In JoVE (1)

Other Publications (200)

Articles by Zhen Zhang in JoVE

Other articles by Zhen Zhang on PubMed

A Gain-of-function ACTC1 3'UTR Mutation That Introduces a MiR-139-5p Target Site May Be Associated with a Dominant Familial Atrial Septal Defect

Scientific Reports. May, 2016  |  Pubmed ID: 27139165

The ostium secundum atrial septal defect (ASDII) is the most common type of congenital heart disease and is characterized by a left to right shunting of oxygenated blood caused by incomplete closure of the septum secundum. We identified a familial form of isolated ASDII that affects four individuals in a family of five and shows autosomal dominant inheritance. By whole genome sequencing, we discovered a new mutation (c.*1784T > C) in the 3'-untranslated region (3'UTR) of ACTC1, which encodes the predominant actin in the embryonic heart. Further analysis demonstrated that the c.*1784T > C mutation results in a new target site for miRNA-139-5p, a microRNA that is involved in cell migration, invasion, and proliferation. Functional analysis demonstrated that the c.*1784T > C mutation specifically downregulates gene expression in a luciferase assay. Additionally, miR-139-5p mimic causes further decrease, whereas miR-139-5p inhibitor can dramatically rescue the decline in gene expression caused by this mutation. These findings suggest that the familial ASDII may be a result of an ACTC1 3'UTR gain-of-function mutation caused by the introduction of a new miR-139-5p target site. Our results provide the first evidence of a pathogenic mutation in the ACTC1 3'UTR that may be associated with familial isolated ASDII.

The Diagnostic Value of Circulating Brain-specific MicroRNAs for Ischemic Stroke

Internal Medicine (Tokyo, Japan). 2016  |  Pubmed ID: 27181533

Objective Circulating microRNAs have been recognized as promising biomarkers for various diseases. The aim of the present study was to explore the potential role of circulating miR-107, miR-128b and miR-153 as non-invasive biomarkers in the diagnosis of ischemia stroke. Methods One hundred and fourteen ischemic stroke patients (61±11.3 years old) and 58 healthy volunteers (56±3.9 years old) matched for age and sex were enrolled in this study. Total RNA was isolated from plasma with TRIzol reagent. The circulating microRNAs levels were measured by quantitative real-time polymerase chain reaction. Results The circulating levels of miR-107, miR-128b and miR-153 significantly increased 2.78-, 2.13- and 1.83-fold in ischemia stroke patients in comparison to the healthy volunteers, respectively. Receiver operating characteristic (ROC) curves were analyzed using the SPSS software program and revealed the areas under the curve for circulating miR-107, miR-128b and miR-153 to be 0.97, 0.903 and 0.893 in ischemia stroke patients in comparison to healthy volunteers, respectively. The levels of circulating miR-107, miR-128b and miR-153 therefore positively correlated with the severity of stroke as defined by NIHSS classes. Conclusion Our results suggest that circulating miR-107, miR-128b and miR-153 might be used as potential novel non-invasive biomarkers for the diagnosis of ischemia stroke. However, future prospective trials in large-sized patient cohorts are needed before drawing any definitive conclusions.

Tunable High-Intensity Electron Bunch Train Production Based on Nonlinear Longitudinal Space Charge Oscillation

Physical Review Letters. May, 2016  |  Pubmed ID: 27203327

High-intensity trains of electron bunches with tunable picosecond spacing are produced and measured experimentally with the goal of generating terahertz (THz) radiation. By imposing an initial density modulation on a relativistic electron beam and controlling the charge density over the beam propagation, density spikes of several-hundred-ampere peak current in the temporal profile, which are several times higher than the initial amplitudes, have been observed for the first time. We also demonstrate that the periodic spacing of the bunch train can be varied continuously either by tuning launching phase of a radio-frequency gun or by tuning the compression of a downstream magnetic chicane. Narrow-band coherent THz radiation from the bunch train was also measured with μJ-level energies and tunable central frequency of the spectrum in the range of ∼0.5 to 1.6 THz. Our results pave the way towards generating mJ-level narrow-band coherent THz radiation and driving high-gradient wakefield-based acceleration.

Validation of a Biomarker Panel and Longitudinal Biomarker Performance for Early Detection of Ovarian Cancer

International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society. Jul, 2016  |  Pubmed ID: 27206285

Longitudinal multimarker combinations have the potential to improve sensitivity while maintaining the high specificity required for the early detection of ovarian cancer. The use of multiple markers to improve sensitivity over cancer antigen 125 (CA125) in longitudinal algorithms for early ovarian cancer detection requires the selection of markers with optimal discriminatory power and low longitudinal variance relative to disease-initiated changes. Our objective was to identify a multimarker panel suitable for ovarian cancer, where each individual marker has its own baseline, permitting longitudinal algorithm development.

[Application of Radiotherapy in Perioperative Comprehensive Treatment for the Elderly with Rectal Cancer]

Zhonghua Wei Chang Wai Ke Za Zhi = Chinese Journal of Gastrointestinal Surgery. May, 2016  |  Pubmed ID: 27215516

Considered that most of the phase II or III clinical trials contain less elderly patients or only contain those who had good health status, these results might not be applied in those elderly patients with some complex status. The patients of 70 years old or more usually have complications or worse organ function, thus the standard treatment for them becomes a gray zone. In rectal cancer patients, the rate of elderly patients receiving standard chemoradiotherapy (CRT) is obviously lower than that of the younger ones. More and more retrospective studies found that the prognosis of the elderly (≥70) who received neo-adjuvant or adjuvant CRT was better than that of those who received surgery or radiotherapy only, and the outcome of the above-mentioned elderly was similar to those of other phase III trial or younger patients with good tolerance. In addition, some studies revealed patients with good status, less or slight complications had a better prognosis. The advance of radiation therapy, such as Image-guided Radiation Therapy (IGRT), Intensity-modulated Radiation Therapy (IMRT), Stereotactic Body Radiation Therapy (SBRT), brachytherapy and particle therapy, will benefit the elderly cancer patients. We think that treatments recommended to the elderly will become more personalized.

[Chiral Transformation of PARC18 Assemblies on NaOH Solution Subphase]

Guang Pu Xue Yu Guang Pu Fen Xi = Guang Pu. Jan, 2016  |  Pubmed ID: 27228738

Achiral molecules with conjugated structures can form chiral supramolecules through interfacial self-assembly. These spontaneous symmetry breaking processes may help elucidate the origin of life and are thus of great importance. So far, the mechanism of interfaciam self-assembly has been discussed in detail. However, dynamics of the chiral assemblies was rarely investigated. In order to clarify whether the chiral structures are stable or dynamic, we employed second harmonic generation linear dichroism (SHG-LD) to investigate the supramolecular chirality of PARC18 at air/aqueous interface. It was shown that PARC18 formed chiral structures with stable chiral state at air/water interface. While at air/NaOH solution interface, the chiral state changed with time. In addition, on NaOH solution subphase, contributions of magnetic dipole to second harmonic signals were dominant. We suggest that this is due to isomerization of PARC18 molecules on NaOH solution subphase. As a result, the two chromophores coupled with each other and the magnetic dipole contribution was enhanced.

Haemonchus Contortus Excretory and Secretory Proteins (HcESPs) Suppress Functions of Goat PBMCs in Vitro

Oncotarget. Jun, 2016  |  Pubmed ID: 27229536

Excretory and secretory products (ESPs) of nematode contain various proteins which are capable of inducing the instigation or depression of the host immune response and are involved in the pathogenesis of the worms. In the present study, Haemonchus contortus excretory and secretory products (HcESPs) were collected from the adult worms. Binding of HcESPs to goat peripheral blood mononuclear cells (PBMCs) was confirmed by immune-fluorescence assay. Effects of the HcESPs on cytokine production, cell proliferation, cell migration and nitric oxide (NO) production of PBMCs were checked by co-incubation of HcESPs with goat PBMCs. The results indicated that the production of IL-4 and IFN-γ were significantly decreased by HcESPs in dose dependent manner. On the contrary, the production of IL-10 and IL-17 were increased. Cell migration was significantly enhanced by HcESPs, whereas, HcESPs treatment significantly suppressed the cell proliferation and NO production. These results indicated that the HcESPs played important suppressive regulatory roles on PBMCs and provided highlights to the understanding of the host-parasite interactions.

O-Linked N-Acetylglucosamine (O-GlcNAc) Transferase and O-GlcNAcase Interact with Mi2β Protein at the Aγ-Globin Promoter

The Journal of Biological Chemistry. Jul, 2016  |  Pubmed ID: 27231347

One mode of γ-globin gene silencing involves a GATA-1·FOG-1·Mi2β repressor complex that binds to the -566 GATA site relative to the (A)γ-globin gene cap site. However, the mechanism of how this repressor complex is assembled at the -566 GATA site is unknown. In this study, we demonstrate that the O-linked N-acetylglucosamine (O-GlcNAc) processing enzymes, O-GlcNAc-transferase (OGT) and O-GlcNAcase (OGA), interact with the (A)γ-globin promoter at the -566 GATA repressor site; however, mutation of the GATA site to GAGA significantly reduces OGT and OGA promoter interactions in β-globin locus yeast artificial chromosome (β-YAC) bone marrow cells. When WT β-YAC bone marrow cells are treated with the OGA inhibitor Thiamet-G, the occupancy of OGT, OGA, and Mi2β at the (A)γ-globin promoter is increased. In addition, OGT and Mi2β recruitment is increased at the (A)γ-globin promoter when γ-globin becomes repressed in postconception day E18 human β-YAC transgenic mouse fetal liver. Furthermore, we show that Mi2β is modified with O-GlcNAc, and both OGT and OGA interact with Mi2β, GATA-1, and FOG-1. Taken together, our data suggest that O-GlcNAcylation is a novel mechanism of γ-globin gene regulation mediated by modulating the assembly of the GATA-1·FOG-1·Mi2β repressor complex at the -566 GATA motif within the promoter.

Variations in Organic Carbon, Aggregation, and Enzyme Activities of Gangue-fly Ash-reconstructed Soils with Sludge and Arbuscular Mycorrhizal Fungi During 6-year Reclamation

Environmental Science and Pollution Research International. Sep, 2016  |  Pubmed ID: 27250093

Mining activities can cause drastic disturbances in soil properties, which adversely affect the nutrient cycling and soil environment. As a result, many efforts have been made to explore suitable reclamation strategies that can be applied to accelerate ecology restoration. In this study, we reconstructed mine soils with fly ash, gangue, sludge, planted ryegrass, and inoculated arbuscular mycorrhizal fungi (AMF) in Pangzhuang mine of Xuzhou during 2009 to 2015. The soil aggregation process, enzyme activities (i.e., invertase, urease and acid phosphatase activities), soil organic carbon (SOC) as well as other soil nutrients such as nitrogen, phosphorus, and potassium contents of the reconstructed mine soils were monitored during 6-year reclamation. The integrated application of sludge and AMF led to a promising reclamation performance of mining areas, in which soil aggregate stability, enzyme activities, SOC, and ryegrass biomass were effectively enhanced. The micro-aggregates (< 0.25 mm) decreased with the increase of macro-aggregates (> 0.25 mm) during the reclamation, indicating that macro-aggregates were gradually formed from micro-aggregates during the pedogenesis of reconstructed mine soils. The correlation analysis shows that SOC contents in aggregate fraction of 0.25∼0.5 mm were correlated with aggregate distribution and enzyme activities. Enzyme activities, however, were not significantly correlated with aggregate distribution. The outcomes from the present study could enrich our understanding on soil property changes in pedogenesis process of reconstructed mine soils, and meanwhile, the employment of sludge combined with AMF is suggested to be an effective alternative for the mine soil reclamation.

Rebalancing Gene Haploinsufficiency in Vivo by Targeting Chromatin

Nature Communications. Jun, 2016  |  Pubmed ID: 27256596

Congenital heart disease (CHD) affects eight out of 1,000 live births and is a major social and health-care burden. A common genetic cause of CHD is the 22q11.2 deletion, which is the basis of the homonymous deletion syndrome (22q11.2DS), also known as DiGeorge syndrome. Most of its clinical spectrum is caused by haploinsufficiency of Tbx1, a gene encoding a T-box transcription factor. Here we show that Tbx1 positively regulates monomethylation of histone 3 lysine 4 (H3K4me1) through interaction with and recruitment of histone methyltransferases. Treatment of cells with tranylcypromine (TCP), an inhibitor of histone demethylases, rebalances the loss of H3K4me1 and rescues the expression of approximately one-third of the genes dysregulated by Tbx1 suppression. In Tbx1 mouse mutants, TCP treatment ameliorates substantially the cardiovascular phenotype. These data suggest that epigenetic drugs may represent a potential therapeutic strategy for rescue of gene haploinsufficiency phenotypes, including structural defects.

Genome-wide Identification of Quantitative Trait Transcripts for Blood Traits in the Liver Samples of a White Duroc × Erhualian F2 Pig Resource Population

Physiological Genomics. Aug, 2016  |  Pubmed ID: 27260842

Blood cell counts are important clinical indicators for health status. The liver plays a crucial role in food digestion and metabolism and is also a blood-forming organ. Here, we conducted a whole-genome quantitative trait transcript (QTT) analysis on 497 liver samples for 16 hematological traits in a White Duroc × Erhualian F2 pig resource population. A total of 20,108 transcripts were explored to detect their association with hematological traits. By using Spearman correlation coefficients, we identified 1,267 QTTs for these 16 hematological traits at the significance threshold of P < 0.001. We found 31 candidate genes for erythrocyte and leukocyte-related traits by a look-up of human and pig genome-wide association study results. Furthermore, we constructed coexpression networks for leukocyte-related QTTs using weighted gene coexpression analysis. These QTTs were clustered into two to eight modules. The highest connection strength in intramodules was identified in a module for white blood cell count. In the module, USP18, RSAD2, and OAS1 appeared to be important genes involved in interferon-stimulated innate immune system. The findings improve our understanding of intrinsic relationships between the liver and blood cells and provide novel insights into the potential therapeutic targets of hematologic diseases.

Evaluation of Rate Law Approximations in Bottom-up Kinetic Models of Metabolism

BMC Systems Biology. Jun, 2016  |  Pubmed ID: 27266508

The mechanistic description of enzyme kinetics in a dynamic model of metabolism requires specifying the numerical values of a large number of kinetic parameters. The parameterization challenge is often addressed through the use of simplifying approximations to form reaction rate laws with reduced numbers of parameters. Whether such simplified models can reproduce dynamic characteristics of the full system is an important question.

Characterization and Classification of Adherent Cells in Monolayer Culture Using Automated Tracking and Evolutionary Algorithms

Bio Systems. Aug, 2016  |  Pubmed ID: 27267455

This paper presents a novel method for tracking and characterizing adherent cells in monolayer culture. A system of cell tracking employing computer vision techniques was applied to time-lapse videos of replicate normal human uro-epithelial cell cultures exposed to different concentrations of adenosine triphosphate (ATP) and a selective purinergic P2X antagonist (PPADS), acquired over a 24h period. Subsequent analysis following feature extraction demonstrated the ability of the technique to successfully separate the modulated classes of cell using evolutionary algorithms. Specifically, a Cartesian Genetic Program (CGP) network was evolved that identified average migration speed, in-contact angular velocity, cohesivity and average cell clump size as the principal features contributing to the separation. Our approach not only provides non-biased and parsimonious insight into modulated class behaviours, but can be extracted as mathematical formulae for the parameterization of computational models.

Age- and Parkinson's Disease-related Evaluation of Gait by General Tau Theory

Experimental Brain Research. Oct, 2016  |  Pubmed ID: 27271504

The degeneration of postural control in the elderly and patients with Parkinson's disease (PD) can be debilitating and may lead to increased fall risk. This study evaluated the changes in postural control during gait affected by PD and aging using a new method based on the General Tau Theory. Fifteen patients with PD, 11 healthy old adults (HOs), and 15 healthy young adults (HYs) were recruited. Foot trajectories of each participant were monitored during walking by a three-camera Optotrak Certus(®) motion capture system. The anteroposterior direction of foot movement during stepping was analyzed by tau-G and tau-J guidance strategies. Two linear regression analyses suggested that the tau of the step-gap was strongly coupled onto the tau-J guidance during walking. The regression slope K could estimate the coupling ratio in the tau-coupling equation which reflects the performance of postural control during gait. The mean K value for the PD group, which was highest among the three groups, was approximately 0.5. Therefore, participants in the PD group walked with the poorest postural control and exhibited a relatively hard contact with the endpoint during stepping when compared with those in the HO and HY groups. The HY and HO groups obtained mean K values significantly lower than 0.5, which indicated that the gait was well controlled and ended at low speed with low deceleration. However, the HO group showed a decreased tendency for postural control, in which the mean K value was significantly higher than that of the HY group. The K value was moderately positively correlated with the double support time and negatively correlated with the stride length and walking speed. The tau-J coupling ratio can provide additional insight into gait disturbances and may serve as a reliable, objective, and quantitative tool to evaluate dynamic postural control during walking.

