largely unknown. Here we tested whether the development of chronic inflammation and renal fibrosis is dependent on C5aR1 in a murine model of chronic pyelonephritis. C5aR1-deficient (C5aR1-/-) mice showed a significant reduction in bacterial load, tubule injury and tubulointerstitial fibrosis in the kidneys following infection, compared with C5aR1-sufficient mice. This was associated with reduced renal leukocyte infiltration specifically for the population of Ly6Chi proinflammatory monocytes/macrophages and reduced intrarenal gene expression of key proinflammatory and profibrogenic factors in C5aR1-/- mice following infection. Antagonizing C5aR1 decreased renal bacterial load, tissue inflammation and tubulointerstitial fibrosis. Ex vivo and in vitro studies showed that under infection conditions, C5a/C5aR1 interaction upregulated the production of proinflammatory and profibrogenic factors by renal tubular epithelial cells and monocytes/macrophages, whereas the phagocytic function of monocytes/macrophages was down-regulated. Thus, C5aR1-dependent bacterial colonization of the tubular epithelium, C5a/C5aR1-mediated upregulation of local inflammatory responses to uropathogenic E. coli and impairment of phagocytic function of phagocytes contribute to persistent bacterial colonization of the kidney, chronic renal inflammation and subsequent tubulointerstitial fibrosis.

A Srikaya-like Light-harvesting Antenna Based on Graphene Quantum Dots and Porphyrin Unimolecular Micelles

Chemical Communications (Cambridge, England). Jul, 2016  |  Pubmed ID: 27374891

A novel hybrid light-harvesting antenna with a srikaya-like structure of multi-graphene quantum dots (GQDs) as donors and one porphyrin unimolecular micelle as the acceptor was constructed through electrostatic self-assembly. The constructed antenna showed a high energy transfer efficiency of up to 93.6% and an antenna effect of 7.3 in an aqueous solution.

Role of Farnesoid X Receptor in Cholestasis

Journal of Digestive Diseases. Aug, 2016  |  Pubmed ID: 27383832

The nuclear receptor farnesoid X receptor (FXR) plays an important role in physiological bile acid synthesis, secretion and transport. Defects of FXR regulation in these processes can cause cholestasis and subsequent pathological changes. FXR regulates the synthesis and uptake of bile acid via enzymes. It also increases bile acid solubility and elimination by promoting conjugation reactions and exports pump expression in cholestasis. The changes in bile acid transporters are involved in cholestasis, which can result from the mutations of transporter genes or acquired dysfunction of transport systems, such as inflammation-induced intrahepatic cholestasis. The modulation function of FXR in extrahepatic cholestasis is not identical to that in intrahepatic cholestasis, but the discrepancy may be reduced over time. In extrahepatic cholestasis, increasing biliary pressure can induce bile duct proliferation and bile infarcts, but the absence of FXR may ameliorate them. This review provides an update on the function of FXR in the regulation of bile acid metabolism, its role in the pathophysiological process of cholestasis and the therapeutic use of FXR agonists.

[Effects of Acaulospora Spinosa on Plant Growth and Lycopene Related Genes (psyl and Psy2) Expression of Tomato]

Ying Yong Sheng Tai Xue Bao = The Journal of Applied Ecology. Feb, 2016  |  Pubmed ID: 27396123

In the present study, an arbuscular mycorrhizal fungus (AMF) strain Acaulospora spinosa XJ27, previously isolated from tomato root rhizosphere in Xinjiang' s suburbs, was used to inoculate root systems of tomato cultivar "Micro-Tom". The biomass, contents of chlorophyll in leaves and lycopene in fruits of plants between the treatments with and without XJ27 were analyzed, and the expression level of lycopene biosynthesis relevant genes (psyl and.psy2) investigated by semi quantitative-PCR and real-time PCR. The results indicated that the application of XJ27 to the rhizosphere of tomato increased the biomass and yield of the treated plants, the expression of psyl and psy2 was improved, and the amount of lycopene accumulation in tomato. It suggested Acaulospora spinosa XJ27 has a great potential in utilization.

Improving Radiation Dose Efficiency of X-ray Differential Phase Contrast Imaging Using an Energy-resolving Grating Interferometer and a Novel Rank Constraint

Optics Express. Jun, 2016  |  Pubmed ID: 27410315

In this paper, a novel method was developed to improve the radiation dose efficiency, viz., contrast to noise ratio normalized by dose (CNRD), of the grating-based X-ray differential phase contrast (DPC) imaging system that is integrated with an energy-resolving photon counting detector. The method exploits the low-dimensionality of the spatial-spectral DPC image matrix acquired from different energy windows. A low rank approximation of the spatial-spectral image matrix was developed to reduce image noise while retaining the DPC signal accuracy for every energy window. Numerical simulations and experimental phantom studies have been performed to validate the proposed method by showing noise reduction and CNRD improvement for each energy window.

Effects of Water-misting Spray Combined with Forced Ventilation on Heat Induced Meat Gelation in Broiler After Summer Transport

Poultry Science. Oct, 2016  |  Pubmed ID: 27418661

This study aims to explore the use of non-chemical addition in improving the functions of meat proteins in broilers transported during summer. The effects of a water-misting spray with forced ventilation on heat induced ground meat gelation in broilers were investigated through rheology, texture, and nuclear magnetic resonance analyses. The facilities of water-misting sprays with forced ventilation characterized with an extremely thin droplet (diameter: approximately 0.05 mm) and supplying updraughting air ventilation in an enclosed space were examined. For comparison, typical processing treatments using sodium bicarbonate or sodium tripolyphosphate were performed to grind the broiler meat which had not undergone water-misting and forced ventilation. Results showed that transport for 45-min followed by application of water-misting spray with forced ventilation for 15-min and resting for 45-min (TWFR) increased water holding capacity (WHC) by 2.51%; this finding was not significantly different from the effect of transport for 45 min followed by 1 h rest and sodium tripolyphosphate treatment (TRT) on meat batter (P > 0.05). TWFR treatment exhibited the highest storage modulus increase among four samples well as significant higher hardness and chewiness values on than those of sample treated with 45-min transport and 1-h rest (TR) (P < 0.05). TWFR, 45 min of transport, 1 h rest, and addition of sodium bicarbonate (TRB) and TRT induced T22 (relaxation time of water trapped within myofibrils) shift to shorter relaxation time and narrower relaxation distribution compared with TR. Overall, TWFR treatment can be a potential non-chemical addition method for improving the heat induced gelation protein function after broiler undergoing summer transport.

A Prodrug Micellar Carrier Assembled from Polymers with Pendant Farnesyl Thiosalicylic Acid Moieties for Improved Delivery of Paclitaxel

Acta Biomaterialia. Oct, 2016  |  Pubmed ID: 27422196

In order to achieve enhanced and synergistic delivery of paclitaxel (PTX), a hydrophobic anticancer agent, two novel prodrug copolymers, POEG15-b-PFTS6 and POEG15-b-PFTS16 composed of hydrophilic poly(oligo(ethylene glycol) methacrylate) (POEG) and hydrophobic farnesylthiosalicylate (FTS, a nontoxic Ras antagonist) blocks, were synthesized. Both POEG-b-PFTS polymers were able to form micelles with intrinsic antitumor activity in vitro and in vivo. Employing these micelles as a carrier to load PTX, their drug loading capacity, stability, in vivo biodistribution and tumor inhibition effect were evaluated. PTX/POEG15-b-PFTS16 mixed micelles exhibited an excellent stability of 9days at 4°C with a PTX loading capacity of 8.2%, which was more effective than PTX/POEG15-b-PFTS6 mixed micelles. In vivo biodistribution data showed that DiR-loaded POEG-b-PFTS micelles were more effectively localized in the tumor than in other organs. Moreover, both PTX/POEG-b-PFTS micelles showed significantly higher antitumor activity than Taxol in a 4T1.2 murine breast tumor model, and the tumor inhibition and animal survival followed the order of PTX/POEG15-b-PFTS16>PTX/POEG15-b-PFTS6>POEG15-b-PFTS16>Taxol≈POEG15-b-PFTS6. Our data suggest that POEG-b-PFTS micelles are a promising anticancer drug carrier that warrants more studies in the future.

Magnetic Resonance Imaging of Skeletal Muscle Disease

Handbook of Clinical Neurology. 2016  |  Pubmed ID: 27430444

Neuromuscular diseases often exhibit a temporally varying, spatially heterogeneous, and multifaceted pathology. The goals of this chapter are to describe and evaluate the use of quantitative magnetic resonance imaging (MRI) methods to characterize muscle pathology. The following criteria are used for this evaluation: objective measurement of continuously distributed variables; clear and well-understood relationship to the pathology of interest; sensitivity to improvement or worsening of clinical status; and the measurement properties of accuracy and precision. Two major classes of MRI methods meet all of these criteria: (1) MRI methods for measuring muscle contractile volume or cross-sectional area by combining structural MRI and quantitative fat-water MRI; and (2) an MRI method for characterizing the edema caused by inflammation, the measurement of the transverse relaxation time constant (T2). These methods are evaluated with respect to the four criteria listed above and examples from neuromuscular disorders are provided. Finally, these methods are summarized and synthesized and recommendations for additional quantitative MRI developments are made.

A Facile Synthesis of Three Dimensional Graphene Sponge Composited with Sulfur Nanoparticles for Flexible Li-S Cathodes

Physical Chemistry Chemical Physics : PCCP. Aug, 2016  |  Pubmed ID: 27443983

Compared with a two dimensional graphene sheet, a three dimensional (3D) graphene sponge has a continuous conductive structure and numerous pores, which are beneficial for sulfur utilization and anchoring. However, strategies for the construction of 3D graphene sponges composited with sulfur nanoparticles (3DGS) are either energy consuming or involve toxic reagents. Herein, a 3DGS is fabricated via a reduction induced self-assembly method, which is simple but facile and scalable. The structural design of this 3DGS promises fast Li(+) transport, superior electrolyte absorbability and effective electrochemical redox reactions of sulfur. As a result, this 3DGS achieves a stable capacity of 580 mA h g(-1) after 500 cycles at a high rate of 1.5 A g(-1), which corresponds to a low fading rate of 0.043% per cycle. The present study effectively demonstrates that the 3D construction strategy is propitious for obtaining flexible high performance Li-S batteries.

Enantiomers of Tetrahedral Metal-organic Cages: a New Class of Highly Efficient G-quadruplex Ligands with Potential Anticancer Activities

Chemical Communications (Cambridge, England). Aug, 2016  |  Pubmed ID: 27465787

Four pairs of enantiomers of water-stable tetrahedral metal-organic cages [Ni4L6](8+) were facilely synthesized. They efficiently stabilized antiparallel G-quadruplex DNA with moderate enantioselectivity, and displayed promising cytotoxicity against the human cancer cell lines HCT116, HepG2 and MCF-7. These results provide a new insight into the rational design of chiral G-quadruplex-based anticancer agents.

Molecular Dynamics Simulation Studies of Hyperbranched Polyglycerols and Their Encapsulation Behaviors of Small Drug Molecules

Physical Chemistry Chemical Physics : PCCP. Aug, 2016  |  Pubmed ID: 27465863

Hyperbranched polyglycerol (HPG) is one of the most important hyperbranched polymers (HBPs) due to its interesting properties and applications. Herein, the conformation of HPGs depending on the degree of polymerization (DP) and the degree of branching (DB) is investigated explicitly by molecular dynamics simulations. This study shows that the radius of gyration (Rg) scales as Rg ∼ DP(1/3), which is in close agreement with the result of the SANS experiment. For HPGs with the same DP, the radius of gyration, asphericities and solvent accessible surface area all monotonically decrease with the increase of DB; while for HPGs with the same DB, the molecular anisotropy decreases with the increase of DP. The radial density investigation discloses that the cavities are randomly distributed in the interior of the HPG core to support the "dendritic box effect", which can be used to encapsulate the guest molecules. Interestingly, the terminal groups of HPGs with a high Wiener index (WI) are more favorable to fold back into the interiors than those with the low WI when in water. For the hyperbranched multi-arm copolymer with a HPG core and many polyethylene glycol (PEG) arms, drug encapsulation studies show that the PEG caps can not only effectively prevent tamoxifen from leaving the HPG core, but also encapsulate tamoxifen inside the PEG chains. These simulation results have provided more details for understanding the structure-property relationships of HPGs in water.

Lobaplatin for the Treatment of SK-MES-1 Lung Squamous Cell Line in Vitro and in Vivo

OncoTargets and Therapy. 2016  |  Pubmed ID: 27471396

Lung squamous cell carcinoma is the second-largest histological subtype of lung cancer, which is the leading cause of cancer-related death worldwide. Lobaplatin, one of the third-generation platinum compounds, has shown encouraging anticancer activity in a variety of tumors. The aim of this study was to determine the therapeutic efficacy of lobaplatin on p53-mutant lung squamous cancer cells SK-MES-1. In order to evaluate the antitumor effect of lobaplatin, several in vitro and in vivo analyses were carried out, including Cell Counting Kit-8 (CCK-8), fluorescence-activated cell sorter, Western blot, and terminal deoxynucleotidyl transferase dUTP nick end labeling. Findings showed that lobaplatin could inhibit cell proliferation and induce apoptosis of SK-MES-1 cells in vitro through both intrinsic and extrinsic apoptotic pathways in a time- and dose-dependent manner. In addition, lobaplatin could arrest cell cycle at S phase in SK-MES-1. Lobaplatin has obvious antitumor efficacy in human SK-MES-1 xenograft models; therefore, it seems to be a promising candidate in lung squamous cancer therapy.

Sector Mapping Method for 3D Detached Retina Visualization

Computer Methods and Programs in Biomedicine. Oct, 2016  |  Pubmed ID: 27480739

A new sphere-mapping algorithm called sector mapping is introduced to map sector images to the sphere of an eyeball. The proposed sector-mapping algorithm is evaluated and compared with the plane-mapping algorithm adopted in previous work. A simulation that maps an image of concentric circles to the sphere of the eyeball and an analysis of the difference in distance between neighboring points in a plane and sector were used to compare the two mapping algorithms. A three-dimensional model of a whole retina with clear retinal detachment was generated using the Visualization Toolkit software. A comparison of the mapping results shows that the central part of the retina near the optic disc is stretched and its edges are compressed when the plane-mapping algorithm is used. A better mapping result is obtained by the sector-mapping algorithm than by the plane-mapping algorithm in both the simulation results and real clinical retinal detachment three-dimensional reconstruction.

Impact of Bowtie Filter and Object Position on the Two-dimensional Noise Power Spectrum of a Clinical MDCT System

Medical Physics. Aug, 2016  |  Pubmed ID: 27487866

Noise characteristics of clinical multidetector CT (MDCT) systems can be quantified by the noise power spectrum (NPS). Although the NPS of CT has been extensively studied in the past few decades, the joint impact of the bowtie filter and object position on the NPS has not been systematically investigated. This work studies the interplay of these two factors on the two dimensional (2D) local NPS of a clinical CT system that uses the filtered backprojection algorithm for image reconstruction.