Biological Nitrogen Removal Through Nitritation Coupled with Thiosulfate-Driven Denitritation

Scientific Reports. Jun, 2016  |  Pubmed ID: 27272192

A novel biological nitrogen removal system based on nitritation coupled with thiosulfate-driven denitritation (Nitritation-TDD) was developed to achieve a high nitrogen removal rate and low sludge production. A nitritation sequential batch reactor (nitritation SBR) and an anoxic up-flow sludge bed (AnUSB) reactor were applied for effective nitritation and denitritation, respectively. Above 75% nitrite was accumulated in the nitritation SBR with an influent ammonia loading rate of 0.43 kg N/d/m(3). During Nitritation-TDD operation, particle sizes (d50) of the sludge decreased from 406 to 225 um in nitritation SBR and from 327-183 um in AnUSB reactor. Pyrosequencing tests revealed that ammonium-oxidizing bacteria (AOB) population was stabilized at approximately 7.0% (calculated as population of AOB-related genus divided by the total microbial population) in the nitritation SBR. In contrast, nitrite-oxidizing bacteria (NOB) population decreased from 6.5-0.6% over the same time, indicating the effective nitrite accumulation in the nitritation SBR. Thiobacillus, accounting for 34.2% in the AnUSB reactor, was mainly responsible for nitrogen removal via autotrophic denitritation, using an external source of thiosulfate as electron donor. Also, it was found that free nitrous acid could directly affect the denitritation activity.

Lmod2 PiggyBac Mutant Mice Exhibit Dilated Cardiomyopathy

Cell & Bioscience. 2016  |  Pubmed ID: 27274810

Leiomodin proteins, Lmod1, Lmod2 and Lmod3, are key regulators of the thin filament length in muscles. While Lmod1 is specifically expressed in smooth muscles, both Lmod2 and Lmod3 are expressed in striated muscles including both cardiac and skeletal muscles. We and others have previously shown that Lmod3 mainly function in skeletal muscles and the mutant mice display disorganized sarcomere. Lmod2 protein has been found to act as an actin filament nucleator in both cell-free assays and in cultured rat and chicken cardiomyocytes.

Anticancer Activity and Computational Modeling of Ternary Copper (II) Complexes with 3-indolecarboxylic Acid and 1,10-phenanthroline

International Journal of Oncology. Aug, 2016  |  Pubmed ID: 27278680

Metal-containing compounds have been extensively studied for many years as potent proteasome inhibitors. The 20S proteasome, the main component of the ubiquitin proteasome pathway, is one of the excellent targets in anticancer drug development. We recently reported that several copper complexes were able to inhibit cancer-special proteasome and induce cell death in human cancer cells. However, the involved molecular mechanism is not known yet. We therefore synthesized three copper complexes and investigated their abilities on inhibiting proteasome activity and inducting apoptosis in human breast cancer cells. Furthermore, we employed molecular dockings to analyze the possible interaction between the synthetic copper complexes and the β5 subunit of proteasome which only reflects the chymotrypsin-like activity. Our results demonstrate that three Cu(II) complexes possess potent proteasome inhibition capability in a dose-dependent and time-dependent manner in MDA-MB-231 human breast cancer cells. They could bind to the β5 subunit of the 20S proteasome, which consequently cause deactivation of the proteasome and tumor cell death. The present study is significant for providing important theoretical basis for design and synthesis of anticancer drugs with low toxicity, high efficiency and high selectivity.

Axin-1 Regulates Meiotic Spindle Organization in Mouse Oocytes

PloS One. 2016  |  Pubmed ID: 27284927

Axin-1, a negative regulator of Wnt signaling, is a versatile scaffold protein involved in centrosome separation and spindle assembly in mitosis, but its function in mammalian oogenesis remains unknown. Here we examined the localization and function of Axin-1 during meiotic maturation in mouse oocytes. Immunofluorescence analysis showed that Axin-1 was localized around the spindle. Knockdown of the Axin1 gene by microinjection of specific short interfering (si)RNA into the oocyte cytoplasm resulted in severely defective spindles, misaligned chromosomes, failure of first polar body (PB1) extrusion, and impaired pronuclear formation. However, supplementing the culture medium with the Wnt pathway activator LiCl improved spindle morphology and pronuclear formation. Downregulation of Axin1 gene expression also impaired the spindle pole localization of γ-tubulin/Nek9 and resulted in retention of the spindle assembly checkpoint protein BubR1 at kinetochores after 8.5 h of culture. Our results suggest that Axin-1 is critical for spindle organization and cell cycle progression during meiotic maturation in mouse oocytes.

Development of Cell-penetrating Peptide-based Drug Leads to Inhibit MDMX:p53 and MDM2:p53 Interactions

Biopolymers. Nov, 2016  |  Pubmed ID: 27287767

The transcription factor p53 has a tumor suppressor role in leading damaged cells to apoptosis. Its activity is regulated/inhibited in healthy cells by the proteins MDM2 and MDMX. Overexpression of MDM2 and/or MDMX in cancer cells inactivates p53, facilitating tumor development. A 12-mer dual inhibitor peptide (pDI) was previously reported to be able to target and inhibit MDMX:p53 and MDM2:p53 interactions with nanomolar potency in vitro. With the aim of improving its cellular inhibitory activity, we produced a series of constrained pDI analogs featuring lactam staples that stabilize the bioactive helical conformation and fused them with a cell-penetrating peptide to increase cytosol delivery. We compared pDI and its analogs on their inhibitory potency, toxicity, and ability to enter cancer cells. Overall, the results show that these analogs keep their nanomolar affinity for MDM2 and MDMX and are highly active against cancer cells. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 853-863, 2016.

Upstream Regulators and Downstream Effectors of NF-κB in Alzheimer's Disease

Journal of the Neurological Sciences. Jul, 2016  |  Pubmed ID: 27288790

Since Alzheimer's disease (AD) is becoming the prevalent dementia in the whole world, more underlying mechanisms are emerging. Long time has the transcription factor NF-κB been identified to participate in AD pathogenesis, various studies have focused on the causes and effects of AD that are linked to NF-κB. In this review we discuss diverse environmental stimuli including oxidative stress, neuroinflammation and metabolism, involved signaling pathways such as PI3K/AKT, MAPK and AGE/RAGE/GSK-3 and newly found ncRNAs that mediate neuron toxicity or neuron protection through NF-κB activation and the following response associated with the same factors in AD. These may provide future orientation of investigation at transcription level and support efficient treatment to AD by a better understanding of the upstream regulators and downstream effectors of NF-κB.

Gross Tumor Volume is the Prognostic Factor for Squamous Cell Esophageal Cancer Patients Treated with Definitive Radiotherapy

Journal of Thoracic Disease. Jun, 2016  |  Pubmed ID: 27293832

To investigate whether gross tumor volume (GTV) defined on radiotherapy planning scans a prognostic factor for esophageal squamous cell carcinoma (ESCC) patients treated with definitive radiotherapy.

Antagonist Targeting MicroRNA-155 Protects Against Lithium-Pilocarpine-Induced Status Epilepticus in C57BL/6 Mice by Activating Brain-Derived Neurotrophic Factor

Frontiers in Pharmacology. 2016  |  Pubmed ID: 27303295

Epilepsy is a severe brain disorder affecting numerous patients. Recently, it is inferred that modulation of microRNA-155 (miR-155) could serve as a promising treatment of mesial temporal lobe epilepsy. In the current study, the therapeutic potential of miR-155 antagonist against temporal lobe epilepsy (TLE) was evaluated and the underlying mechanism involved in this regulation was explored. TLE model was induced by lithium-pilocarpine method. The effect of miR-155 antagonist on epilepticus symptoms of TLE mice was assessed using Racine classification and electroencephalogram (EEG) recordings. The expression of brain-derived neurotrophic factor (BDNF) and its association with miR-155 were also assessed with a series of experiments. Our results showed that level of miR-155 was significantly up-regulated after induction of TLE model. Based on the results of EEG and behavior analyses, seizures in mice were alleviated by miR-155 antagonist. Moreover, administration of miR-155 antagonist also significantly increased the level of BDNF. The results of dual luciferase assay and Western blotting showed that miR-155 antagonist exerted its action on status epilepticus by directly regulating the activity of BDNF. Taken all the information together, our results demonstrated that miR-155 antagonist might firstly induce the expression of BDNF, which then contributed to the alleviation of epilepsy in the current study.

Hemodialysis-induced Regional Left Ventricular Systolic Dysfunction

Hemodialysis International. International Symposium on Home Hemodialysis. Oct, 2016  |  Pubmed ID: 27312507

Introduction Hemodialysis (HD) patients are under observably elevated cardiovascular mortality. Cardiac dysfunction is closely related to death caused by cardiovascular diseases (CVD). In the general population, repetitive myocardial ischemia induced left ventricular (LV) dysfunction may progress to irreversible loss of contraction step by step, and finally lead to cardiac death. In HD patients, to remove water and solute accumulated from 48 or 72 hours of interdialysis period in a 4-hour HD session will induce myocardial ischemia. In this study, we evaluated the prevalence and potential risk factors associated with HD-induced LV systolic dysfunction and provide some evidences for clinical strategies. Methods We recruited 31 standard HD patients for this study from Fudan University Zhongshan hospital. Echocardiography was performed predialysis, at peak stress during HD (15 minutes prior to the end of dialysis), and 30 minutes after HD. Auto functional imaging (AFI) was used to assess the incidence and persistence of HD-induced regional wall motion abnormalities (RWMAs). Blood samples were drawn to measure biochemical variables. Findings Among totally 527 segments of 31 patients, 93.54% (29/31) patients and 51.40% (276/527) segments were diagnosed as RWMAs. Higher cTnT (0.060 ± 0.030 vs. 0.048 ± 0.015 ng/mL, P = 0.023), phosphate (2.07 ± 0.50 vs. 1.49 ± 0.96 mmol/L, P = 0.001), UFR (11.00 ± 3.89 vs. 8.30 ± 2.66 mL/Kg/h, P = 0.039) and lower albumin (37.83 ± 4.48 vs. 38.38 ± 2.53 g/L, P = 0.050) were found in patients with severe RWMAs (RWMAs in more than 50% segments). After univariate and multivariate analysis, interdialytic weight gain (IDWG) was found as independent risk factor of severe RWMAs (OR = 1.047, 95%CI 1.155-4.732, P = 0.038). Discussion LV systolic dysfunction induced by HD is prevalent in conventional HD patients and should be paid attention to. Patients would benefit from better weight control during interdialytic period to reduce ultrafiltration rate.

Predicting Ovarian Cancer Patients' Clinical Response to Platinum-Based Chemotherapy by Their Tumor Proteomic Signatures

Journal of Proteome Research. Aug, 2016  |  Pubmed ID: 27312948

Ovarian cancer is the deadliest gynecologic malignancy in the United States with most patients diagnosed in the advanced stage of the disease. Platinum-based antineoplastic therapeutics is indispensable to treating advanced ovarian serous carcinoma. However, patients have heterogeneous responses to platinum drugs, and it is difficult to predict these interindividual differences before administering medication. In this study, we investigated the tumor proteomic profiles and clinical characteristics of 130 ovarian serous carcinoma patients analyzed by the Clinical Proteomic Tumor Analysis Consortium (CPTAC), predicted the platinum drug response using supervised machine learning methods, and evaluated our prediction models through leave-one-out cross-validation. Our data-driven feature selection approach indicated that tumor proteomics profiles contain information for predicting binarized platinum response (P < 0.0001). We further built a least absolute shrinkage and selection operator (LASSO)-Cox proportional hazards model that stratified patients into early relapse and late relapse groups (P = 0.00013). The top proteomic features indicative of platinum response were involved in ATP synthesis pathways and Ran GTPase binding. Overall, we demonstrated that proteomic profiles of ovarian serous carcinoma patients predicted platinum drug responses as well as provided insights into the biological processes influencing the efficacy of platinum-based therapeutics. Our analytical approach is also extensible to predicting response to other antineoplastic agents or treatment modalities for both ovarian and other cancers.

How Do We Trust Strangers? The Neural Correlates of Decision Making and Outcome Evaluation of Generalized Trust

Social Cognitive and Affective Neuroscience. Oct, 2016  |  Pubmed ID: 27317927

This study investigates the brain correlates of decision making and outcome evaluation of generalized trust (i.e. trust in unfamiliar social agents)-a core component of social capital which facilitates civic cooperation and economic exchange. We measured 18 (9 male) Chinese participants' event-related potentials while they played the role of the trustor in a one-shot trust game with unspecified social agents (trustees) allegedly selected from a large representative sample. At the decision-making phase, greater N2 amplitudes were found for trustors' distrusting decisions compared to trusting decisions, which may reflect greater cognitive control exerted to distrust. Source localization identified the precentral gyrus as one possible neuronal generator of this N2 component. At the outcome evaluation phase, principal components analysis revealed that the so called feedback-related negativity was in fact driven by a reward positivity, which was greater in response to gain feedback compared to loss feedback. This reduced reward positivity following loss feedback may indicate that the absence of reward for trusting decisions was unexpected by the trustor. In addition, we found preliminary evidence suggesting that the decision-making processes may differ between high trustors and low trustors.

Highly Efficient Detection of Paclobutrazol in Environmental Water and Soil Samples by Time-resolved Fluoroimmunoassay

The Science of the Total Environment. Nov, 2016  |  Pubmed ID: 27320734

A fast and ultrasensitive indirect competitive time-resolved fluoroimmunoassay (TRFIA) was developed for the analysis of paclobutrazol in environmental water and soil samples. Paclobutrazol hapten was synthesized and conjugated to bovine serum albumin (BSA) for producing polyclonal antibodies. Under optimal conditions, the 50% inhibitory concentration (IC50 value) and limit of detection (LOD, IC20 value) were 1.09μgL(-1) and 0.067μgL(-1), respectively. The LOD of TRFIA was improved 30-fold compared to the already reported ELISA. There was almost no cross-reactivity of the antibody with the other structural analogues of triazole compounds, indicating that the antibody had high specificity. The average recoveries from spiked samples were in the range from 80.2% to 104.7% with a relative standard deviation of 1.0-9.5%. The TRFIA results for the real samples were in good agreement with that obtained by high-performance liquid chromatography analyses. The results indicate that the established TRFIA has potential application for screening paclobutrazol in environmental samples.

Nanofibrous Asymmetric Membranes Self-organized from Chemically Heterogeneous Electrospun Mats for Skin Tissue Engineering

Biomedical Materials (Bristol, England). Jun, 2016  |  Pubmed ID: 27327625

Asymmetric membranes, which mimic the structure and functions of human skin, have been extensively pursued as ideal skin tissue engineering constructs. In this study, we demonstrated that nanostructured asymmetric membranes can be prepared by the self-organization of chemically heterogeneous bilayer electrospun membranes in aqueous solutions. Structurally, the skin layer consists of hydrophobic β-glucan butyrate nanofibers and its inner layer consists of hydrophilic β-glucan acetate nanofibers. After the electrospinning process, both of the layers are in a dense state. When placed in water, the skin layer absorbs little water and still remains dense, but the fibers in the inner layer become extensively hydrated and spontaneously reorganize into a fully stretched structure, resulting in a significant volume increase and a density decrease of the inner layer. SEM imaging showed that β-glucan ester nanofibers exhibited a bead-free and uniform structure. Contact angle measurement and swelling tests showed that the inner layer was highly hydrophilic with extensive swelling, but the skin layer was highly hydrophobic with little swelling. Mechanical tests indicated that the nanofibrous asymmetric membranes had good mechanical properties in both the dry and wet states. In vitro cytocompatibility tests showed that nanofibrous asymmetric membranes could promote the adhesion and proliferation of fibroblasts and keratinocytes. A preliminary in vivo study performed on a full thickness mouse skin wound model demonstrated that the nanofibrous asymmetric membranes significantly accelerated the wound healing process by promoting re-epithelialization, tissue remodeling and collagen deposition. Taken together, our study provides a novel model for the design and fabrication of nanostructured asymmetric membranes, and our β-glucan based nanofibrous asymmetric membranes could be used as an advanced platform for skin tissue engineering.

Inhibition of SALL4 Reduces Tumorigenicity Involving Epithelial-mesenchymal Transition Via Wnt/β-catenin Pathway in Esophageal Squamous Cell Carcinoma

Journal of Experimental & Clinical Cancer Research : CR. Jun, 2016  |  Pubmed ID: 27329034

Growing evidence suggests that SALL4 plays a vital role in tumor progression and metastasis. However, the molecular mechanism of SALL4 promoting esophageal squamous cell carcinoma (ESCC) remains to be elucidated.

E3 Ubiquitin Ligase RFWD2 Controls Lung Branching Through Protein-level Regulation of ETV Transcription Factors

Proceedings of the National Academy of Sciences of the United States of America. Jul, 2016  |  Pubmed ID: 27335464

The mammalian lung is an elaborate branching organ, and it forms following a highly stereotypical morphogenesis program. It is well established that precise control at the transcript level is a key genetic underpinning of lung branching. In comparison, little is known about how regulation at the protein level may play a role. Ring finger and WD domain 2 (RFWD2, also termed COP1) is an E3 ubiquitin ligase that modifies specific target proteins, priming their degradation via the ubiquitin proteasome system. RFWD2 is known to function in the adult in pathogenic processes such as tumorigenesis. Here, we show that prenatal inactivation of Rfwd2 gene in the lung epithelium led to a striking halt in branching morphogenesis shortly after secondary branch formation. This defect is accompanied by distalization of the lung epithelium while growth and cellular differentiation still occurred. In the mutant lung, two E26 transformation-specific (ETS) transcription factors essential for normal lung branching, ETS translocation variant 4 (ETV4) and ETV5, were up-regulated at the protein level, but not at the transcript level. Introduction of Etv loss-of-function alleles into the Rfwd2 mutant background attenuated the branching phenotype, suggesting that RFWD2 functions, at least in part, through degrading ETV proteins. Because a number of E3 ligases are known to target factors important for lung development, our findings provide a preview of protein-level regulatory network essential for lung branching morphogenesis.

Wall-like Hierarchical Metal Oxide Nanosheet Arrays Grown on Carbon Cloth for Excellent Supercapacitor Electrodes

Nanoscale. Jul, 2016  |  Pubmed ID: 27336591

Recently, considerable efforts have been made to satisfy the future requirements of electrochemical energy storage using novel functional electrode materials. Binary transition metal oxides (BTMOs) possess multiple oxidation states that enable multiple redox reactions, showing higher supercapacitive properties than single component metal oxides. In this work, a facile hydrothermal method is provided for the synthesis of wall-like hierarchical metal oxide MMoO4 (M = Ni, Co) nanosheet arrays, which are directly grown on flexible carbon cloth for use as advanced binder-free electrodes for supercapacitors. By virtue of their intriguing structure, the resulted active material nanosheets with a high specific surface area can provide a large electroactive region, which could facilitate easy accession of electrolyte ions and fast charge transport, resulting in an enhanced electrochemical performance. Separately, the as-synthesized MMoO4 (M = Ni, Co) samples have exhibited superior specific capacitances (1483 F g(-1) of NiMoO4 and 452 F g(-1) of CoMoO4 at a current density of 2 A g(-1)), as well as excellent cycling stability (93.1% capacitance retention of NiMoO4 and 95.9% capacitance retention of CoMoO4 after 2000 cycles). The results show that the binder-free electrodes constructed by deposition of MMoO4 (M = Ni, Co) nanosheets on carbon cloth are promising candidates for the application of supercapacitors.

[Radiotherapy Standard and Progress in Locally Advanced Rectal Cancer]

Zhonghua Wei Chang Wai Ke Za Zhi = Chinese Journal of Gastrointestinal Surgery. Jun, 2016  |  Pubmed ID: 27353094

Recently, treatment strategy optimization for neoadjuvant therapy of rectal cancer includes two aspects: (1) Increasing treatment intensity may improve pathological complete response rate, including increasing radiation dose or concurrent chemotherapy intensity, or shifting adjuvant chemotherapy; (2) Short-course radiotherapy or neoadjuvant chemotherapy which can promise treatment efficacy will decrease toxicity and lead to better tolerance. Long-course chemoradiotherapy is the recent treatment standard for locally advanced rectal cancer. NCCN guidelines do not recommend combined chemotherapy in the radiotherapy period. However, it is important for individualized treatment of rectal cancer if appropriate patients who may benefit from the combined concurrent chemotherapy can be selected. Short-course radiotherapy is defined as 5 Gy × 5. It is recommended for T3 or N+ rectal cancer in NCCN guidelines, but not for T4 patients. In ESMO guidelines, stratified patients of intermediate risk by MRI can be treated with either short-course or long-course radiotherapy, but short-course radiotherapy is not recommended for T4 or positive mesorectum fascia (MRF+) patients with high risk. Neoadjuvant chemotherapy incorporated in the neoadjuvant part has been a therapeutic choice in NCCN guidelines. However, It is still unclear whether chemotherapy upfront as a component of neoadjuvant treatment or even completion of chemotherapy before surgery can improve treatment outcome or not. There are phase II( studies focused on this issue and final results are pending.

A Novel Paradigm for the High-efficient Production of Phycocyanin from Galdieria Sulphuraria

Bioresource Technology. Oct, 2016  |  Pubmed ID: 27372006

A novel cultivation strategy called "Sequential Heterotrophy-Dilution-Photoinduction" was successfully applied in the cultivation of Galdieria sulphuraria for efficient production of phycocyanin (PC). Algae cells were firstly cultivated heterotrophically to achieve high cell density. The maximal dry cell weight of 17.8gL(-1) and maximal biomass productivity of 103.1mgL(-1)h(-1) were obtained. Then, a dilution step was applied to obtain a suitable cell concentration and finally these cells were transferred to high light condition for phycocyanin accumulation. During the photoinduction step, cells could accumulate phycocyanin up to 13.88% of dry cell weight in a cultivation period of 8days. By this technology, total PC productivity far surpassed those reported in all literatures of Galdieria sulphuraria, and was 147-fold and 12-fold of those in photoautotrophic and heterotrophic technologies, respectively. Therefore, this strategy provides a promising approach for high-efficient phycocyanin production from Galdieria sulphuraria to meet its mass cultivation and commercialization application.

Integrated Proteogenomic Characterization of Human High-Grade Serous Ovarian Cancer

Cell. Jul, 2016  |  Pubmed ID: 27372738

To provide a detailed analysis of the molecular components and underlying mechanisms associated with ovarian cancer, we performed a comprehensive mass-spectrometry-based proteomic characterization of 174 ovarian tumors previously analyzed by The Cancer Genome Atlas (TCGA), of which 169 were high-grade serous carcinomas (HGSCs). Integrating our proteomic measurements with the genomic data yielded a number of insights into disease, such as how different copy-number alternations influence the proteome, the proteins associated with chromosomal instability, the sets of signaling pathways that diverse genome rearrangements converge on, and the ones most associated with short overall survival. Specific protein acetylations associated with homologous recombination deficiency suggest a potential means for stratifying patients for therapy. In addition to providing a valuable resource, these findings provide a view of how the somatic genome drives the cancer proteome and associations between protein and post-translational modification levels and clinical outcomes in HGSC. VIDEO ABSTRACT.

Achieving Optimal Self-Adaptivity for Dynamic Tuning of Organic Semiconductors Through Resonance Engineering

Journal of the American Chemical Society. Aug, 2016  |  Pubmed ID: 27403886

Current static-state explorations of organic semiconductors for optimal material properties and device performance are hindered by limited insights into the dynamically changed molecular states and charge transport and energy transfer processes upon device operation. Here, we propose a simple yet successful strategy, resonance variation-based dynamic adaptation (RVDA), to realize optimized self-adaptive properties in donor-resonance-acceptor molecules by engineering the resonance variation for dynamic tuning of organic semiconductors. Organic light-emitting diodes hosted by these RVDA materials exhibit remarkably high performance, with external quantum efficiencies up to 21.7% and favorable device stability. Our approach, which supports simultaneous realization of dynamically adapted and selectively enhanced properties via resonance engineering, illustrates a feasible design map for the preparation of smart organic semiconductors capable of dynamic structure and property modulations, promoting the studies of organic electronics from static to dynamic.

Sex, Race, and Age Disparities in the Improvement of Survival for Gastrointestinal Cancer over Time

Scientific Reports. Jul, 2016  |  Pubmed ID: 27406065

There have been notable improvements in survival over the past 2 decades for gastrointestinal (GI) cancer. However, the degree of improvement by age, race, and sex remains unclear. We analyzed data from 9 population-based cancer registries included in the SEER program of the National Cancer Institute (SEER 9) in 1990 to 2009 (n = 288,337). The degree of survival improvement over time by age, race, and sex was longitudinally measured. From 1990 to 2009, improvements in survival were greater for younger age groups. For patients aged 20 to 49 years and diagnosed from 2005 to 2009, adjusted HRs (95% CIs) were 0.74 (95% CI, 0.66-0.83), 0.49 (95% CI, 0.37-0.64), 0.69 (95% CI, 0.65-0.76), 0.62 (95% CI, 0.54-0.69), and 0.56 (95% CI, 0.42-0.76), for cancer of the stomach, small intestine, colon, rectum and anus, respectively, compared with the same age groups of patients diagnosed during 1990 to 1994. Compared with African Americans, whites experienced greater improvement in small intestinal and anal cancer survival. Female anal cancer and regional anal cancer patients experienced no improvement. Our data suggest that different improvement in survival in age, sex and race exists.

Low-complexity Joint Symbol Synchronization and Sampling Frequency Offset Estimation Scheme for Optical IMDD OFDM Systems

Optics Express. Jun, 2016  |  Pubmed ID: 27410279

A low-complexity joint symbol synchronization and SFO estimation scheme for asynchronous optical IMDD OFDM systems based on only one training symbol is proposed. Numerical simulations and experimental demonstrations are also under taken to evaluate the performance of the mentioned scheme. The experimental results show that robust and precise symbol synchronization and the SFO estimation can be achieved simultaneously at received optical power as low as -20dBm in asynchronous OOFDM systems. SFO estimation accuracy in MSE can be lower than 1 × 10-11 under SFO range from -60ppm to 60ppm after 25km SSMF transmission. Optimal System performance can be maintained until cumulate number of employed frames for calculation is less than 50 under above-mentioned conditions. Meanwhile, the proposed joint scheme has a low level of operation complexity comparing with existing methods, when the symbol synchronization and SFO estimation are considered together. Above-mentioned results can give an important reference in practical system designs.

Selective Oxytrifluoromethylation of Allylamines with CO2

Angewandte Chemie (International Ed. in English). Aug, 2016  |  Pubmed ID: 27411560

Reported is the first oxy-trifluoromethylation of allylamines with carbon dioxide (CO2 ) using copper catalysis, thus leading to important CF3 -containing 2-oxazolidones. It is also the first time CO2 , a nontoxic and easily available greenhouse gas, has been used to tune the difunctionalization of alkenes from amino- to oxy-trifluoromethylation. Of particular note, this multicomponent reaction is highly chemo-, regio-, and diastereoselective under redox-neutral and mild reaction conditions. Moreover, these reactions feature good functional-group tolerance, broad substrate scope, easy scalability and facile product diversification. The important products could also be formed with either spirocycles or two adjacent tetrasubstituted carbon centers.

Core-shell Self-assembly Triggered Via a Thiol-disulfide Exchange Reaction for Reduced Glutathione Detection and Single Cells Monitoring

Scientific Reports. Jul, 2016  |  Pubmed ID: 27412605

A novel core-shell DNA self-assembly catalyzed by thiol-disulfide exchange reactions was proposed, which could realize GSH-initiated hybridization chain reaction (HCR) for signal amplification and molecules gathering. Significantly, these self-assembled products via electrostatic interaction could accumulate into prominent and clustered fluorescence-bright spots in single cancer cells for reduced glutathione monitoring, which will effectively drive cell monitoring into a new era.

Optimization of Bioenergy Crop Selection and Placement Based on a Stream Health Indicator Using an Evolutionary Algorithm

Journal of Environmental Management. Oct, 2016  |  Pubmed ID: 27420165

The emission of greenhouse gases continues to amplify the impacts of global climate change. This has led to the increased focus on using renewable energy sources, such as biofuels, due to their lower impact on the environment. However, the production of biofuels can still have negative impacts on water resources. This study introduces a new strategy to optimize bioenergy landscapes while improving stream health for the region. To accomplish this, several hydrological models including the Soil and Water Assessment Tool, Hydrologic Integrity Tool, and Adaptive Neruro Fuzzy Inference System, were linked to develop stream health predictor models. These models are capable of estimating stream health scores based on the Index of Biological Integrity. The coupling of the aforementioned models was used to guide a genetic algorithm to design watershed-scale bioenergy landscapes. Thirteen bioenergy managements were considered based on the high probability of adaptation by farmers in the study area. Results from two thousand runs identified an optimum bioenergy crops placement that maximized the stream health for the Flint River Watershed in Michigan. The final overall stream health score was 50.93, which was improved from the current stream health score of 48.19. This was shown to be a significant improvement at the 1% significant level. For this final bioenergy landscape the most often used management was miscanthus (27.07%), followed by corn-soybean-rye (19.00%), corn stover-soybean (18.09%), and corn-soybean (16.43%). The technique introduced in this study can be successfully modified for use in different regions and can be used by stakeholders and decision makers to develop bioenergy landscapes that maximize stream health in the area of interest.

BH3 Mimetic ABT-737 Sensitizes Colorectal Cancer Cells to Ixazomib Through MCL-1 Downregulation and Autophagy Inhibition

American Journal of Cancer Research. 2016  |  Pubmed ID: 27429848

The proteasome inhibitor MLN9708 is an orally administered drug that is hydrolyzed into its active form, MLN2238 (ixazomib). Compared with Bortezomib, MLN2238 has a shorter proteasome dissociation half-life and a lower incidence and severity of peripheral neuropathy, which makes it an attractive candidate for colorectal cancer treatment. In the present study, we observed that MLN2238 induced autophagy, as evidenced by conversion of the autophagosomal marker LC3 from LC3I to LC3II, in colorectal cancer cell lines. Mcl-1, an anti-apoptotic Bcl-2 family protein, was markedly elevated after treating a colorectal cancer cell line with MLN2238. We proved that inhibiting Mcl-1 expression enhances MLN2238 induced apoptosis and negatively regulates autophagy. Co-administration of BH3 mimetic ABT-737 with MLN2238 synergistically kills colorectal cancer cells through MCL-1 neutralization and autophagy inhibition. Furthermore, the synergistic killing effect of the combination therapy is correlated with P53 status in colorectal cancer. These data highlight that the combination of ABT-737 with MLN9708 is a promising therapeutic strategy for human colorectal cancer.

Methoxychlor Exposure Induces Oxidative Stress and Affects Mouse Oocyte Meiotic Maturation

Molecular Reproduction and Development. Sep, 2016  |  Pubmed ID: 27434785

Methoxychlor (MXC) is used worldwide against insects and other pests. This organochlorine pesticide acts as a xenoestrogen, promotes oxidative stress, and is considered cytotoxic and genotoxic, causing abortions and stillbirths in females. Mechanistically related estrogens and oxidants affect oocyte meiosis, so we investigated the effects of MXC on mouse oocyte meiotic maturation. Our results showed that maturation rates of MXC-treated oocytes were lower than those of controls, which was due to abnormal spindle morphologies and DNA double-strand breaks, as confirmed by increased γ-H2AX foci. Our findings also suggest that MXC may affect oocyte quality by causing the accumulation of superoxide radicals and other reactive oxygen species, aberrant mitochondrial distribution, decreased mitochondrial membrane potential, and increased lipid peroxidation. Thus, exposure to MXC negatively affects oocyte meiotic maturation, primarily through impairments in cellular ROS metabolism. Mol. Reprod. Dev. 83: 768-779, 2016 © 2016 Wiley Periodicals, Inc.

Taxonomic Status and Phylogenetic Relationship of Tits Based on Mitogenomes and Nuclear Segments

Molecular Phylogenetics and Evolution. Nov, 2016  |  Pubmed ID: 27444707

The phylogeny of tits has been studied using various molecular markers, but their phylogenetic relationships remain controversial. To further investigate their taxonomic status and phylogenetic relationships, the entire mitochondrial genomes (mitogenomes) and five nuclear segments were sequenced from 10 species of tits and two outgroups (Sylviparus modestus and Remiz consobrinus), followed by the comparison of mitogenomic characteristics and reconstruction of phylogenetic relationship based on the different datasets. The results revealed the following: the mitogenomes of 10 ingroup tits, each 16,758-16,799bp in length, displayed typical mitogenome organization and the gene order found in most previously determined Passeriformes mitogenomes; close relationships existed between Parus major and P. monticolus, between P. montanus and P. palustris, and between P. ater and P. venustulus; and Pseudopodoces humilis was a sister group to P. spilonotus, P. cyanus, or the clade containing P. major and P. monticolus.