Chemical Modulation of Cell Fate in Stem Cell Therapeutics and Regenerative Medicine

Cell Chemical Biology. Aug, 2016  |  Pubmed ID: 27524294

Regenerative medicine aims to repair and regenerate injured tissues and restore their impaired functions. Recent developments in stem cell biology have attracted significant interest in their applications in regenerative medicine. Chemical approaches using small molecules have yielded exciting results in induction and differentiation of pluripotent stem cells, lineage conversion of somatic cells, and ex vivo as well as in vivo modulation of adult stem cells. In this review, we discuss recent progress, new insights, and future challenges of the chemical approaches in stem cell biology and regenerative medicine.

Mapping the Effect of Escitalopram Treatment on Amplitude of Low-frequency Fluctuations in Patients with Depression: a Resting-state FMRI Study

Metabolic Brain Disease. Aug, 2016  |  Pubmed ID: 27524655

Antidepressant medications represent the most common treatment option for major depressive disorder (MDD), but the neuro-psychological mechanisms by which antidepressants act to improve depressive symptoms remain under-specified. We designed this study to assess the effects of escitalopram treatment on spontaneous brain activity of MDD patients using functional magnetic resonance imaging (fMRI). Twenty first-episode drug-naive MDD patients received resting-state fMRI scans before and after 8 weeks of treatment with a selective serotonin reuptake inhibitor - escitalopram. Twenty age- and gender-matched healthy controls were also scanned twice with an 8-week interval. The fractional amplitude of low-frequency fluctuation (fALFF) was used to characterize the spontaneous brain activity. The analysis of covariance (ANCOVA) was performed to determine treatment-related changes in fALFF. The symptoms were significantly improved in MDD patients after treatment. We observed significant group-by-time interaction on fALFF in the left dorsomedial prefrontal cortex, the right middle frontal gyrus, and the left putamen. Post-hoc analyses showed that the fALFF values in these regions were significantly higher in the MDD patients compared to healthy controls at baseline and were reduced after treatment. The findings suggest that abnormalities in the brain areas involved in emotional processing and regulation could be normalized by effective antidepressant treatment with escitalopram in the MDD patients and free of a task situation.

Frequency Shift of the Bragg and Non-Bragg Backscattering from Periodic Water Wave

Scientific Reports. Aug, 2016  |  Pubmed ID: 27531469

Doppler effect is used to measure the relative speed of a moving target with respect to the radar, and is also used to interpret the frequency shift of the backscattering from the ocean wave according to the water-wave phase velocity. The widely known relationship between the Doppler shift and the water-wave phase velocity was deduced from the scattering measurements data collected from actual sea surface, and has not been verified under man-made conditions. Here we show that this ob- served frequency shift of the scattering data from the Bragg and Non-Bragg water wave is not the Doppler shift corresponding to the water-wave phase velocity as commonly believed, but is the water-wave frequency and its integral multiple frequency. The power spectrum of the backscatter from the periodic water wave consists of serials discrete peaks, which is equally spaced by water wave frequency. Only when the water-wave length is the integer multiples of the Bragg wave, and the radar range resolution is infinite, does the frequency shift of the backscattering mathematically equal the Doppler shift according to the water-wave phase velocity.

Reactivity of P-Toluenesulfonylmethyl Isocyanide: Iron-Involved C-H Tosylmethylation of Imidazopyridines in Nontoxic Media

The Journal of Organic Chemistry. Sep, 2016  |  Pubmed ID: 27557624

A novel iron-involved tosylmethylation of imidazo[1,2-α]pyridines with p-toluenesulfonylmethyl isocyanide in a solvent mixture of H2O and PEG400 under an Ar atmosphere has been developed. This protocol provides a facile synthetic route for the functionalization of the imidazo[1,2-α]pyridine scaffold with broad substrate compatibility, which is less expensive and environmentally friendly. The current methodology could further enable regioselective C-H tosylmethylation of indole at the C3 position. Also, p-toluenesulfonylmethyl isocyanide was utilized as the tosylmethylating reagent for the first time.

Quantification of Oxidized and Unsaturated Bile Alcohols in Sea Lamprey Tissues by Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry

Molecules (Basel, Switzerland). Aug, 2016  |  Pubmed ID: 27563866

A sensitive and reliable method was developed and validated for the determination of unsaturated bile alcohols in sea lamprey tissues using liquid-liquid extraction and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The liver, kidney, and intestine samples were extracted with acetonitrile and defatted by n-hexane. Gradient UHPLC separation was performed using an Acquity BEH C18 column with a mobile phase of water and methanol containing 20 mM triethylamine. Multiple reaction monitoring modes of precursor-product ion transitions for each analyte was used. This method displayed good linearity, with correlation coefficients greater than 0.99, and was validated. Precision and accuracy (RSD %) were in the range of 0.31%-5.28%, while mean recoveries were between 84.3%-96.3%. With this technique, sea lamprey tissue samples were analyzed for unsaturated bile alcohol analytes. This method is practical and particularly suitable for widespread putative pheromone residue analysis.

Rationally Designed Particle Preloading Method to Improve Protein Delivery Performance of Electrospun Polyester Nanofibers

International Journal of Pharmaceutics. Oct, 2016  |  Pubmed ID: 27568495

Particle preloading method by first loading proteins onto nano- or microparticles and then integrating these particles into electrospun polyester nanofibers has been widely used to encapsulate therapeutic proteins into polyester nanofibers. However, poor method design has resulted in unsatisfactory protein delivery performance. For example, the harsh conditions involved in preloading procedures damage the bioactivities of proteins, the improper integration leads to an uneven distribution of particles in nanofibers or insecure attachment of particles to nanofibers, producing uncontrolled protein release profiles. This study aimed to improve the protein delivery performance of polyester nanofibers by rationally designing a particle preloading method. Positively charged chitosan nanoparticles (CNPs) were used as carriers to adsorb negatively charged proteins in mild conditions and as primary barriers for protein release. The polar CNPs were then homogeneously dispersed in a polar polyester solution and subjected to electrospinning. Microscope observations indicated that CNPs were homogeneously embedded within polyester nanofibers. In vitro release behaviour and cell studies showed that proteins retained their bioactivity and could release from polyester nanofibers in a sustained manner for more than 4 weeks without any initial burst. Epidermal growth factor encapsulated in polyester nanofibers enhanced diabetic wound healing in vivo, demonstrating an application potential in biomedicine. Other properties of the nanofibers, including composition, wettability, cytotoxicity, and cell adhesion and spreading, were examined in detail as well.

Conformational-Sensitive Fast Photochemical Oxidation of Proteins and Mass Spectrometry Characterize Amyloid Beta 1-42 Aggregation

Journal of the American Chemical Society. Sep, 2016  |  Pubmed ID: 27568528

Preventing and treating Alzheimer's disease require understanding the aggregation of amyloid beta 1-42 (Aβ1-42) to give oligomers, protofibrils, and fibrils. Here we describe footprinting of Aβ1-42 by hydroxyl radical-based fast photochemical oxidation of proteins (FPOP) and mass spectrometry (MS) to monitor the time-course of Aβ1-42 aggregation. We resolved five distinct stages characterized by two sigmoidal behaviors, showing the time-dependent transitions of monomers-paranuclei-protofibrils-fibrillar aggregates. Kinetic modeling allows deciphering the amounts and interconversion of the dominant Aβ1-42 species. Moreover, the irreversible footprinting probe provides insights into the kinetics of oligomerization and subsequent fibrillar growth by allowing the conformational changes of Aβ1-42 at subregional and even amino-acid-residue levels to be revealed. The middle domain of Aβ1-42 plays a major role in aggregation, whereas the N-terminus retains most of its solvent-accessibility during aggregation, and the hydrophobic C-terminus is involved to an intermediate extent. This approach affords an in situ, real-time monitoring of the solvent accessibility of Aβ1-42 at various stages of oligomerization, and provides new insights on site-specific aggregation of Aβ1-42 for a sample state beyond the capabilities of most other biophysical methods.