Impaired T Cell Function in Malignant Pleural Effusion is Caused by TGF-β Derived Predominantly from Macrophages

International Journal of Cancer. Nov, 2016  |  Pubmed ID: 27459735

Malignant pleural effusion (MPE) is an indication of advanced cancer. Immune dysfunction often occurs in MPE. We aimed to identify the reason for impaired T cell activity in MPE from lung cancer patients and to provide clues toward potential immune therapies for MPE. The surface inhibitory molecules and cytotoxic activity of T cells in MPE and peripheral blood (PB) were analyzed using flow cytometry. Levels of inflammatory cytokines in MPE and PB were tested using ELISA. TGF-β expression in tumor-associated macrophages (TAMs) was also analyzed. The effect of TAMs on T cells was verified in vitro. Lastly, changes in T cells were evaluated following treatment with anti-TGF-β antibody. We found that expression levels of Tim-3, PD-1 and CTLA-4 in T cells from MPE were upregulated compared with those from PB, but levels of IFN-γ and Granzyme B were downregulated (p < 0.05). The amount of TGF-β was significantly higher in MPE than in PB (p < 0.05). TGF-β was mainly produced by TAMs in MPE. When T cells were co-cultured with TAMs, expression levels of Tim-3, PD-1 and CTLA-4 were significantly higher than controls, whereas levels of IFN-γ and Granzyme B were significantly decreased, in a dose-dependent manner (p < 0.05). In vitro treatment with anti-TGF-β antibody restored the impaired T cell cytotoxic activity in MPE. Our results indicate that macrophage-derived TGF-β plays an important role in impaired T cell cytotoxicity. It will therefore be valuable to develop therapeutic strategies against TGF-β pathway for MPE therapy of lung cancer.

Polymorphisms in the Telomerase Reverse Transcriptase Promoter Are Associated with Risk of Breast Cancer: A Meta-analysis

Journal of Cancer Research and Therapeutics. Apr-Jun, 2016  |  Pubmed ID: 27461695

Recently, the relationship between telomerase reverse transcriptase (TERT) polymorphisms and breast cancer risk has been investigated in several publications. However, the results were inconclusive. In this study, we examined the association between TERT polymorphisms and breast cancer risk by meta-analysis.

Secret Sharing of a Quantum State

Physical Review Letters. Jul, 2016  |  Pubmed ID: 27472103

Secret sharing of a quantum state, or quantum secret sharing, in which a dealer wants to share a certain amount of quantum information with a few players, has wide applications in quantum information. The critical criterion in a threshold secret sharing scheme is confidentiality: with less than the designated number of players, no information can be recovered. Furthermore, in a quantum scenario, one additional critical criterion exists: the capability of sharing entangled and unknown quantum information. Here, by employing a six-photon entangled state, we demonstrate a quantum threshold scheme, where the shared quantum secrecy can be efficiently reconstructed with a state fidelity as high as 93%. By observing that any one or two parties cannot recover the secrecy, we show that our scheme meets the confidentiality criterion. Meanwhile, we also demonstrate that entangled quantum information can be shared and recovered via our setting, which shows that our implemented scheme is fully quantum. Moreover, our experimental setup can be treated as a decoding circuit of the five-qubit quantum error-correcting code with two erasure errors.

A GWA Study Reveals Genetic Loci for Body Conformation Traits in Chinese Laiwu Pigs and Its Implications for Human BMI

Mammalian Genome : Official Journal of the International Mammalian Genome Society. Dec, 2016  |  Pubmed ID: 27473603

Pigs share numerous physiological and phenotypic similarities with human and thus have been considered as a good model in nonrodent mammals for the study of genetic basis of human obesity. Researches on candidate genes for obesity traits have successfully identified some common genes between humans and pigs. However, few studies have assessed how many similarities exist between the genetic architecture of obesity in pigs and humans by large-scale comparative genomics. Here, we performed a genome-wide association study (GWAS) using the porcine 60 K SNP Beadchip for BMI and other four conformation traits at three different ages in a Chinese Laiwu pig population, which shows a large variability in fat deposition. In total, 35 SNPs were found to be significant at Bonferroni-corrected 5 % chromosome-wise level (P = 2.13 × 10(-5)) and 88 SNPs had suggestive (P < 10(-4)) association with the conformation traits. Some SNPs showed age-dependent association. Intriguingly, out of 32 regions associated with BMI in pigs, 18 were homologous with the loci for BMI in humans. Furthermore, five closest genes to GWAS peaks including HIF1AN, SMYD3, COX10, SLMAP, and GBE1 have been already associated with BMI in humans, which makes them very promising candidates for these QTLs. The result of GO analysis provided strong support to the fact that mitochondria and synapse play important roles in obesity susceptibility, which is consistent with previous findings on human obesity, and it also implicated new gene sets related to chromatin modification and Ig-like C2-type 5 domain. Therefore, these results not only provide new insights into the genetic architecture of BMI in pigs but also highlight that humans and pigs share the significant overlap of obesity-related genes.

The Salmonella Effector SopB Prevents ROS-induced Apoptosis of Epithelial Cells by Retarding TRAF6 Recruitment to Mitochondria

Biochemical and Biophysical Research Communications. Sep, 2016  |  Pubmed ID: 27473656

Microbial pathogens enter host cells by injecting effector proteins of the Type III secretion system (T3SS), which facilitate pathogen translocation across the host cell membrane. These effector proteins exert their effects by modulating a variety of host innate immune responses, thereby facilitating bacterial replication and systemic infection. Salmonella enterica serovar typhimurium (S.typhimurium) is a clinically important pathogen that causes food poisoning and gastroenteritis. The SopB effector protein of S. typhimurium, encoded by Salmonella pathogenicity islands (SPI)-1 T3SS, protects host epithelial cells from infection-induced apoptosis. However, how SopB influences apoptosis induction remains unclear. Here, we investigated the mechanism of SopB action in host cells. We found that SopB inhibits infection-induced apoptosis by attenuating the production of reactive oxygen species (ROS) in mitochondria, the crucial organelles for apoptosis initiation. Further investigation revealed that SopB binds to cytosolic tumor necrosis factor receptor associated factor 6 (TRAF6) and forms a trap preventing the mitochondrial recruitment of TRAF6, an essential event for ROS generation within mitochondria. By studying the response of Traf6(+/+) and Traf6(-/-)mouse embryonic fibroblasts to S. typhimurium infection, we found that TRAF6 promoted apoptosis by increasing ROS accumulation, which led to increased Bax/Bcl-2 ratio, Bax recruitment to mitochondrial membrane, and release of Cyt c into the cytoplasm. These findings show that SopB suppresses host cell apoptosis by binding to TRAF6 and preventing mitochondrial ROS generation.

Particle Swarm Optimization Algorithm Based Parameters Estimation and Control of Epileptiform Spikes in a Neural Mass Model

Chaos (Woodbury, N.Y.). Jul, 2016  |  Pubmed ID: 27475078

This paper proposes an epilepsy detection and closed-loop control strategy based on Particle Swarm Optimization (PSO) algorithm. The proposed strategy can effectively suppress the epileptic spikes in neural mass models, where the epileptiform spikes are recognized as the biomarkers of transitions from the normal (interictal) activity to the seizure (ictal) activity. In addition, the PSO algorithm shows capabilities of accurate estimation for the time evolution of key model parameters and practical detection for all the epileptic spikes. The estimation effects of unmeasurable parameters are improved significantly compared with unscented Kalman filter. When the estimated excitatory-inhibitory ratio exceeds a threshold value, the epileptiform spikes can be inhibited immediately by adopting the proportion-integration controller. Besides, numerical simulations are carried out to illustrate the effectiveness of the proposed method as well as the potential value for the model-based early seizure detection and closed-loop control treatment design.

Surface Immobilization of Human Arginase-1 with an Engineered Ice Nucleation Protein Display System in E. Coli

PloS One. 2016  |  Pubmed ID: 27479442

Ice nucleation protein (INP) is frequently used as a surface anchor for protein display in gram-negative bacteria. Here, MalE and TorA signal peptides, and three charged polypeptides, 6×Lys, 6×Glu and 6×Asp, were anchored to the N-terminus of truncated INP (InaK-N) to improve its surface display efficiency for human Arginase1 (ARG1). Our results indicated that the TorA signal peptide increased the surface translocation of non-protein fused InaK-N and human ARG1 fused InaK-N (InaK-N/ARG1) by 80.7% and 122.4%, respectively. Comparably, the MalE signal peptide decreased the display efficiencies of both the non-protein fused InaK-N and InaK-N/ARG1. Our results also suggested that the 6×Lys polypeptide significantly increased the surface display efficiency of K6-InaK-N/ARG1 by almost 2-fold, while also practically abolishing the surface translocation of non-protein fused InaK-N, indicating the interesting roles of charged polypeptides in bacteria surface display systems. Cell surface-immobilized K6-InaK-N/ARG1 presented an arginase activity of 10.7 U/OD600 under the optimized conditions of 40°C, pH 10.0 and 1 mM Mn2+, which could convert more than 95% of L-Arginine (L-Arg) to L-Ornithine (L-Orn) in 16 hours. The engineered InaK-Ns expanded the INP surface display system, which aided in the surface immobilization of human ARG1 in E. coli cells.

Circulating Tumor Cells: A Promising Marker of Predicting Tumor Response in Rectal Cancer Patients Receiving Neoadjuvant Chemo-radiation Therapy

Oncotarget. Oct, 2016  |  Pubmed ID: 27486758

The aim of this study was to investigate the role of circulating tumor cells (CTCs) in assessing and predicting tumor response to neoadjuvant chemoradiotherapy (CRT) for patients with locally advanced rectal cancer (LARC).

Postoperative Chemoradiotherapy Versus Chemotherapy for R0 Resected Gastric Cancer with D2 Lymph Node Dissection: an Up-to-date Meta-analysis

World Journal of Surgical Oncology. Aug, 2016  |  Pubmed ID: 27502921

This meta-analysis aims to provide more evidence on the role of postoperative chemoradiotherapy (CRT) for gastric cancer (GC) patients in Asian countries where D2 lymphadenectomy is prevalent.

Are Genetic and Environmental Influences on Job Satisfaction Stable over Time? A Three-wave Longitudinal Twin Study

The Journal of Applied Psychology. Nov, 2016  |  Pubmed ID: 27504661

Job satisfaction research has unfolded as an exemplary manifestation of the "person versus environment" debate in applied psychology. With the increasing recognition of the importance of time, it is informative to examine a question critical to the dispositional view of job satisfaction: Are genetic influences on job satisfaction stable across different time points? Drawing upon dispositional and situational perspectives on job satisfaction and recent research in developmental behavioral genetics, we examined whether the relative potency of genetic (i.e., the person) and environmental influences on job satisfaction changed over time in a 3-wave longitudinal twin study. Biometric behavioral genetics analyses showed that genetic influences accounted for 31.2% of the variance in job satisfaction measured at approximately Age 21, which was markedly greater than the 18.7% and 19.8% of variance explained by genetic factors at Age 25 and Age 30. Such genetic influences were mediated via positive affectivity and negative affectivity, but not via general mental ability. After partialing out genetic influences, environmental influences on job satisfaction were related to interpersonal conflict at work and occupational status, and these influences were relatively stable across the 3 time points. These results offer important implications for organizations and employees to better understand and implement practices to enhance job satisfaction. (PsycINFO Database Record

G-protein-coupled Receptors Mediate ω-3 PUFAs-inhibited Colorectal Cancer by Activating the Hippo Pathway

Oncotarget. Sep, 2016  |  Pubmed ID: 27506947

Colorectal cancer (CRC) is one of the most common cancers leading to high mortality. However, long-term administration of anti-tumor therapy for CRC is not feasible due to the side effects. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), particularly DHA and EPA, exert protection against CRC, but the mechanisms are unclear. Here, we show that ω-3 PUFAs inhibit proliferation and induce apoptosis of CRC cells in vitro and alleviate AOM/DSS-induced mice colorectal cancer in vivo. Moreover, ω-3 PUFAs promote phosphorylation and cytoplasmic retention of YAP and this effect was mediated by MST1/2 and LATS1, suggesting that the canonical Hippo Pathway is involved in ω-3 PUFAs function. We further confirmed that increase of pYAP by ω-3 PUFAs was mediated by GPRs, including GPR40 and GPR120, which subsequently activate PKA via Gαs, thus inducing the Hippo pathway activation. These data provide a novel DHA/EPA-GPR40/120-Gαs-PKA-MST1/2-LATS1-YAP signaling pathway which is linked to ω-3 PUFAs-induced inhibition of cell proliferation and promotion of apoptosis in CRC cells, indicating a mechanism that could explain the anti-cancer action of ω-3 PUFAs.

Tanshinone IIA Inhibits Apoptosis in the Myocardium by Inducing MicroRNA-152-3p Expression and Thereby Downregulating PTEN

American Journal of Translational Research. 2016  |  Pubmed ID: 27508033

Progressive loss of cardiac myocytes through apoptosis contributes to heart failure (HF). In this study, we tested whether tanshinone IIA, one of the most abundant constituents of the root of Salvia miltiorrhiza, protects rat myocardium-derived H9C2 cells against apoptosis. Treatment of H9C2 cells with tanshinone IIA inhibited angiotensin II-induced apoptosis by downregulating the expression of PTEN (phosphatase and tensin homolog), a tumor suppressor that plays a critical role in apoptosis. Furthermore, tanshinone IIA was found to inhibit PTEN expression by upregulating the microRNA miR-152-3p, a potential PTEN regulator that is highly conserved in both rat and human. Notably, the antiapoptotic effect of tanshinone IIA was partially reversed when H9C2 cells were transfected with an inhibitor of miR-152-3p. Collectively, our findings reveal a previously unrecognized mechanism underlying the cardioprotective role of tanshinone IIA, and further suggest that tanshinone IIA could represent a promising drug candidate for HF therapy.

Pd/RGO Modified Carbon Felt Cathode for Electro-Fenton Removing of EDTA-Ni

Water Science and Technology : a Journal of the International Association on Water Pollution Research. 2016  |  Pubmed ID: 27508368

Ethylenediaminetetraacetic acid (EDTA) forms stable complexes with toxic metals such as nickel due to its strong chelation. The electro-Fenton (EF) process using a cathode made from palladium (Pd), reduced graphene oxide (RGO) and carbon felt, fed with air, exhibited high activities and stability for the removal of 10 mg L(-1) EDTA-Ni solution. Pd/RGO catalyst was prepared by one-pot synthesis; the scanning electron microscopy and X-ray diffraction analysis indicated nanoparticles and RGO were well distributed on carbon felt, forming three dimensional architecture with both large macropores and a mesoporous structure. The cyclic voltammetric results showed that the presence of RGO in Pd/RGO/carbon felt significantly increased the current response of two-electron reduction of O2 (0.45 V). The key factors influencing the removal efficiency of EDTA-Ni, such as pH, current and Fe(2+) concentration, were investigated. Under the optimum conditions, the removal efficiency of EDTA-Ni reached 83.8% after 100 min EF treatment. Mechanism analysis indicated that the introduction of RGO in Pd/RGO/carbon felt significantly enhanced the electrocatalytic activities by inducing •OH in the EF process; direct H2O2 oxidation still accounted for a large amount of EDTA-Ni removal efficiency.

A Molecular Tetrapod for Organic Photovoltaics

ACS Applied Materials & Interfaces. Aug, 2016  |  Pubmed ID: 27514435

The synthesis and characterization of a molecular tetrapod, SFBTD, featuring a tetraphenylsilane center and four identical conjugated arms, which structurally resembles breakwaters in common wave-reducing shore constructions, are reported. Cyclic voltammetry reveals that SFBTD has a medium band gap of ca. 2.0 eV and a low-lying HOMO energy level at ca. -5.2 eV. Absorption spectroscopy, X-ray diffraction, and differential scanning calorimetry experiments reveal a low degree of crystallinity in this compound and slow crystallization kinetics. Bulk heterojunction organic photovoltaics (OPVs) employing SFBTD and fullerene derivatives exhibit power conversion efficiencies (PCEs) up to 1.05% and open-circuit voltage (VOC) values as high as 1.02 V. To the best of our knowledge, this is the highest PCE obtained for OPVs employing molecular tetrapods as donor materials. These devices are relatively thermally stable due to the known ability of breakwater tetrapods to interlock, preventing dislodging and sliding. The lack of favorable phase separations and low hole mobilities of the blend films are the major factors limiting the device performance. Ternary blend devices by the addition of three low band gap poly(thienylene vinylene) (PTV) derivatives were fabricated and tested. We found that the added PTVs acted to be either the major hole conductor or a competing hole conduction channel depending on the HOMO level positions relative to that of SFBTD. Some of the ternary OPV devices out-performed the corresponding binary counterparts employing SFBTD or PTVs alone, suggesting cooperative effects in the ternary systems.

Total Synthesis of the Diterpenoid (+)-Harringtonolide

Angewandte Chemie (International Ed. in English). Sep, 2016  |  Pubmed ID: 27529411

Described herein is the first asymmetric total synthesis of (+)-harringtonolide, a natural diterpenoid with an unusual tropone imbedded in a cagelike framework. The key transformations include an intramolecular Diels-Alder reaction and a rhodium-complex-catalyzed intramolecular [3+2] cycloaddition to install the tetracyclic core as well as a highly efficient tropone formation.

Numerical Investigation of the Flow Dynamics and Evaporative Cooling of Water Droplets Impinging Onto Heated Surfaces: An Effective Approach To Identify Spray Cooling Mechanisms

Langmuir : the ACS Journal of Surfaces and Colloids. Sep, 2016  |  Pubmed ID: 27531256

Numerical investigations of the dynamics and evaporative cooling of water droplets impinging onto heated surfaces can be used to identify spray cooling mechanisms. Droplet impingement dynamics and evaporation are simulated using the presented numerical model. Volume-of-fluid method is used in the model to track the free surface. The contact line dynamics was predicted from a dynamic contact angle model with the evaporation rate predicted by a kinetic theory model. A species transport equation was solved in the gas phase to describe the vapor convection and diffusion. The numerical model was validated by experimental data. The physical effects including the contact angle hysteresis and the thermocapillary effect are analyzed to offer guidance for future numerical models of droplet impingement cooling. The effects of various parameters including surface wettability, surface temperature, droplet velocity, droplet size, and droplet temperature were numerically studied from the standpoint of spray cooling. The numerical simulations offer profound analysis and deep insight into the spray cooling heat transfer mechanisms.

A Neglected Point in Surgical Treatment of Adolescent Idiopathic Scoliosis: Variations in the Number of Vertebrae

Medicine. Aug, 2016  |  Pubmed ID: 27559975

Inaccurate identification of vertebral levels is the main cause of wrong-site spine surgery which is performed by nearly half of the spine surgeons. Unusual anatomy and failure to verify the surgical level on radiographs have been commonly reported. We aimed at investigating the variations in vertebral number in adolescent idiopathic scoliosis (AIS) patients and thus to raise awareness of the possibility for wrong-level spinal surgery and to make a comparison with normal adolescents. A cohort of 657 AIS patients and 248 normal adolescents, presented to our center from June 2008 to February 2013, who met the inclusion criteria, were recruited. Radiographs were reviewed to identify the number of thoracic or lumbar vertebrae and the presence of a lumbosacral transitional vertebra. In the AIS group, 70 (10.6%) patients had variations in the number of thoracic and/or lumbar vertebrae. Remarkably, the prevalence of variations in male subjects was significantly higher than that in female subjects (P < 0.05). Thirty-seven patients (5.6%) had an atypical number of thoracic vertebrae, with 33 having 11 thoracic vertebrae and 4 patients having 13. Forty-eight patients (7.3%) had an atypical number of lumbar vertebrae, with 14 having 4 lumbar vertebrae and 34 patients having 6. Multilevel vertebral anomalies were present in 2.3% of the patients (15 of 657). A variation in the number of vertebrae had been identified in 1.7% (11) of the reports by the radiologist. In the normal group, 27 (10.9%) subjects showed variations in the vertebral number. There was no significant difference in the prevalence of atypical numbers of vertebral number between the AIS and normal groups (P > 0.05). Therefore, we concluded that variations in the number of thoracic-lumbar vertebrae were found in up to10.6% of AIS patients. Identification of variations in the number of vertebrae is crucial to serve to decrease the risk of wrong-level surgery.

A New Paradigm for Producing Astaxanthin from the Unicellular Green Alga Haematococcus Pluvialis

Biotechnology and Bioengineering. Oct, 2016  |  Pubmed ID: 27563850

The unicellular green alga Haematococcus pluvialis has been exploited as a cell factory to produce the high-value antioxidant astaxanthin for over two decades, due to its superior ability to synthesize astaxanthin under adverse culture conditions. However, slow vegetative growth under favorable culture conditions and cell deterioration or death under stress conditions (e.g., high light, nitrogen starvation) has limited the astaxanthin production. In this study, a new paradigm that integrated heterotrophic cultivation, acclimation of heterotrophically grown cells to specific light/nutrient regimes, followed by induction of astaxanthin accumulation under photoautotrophic conditions was developed. First, the environmental conditions such as pH, carbon source, nitrogen regime, and light intensity, were optimized to induce astaxanthin accumulation in the dark-grown cells. Although moderate astaxanthin content (e.g., 1% of dry weight) and astaxanthin productivity (2.5 mg L(-1)  day(-1) ) were obtained under the optimized conditions, a considerable number of cells died off when subjected to stress for astaxanthin induction. To minimize the susceptibility of dark-grown cells to light stress, the algal cells were acclimated, prior to light induction of astaxanthin biosynthesis, under moderate illumination in the presence of nitrogen. Introduction of this strategy significantly reduced the cell mortality rate under high-light and resulted in increased cellular astaxanthin content and astaxanthin productivity. The productivity of astaxanthin was further improved to 10.5 mg L(-1)  day(-1) by implementation of such a strategy in a bubbling column photobioreactor. Biochemical and physiological analyses suggested that rebuilding of photosynthetic apparatus including D1 protein and PsbO, and recovery of PSII activities, are essential for acclimation of dark-grown cells under photo-induction conditions. Biotechnol. Bioeng. 2016;113: 2088-2099. © 2016 The Authors. Biotechnology and Bioengineering Published by Wiley Periodicals, Inc.

Water in Contact with a Cationic Lipid Exhibits Bulklike Vibrational Dynamics

The Journal of Physical Chemistry. B. Sep, 2016  |  Pubmed ID: 27564997

Water in contact with lipids is an important aspect of most biological systems and has been termed "biological water". We used time-resolved infrared spectroscopy to investigate the vibrational dynamics of lipid-bound water molecules, to shed more light on the properties of these important molecules. We studied water in contact with a positively charged lipid monolayer using surface-specific two-dimensional sum frequency generation vibrational spectroscopy with subpicosecond time resolution. The dynamics of the O-D stretch vibration was measured for both pure D2O and isotopically diluted D2O under a monolayer of 1,2-dipalmitoyl-3-trimethylammonium-propane. It was found that the lifetime of the stretch vibration depends on the excitation frequency and that efficient energy transfer occurs between the interfacial water molecules. The spectral diffusion and vibrational relaxation of the stretch vibration were successfully explained with a simple model, taking into account the Förster transfer between stretch vibrations and vibrational relaxation via the bend overtone. These observations are very similar to those made for bulk water and as such lead us to conclude that water at a positively charged lipid interface behaves similarly to bulk water. This contrasts the behavior of water in contact with negative or zwitterionic lipids and can be understood by noting that for cationic lipids the charge-induced alignment of water molecules results in interfacial water molecules with O-D groups pointing toward the bulk.

Combining Antiangiogenic Therapy with Neoadjuvant Chemotherapy Increases Treatment Efficacy in Stage IIIA (N2) Non-small Cell Lung Cancer Without Increasing Adverse Effects

Oncotarget. Sep, 2016  |  Pubmed ID: 27566586

To evaluate the safety and efficacy of combining Endostar antiangiogenic therapy with neoadjuvant chemotherapy for the treatment of stage IIIA (N2) NSCLC, we conducted a randomized, controlled, open-label clinical study of 30 NSCLC patients. Patients were randomly assigned to the test or control groups, which received either two cycles of an NP neoadjuvant chemotherapy regimen combined with Endostar or the NP regimen alone, respectively, at a 2:1 ratio. Efficacy was assessed after 3 weeks, and surgical resection occurred within 4 weeks, in the 26 patients who successfully completed treatment. While total response rates (RR) and clinical benefit rates (CBR) did not differ between the experimental groups, total tumor regression rates (TRR) were higher in the test group than in the control group. Median DFS and OS also did not differ between the test and control groups. Clinical perioperative indicators, including intraoperative blood loss, number of dissected lymph node groups, duration of postoperative indwelling catheter use, and time to postoperative discharge, were comparable in the test and control groups. Finally, hematological and non-hematological toxicities and postoperative pathological indicators, including down-staging ratio, complete resection ratio, and metastatic lymph node ratio, also did not differ between the groups. Overall, combining Endostar with NP neoadjuvant chemotherapy increased therapeutic efficacy without increasing adverse effects in stage IIIA-N2 NSCLC patients. This study is registered with (number NCT02497118).

Connexin43 Hemichannels Contributes to the Disassembly of Cell Junctions Through Modulation of Intracellular Oxidative Status

Redox Biology. Oct, 2016  |  Pubmed ID: 27567473

Connexin (Cx) hemichannels regulate many cellular processes with little information available regarding their mechanisms. Given that many pathological factors that activate hemichannels also disrupts the integrity of cellular junctions, we speculated a potential participation of hemichannels in the regulation of cell junctions. Here we tested this hypothesis. Exposure of renal tubular epithelial cells to Ca(2+)-free medium led to disassembly of tight and adherens junctions, as indicated by the reduced level of ZO-1 and cadherin, disorganization of F-actin, and severe drop in transepithelial electric resistance. These changes were preceded by an activation of Cx43 hemichannels, as revealed by extracellular efflux of ATP and intracellular influx of Lucifer Yellow. Inhibition of hemichannels with chemical inhibitors or Cx43 siRNA greatly attenuated the disassembly of cell junctions. Further analysis using fetal fibroblasts derived from Cx43 wide-type (Cx43(+/+)), heterozygous (Cx43(+/-)) and knockout (Cx43(-/-)) littermates showed that Cx43-positive cells (Cx43(+/+)) exhibited more dramatic changes in cell shape, F-actin, and cadherin in response to Ca(2+) depletion, as compared to Cx43-null cells (Cx43(-/-)). Consistently, these cells had higher level of protein carbonyl modification and phosphorylation, and much stronger activation of P38 and JNK. Hemichannel opening led to extracellular loss of the major antioxidant glutathione (GSH). Supplement of cells with exogenous GSH or inhibition of oxidative sensitive kinases largely prevented the above-mentioned changes. Taken together, our study indicates that Cx43 hemichannels promote the disassembly of cell junctions through regulation of intracellular oxidative status.

Pex14/17, a Filamentous Fungus-specific Peroxin, is Required for the Import of Peroxisomal Matrix Proteins and Full Virulence of Magnaporthe Oryzae

Molecular Plant Pathology. Aug, 2016  |  Pubmed ID: 27571711

Peroxisomes are ubiquitous organelles in eukaryotic cells that fulfil a variety of biochemical functions. The biogenesis of peroxisomes requires a variety of proteins, named peroxins, which are encoded by PEX genes. Pex14/17 is a putative recently identified peroxin, specifically present in filamentous fungal species. Its function in peroxisomal biogenesis is still obscure and its roles in fungal pathogenicity have not yet been documented. Here, we demonstrate the contributions of Pex14/17 in the rice blast fungus Magnaporthe oryzae (Mopex14/17) to peroxisomal biogenesis and fungal pathogenicity by targeting gene replacement strategies. Mopex14/17 has properties of both Pex14 and Pex17 with regard to its protein sequence. Mopex14/17 is distributed at the peroxisomal membrane and is essential for efficient peroxisomal targeting of proteins containing peroxisomal targeting signal 1. MoPEX19 deletion leads to the cytoplasmic distribution of Mopex14/17, indicating that the peroxisomal import of Pex14/17 is dependent on Pex19. The knockout mutants of MoPEX14/17 show reduced fatty acid utilization, reactive oxygen species (ROS) degradation and cell wall integrity. Moreover, Δmopex14/17 mutants show delayed conidial generation and appressorial formation, and a reduction in appressorial turgor accumulation and penetration ability in host plants. These defects result in a significant reduction in the virulence of the mutant. These data indicate that MoPEX14/17 plays a crucial role in peroxisome biogenesis and contributes to fungal development and pathogenicity.

Correlated Perovskites As a New Platform for Super-Broadband-Tunable Photonics

Advanced Materials (Deerfield Beach, Fla.). Nov, 2016  |  Pubmed ID: 27573540

The electron-doping-induced phase transition of a prototypical perovskite SmNiO3 induces a large and non-volatile optical refractive-index change and has great potential for active-photonic-device applications. Strong optical modulation from the visible to the mid-infrared is demonstrated using thin-film SmNiO3 . Modulation of a narrow band of light is demonstrated using plasmonic metasurfaces integrated with SmNiO3 .

Glucagon-like Peptide-1 Attenuates Advanced Oxidation Protein Product-mediated Damage in Islet Microvascular Endothelial Cells Partly Through the RAGE Pathway

International Journal of Molecular Medicine. Oct, 2016  |  Pubmed ID: 27574116

Advanced oxidation protein products (AOPPs) are knownt to play a role in the pathogenesis of diseases and related complications. However, whether AOPPs affect the survival of islet microvascular endothelial cells (IMECs) has not been reported to date, at least to the best of our knowledge. In this study, we aimed to investigate the mechanisms underlying AOPP-mediated damage in IMECs and the protective role of glucagon-like peptide-1 (GLP-1), which has been suggested to exert beneficial effects on the cardiovascular system. IMECs were treated with AOPPs (0-200 µg/ml) for 0-72 h in the presence or absence of GLP-1 (100 nmol/l). Apoptosis, cell viability and reactive oxygen species (ROS) production were examined, the expression levels of p53, Bax, receptor for advanced glycation end-products (RAGE) and NAD(P)H oxidase subunit were determined, and the activity of NAD(P)H oxidase, caspase-9 and caspase-3 was also determined. The results revealed that AOPPs increased the expression of RAGE, p47phox and p22phox; induced NAD(P)H oxidase-dependent ROS generation, increased p53 and Bax expression, enhanced the activity of caspase-9 and caspase-3, and induced cell apoptosis. Treatment with GLP-1 decreased the expression of RAGE, inhibited NAD(P)H oxidase activity, decreased cell apoptosis and increased cell viability. On the whole, our findings indicate that AOPPs induce the apoptosis of IMECs via the RAGE-NAD(P)H oxidase-dependent pathway and that treatment with GLP-1 effectively reverses these detrimental effects by decreasing AOPP-induced RAGE expression and restoring the redox balance. Our data may indicate that GLP-1 may prove to be beneficial in attenuating the progression of diabetes mellitus.

Efficient Production of Gene-Modified Mice Using Staphylococcus Aureus Cas9

Scientific Reports. Sep, 2016  |  Pubmed ID: 27586692

The CRISPR/Cas system is an efficient genome-editing tool to modify genes in mouse zygotes. However, only the Streptococcus pyogenes Cas9 (SpCas9) has been systematically tested for generating gene-modified mice. The protospacer adjacent motif (PAM, 5'-NGG-3') recognized by SpCas9 limits the number of potential target sites for this system. Staphylococcus aureus Cas9 (SaCas9), with its smaller size and unique PAM (5'-NNGRRT-3') preferences, presents an alternative for genome editing in zygotes. Here, we showed that SaCas9 could efficiently and specifically edit the X-linked gene Slx2 and the autosomal gene Zp1 in mouse zygotes. SaCas9-mediated disruption of the tyrosinase (Tyr) gene led to C57BL/6J mice with mosaic coat color. Furthermore, multiplex targeting proved efficient multiple genes disruption when we co-injected gRNAs targeting Slx2, Zp1, and Tyr together with SaCas9 mRNA. We were also able to insert a Flag tag at the C-terminus of histone H1c, when a Flag-encoding single-stranded DNA oligo was co-introduced into mouse zygotes with SaCas9 mRNA and the gRNA. These results indicate that SaCas9 can specifically cleave the target gene locus, leading to successful gene knock-out and precise knock-in in mouse zygotes, and highlight the potential of using SaCas9 for genome editing in preimplantation embryos and producing gene-modified animal models.