Risk of Colorectal Cancer with Hysterectomy and Oophorectomy: A systematic Review and Meta-analysis

International Journal of Surgery (London, England). Oct, 2016  |  Pubmed ID: 27568653

Colorectal cancer (CRC) is the second most commonly diagnosed cancer worldwide in females. Sex hormones may play a protective effect in CRC pathogenesis. Ovarian sex steroid levels are reduced in premenopausal women after hysterectomy. Prospective studies have revealed an 80% decrease in serum oestradiol levels after bilateral oophorectomy in premenopausal women. We aimed to elucidate the relationship between hysterectomy or oophorectomy and risk of CRC.

Eupatilin Inhibits EGF-induced JB6 Cell Transformation by Targeting PI3K

International Journal of Oncology. Sep, 2016  |  Pubmed ID: 27573489

Phosphatidylinositol 3-kinases (PI3Ks) are lipid kinases that play fundamental roles in regulation of multiple signaling pathways, including cell proliferation, survival and cell cycle. Increasing evidence has shown that abnormal activation of PI3K pathway contributes to tumorigenesis and progression of various malignant tumors. Therefore, it is an attractive target of chemoprevention and chemotherapy. Eupatilin, a natural flavone compound extracted from Artemisia vulgaris, has antitumor and anti-inflammation efficacy. However, the direct target(s) of eupatilin in cancer chemoprevention are still elusive. In the present study, we reported eupatilin suppressed JB6 cell proliferation and its EGF-induced colony formation. Eupatilin attenuated phosphorylation of PI3K downstream signaling molecules. Downregulation of cyclin D1 expression and arresting in G1 phase were induced through eupatilin treatment. Furthermore, we found it could bind to the p110α, a catalytic subunit of PI3K, by computational docking methods. Pull down assay outcomes also verified the binding of eupatilin with PI3K. Taken together, our results suggest that epatilin is a potential chemopreventive agent in inhibition of skin cell transformation by targeting PI3K.

The Brain Effective Connectivity of Chinese During Rhyming Task

PloS One. 2016  |  Pubmed ID: 27583349

With regard to brain language processing, the activation patterns have been well studied, and recently there are great interest in the connectivity models. The crucial brain areas for phonological processing involves left inferior frontal gyrus (LIFG), left inferior parietal lobule (LIPL) and left posterior middle temporal gyrus (LpMTG). Specially in Chinese processing, the left middle frontal gyrus (LMFG) is considered as an essential region. However, the connectivity pattern among these brain areas is not well understood. In this study, a rhyming experiment of Chinese was conducted, and the Dynamic causal modeling (DCM) and the Bayesian model selection (BMS) were used to examine the interaction between brain regions and choose the best model for rhyming task of Chinese. By examining the interactions, it was found that LMFG exerted inhibitory modulation on LIPL and LIFG; the phonological processing enhanced the connection from LIPL to LIFG and LMFG, which suggested the important roles of these connections for the increased phonological load; And LpMTG modulated LIFG and LMFG negatively, and LIPL positively under rhyming judgment task.

Cross-sectional Study on the Relationship Between the Level of Serum Cystatin C and Blood Pressure Reverse Dipping in Hypertensive Patients

BMJ Open. Sep, 2016  |  Pubmed ID: 27591018

To investigate the relationship between the level of serum cystatin C (s-CC) and reverse-dipper blood pressure (BP) pattern.

Prospective Evaluation of Reduced Dose Computed Tomography for the Detection of Low-Contrast Liver Lesions: Direct Comparison with Concurrent Standard Dose Imaging

European Radiology. Sep, 2016  |  Pubmed ID: 27595834

To prospectively compare the diagnostic performance of reduced-dose (RD) contrast-enhanced CT (CECT) with standard-dose (SD) CECT for detection of low-contrast liver lesions.

Quercetin Ameliorates Aβ Toxicity in Drosophila AD Model by Modulating Cell Cycle-related Protein Expression

Oncotarget. Sep, 2016  |  Pubmed ID: 27626494

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder characterized by β amyloid (Aβ) deposition and neurofibril tangles. It has been reported that a bioflavonoid, quercetin, could ameliorate AD phenotypes in C. elegans and mice. However, the mechanism underlying the ameliorative effect of quercetin is not fully understood yet. Drosophila models could recapitulate AD-like phenotypes, such as shortened lifespan, impaired locomotive ability as well as defects in learning and memory. So in this study, we investigated the effects of quercetin on AD in Drosophila model and explored the underlying mechanisms. We found quercetin could effectively intervene in AD pathogenesis in vivo. Mechanism study showed quercetin could restore the expression of genes perturbed by Aβ accumulation, such as those involved in cell cycle and DNA replication. Cyclin B, an important cell cycle protein, was chosen to test whether it participated in the AD ameliorative effects of quercetin. We found that cyclin B RNAi in the brain could alleviate AD phenotypes. Taken together, the current study suggested that the neuroprotective effects of quercetin were mediated at least partially by targeting cell cycle-related proteins.

Silencing of CDC20 Suppresses Metastatic Castration-resistant Prostate Cancer Growth and Enhances Chemosensitivity to Docetaxel

International Journal of Oncology. Oct, 2016  |  Pubmed ID: 27633058

The role of cell division cycle 20 (CDC20) was investigated in chemoresistance to decetaxel and the underlying mechanisms in metastatic castration-resistant prostate cancer (mCRPC). MTT assays were performed to determine effects of siRNA-mediated CDC20 knockdown on cell proliferation and anticancer activity of docetaxel. Western blot analyses were conducted to detect changes of Akt and Wnt signaling. Furthermore, in vivo growth of PCa was examined in nude mice treated with siCDC20 or docetaxel alone or in combination. CDC20 was overexpressed in mCRPC cells. Knockdown of CDC20 suppressed cell proliferation and enhanced anticancer effect of docetaxel with IC50 reducing from 0.358 to 0.188 µg/ml in PC3 cells and 0.307 to 0.162 µg/ml in DU145 cells (P<0.01). While no change of Akt signaling was observed, inhibition of Wnt/β-catenin signaling was detected upon CDC20 silencing. Xenograft tumor growth was significantly reduced in nude mice by CDC20 inhibition. The additional treatment of siCDC20 achieved better anticancer effects than that of docetaxel alone. Silencing of CDC20 may be a new strategy to improve chemosensitization to docetaxel in mCRPC.

Cellulose/soy Protein Composite-based Nerve Guidance Conduits with Designed Microstructure for Peripheral Nerve Regeneration

Journal of Neural Engineering. Sep, 2016  |  Pubmed ID: 27651128

The objective of this work was to develop nerve guidance conduits from natural polymers, cellulose and soy protein isolate (SPI), by evaluating the effects of cellulose/SPI film-based conduit (CSFC) and cellulose/SPI sponge-based conduit (CSSC) on regeneration of nerve defects in rats.

Advanced Separators for Lithium-Ion and Lithium-Sulfur Batteries: A Review of Recent Progress

ChemSusChem. Nov, 2016  |  Pubmed ID: 27667306

Li-ion and Li-S batteries find enormous applications in different fields, such as electric vehicles and portable electronics. A separator is an indispensable part of the battery design, which functions as a physical barrier for the electrode as well as an electrolyte reservoir for ionic transport. The properties of the separators directly influence the performance of the batteries. Traditional polyolefin separators showed low thermal stability, poor wettability toward the electrolyte, and inadequate barrier properties to polysulfides. To improve the performance and durability of Li-ion and Li-S batteries, development of advanced separators is required. In this review, we summarize recent progress on the fabrication and application of novel separators, including the functionalized polyolefin separator, polymeric separator, and ceramic separator, for Li-ion and Li-S batteries. The characteristics, advantages, and limitations of these separators are discussed. A brief outlook for the future directions of the research in the separators is also provided.

MicroRNA-27b Exerts an Oncogenic Function by Targeting Fbxw7 in Human Hepatocellular Carcinoma

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine. Nov, 2016  |  Pubmed ID: 27704356

Aberrant expression of microRNAs (miRNAs) plays fundamental effect on the pathogenesis of hepatocellular carcinoma (HCC). MiR-27b was previously found to play important roles in human cancers. However, its expression status, clinical significance, and biological functions in HCC remain largely unclear. The expression status of miR-27b in HCC specimens and cells were determined with qRT-PCR. MTT, 5-bromodeoxyuridine (BrdU) proliferation assays, and flow cytometry analysis were carried out to assay proliferation, cell cycle, and apoptosis. A subcutaneous model was used to evaluated the HCC tumor growth in vivo. The putative target gene of miR-27b was disclosed by TargetScan and a luciferase reporter assay. The levels of miR-27b were overexpressed in HCC. Overexpression of miR-27b was correlated with adverse prognostic features and reduced survival rate. Inhibition of miR-27b in SMMC-7721 cells remarkably suppressed proliferative ability and cell-cycle progression while enhanced apoptosis. In contrast, miR-27b overexpression resulted in prominent increased proliferation and process of cell cycle and reduced apoptosis of Hep3B cells. In vivo studies showed that knockdown of miR-27b inhibited the in vivo growth of SMMC-7721 cells in mouse xenograft model. Furthermore, we confirmed that Fbxw7 was directly regulated by miR-27b and mediated the roles of miR-27b in HCC. We suggest that miR-27b serves as an oncogenic miRNA in HCC by modulating proliferation, cell-cycle progression, and apoptosis, and its oncogenic effect is mediated by its downstream target gene, Fbxw7.

A New Strategy to Obtain Tetranuclear Cobalt(ii) Metal-organic Frameworks Based on the [Co4(μ3-OH)2] Cluster: Synthesis, Structures and Properties

Dalton Transactions (Cambridge, England : 2003). Sep, 2016  |  Pubmed ID: 27722583

Three metal-organic frameworks (MOFs) {[Co4(OH)2(adc)6(H2O)5][Co2(OH)(btrb)]2·8H2O}n (1), {[Co4(OH)2(btrb)(nip)3(H2O)3]·4H2O}n (2·4H2O) and {[Co4(OH)2(btrb)(btc)2(H2O)2]·9H2O}n (3·9H2O) (btrb = 1,4-bis(1,2,4-triazol-4-ylmethyl)benzene, H2adc = 1,3-adamantanedicarboxylic acid, H2nip = 5-nitroisophthalic acid and H3btc = 1,3,5-benzenetricarboxylic acid) were synthesized by a hydrothermal method. 1 shows an unusual (3,4)-connected 2D network with a point symbol of (4·6(2))2(4(2)·6(2)·8(2)) based on [Co4(μ3-OH)2] and [Co2(μ3-OH)] units. 2 is a 6-connected pcu topology based on the [Co4(μ3-OH)2] unit. 3 is a rare (3,8)-connected 3D framework with a rare point symbol of (4·5·6)2(4(2)·5(6)·6(16)·7(2)·8(2)) based on the [Co4(μ3-OH)2] unit. The magnetic measurements reveal that 1-3 exhibit antiferromagnetic interactions between the adjacent cobalt(ii) centers. 1-3 are good photocatalysts for the degradation of methylene blue (MB). The 1,2-position nitrogen atoms of the 4-substituted 1,2,4-triazole ligand act as strong σ-donators to form a quite stable coordination quadrangle with two metal ions. The btrb ligand containing two 4-substituted 1,2,4-triazole rings is favorable to form tetranuclear metal units. By the regulation of the multicarboxylate ligands, the connection number of [Co4(μ3-OH)2] clusters increases from 4 in 1 to 6 in 2 and then 8 in 3. This work presents a novel but effective method to design and regulate the connection number (4, 6 and 8 connected in this work) of MOFs with 4-substituted 1,2,4-triazole and rigid multicarboxylate ligands.

The Neural Transfer Effect of Working Memory Training to Enhance Hedonic Processing in Individuals with Social Anhedonia

Scientific Reports. Oct, 2016  |  Pubmed ID: 27752140

Anhedonia, the diminished ability to experience pleasure, is a challenging negative symptom in patients with schizophrenia and can be observed in at-risk individuals with schizotypy. Deficits in hedonic processing have been postulated to be related to decreased motivation to engage in potentially rewarding events. It remains unclear whether non-pharmacological interventions, such as cognitive training, could improve anhedonia. The present study aimed to examine the neural mechanism for alleviating hedonic deficits with working memory (WM) training in individuals with social anhedonia. Fifteen individuals with social anhedonia were recruited and received 20 sessions of training on a dual n-back task, five sessions a week. Functional imaging paradigms of the Monetary Incentive Delay (MID) and the Affective Incentive Delay (AID) tasks were administered both before and after the training to evaluate the neural transfer effects on hedonic processing ability. Enhanced brain activations related to anticipation were observed at the anterior cingulate cortex, the left dorsal striatum and the left precuneus with the AID task, and at the dorsolateral prefrontal cortex and the supramarginal gyrus with the MID task. The present findings support that WM training may improve monetary-based and affective-based hedonic processing in individuals with social anhedonia.

Negative Effects of Retinoic Acid on Stem Cell Niche of Mouse Incisor

Stem Cell Research. Sep, 2016  |  Pubmed ID: 27771497

The continuous growth of mouse incisors depends on epithelial stem cells (SCs) residing in the SC niche, called labial cervical loop (LaCL). The homeostasis of the SCs is subtly regulated by complex signaling networks. In this study, we focus on retinoic acid (RA), a derivative of Vitamin A and a known pivotal signaling molecule in controlling the functions of stem cells (SCs). We analyzed the expression profiles of several key molecules of the RA signaling pathway in cultured incisor explants upon exogenous RA treatment. The expression patterns of these molecules suggested a negative feedback regulation of RA signaling in the developing incisor. We demonstrated that exogenous RA had negative effects on incisor SCs and that this was accompanied by downregulation of Fgf10, a mesenchymally expressed SC survival factor in the mouse incisor. Supplement of Fgf10 in incisor cultures completely blocked RA effects by antagonizing apoptosis and increasing proliferation in LaCL epithelial SCs. In addition, Fgf10 obviously antagonized RA-induced downregulation of the SC marker Sox2 in incisor epithelial SCs. Our findings suggest that the negative effects of RA on incisor SCs result from inhibition of mesenchymal Fgf10.

Pentraxin 3 (PTX3) Promoter Methylation Associated with PTX3 Plasma Levels and Neutrophil to Lymphocyte Ratio in Coronary Artery Disease

Journal of Geriatric Cardiology : JGC. Aug, 2016  |  Pubmed ID: 27781062

Pentraxin 3 (PTX3) is expressed in the heart under inflammatory conditions and plays an important role in atherogenesis. Patients with increased PTX3 levels may suffer from higher rates of cardiac events. Regulation of specific genes by promoter methylation is important in atherogenesis. The factors influencing PTX3 levels and the association between epigenetics and PTX3 levels have not been investigated.