Validation of the Memorial Sloan Kettering Cancer Center Nomogram to Predict Disease-specific Survival in a Chinese Gastric Cancer Population Receiving Postoperative Chemoradiotherapy After an R0 Resection

Oncotarget. 10, 2016  |  Pubmed ID: 27588465

The widely validated Memorial Sloan Kettering Cancer Center (MSKCC) nomogram for gastric carcinoma (GC) was developed based on patients who received R0 resection only. The purpose of the current study was to assess the performance of this nomogram in Chinese patients who received postoperative chemoradiotherapy (CRT) after an R0 resection for GC. From 2006 to 2015, the clinical data of 150 eligible patients were retrospectively collected from the Fudan University Shanghai Cancer Center (FUSCC) and used for external validation. The nomogram was validated by means of the concordance index (CI) and a calibration plot. The CI for the nomogram was 0.657, which was lower than the CI of the nomogram for patients who received surgery alone (0.80). In the calibration plot, the gap between the observed and the predicted survival gradually increased as the predicted 5-year disease-specific survival (DSS) decreased. Thus the MSKCC nomogram for GC significantly underestimated the survival of patients in the FUSCC cohort, especially the survival of patients whose predicted 5-year DSS was less than 50%. The current study indicates the potential for the nomogram to be developed as an ideal tool to identify target patients for postoperative CRT.

Safety and Effectiveness of Total Splenic Vessel Ligations in Paediatric Patients with Splenomegaly

Journal of Minimal Access Surgery. Oct-Dec, 2016  |  Pubmed ID: 27609328

Splenomegaly may contribute to hypersplenism and can result in thrombocytopenia. Many approaches are used to treat splenomegaly; however, the current management of splenomegaly has intrinsic limitations or disadvantages. Now, we initiate a new approach, that of total splenic vessel (artery and vein) ligations (TSVLs) in paediatric patients with splenomegaly. The purpose of our study is to evaluate the results obtained with TVSLs procedure for paediatric patients.

Probe-Based Confocal Laser Endomicroscopy for Imaging TRAIL-Expressing Mesenchymal Stem Cells to Monitor Colon Xenograft Tumors In Vivo

PloS One. 2016  |  Pubmed ID: 27617958

Mesenchymal stem cells (MSCs) can serve as vehicles for therapeutic genes. However, little is known about MSC behavior in vivo. Here, we demonstrated that probe-based confocal laser endomicroscopy (pCLE) can be used to track MSCs in vivo and individually monitor tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) gene expression within carcinomas.

Deregulation of the Planar Cell Polarity Genes CELSR3 and FZD3 in Hirschsprung Disease

Experimental and Molecular Pathology. Oct, 2016  |  Pubmed ID: 27619161

Hirschsprung disease (HSCR) is a congenital disorder characterized by the absence of intrinsic ganglion cells in the lower intestine. Genetic factors in the pathogenesis of this disease are under active investigation. As core genes in the planar cell polarity pathway, Celsr3 and Fzd3 are believed to play vital roles in the development of the murine enteric nervous system. The potential association of CELSR3 and FZD3 with the development of HSCR in humans, however, is still unknown. We determined the genotypes of eight CELSR3 and FZD3 polymorphisms in 113 patients. Furthermore, target gene sequencing was used to search for rare mutations in the planar cell polarity genes. The mRNA and protein expression of CELSR3 and FZD3 were explored in patients with HSCR. Class III β-tubulin in colon tissue samples was examined to elucidate enteric innervation patterns. We observed a significant association between the FZD3 rs17059206 polymorphism and HSCR susceptibility (p<0.001). In addition, five rare mutations in CELSR3 were identified in six patients with HSCR. Upregulation of CELSR3 mRNA expression was detected in 80% of aganglionic segments; a similar increase was found for FZD3 protein expression in 81.8% of aganglionic tissues, compared with the ganglionic segments. Immunohistochemical staining on tissue sections revealed obvious excess expression of both molecules in the mucosal layer. The neurite patterns were highly disorganized in the aganglionic bowel segments, with a marked reduction in the prominence of TUJ1 bundles in number, thickness, and length. Our results showed that deregulation of the planar cell polarity genes CELSR3 and FZD3 might disrupt the enteric innervation pattern and consequently contribute to the susceptibility to HSCR.

A Broadly Neutralizing Anti-influenza Antibody Reveals Ongoing Capacity of Haemagglutinin-specific Memory B Cells to Evolve

Nature Communications. Sep, 2016  |  Pubmed ID: 27619409

Understanding the natural evolution and structural changes involved in broadly neutralizing antibody (bnAb) development holds great promise for improving the design of prophylactic influenza vaccines. Here we report an haemagglutinin (HA) stem-directed bnAb, 3I14, isolated from human memory B cells, that utilizes a heavy chain encoded by the IGHV3-30 germline gene. MAb 3I14 binds and neutralizes groups 1 and 2 influenza A viruses and protects mice from lethal challenge. Analysis of VH and VL germline back-mutants reveals binding to H3 and H1 but not H5, which supports the critical role of somatic hypermutation in broadening the bnAb response. Moreover, a single VLD94N mutation improves the affinity of 3I14 to H5 by nearly 10-fold. These data provide evidence that memory B cell evolution can expand the HA subtype specificity. Our results further suggest that establishing an optimized memory B cell pool should be an aim of 'universal' influenza vaccine strategies.

Asymmetric Multifunctional Heterogeneous Membranes for PH- and Temperature-Cooperative Smart Ion Transport Modulation

Advanced Materials (Deerfield Beach, Fla.). Nov, 2016  |  Pubmed ID: 27629083

Asymmetric multifunctional heterogeneous membranes are demonstrated by combing a block copolymer polystyrene-block-poly(N,N-dimethylaminoethylmethacrylate) membrane with a track-etched porous poly(ethylene terephthalate) membrane. This hybrid membrane is capable of integrating pH- and temperature-cooperative high-performance ionic rectification, highly efficient cation gating, and excellent stability and controllability, which allows broad application in biosensing, energy conversion, and filtration.

Dynamically Regulated Ag Nanowire Arrays for Detecting Molecular Information of Substrate-Induced Stretched Cell Growth

Advanced Materials (Deerfield Beach, Fla.). Nov, 2016  |  Pubmed ID: 27629386

The modified coffee-ring effect is used to self-assemble highly uniform, long-range-ordered Ag nanowire arrays. As the oriented Ag nanowire arrays provide excellent membranes for surface-enhanced Raman scattering, the molecular mechanism of cell adhesion and growth is systematically studied and well understood. This work has important significance for life science research.

Neuroprotective Role of MicroRNA-22 in a 6-Hydroxydopamine-Induced Cell Model of Parkinson's Disease Via Regulation of Its Target Gene TRPM7

Journal of Molecular Neuroscience : MN. Dec, 2016  |  Pubmed ID: 27631550

Parkinson's disease (PD), the second most prevalent neurodegenerative disorder with only symptomatic treatment available, is characterized by a progressive loss of dopaminergic neurons in the midbrain. Ample evidence indicated that microRNAs (miRs) could regulate post-transcriptional gene expression and neuronal disease. In the present study, we have evaluated the effects and mechanism of miR-22 in PC12 pheochromocytoma cells treated with 6-hydroxydopamine (6-OHDA) to mimic PD. RT-PCR results showed that the expression of miR-22 is downregulated in 6-OHDA-treated PC12 cells, and the overexpression of miR-22 significantly promoted the survival and proliferation of 6-OHDA-induced PC12 cells, whereas miR-22 inhibitor reversed these effects. In addition, PC12 cells were treated with miR-22 mimics or inhibitor following 6-OHDA administration, which medicated ROS production and upregulation or downregulation of caspase-3 activity, respectively. A luciferase reporter assay revealed that transient receptor potential melastatin 7 (TRPM7) is a direct target gene of miR-22, and miR-22 overexpression markedly downregulated the level of TRPM7. Strikingly, further analysis showed that miR-22 mediated 6-OHDA-induced PC12 cell survival and proliferation by targeting TRPM7. Taken together, the present study showed that miR-22 overexpression exhibited neuroprotective and reversal effects on the 6-OHDA-induced PC12 cell growth and apoptosis by targeting TRPM7.

Cyclization of Tetraaryl-Substituted Benzoquinones and Hydroquinones Through the Scholl Reaction

The Journal of Organic Chemistry. Oct, 2016  |  Pubmed ID: 27648729

2,3,5,6-Tetrakis(5'-dodecylthiophen-2-yl)-benzoquinones and 2,3,5,6-tetrakis(5'-dodecylthiophen-2'-yl)-hydroquinones were prepared via the Stille or Suzuki cross-coupling reactions, followed by oxidation by 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in the case that aryl groups are dodecylthiophenyl. 2,3,5,6-Tetrakis(5'-dodecylthiophen-2'-yl)benzoquinone and 2,3,5,6-tetrakis(5'-dodecylthiophen-2'-yl)-1,4-bis(dodecyloxy)benzene underwent the Scholl reaction to give their corresponding predictable cyclization products anthra[2,1-b:3,4-b':6,5-b″:7,8-b‴]tetrathiophene-7,14-dione (3) and anthra[1,2-b:4,3-b':5,6-b″:8,7-b‴]tetrathiophene (5), respectively. Cyclization of 2,3,4,5-tetra(p-tert-butyl-phenyl) benzoquinones through the Scholl reaction, however, gave rise to a mixture of two cyclization products including an unusual major product, benzo[4',5']furo[3',2':3,4]triphenyleno[1,2-b]benzofuran (9), with 84% yield and a minor product, 2,3-diphenyltriphenylene-1,4-diol (10), with 11% yield. In contrast, cyclization of 2,3,4,5-tetrakis(p-dodecyloxyphenyl)benzoquinone only afforded 2,3-diphenyltriphenylene-1,4-diol (8) with 34% yield. The optical and electrochemistry properties of these fused aromatics were studied. Light emitting diode devices using compound 9 as the fluorescent dopant were fabricated. A maximum external quantum efficiency of 3.23% was achieved for a 4,4'-bis(carbazole)biphenyl/9 based device, revealing the potential for such fused aromatics as dopant to be a blue LED component, subject to the functionalization on these novel π-structures as well as further device optimization.

Electrostatic-Charge- and Electric-Field-Induced Smart Gating for Water Transportation

ACS Nano. Sep, 2016  |  Pubmed ID: 27648730

Regulating and controlling the transport of water across nanochannels is of great importance in both fundamental research and practical applications because it is difficult to externally control water flow through nanochannels as in biological channels. To date, only a few hydrophobic nanochannels controlling the transport of water have been reported, all of which use exotic hydrophobic molecules. However, the effect of electrostatic charges, which plays an indispensable role in membrane proteins and dominates the energetics of water permeation across aquaporins, has not gained enough attention to control water transport through a solid-state nanochannel/nanopore. Here, we report electrostatic-charge-induced water gating of a single ion track-etched sub-10 nm channel. This system can directly realize the gating transition between an open, conductive state and a closed, nonconductive state by regulating the surface charge density through a process that involves alternating capillary evaporation and capillary condensation. Compared to the introduction of exotic hydrophobic molecules, water gating controlled by electrostatic charges is simple, convenient, and effective. Such a system anticipates potential applications including desalination, controllable valves, and drug delivery systems.

Biomimetic Nanofluidic Diode Composed of Dual Amphoteric Channels Maintains Rectification Direction over a Wide PH Range

Angewandte Chemie (International Ed. in English). Oct, 2016  |  Pubmed ID: 27651002

pH-gated ion channels in cell membranes play important roles in the cell's physiological activities. Many artificial nanochannels have been fabricated to mimic the natural phenomenon of pH-gated ion transport. However, these nanochannels show pH sensitivity only within certain pH ranges. Wide-range pH sensitivity has not yet been achieved. Herein, for the first time, we provide a versatile strategy to increase the pH-sensitive range by using dual amphoteric nanochannels. In particular, amphoteric polymeric nanochannels with carboxyl groups derived from a block copolymer (BCP) precursor and nanochannels with hydroxyl groups made from anodic alumina oxide (AAO) were used. Due to a synergistic effect, the hybrid nanochannels exhibit nanofluidic diode properties with single rectification direction over a wide pH range. The novel strategy presented here is a scalable, low-cost, and robust alternative for the construction of large-area membranes for nanofluidic applications, such as the separation of biomolecules.

Two-Photon-Induced Isomerization of Spiropyran/Merocyanine at the Air/Water Interface Probed by Second Harmonic Generation

The Journal of Physical Chemistry. A. Oct, 2016  |  Pubmed ID: 27652815

Photochromic molecules often exhibit switchable hyperpolarizabilities upon photoisomerization between two molecular states and can be widely applied in nonlinear optical materials. Photoisomerization can occur through either one-photon or two-photon processes. Two-photon-induced isomerization has several advantages over one-photon process but has not been fully explored. In the present study, we have used second harmonic generation to investigate the two-photon-induced isomerization between spiropyran and merocyanine at the air/water interface. We show that spiropyran and merocyanine can be converted into each other reversibly with 780-nm laser-beam irradiation through two-photon processes. We also investigated the isomerization rates under various incident laser powers. Quantitative analysis revealed that the isomerization rates of spiropyran and merocyanine depend differently on the laser power. We attribute the difference to the distinct molecular structures of spiropyran and merocyanine. At the interface, nonplanar spiropyran molecules exist mainly as monomers, whereas planar merocyanine molecules form aggregates. Upon aggregation, steric hindrance effects and excitonic coupling efficiently arrest the photoisomerization of merocyanine. This work provides an in-depth understanding of two-photon-induced isomerization at the interface, which is beneficial for designing and controlling optical thin-film materials.

Reproducibility with Repeat CT in Radiomics Study for Rectal Cancer

Oncotarget. Nov, 2016  |  Pubmed ID: 27669756

To evaluate the reproducibility of radiomics features by repeating computed tomographic (CT) scans in rectal cancer. To choose stable radiomics features for rectal cancer.

Precisely Controllable Core-Shell Ag@Carbon Dots Nanoparticles: Application to in Situ Super-Sensitive Monitoring of Catalytic Reactions

ACS Applied Materials & Interfaces. Oct, 2016  |  Pubmed ID: 27673572

Carbon dots (CDs) have attracted extensive interest owing to their unparalleled physical and chemical characteristics. CDs based nanocomposites have also drawn increasing attention because the combination of different characteristics could offer additional brilliant properties (such as photocatalysis and Raman scattering). In this work, we developed a fast, facile, and controllable method for fabricating core-shell Ag@CDs nanoparticles (NPs) based on the ability of CDs to directly reduce Ag(+) to Ag NPs without an external photoirradiation process or additional reductants. The as-prepared Ag@CDs NPs caused efficient CDs fluorescence quenching, and the typical bands of carbon species were obtained in the Raman spectrum of CDs. In addition, we found that the Ag@CDs NPs could be utilized as an efficient surface-enhanced Raman scattering (SERS) substrate, showing a discernible detection concentration as low as 10(-8) M by using p-aminothiophenol (PATP) as the probe molecules. The as-prepared Ag@CDs NPs used as the SERS substrate also exhibited excellent peroxidase-like catalytic activity for in situ super-sensitive monitoring of the oxidation of 3,3',5,5'-tetramethylbenzidine by H2O2, a plasmon-enhanced driven photocatalytic reaction of p-nitrothiophenol (PNTP) dimerizing into 4,4'-dimercaptoazobenzene, and catalytic driven reduction of PNTP to PATP in the presence of NaBH4 in real time. Moreover, the determination of H2O2 with a significantly lower discernible detection concentration was obtained. This work demonstrated that the hybrid nanostructures not only exhibited unique SERS properties but also showed excellent catalytic activities, especially as an ultrasensitive SERS substrate for monitoring heterogeneous catalytic reactions in real time. This would make it possible to not only obtain the information about catalytic molecular changes but also conduct quantitative and qualitative analysis, and widen the application of CDs in SERS and catalytic reactions.

[Research Progress in Molecular Classification of Gastric Cancer]

Zhonghua Wei Chang Wai Ke Za Zhi = Chinese Journal of Gastrointestinal Surgery. Sep, 2016  |  Pubmed ID: 27680079

Gastric cancer(GC) is a highly heterogeneous malignancy. The present widely used histopathological classifications have gradually failed to meet the needs of individualized diagnosis and treatment. Development of technologies such as microarray and next-generation sequencing (NGS) has allowed GC to be studied at the molecular level. Mechanisms about tumorigenesis and progression of GC can be elucidated in the aspects of gene mutations, chromosomal alterations, transcriptional and epigenetic changes, on the basis of which GC can be divided into several subtypes. The classifications of Tan's, Lei's, TCGA and ACRG are relatively comprehensive. Especially the TCGA and ACRG classifications have large sample size and abundant molecular profiling data, thus, the genomic characteristics of GC can be depicted more accurately. However, significant differences between both classifications still exist so that they cannot be substituted for each other. So far there is no widely accepted molecular classification of GC. Compared with TCGA classification, ACRG system may have more clinical significance in Chinese GC patients since the samples are mostly from Asian population and show better association with prognosis. The molecular classification of GC may provide the theoretical and experimental basis for early diagnosis, therapeutic efficacy prediction and treatment stratification while their clinical application is still limited. Future work should involve the application of molecular classifications in the clinical settings for improving the medical management of GC.

Restoration of Mimecan Expression by Grape Seed Procyanidin B2 Through Regulation of Nuclear Factor-kappaB in Mice With Diabetic Nephropathy

Iranian Journal of Kidney Diseases. Sep, 2016  |  Pubmed ID: 27721232

Grape seed procyanidin B2 (GSPB2) exerts a variety of potent protective pharmacological effects on diabetic complications. The renal protective effects of GSPB2 and the target protein mimecan regulated by GSPB2, discovered in a previous quantitative proteomic analysis, were assessed in mice with diabetic nephropathy Twenty-four db/db mice were divided into 2 groups of the vehicle-treated and GSPB2-treated (30 mg/kg/d) diabetic groups. All animals were observed for 10 weeks. Treatment with GSPB2 resulted in an improvement in body weight increase and serum levels of triglyceride, total cholesterol, advanced glycation end products, and urinary albumin excretion in comparison with the vehicle-treated diabetic mice (P < .05), although these levels were still higher than those in the control group. Treatment with GSPB2 significantly reduced the extent of glomerular basement membranes thickening, mesangial expansion, and glomerular area as well. Mimecan protein expressions in diabetes mellitus were decreased approximately by 28% when compared with those in the control group (P < .05), and restored remarkably after GSPB2 treatment (P < .05). The expression of nuclear factor-κB (NF-κB) p65 in nuclear extracts, markedly higher in the diabetic mice than in the controls, was significantly suppressed by GSPB2. The findings of this study revealed that mimecan might become a new therapeutic target in the future and indicated that GSPB2 had beneficial effects not only on oxidative stress, but also on renal fibrosis, particularly in the diabetic kidney.

Scutellarin Inhibits RANKL-mediated Osteoclastogenesis and Titanium Particle-induced Osteolysis Via Suppression of NF-κB and MAPK Signaling Pathway

International Immunopharmacology. Nov, 2016  |  Pubmed ID: 27728897

Aseptic prosthetic loosening is a major complication after hip joint replacement. Wear particle-induced periprosthetic osteolysis plays a key role in aseptic prosthetic loosening. Attempting to modulate receptor activator of nuclear factor-κB (RANKL) mediated signaling pathways is a promising strategy to prevent aseptic prosthetic loosening. In the present study, we determined the effect of scutellarin (SCU) on titanium (Ti) particle-induced osteolysis in a mouse calvarial model and RANKL-mediated osteoclastogenesis. We determined that SCU, the major effective constituent of breviscapine isolated from a Chinese herb, has potential effects on preventing Ti particle-caused osteolysis in calvarial model of mouse. In vitro, SCU could suppress RANKL-mediated osteoclastogenesis, the function of osteoclast bone resorption, and the expression levels of osteoclast-specific genes (tartrate-resistant acid phosphatase (TRAP), cathepsin K, c-Fos, NFATc1). Further investigation indicated that SCU could inhibit RANKL-mediated MAPK and NF-κB signaling pathway, including JNK1/2, p38, ERK1/2, and IκBα phosphorylation. Taken together, these results indicate that SCU could inhibit osteoclastogenesis and prevent Ti particle-induced osteolysis by suppressing RANKL-mediated MAPK and NF-κB signaling pathway. These results suggest that SCU is a promising therapeutic agent for preventing wear particle-induced periprosthetic osteolysis.

Meta-Analysis of the Clinical Effectiveness and Safety of Ligustrazine in Cerebral Infarction

Evidence-based Complementary and Alternative Medicine : ECAM. 2016  |  Pubmed ID: 27738442

Objectives. To evaluate the efficacy and safety of ligustrazine in the treatment of cerebral infarction. Methods. A systematic literature search was conducted in 6 databases until 30 June 2016 to identify randomized controlled trials (RCTs) of ligustrazine in the treatment of cerebral infarction. The quality of all the included studies was evaluated. All data were analyzed by Review Manager 5.1 Software. Results. 19 RCTs totally involving 1969 patients were included. The primary outcome measures were Neurological Deficit Score (NDS) and clinical effective rate. The secondary outcome measure was adverse events. Meta-analysis showed that ligustrazine could improve clinical efficacy and NDS of cerebral infarction with [OR = 3.60, 95% CI (2.72, 4.78), P < 0.00001] and [WMD = -3.87, 95% CI (-4.78, -2.95), P < 0.00001]. Moreover, ligustrazine in treatment group exerted better clinical effects in improving the Blood Rheology Index (BRI) in patients compared with control group. Ten trials contained safety assessments and stated that no obvious side effects were found. Conclusions. Ligustrazine demonstrated definite clinical efficacy for cerebral infarction, and it can also improve NDS in patients without obvious adverse events. However, due to the existing low-quality research, more large-scale and multicentric RCTs are required to provide clear evidence for its clinical efficacy in the near future.

Rapid and Sensitive Detection of Cancer Cells Based on the Photothermal Effect of Graphene Functionalized Magnetic Microbeads

ACS Applied Materials & Interfaces. Nov, 2016  |  Pubmed ID: 27739298

A strategy based on an immune-graphene oxide (GO)-magnetic microbead complex for the sensitive, rapid, portable, and low-cost detection of cancer cells was developed. The high-efficiency cell capture and high sensitive thermal contrast detection could be simultaneously achieved using magnetic microbeads and the photothermal effect of GOs. The temperature variation caused by irradiating the GOs with a laser was used to establish the standard curve of temperature variation and cancer cell number. Under optimal conditions, the limit of detection could reach 100 cells. 4T1 cells spiked in human blood could be successfully detected in 1.5 h, and the recovery was between 90.8% and 116.5%.

Nonreciprocal Acoustics and Dynamics in the In-plane Oscillations of a Geometrically Nonlinear Lattice

Physical Review. E. Sep, 2016  |  Pubmed ID: 27739799

We study the dynamics and acoustics of a nonlinear lattice with fixed boundary conditions composed of a finite number of particles coupled by linear springs, undergoing in-plane oscillations. The source of the strongly nonlinearity of this lattice is geometric effects generated by the in-plane stretching of the coupling linear springs. It has been shown that in the limit of low energy the lattice gives rise to a strongly nonlinear acoustic vacuum, which is a medium with zero speed of sound as defined in classical acoustics. The acoustic vacuum possesses strongly nonlocal coupling effects and an orthogonal set of nonlinear standing waves [or nonlinear normal modes (NNMs)] with mode shapes identical to those of the corresponding linear lattice; in contrast to the linear case, however, all NNMs except the one with the highest wavelength are unstable. In addition, the lattice supports two types of waves, namely, nearly linear sound waves (termed "L waves") corresponding to predominantly axial oscillations of the particles and strongly nonlinear localized propagating pulses (termed "NL pulses") corresponding to predominantly transverse oscillating wave packets of the particles with localized envelopes. We show the existence of nonlinear nonreciprocity phenomena in the dynamics and acoustics of the lattice. Two opposite cases are examined in the limit of low energy. The first gives rise to nonreciprocal dynamics and corresponds to collective, spatially extended transverse loading of the lattice leading to the excitation of individual, predominantly transverse NNMs, whereas the second case gives rise to nonreciprocal acoutics by considering the response of the lattice to spatially localized, transverse impulse or displacement excitations. We demonstrate intense and recurring energy exchanges between a directly excited NNM and other NNMs with higher wave numbers, so that nonreciprocal energy exchanges from small-to-large wave numbers are established. Moreover, we show the existence of nonreciprocal wave interaction phenomena in the form of irreversible targeted energy transfers from L waves to NL pulses during collisions of these two types of waves. Additional nonreciprocal acoustics are found in the form of complex "cascading processes, as well as nonreciprocal interactions between L waves and stationary discrete breathers. The computational studies confirm the theoretically predicted transition of the lattice dynamics to a low-energy state of nonlinear acoustic vacum with strong nonlocality.

Metal-organic Framework-derived Graphene@nitrogen Doped Carbon@ultrafine TiO2 Nanocomposites As High Rate and Long-life Anodes for Sodium Ion Batteries

Chemical Communications (Cambridge, England). Oct, 2016  |  Pubmed ID: 27747337

Graphene@nitrogen doped carbon@ultrafine TiO2 nanoparticles (G-NC@TiO2) with porous structure are obtained through annealing the precursor of graphene oxide/metal-organic frameworks (MOFs) for the first time. As an anode material for sodium ion batteries (SIB), the G-NC@TiO2 composite can deliver an excellent capacity retention of 93% even after 5000 cycles, and a superior rate capability.

Measuring Dyspnea and Perceived Exertion in Healthy Adults and with Respiratory Disease: New Pictorial Scales

Sports Medicine - Open. Dec, 2016  |  Pubmed ID: 27747773

Dyspnea or perceived exertion during exercise is most commonly measured using Borg or visual analog scales, created for use in adults. In contrast, pictorial scales have been promoted for children due to skepticism concerning applicability of the said scales in pediatrics. We sought to validate our newly created, pictorial Dalhousie Dyspnea and Perceived Exertion Scales in adult populations and compare ratings with the Borg scale.

Differentiation of Human Embryonic Stem Cells to HOXA(+) Hemogenic Vasculature That Resembles the Aorta-gonad-mesonephros

Nature Biotechnology. Nov, 2016  |  Pubmed ID: 27748754

The ability to generate hematopoietic stem cells from human pluripotent cells would enable many biomedical applications. We find that hematopoietic CD34(+) cells in spin embryoid bodies derived from human embryonic stem cells (hESCs) lack HOXA expression compared with repopulation-competent human cord blood CD34(+) cells, indicating incorrect mesoderm patterning. Using reporter hESC lines to track the endothelial (SOX17) to hematopoietic (RUNX1C) transition that occurs in development, we show that simultaneous modulation of WNT and ACTIVIN signaling yields CD34(+) hematopoietic cells with HOXA expression that more closely resembles that of cord blood. The cultures generate a network of aorta-like SOX17(+) vessels from which RUNX1C(+) blood cells emerge, similar to hematopoiesis in the aorta-gonad-mesonephros (AGM). Nascent CD34(+) hematopoietic cells and corresponding cells sorted from human AGM show similar expression of cell surface receptors, signaling molecules and transcription factors. Our findings provide an approach to mimic in vitro a key early stage in human hematopoiesis for the generation of AGM-derived hematopoietic lineages from hESCs.

[Effect of β-lactamase Detection on Reducing the Incidence of Antibiotic-associated Diarrhea in Children with Severe Bacterial Pneumonia]

Zhongguo Dang Dai Er Ke Za Zhi = Chinese Journal of Contemporary Pediatrics. Oct, 2016  |  Pubmed ID: 27751220

To study the effect of β-lactamase (BLs) detection and β-lactam/β-lactamase inhibitor (BL/BLI) on the incidence of antibiotic-associated diarrhea (AAD) in children with severe bacterial pneumonia.

Self-Tuning Fully-Connected PID Neural Network System for Distributed Temperature Sensing and Control of Instrument with Multi-Modules

Sensors (Basel, Switzerland). Oct, 2016  |  Pubmed ID: 27754436

High integration of multi-functional instruments raises a critical issue in temperature control that is challenging due to its spatial-temporal complexity. This paper presents a multi-input multi-output (MIMO) self-tuning temperature sensing and control system for efficiently modulating the temperature environment within a multi-module instrument. The smart system ensures that the internal temperature of the instrument converges to a target without the need of a system model, thus making the control robust. The system consists of a fully-connected proportional-integral-derivative (PID) neural network (FCPIDNN) and an on-line self-tuning module. The experimental results show that the presented system can effectively control the internal temperature under various mission scenarios, in particular, it is able to self-reconfigure upon actuator failure. The system provides a new scheme for a complex and time-variant MIMO control system which can be widely applied for the distributed measurement and control of the environment in instruments, integration electronics, and house constructions.

Injectable, Biomolecule-Responsive Polypeptide Hydrogels for Cell Encapsulation and Facile Cell Recovery Through Triggered Degradation

ACS Applied Materials & Interfaces. Nov, 2016  |  Pubmed ID: 27762560

Injectable hydrogels have been widely investigated in biomedical applications, and increasing demand has been proposed to achieve dynamic regulation of physiological properties of hydrogels. Herein, a new type of injectable and biomolecule-responsive hydrogel based on poly(l-glutamic acid) (PLG) grafted with disulfide bond-modified phloretic acid (denoted as PLG-g-CPA) was developed. The hydrogels formed in situ via enzymatic cross-linking under physiological conditions in the presence of horseradish peroxidase and hydrogen peroxide. The physiochemical properties of the hydrogels, including gelation time and the rheological property, were measured. Particularly, the triggered degradation of the hydrogel in response to a reductive biomolecule, glutathione (GSH), was investigated in detail. The mechanical strength and inner porous structure of the hydrogel were influenced by the addition of GSH. The polypeptide hydrogel was used as a three-dimensional (3D) platform for cell encapsulation, which could release the cells through triggered disruption of the hydrogel in response to the addition of GSH. The cells released from the hydrogel were found to maintain high viability. Moreover, after subcutaneous injection into rats, the PLG-g-CPA hydrogels with disulfide-containing cross-links exhibited a markedly faster degradation behavior in vivo compared to that of the PLG hydrogels without disulfide cross-links, implying an interesting accelerated degradation process of the disulfide-containing polypeptide hydrogels in the physiological environment in vivo. Overall, the injectable and biomolecule-responsive polypeptide hydrogels may serve as a potential platform for 3D cell culture and easy cell collection.

D-PET-controlled "off-on" Polarity-sensitive Probes for Reporting Local Hydrophilicity Within Lysosomes

Scientific Reports. Oct, 2016  |  Pubmed ID: 27767190

Polarity-sensitive fluorescent probes are powerful chemical tools for studying biomolecular structures and activities both in vitro and in vivo. However, the lack of "off-on" polarity-sensing probes has limited the accurate monitoring of biological processes that involve an increase in local hydrophilicity. Here, we design and synthesize a series of "off-on" polarity-sensitive fluorescent probes BP series consisting of the difluoroboron dippyomethene (BODIPY) fluorophore connected to a quaternary ammonium moiety via different carbon linkers. All these probes showed low fluorescence quantum yields in nonpolar solution but became highly fluorescent in polar media. BP-2, which contains a two-carbon linker and a trimethyl quaternary ammonium, displayed a fluorescence intensity and quantum yield that were both linearly correlated with solvent polarity. In addition, BP-2 exhibited high sensitivity and selectivity for polarity over other environmental factors and a variety of biologically relevant species. BP-2 can be synthesized readily via an unusual Mannich reaction followed by methylation. Using electrochemistry combined with theoretical calculations, we demonstrated that the "off-on" sensing behavior of BP-2 is primarily due to the polarity-dependent donor-excited photoinduced electron transfer (d-PET) effect. Live-cell imaging established that BP-2 enables the detection of local hydrophilicity within lysosomes under conditions of lysosomal dysfunction.

Accuracy of Conventional MRI for Preoperative Diagnosis of Intracranial Tumors: A Retrospective Cohort Study of 762 Cases

International Journal of Surgery (London, England). Dec, 2016  |  Pubmed ID: 27773598

Conventional magnetic resonance imaging (MRI) is considered a valuable tool for preoperative diagnosis of intracranial tumors. We assessed its accuracy in the diagnosis of intracranial tumors in usual clinical practice.

"Uphill" Cation Transport: A Bioinspired Photo-driven Ion Pump

Science Advances. Oct, 2016  |  Pubmed ID: 27774511

Biological ion pumps with active ionic transport properties lay the foundation for many life processes. However, few analogs have been produced because extra energy is needed to couple to this "uphill" process. We demonstrate a bioinspired artificial photo-driven ion pump based on a single polyethylene terephthalate conical nanochannel. The pumping process behaving as an inversion of zero-volt current can be realized by applying ultraviolet irradiation from the large opening. The light energy can accelerate the dissociation of the benzoic acid derivative dimers existing on the inner surface of nanochannel, which consequently produces more mobile carboxyl groups. Enhanced electrostatic interaction between the ions traversing the nanochannel and the charged groups on the inner wall is the key reason for the uphill cation transport behavior. This system creates an ideal experimental and theoretical platform for further development and design of various stimuli-driven and specific ion-selective bioinspired ion pumps, which anticipates wide potential applications in biosensing, energy conversion, and desalination.