Total Synthesis of Camptothecin and Related Natural Products by a Flexible Strategy

Angewandte Chemie (International Ed. in English). Nov, 2016  |  Pubmed ID: 27781350

A flexible strategy for constructing natural products containing indolizinone or quinolizinone scaffolds and their analogues was developed, which was based on a cascade exo hydroamination followed by spontaneous lactamization. This method was applied in the total synthesis of camptothecin in nine steps in a new ring-forming approach. It was also used to efficiently prepare five biogenetically or structurally related natural alkaloids, including 22-hydroxyacuminatine, oxypalmatine, norketoyobyrine, naucleficine, and nauclefine, as well as 35 natural-product-like molecules. We believe that this method and the small-molecule library prepared with it can open new avenues for studying the bioactivity of camptothecin and Nauclea natural products.

PH Sensitive Chitosan-mesoporous Silica Nanoparticles for Targeted Delivery of a Ruthenium Complex with Enhanced Anticancer Effects

Dalton Transactions (Cambridge, England : 2003). Nov, 2016  |  Pubmed ID: 27785492

Nanocarriers are widely used for delivering drugs to tumors and their development is progressing steadily. In this study, a pH sensitive mesoporous silica nanocarrier, RuNHC@MSNs-CTS-Biotin (CTS = chitosan), is developed for the targeted delivery and controlled release of a ruthenium(ii) N-heterocyclic carbene (RuNHC) complex. The RuNHC@MSNs-CTS-Biotin nanoparticles were composed of RuNHC loaded mesoporous silica nanoparticles (MSNs) coated with chitosan-biotin (CTS-Biotin) conjugates. CTS traps the RuNHC complex inside the mesopores and biotin is used as a targeting ligand to improve specific cell uptake. The particle size of RuNHC@MSNs-CTS-Biotin was around 90 nm with a zeta potential of 12.0 mV and the RuNHC loading capacity was 26.31%. The release of RuNHC from RuNHC@MSNs-CTS-Biotin was in a pH-dependent manner, and it exhibited a 59.71% terminal release ratio at pH 5.0, but almost no release under neutral conditions (pH 7.4). Its in vitro cellular uptake and anticancer activity revealed that RuNHC@MSNs-CTS-Biotin could be selectively internalized in cancer cells by biotin receptor-mediated endocytosis and this resulted in a significant improvement in anticancer activities as compared with the RuNHC complex. This multifunctional nanocarrier system provides a promising platform for the development of precisely controllable cancer therapy.

Efficacy and Safety of Laser Surgery and Transurethral Resection of the Prostate for Treating Benign Prostate Hyperplasia: a Network Meta-analysis

Asian Pacific Journal of Cancer Prevention : APJCP. 2016  |  Pubmed ID: 27797231

Traditional meta-analyses or systematic reviews of randomized controlled trials (RCTs) have been used to compare laser surgeries and transurethral resection of the prostate (TURP) for benign prostate hyperplasia (BHP), but they cannot provide a hierarchy regarding efficacy and safety of treatment.

Metformin Uniquely Prevents Thrombosis by Inhibiting Platelet Activation and MtDNA Release

Scientific Reports. Nov, 2016  |  Pubmed ID: 27805009

Thrombosis and its complications are the leading cause of death in patients with diabetes. Metformin, a first-line therapy for type 2 diabetes, is the only drug demonstrated to reduce cardiovascular complications in diabetic patients. However, whether metformin can effectively prevent thrombosis and its potential mechanism of action is unknown. Here we show, metformin prevents both venous and arterial thrombosis with no significant prolonged bleeding time by inhibiting platelet activation and extracellular mitochondrial DNA (mtDNA) release. Specifically, metformin inhibits mitochondrial complex I and thereby protects mitochondrial function, reduces activated platelet-induced mitochondrial hyperpolarization, reactive oxygen species overload and associated membrane damage. In mitochondrial function assays designed to detect amounts of extracellular mtDNA, we found that metformin prevents mtDNA release. This study also demonstrated that mtDNA induces platelet activation through a DC-SIGN dependent pathway. Metformin exemplifies a promising new class of antiplatelet agents that are highly effective at inhibiting platelet activation by decreasing the release of free mtDNA, which induces platelet activation in a DC-SIGN-dependent manner. This study has established a novel therapeutic strategy and molecular target for thrombotic diseases, especially for thrombotic complications of diabetes mellitus.

Tetramethylpyrazine Effects on the Expression of Scar-Related Genes in Rabbit Benign Biliary Stricture Fibroblasts

Journal of the College of Physicians and Surgeons--Pakistan : JCPSP. Oct, 2016  |  Pubmed ID: 27806808

To investigate the effects of tetramethylpyrazine (TMP) on transforming growth factor-β1 (TGF- β1), α-smooth muscle actin (α-SMA), and neuronal regeneration related protein (P311) in benign biliary stricture fibroblasts of rabbit.

Paclitaxel Plus Cisplatin Vs. 5-fluorouracil Plus Cisplatin As First-line Treatment for Patients with Advanced Squamous Cell Esophageal Cancer

American Journal of Cancer Research. 2016  |  Pubmed ID: 27822423

Paclitaxel plus cisplatin and 5-fluorouracil plus cisplatin treatments are effective strategies for patients with advanced esophageal squamous cell carcinoma. This study was to evaluate the safety and efficacy of paclitaxel plus cisplatin and 5-fluorouracil plus cisplatin as first-line chemotherapy for patients with advanced esophageal squamous cell carcinoma. A total of 398 patients with advanced esophageal squamous cell carcinoma who received chemotherapy were included and divided into 2 groups: paclitaxel plus cisplatin group and 5-fluorouracil plus cisplatin group. 195 patients received paclitaxel plus cisplatin and 203 patients received 5-fluorouracil plus cisplatin. The objective response rates were 42.5% and 38.4% for paclitaxel plus cisplatin group and 5-fluorouracil plus cisplatin group, respectively (P=0.948). The median progression-free survival was 7.85 months (95% CI, 6.77-8.94 months) for the paclitaxel plus cisplatin group and 6.53 months (95% CI, 5.63-7.43 months) for the 5-fluorouracil plus cisplatin group with significant difference (P=0.02). The median overall survival was 13.46 months (95% CI, 12.01-14.91 months) for the paclitaxel plus cisplatin group and 12.67 months (95% CI, 11.87-13.47 months) for the 5-fluorouracil plus cisplatin group (P=0.204). The first-line chemotherapy of paclitaxel plus cisplatin had better median progression-free survival than 5-fluorouracil plus cisplatin in patients with advanced esophageal squamous cell carcinoma with tolerable toxicities.

The Mutation of Glu at Amino Acid 3838 of AtMDN1 Provokes Pleiotropic Developmental Phenotypes in Arabidopsis

Scientific Reports. Nov, 2016  |  Pubmed ID: 27824150

MDN1/Rea1, as an AAA-type ATPase, is predicted to be the largest protein involved in pre-ribosome maturation in most organisms. However, its function in plant growth and development is poorly understood. Here, we characterized a novel Arabidopsis mutant, dwarf &short root (dsr) 1, which shows pleiotropic developmental phenotypes, such as slow germination, short root, dwarf shoot, and reduced seed set under normal growth conditions. Using positional cloning, we revealed that the AtMDN1 function is impaired by a 'glutamic acid' to 'lysine' change at position 3838 of the amino acid sequence in dsr1. Multiple sequence alignment analysis revealed that the mutated Glu residue, which located in the linker domain of AtMDN1, is extremely conserved among organisms. AtMDN1 is expressed in various tissues, particularly in the shoot apex and root tip. Moreover, the results of transcript profile analyses showed that the dysfunction of AtMDN1 in dsr1 impairs the expression of genes related to plant growth and development, which is tightly associated with the pleiotropic phenotypes of dsr1. Thus, we concluded that the Glu residue plays a vital role in maintaining AtMDN1 functions, which are essential for plant growth and development.

Efficient Nondomination Level Update Method for Steady-State Evolutionary Multiobjective Optimization

IEEE Transactions on Cybernetics. Nov, 2016  |  Pubmed ID: 27845681

Nondominated sorting (NDS), which divides a population into several nondomination levels (NDLs), is a basic step in many evolutionary multiobjective optimization (EMO) algorithms. It has been widely studied in a generational evolution model, where the environmental selection is performed after generating a whole population of offspring. However, in a steady-state evolution model, where a population is updated right after the generation of a new candidate, the NDS can be extremely time consuming. This is especially severe when the number of objectives and population size become large. In this paper, we propose an efficient NDL update method to reduce the cost for maintaining the NDL structure in steady-state EMO. Instead of performing the NDS from scratch, our method only updates the NDLs of a limited number of solutions by extracting the knowledge from the current NDL structure. Notice that our NDL update method is performed twice at each iteration. One is after the reproduction, the other is after the environmental selection. Extensive experiments fully demonstrate that, comparing to the other five state-of-the-art NDS methods, our proposed method avoids a significant amount of unnecessary comparisons, not only in the synthetic data sets, but also in some real optimization scenarios. Last but not least, we find that our proposed method is also useful for the generational evolution model.

Effects of Tactile Sensitivity on Structural Variability of Digit Forces During Stable Precision Grip

BioMed Research International. 2016  |  Pubmed ID: 27847823

This study investigated the effects of fingertip tactile sensitivity on the structural variability of thumb and index finger forces during stable precision grip. Thirty right-handed healthy subjects participated in the experiment. Transient perturbation of tactile afferents was achieved by wrapping up the distal pads of the thumb or index finger with transparent polyethylene films. The time-dependent structure of each digit force and the variability of interdigit force correlation were examined by detrended fluctuation analysis (DFA) and detrended cross-correlation analysis (DCCA), respectively. Results showed that the tactile sensitivity affected αDFA of the vertical shear force Fx (F3,239 = 6.814, p < 0.001) and αDCCA of Fx (χ(2) = 16.440, p < 0.001). No significant difference was observed in αDFA or αDCCA of the normal forces produced by the thumb or index finger. These results suggested that with blurred tactile sensory inputs the central nervous system might decrease the vertical shear force flexibility and increase the interdigit shear force coupling in order to guarantee a stable grip control of an object against gravity. This study shed light on the feedback and feed-forward strategies involved in digit force control and the role of SA-II afferent fibers in regulation of vertical shear force variability for precision grip.

A Simultaneous Disulfide Bond Cleavage, N,S-bialkylation/N-protonation and Self-assembly Reaction: Syntheses, Structures and Properties of Two Hybrid Iodoargentates with Thiazolyl-based Heterocycles

Dalton Transactions (Cambridge, England : 2003). Dec, 2016  |  Pubmed ID: 27858012

Solvothermal reactions of AgI with the vulcanization accelerator 2,2'-dibenzothiazolyl disulfide and hydroiodic acid in alcohols afford two hybrid iodoargentates with one-dimensional structures, namely (Et2mbt)[Ag2I3] (1, Hmbt = 2-mercaptobenzothiazole) and {(Hmbt)[AgI]}n (2). The syntheses of both 1 and 2 involve unprecedented multiple in situ reactions. Specifically, a simultaneous disulfide bond cleavage, N and S donor atoms bialkylation, and self-assembly reaction lead to 1 that contains a discrete N,S-biethylated cation (Et2mbt)(+) and a rare inorganic (Ag2I3)(-) anionic chain, while a simultaneous disulfide bond cleavage, N-protonation and self-assembly reaction affords 2 which features zwitterionic Hmbt molecules coordinating with the opposite side Ag atoms of a neutral inorganic (AgI)n chain via forming Ag-S coordination bonds. The simultaneous alkylation on a thiazolyl-N donor and a thiol-S donor atom for a thiazolyl-based heterocycle using inexpensive alcohols and haloids under solvothermal conditions instead of traditional two-step organic synthesis was found for the first time. The two compounds have band gaps of 2.95 eV for 1, and 2.78 eV for 2 exhibiting an observed blue shift compared with bulk AgI. Also, 1 and 2 can be used as effective heterogeneous photocatalysts for methyl orange dye treatment under UV light irradiation.

Direct Growth of Nanographene at Low Temperature from Carbon Black for Highly Sensitive Temperature Detectors

Nanotechnology. Dec, 2016  |  Pubmed ID: 27861166

Graphene has attracted tremendous research interest owing to its widespread potential applications. However, these applications are partially hampered by the lack of a general method to produce high-quality graphene at low cost. Here, to the best of our knowledge, we use low-cost solid carbon allotropes as the precursor in plasma-enhanced chemical vapor deposition (PECVD) for the first time, and find that the hydrogen plasma and reaction temperature play a crucial role in the process. Hydrogen plasma etches carbon black, and produces graphene crystals in a high-temperature zone. Based on this finding, a modified PECVD technology is developed, which produces transparent conductive nanographene films directly on various substrates at a temperature as low as 600 °C. For application, the closely packed structure of the nanographene film enables a remarkable temperature-dependent behavior of the resistance with a ratio higher than that previously reported, indicating its great potential for usage in highly sensitive temperature detectors.

Synthesis and Preliminary Biological Evaluation of a (99m) Tc-chlorambucil Derivative As a Potential Tumor Imaging Agent

Journal of Labelled Compounds & Radiopharmaceuticals. Nov, 2016  |  Pubmed ID: 27862213

Technetium-99 m-based radiopharmaceuticals have been used widely as diagnostic agents in the nuclear medicine. Chlorambucil (CLB) as one typical alkylating drug exhibits excellent inhibition effects against many human malignancies. In order to develop and explore a novel potential imaging agent for early diagnosis of tumors, tricarbonyl technetium-99 m and rhenium complexes based on the tridentate ligand dipicolylamine (DPA) bound to the chlorambucil pharmacophore were designed and synthesized: (99m) Tc-DPA-CLB (3) and Re-DPA-CLB (4). HPLC analyses showed that the retention time of 3 and 4 was 13.5 and 13.6 min, respectively. Radiolabeling efficiency (RE) of the (99m) Tc-DPA-CLB tracer was 97% and the radiochemical purity (RCP) was larger than 95% after 6 h stored in phosphate buffered saline or human serum as observed by TLC and HPLC. Biodistribution studies in a mouse model of breast cancer showed (99m) Tc-DPA-CLB exhibited a favorable tumor affinity. The radiotracer cleared quickly in the first hour via hepatobiliary and renal routes of excretion, resulted in a very low background at 4 h p.i.. It had moderate uptake ratios of tumor to blood and tumor to muscle. These results suggested (99m) Tc-DPA-CLB might be a promising SPECT imaging agent for tumor diagnosis.

Decreased Levels of MiR-34a and MiR-217 Act As Predictor Biomarkers of Aggressive Progression and Poor Prognosis in Hepatocellular Carcinoma

Minerva Medica. Nov, 2016  |  Pubmed ID: 27879964

MicroRNAs (miRNAs) play key roles in tumor development and progression. The aim of this study was to explore the expression levels of miR-34a and miR-217 in hepatocellular carcinoma (HCC) and to further investigate the clinicopathological and prognostic value of miR-34a and miR-217.

Evidence for Partial Overlap of Male Olfactory Cues in Lampreys

The Journal of Experimental Biology. Nov, 2016  |  Pubmed ID: 27885042

Animals rely on a mosaic of complex information to find and evaluate mates. Pheromones, often comprised of multiple components, are considered to be particularly important for species-recognition in many species. While the evolution of species-specific pheromone blends is well-described in many insects, very few vertebrate pheromones have been studied in a macro-evolutionary context. Here, we report a phylogenetic comparison of multi-component male odours that guide reproduction in lampreys. Chemical profiling of sexually mature males from eleven species of lamprey, representing six of ten genera and two of three families, indicated the chemical profiles of sexually mature male odours are partially shared among species. Behavioural assays conducted with four species sympatric in the Laurentian Great Lakes indicated asymmetric female responses to heterospecific odours, where Petromyzon marinus were attracted to male odour collected from all species tested but other species generally preferred only the odour of conspecifics. Electro-olfactogram recordings from P. marinus indicated that although P. marinus exhibited behavioural responses to odours from males of all species, at least some of the compounds that elicited olfactory responses were different in conspecific male odours compared to heterospecific male odours. We conclude that some of the compounds released by sexually mature males are shared among species and elicit olfactory and behavioural responses in P. marinus, and suggest that our results provide evidence for partial overlap of male olfactory cues among lampreys. Further characterization of the chemical identities of odour components is needed to confirm shared pheromones among species.

Improving Estimation of Fiber Orientations in Diffusion MRI Using Inter-Subject Information Sharing

Scientific Reports. Nov, 2016  |  Pubmed ID: 27892534

Diffusion magnetic resonance imaging is widely used to investigate diffusion patterns of water molecules in the human brain. It provides information that is useful for tracing axonal bundles and inferring brain connectivity. Diffusion axonal tracing, namely tractography, relies on local directional information provided by the orientation distribution functions (ODFs) estimated at each voxel. To accurately estimate ODFs, data of good signal-to-noise ratio and sufficient angular samples are desired. This is however not always available in practice. In this paper, we propose to improve ODF estimation by using inter-subject image correlation. Specifically, we demonstrate that diffusion-weighted images acquired from different subjects can be transformed to the space of a target subject to drastically increase the number of angular samples to improve ODF estimation. This is largely due to the incoherence of the angular samples generated when the diffusion signals are reoriented and warped to the target space. To reorient the diffusion signals, we propose a new spatial normalization method that directly acts on diffusion signals using local affine transforms. Experiments on both synthetic data and real data show that our method can reduce noise-induced artifacts, such as spurious ODF peaks, and yield more coherent orientations.

A Comparative Assessment of Preclinical Chemotherapeutic Response of Tumors Using Quantitative Non-Gaussian Diffusion MRI

Magnetic Resonance Imaging. Dec, 2016  |  Pubmed ID: 27919785

Diffusion-weighted MRI (DWI) signal attenuation is often not mono-exponential (i.e. non-Gaussian diffusion) with stronger diffusion weighting. Several non-Gaussian diffusion models have been developed and may provide new information or higher sensitivity compared with the conventional apparent diffusion coefficient (ADC) method. However the relative merits of these models to detect tumor therapeutic response is not fully clear.

Eupafolin Nanoparticle Improves Acute Renal Injury Induced by LPS Through Inhibiting ROS and Inflammation

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. Dec, 2016  |  Pubmed ID: 27923689

Acute renal injury is a common severe clinical syndrome, occurring in many clinical situations. It is necessary to explore effective drugs to treat it. Eupafolin is a flavonoid compound, derived from Phyla nodiflora, which has been previously reported to possess a variety of pharmacological activities, including anti-inflammatory and antioxidant effects. However, it is known little about how it works in acute renal injury. Also, eupafolin is characterized by skin penetration and poor water solubility, limiting its clinical applications. Thus, we synthesized an eupafolin nanoparticle delivery system. We found that eupafolin nanoparticle could address the physicochemical defects of raw eupafolin and increase water solubility without any toxicity to normal renal cells via reducing particle size. Eupafolin nanoparticle attenuated LPS-induced acute renal injury in mice through inhibiting oxidative stress and inflammation accompanied with up-regulated SOD activity and down-regulated pro-inflammatory cytokines. Additionally, inactivation of NF-κB and MAPKs of p38, ERK1/2 and JNK signaling pathways was a main molecular mechanism by which eupafolin nanoparticle improved renal injury. Together, eupafolin nanoparticle exhibits effective anti-oxidant and anti-inflammatory activities, which could be used as a potential drug to ameliorate acute renal injury clinically.

Efficacy and Safety Outcomes of Fractional Flow Reserve in Guiding Clinical Therapy of Non-ST-segment Elevation Myocardial Infarction Compared with Angiography Alone in Elderly Chinese Patients

Clinical Interventions in Aging. 2016  |  Pubmed ID: 27932871

Fractional flow reserve (FFR) is an innovative method for evaluating the physiological significance of a coronary stenosis, but its validity is less certain in patients with non-ST-segment elevation myocardial infarction (NSTEMI). It is important to assess whether FFR is effective and safe in patients, especially elderly Chinese patients, with NSTEMI. As the first one in China, the purpose of this study was to establish the efficacy and safety outcomes of FFR in guiding clinical therapy of NSTEMI compared with angiography alone in elderly Chinese patients.

Changes in Prevalence of HIV or Syphilis Among Male Sex Workers and Non-Commercial Men Who Have Sex with Men in Shenzhen, China: Results of a Second Survey

PloS One. 2016  |  Pubmed ID: 27935980

A previous time-location sampling survey (TLS) was performed in 2008 to evaluate the HIV or syphilis infection rate among male sex workers (MSWs) and non-commercial men who have sex with men (ncMSM) in Shenzhen, China. This is a second TLS performed in 2014. This article describes the findings and changes in the prevalence of HIV and syphilis.

Rapid and Efficient Crossing Blood-brain Barrier: Hydrophobic Drug Delivery System Based on Propionylated Amylose Helix Nanoclusters

Biomaterials. Jan, 2017  |  Pubmed ID: 27815997

A novel strategy of rapid transport across the blood-brain barrier (BBB) via phosphatidylethanolamine-triggered release is developed through both molecular dynamics (MD) simulation and experiments. Hydrophobic drugs, namely, propofol, iodine, and 1,1'-dioctadecyltetramethyl indotricarbocyanine iodide, were loaded with propionylated amylose helix (HLPAH) nanoclusters to form PLPAH, ILPAH, and DLPAH nanoclusters, respectively. These clusters were subjected to MD simulation, structure measurement, in vitro triggered study, in vivo DLPAH imaging, and analysis of PLPAH sedative effects on rabbits. Results indicated that HLPAH nanoclusters were initially located on the BBB, and the helix was unfolded to release the loaded hydrophobic drugs. The released drugs crossed the BBB and performed their functions in the central nervous system (CNS) through concentration gradient and hydrophobicity. This mechanism of HLPAH across the BBB featured high membrane permeability and specificity, rapid onset, short maintenance, rapid recovery, and lower dosage of drugs. Hence, this novel strategy is very meaningful for the development of CNS drug carriers and the proposed system could be used to improve the therapeutic effects of CNS diseases.

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