Design, Synthesis and Biological Evaluation of 6-(2,6-Dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazoles As Potent Fibroblast Growth Factor Receptor Inhibitors

Molecules (Basel, Switzerland). Oct, 2016  |  Pubmed ID: 27782099

Tyrosine kinase fibroblast growth factor receptor (FGFR), which is aberrant in various cancer types, is a promising target for cancer therapy. Here we reported the design, synthesis, and biological evaluation of a new series of 6-(2,6-dichloro-3,5-dimethoxyphenyl)-4-substituted-1H-indazole derivatives as potent FGFR inhibitors. The compound 6-(2,6-dichloro-3,5-dimethoxyphenyl)-N-phenyl-1H-indazole-4-carboxamide (10a) was identified as a potent FGFR1 inhibitor, with good enzymatic inhibition. Further structure-based optimization revealed that 6-(2,6-dichloro-3,5-dimethoxyphenyl)-N-(3-(4-methylpiperazin-1-yl)phenyl)-1H-indazole-4-carboxamide (13a) is the most potent FGFR1 inhibitor in this series, with an enzyme inhibitory activity IC50 value of about 30.2 nM.

Isolated Exopolysaccharides from Lactobacillus Rhamnosus GG Alleviated Adipogenesis Mediated by TLR2 in Mice

Scientific Reports. Oct, 2016  |  Pubmed ID: 27786292

The fibroblast cell line of 3T3-L1 was used as a cell model for screening and evaluating the feasibility of probiotic components in improving animal lipid metabolisms. The extracts from 12 Lactobacillus strains caused significantly reduced triacylglycerol (TAG) accumulation but with severe inflammation induction in 3T3-L1 adipocytes. Interestingly, exopolysaccharides (EPS) from LGG (Lactobacillus rhamnosus GG) significantly decreased the TAG accumulation without any inflammation. The anti-obesity effect of EPS was confirmed in high-fat-diets feeding mice. Fat pads of mice injected with EPS (50 mg/kg) every two days for two weeks were significantly reduced with much smaller adipocytes, compared with the counterparts. The levels of TAG and cholesterol ester in liver, as well as serum TAG, were decreased in EPS injected mice. In addition, down-regulated inflammation was observed in adipose tissue and liver. Interestingly, the expression of TLR2 in adipose tissue and 3T3-L1 cells was significantly increased by EPS addition. Moreover, the reverse of TAG accumulation in TLR2 knockdown 3T3-L1 in the presence of EPS confirmed that the inhibition effect of EPS on adipogenesis was mediated by TLR2. EPS from LGG has the potential for therapeutic development to intervene lipid metabolic disorders in mammals.

Quantitative Trait Loci Analysis of Verticillium Wilt Resistance in Interspecific Backcross Populations of Gossypium Hirsutum × Gossypium Barbadense

BMC Genomics. Nov, 2016  |  Pubmed ID: 27814678

Verticillium wilt (VW) caused by Verticillium dahliae (Kleb) is one of the most destructive diseases of cotton. The identification of highly resistant QTLs or genes in the whole cotton genome is quite important for developing a VW-resistant variety and for further molecular design breeding.

Development and Evaluation of Topotecan Loaded Solid Lipid Nanoparticles: A Study in Cervical Cancer Cell Lines

Journal of Photochemistry and Photobiology. B, Biology. Dec, 2016  |  Pubmed ID: 27816641

The study aims at statistical development of solid lipid nanoparticles (SLNs) loaded with topotecan hydrochloride for avoiding the drawbacks of conventional drug therapies used in cervical cancer. Twenty SLN batches were prepared using organic solvent evaporation method to provide response surface curves. Thereafter, optimized SLNs were obtained using numeric method based on desirability functions providing maximum drug loading and appropriate particle size. Physical characterization of optimized TPH loaded SLNs was performed in terms of particle size, zeta potential, transmission and scanning electron microscopic evaluation. Cytotoxicity studies were performed against cervical cancer cell lines, including cervical squamous cell carcinoma cell line (HeLa) and human squamous cell carcinoma cell line (SiHa). Also, Swiss mouse embryo fibroblast cells (3T3-L1) and African green monkey kidney epithelial (Vero) cells were used to evaluate biocompatibility in normal cells. As pronounced from the results, optimized SLNs may provide an attractive alternative to conventional cervical cancer drug products.

Dosimetric Superiority of Flattening Filter Free Beams for Single-fraction Stereotactic Radiosurgery in Single Brain Metastasis

Oncotarget. Nov, 2016  |  Pubmed ID: 27823985

For single-fraction stereotactic radiosurgery (SRS) using linac in brain metastases, more accurate treatment delivery with higher tumor absorbed doses and lower absorbed doses to normal tissues remains an enormous challenge. The purpose of this study was to investigate the dosimetric superiority in flattening filter free beams (FFF) for volumetric modulated arc therapy (VMAT) in single brain metastasis. 68 patients with single brain metastasis were included in this study. Every patient was subjected to VMAT treatment plans using 6 MV standard flattened (FF) beams (VMAT_FF) and 6 MV FFF beams (VMAT_FFF) with single fraction doses of 20 Gy. Dosimetric evaluation was performed by analysis of target coverage, dose gradients, beam-on time (BOT), gantry speed and number of monitor units (MU). There were no differences between VMAT_FF and VMAT_FFF plans in conformity and MU. VMAT_FFF plans showed obvious superiority in homogeneity, dose gradients and efficiency. For the mean BOT, VMAT_FFF plans provided a significant decrease by 42.8% compared with VMAT_FF. By the use of FFF beams, brain irradiation was minimized with about 2% reductions in low-dose regions (about 5-10 Gy). FFF beams not only resulted in more efficiency by reducing treatment time, but also provided further brain sparing compared to traditional techniques for SRS in single brain metastasis.

Conventional Tumor Markers in Cerebralspinal Fluid in Patients with Elevated Serum
Tumor Markers and Without Central Nervous System Malignant Diseases

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae. Oct, 2016  |  Pubmed ID: 27825410

Objective To explore the diffusion pattern of tumor markers (TM) from serum to cerebrospinal fluid (CSF) via the blood-brain barrier in patients with elevated serum tumor markers (TM).Methods Inpatients receiving lumbar puncture during hospitalization in our center from January 1, 2013 to December 31, 2015 were divided into study group (n=181) and control group (n=251). The study group consisted of patients with elevated serum TMs but without malignant central nervous system diseases. The control group consisted of patients with normal serum TM levels and without malignant diseases. TMs measured in the study group included elevated serum alpha-fetoprotein (AFP) (n=0), carcinoembryonic antigen (CEA) (n=26), carcinomic antigen(CA)125 (n=39), CA15- 3 (n=3),CA19- 9 (n=19), CA724 (n=47), CYFRA21- 1 (n=49), and SCC (n=17).Levels of TMs in the CSF of study group was compared with that of control group.Results Median CEA (U=0.00,P=0.00),CA19- 9 (U=0.00,P=0.00),CA15- 3 (U=0.00,P=0.04),SCC (U=0.00,P=0.00),CA125 (U=0.00,P=0.00),CA72- 4 (U=3.00,P=0.00)),and CYFRA21- 1 (U=0.00,P=0.00) in CSF were significantly lower than the corresponding serum TM levels in the study group.There was no significant difference between study group and control group for the CSF level of CEA (U=3091.00,P=0.18),CA19- 9 (U=1897.00,P=0.14), CA15- 3 (U=373.50,P=0.91)and SCC (U=1925.50,P=0.76). CSF CA125 (U=2188.00,P=0.00) and CA724 (U=1279.00,P=0.00) levels in the study group were lower than those in control group. CSF level of CYFRA21- 1 (U=1826.50,P=0.00) in study group was higher than that in control group;however, it was still lower than the upper limit of reference value. Conclusion In patients with elevated serum CEA, CA19- 9, CA15- 3, SCC, CA125, and CA72- 4 levels, transblood-brain-barrier diffusion of TMs from serum to CSF is highly unlikely.

Gastroenteritis Outbreaks Associated with the Emergence of the New GII.4 Sydney Norovirus Variant During the Epidemic of 2012/13 in Shenzhen City, China

PloS One. 2016  |  Pubmed ID: 27829005

Noroviruses (NoVs) are the leading cause of gastroenteritis outbreaks in humans worldwide. Since late 2012, a new GII.4 variant Sydney 2012 has caused a significant increase in NoV epidemics in several countries. From November of 2012 to January of 2013, three gastroenteritis outbreaks occurred in two social welfare homes (Outbreaks A and B) and a factory (Outbreak C) in Shenzhen city of China. Feces and swabs were collected for laboratory tests for causative agents. While no bacterial pathogen was identified, all three outbreaks were caused by NoVs with detection rates of 26.2% (16/61) at Outbreak A, 35.2% (38/108) at Outbreak B), and 59.3% (16/27) at Outbreaks C. For Outbreak B, 25 of the 29 symptomatic individuals (86.2%) and 13 of the 79 asymptomatic individuals (16.5%) were found NoV-positive. For Outbreak C, an asymptomatic food handler was NoV-positive. All thirteen NoV sequences from the three outbreaks were classified into genogroup II and genotype 4 (GII.4), which we identified to be the GII.4 Sydney 2012 variant. The genome of two isolates from Outbreaks A and B were recombinant with the opening reading frame (ORF) 1 of GII.4 Osaka 2007 and ORF2 and 3 of the GII.4 New Orleans. Our study indicated that the GII.4 Sydney 2012 variant emerged and caused the outbreaks in China.

Interaction Between Thalamus and Hippocampus in Termination of Amygdala-Kindled Seizures in Mice

Computational and Mathematical Methods in Medicine. 2016  |  Pubmed ID: 27829869

The thalamus and hippocampus have been found both involved in the initiation, propagation, and termination of temporal lobe epilepsy. However, the interaction of these regions during seizures is not clear. The present study is to explore whether some regular patterns exist in their interaction during the termination of seizures. Multichannel in vivo recording techniques were used to record the neural activities from the cornu ammonis 1 (CA1) of hippocampus and mediodorsal thalamus (MDT) in mice. The mice were kindled by electrically stimulating basolateral amygdala neurons, and Racine's rank standard was employed to classify the stage of behavioral responses (stage 1~5). The coupling index and directionality index were used to investigate the synchronization and information flow direction between CA1 and MDT. Two main results were found in this study. (1) High levels of synchronization between the thalamus and hippocampus were observed before the termination of seizures at stage 4~5 but after the termination of seizures at stage 1~2. (2) In the end of seizures at stage 4~5, the information tended to flow from MDT to CA1. Those results indicate that the synchronization and information flow direction between the thalamus and the hippocampus may participate in the termination of seizures.

5-Aminolevulinic Acid Loaded Ethosomal Vesicles with High Entrapment Efficiency for in Vitro Topical Transdermal Delivery and Photodynamic Therapy of Hypertrophic Scars

Nanoscale. Nov, 2016  |  Pubmed ID: 27830857

Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is an alternative therapy for hypertrophic scars (HS), which destroys human hypertrophic scar fibroblasts (HSF). However, the poor permeability of ALA both in HS tissue and HSF significantly restricts the PDT of HS. To overcome these barriers, ALA-loaded ethosomal vesicles (ALA-ES) were developed by a pH gradient active loading method and characterized by morphology, entrapment efficiency (EE) and stability. Results show that prepared ALA-ES are homogenous spherical lamellar vesicles, 53 ± 7 nm in size, 50.6 ± 2.3% in EE and have excellent stability. In vitro transdermal delivery studies through HS tissue were carried out by using Franz diffusion cells. Compared to the traditional ALA hydroalcoholic solution (ALA-HA), ALA-ES achieve higher drug retention in less administration time, and fluorescence microscopy showed that ALA-ES penetrate into the deeper dermis of HS in a shorter time, indicating that ALA-ES can enhance the penetration of ALA into HS. Additionally, ALA-ES was visualized in HS tissue for the first time by transmission electron microscopy (TEM). The irregular and collapsed ALA-ES suggest that they can squeeze through narrow spaces to the target area and release ALA into HS. Taking HSF as the target, the transcellular delivery of ALA-ES into HSF cells was investigated by intracellular protoporphyrin IX (PpIX) accumulation. The efficiency of PDT for HSF cells, including the formation of reactive oxygen species (ROS) and cell apoptosis, were also well investigated. Furthermore, the detailed changes of HSF were observed by TEM. The results strongly indicate that ALA-ES can facilitate ALA penetration into HSF cells, and can cause a higher level of cell apoptosis or necrosis than ALA-HA. ALA-ES with high EE is therefore a promising transdermal delivery system for topical ALA administration and has great potential in ALA-PDT of HS.

SiO2-coated LiNi0.915Co0.075Al0.01O2 Cathode Material for Rechargeable Li-ion Batteries

Nanoscale. Nov, 2016  |  Pubmed ID: 27830858

We reported a one-step dry coating of amorphous SiO2 on spherical Ni-rich layered LiNi0.915Co0.075Al0.01O2 (NCA) cathode materials. Combined characterization of XRD, EDS mapping, and TEM indicates that a SiO2 layer with an average thickness of ∼50 nm was uniformly coated on the surface of NCA microspheres, without inducing any change of the phase structure and morphology. Electrochemical tests show that the 0.2 wt% SiO2-coated NCA material exhibits enhanced cyclability and rate properties, combining with better thermal stability compared with those of pristine NCA. For example, 0.2 wt% SiO2-coated NCA delivers a high specific capacity of 181.3 mA h g(-1) with a capacity retention of 90.7% after 50 cycles at 1 C rate and 25 °C. Moreover, the capacity retention of this composite at 60 °C is 12.5% higher than that of pristine NCA at 1 C rate after 50 cycles. The effects of SiO2 coating on the electrochemical performance of NCA are investigated by EIS, CV, and DSC tests, the improved performance is attributed to the surface coating layer of amorphous SiO2, which effectively suppresses side reactions between NCA and electrolytes, decreases the SEI layer resistance, and retards the growth of charge-transfer resistance, thus enhancing structural and cycling stability of NCA.

Actin Is Crucial for All Kinetically Distinguishable Forms of Endocytosis at Synapses

Neuron. Dec, 2016  |  Pubmed ID: 27840001

Mechanical force is needed to mediate endocytosis. Whether actin, the most abundant force-generating molecule, is essential for endocytosis is highly controversial in mammalian cells, particularly synapses, likely due to the use of actin blockers, the efficiency and specificity of which are often unclear in the studied cell. Here we addressed this issue using a knockout approach combined with measurements of membrane capacitance and fission pore conductance, imaging of vesicular protein endocytosis, and electron microscopy. We found that two actin isoforms, β- and γ-actin, are crucial for slow, rapid, bulk, and overshoot endocytosis at large calyx-type synapses, and for slow endocytosis and bulk endocytosis at small hippocampal synapses. Polymerized actin provides mechanical force to form endocytic pits. Actin also facilitates replenishment of the readily releasable vesicle pool, likely via endocytic clearance of active zones. We conclude that polymerized actin provides mechanical force essential for all kinetically distinguishable forms of endocytosis at synapses.

LRG1 Promotes Angiogenesis Through Upregulating the TGF‑β1 Pathway in Ischemic Rat Brain

Molecular Medicine Reports. Dec, 2016  |  Pubmed ID: 27840991

Stroke is a life-threatening disease that results in significant disability in the human population. Despite the advances in current stroke therapies, a host of patients do not benefit from the conventional treatments. Thus, more effective therapies are required. It has been previously reported that leucine‑rich‑α2‑glycoprotein 1 (LRG1) is crucial during the formation of new blood vessels in retinal diseases. However, the function of LRG1 in the brain during the neovessel growth process following ischemic stroke has not been fully elucidated and the mechanism underlying its effect on angiogenesis remains unclear. The purpose of the current study was to demonstrate whether LRG1 may promote angiogenesis through the transforming growth factor (TGF)‑β1 signaling pathway in ischemic rat brain following middle cerebral artery occlusion (MCAO). In the present study, the spatial and temporal expression of LRG1, TGF‑β1, vascular endothelial growth factor (VEGF) and angiopoietin‑2 (Ang‑2) were detected in ischemic rat brain following MCAO using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR), western blot analysis and immunohistochemistry. CD34 immunohistochemistry staining was used as an indicator of microvessel density (MVD). The RT‑qPCR and western blotting results revealed that the levels of LRG1 and TGF‑β1 mRNA and protein expression were significantly increased as early as 6 and 12 h after MCAO (P<0.05), respectively, peaked at 3 days and persisted at significantly higher level until 14 days, in comparison with the control group. Additionally, VEGF and Ang‑2 were also increased following MCAO. Furthermore, the immunohistochemistry results suggested that the MVD was increased following MCAO. In addition, the results also revealed that the percentage of LRG1‑positive cells was positively correlated with the percentage of TGF‑β1‑positive cells, and the percentage of LRG1‑positive and TGF‑β1‑positive cells had a positively correlation with the MVD. Taken together, the present study indicated that LRG1 may promote angiogenesis through upregulating the TGF‑β1 signaling pathway in ischemic rat brain following MCAO. This may provide a potential therapeutic target for the treatment of ischemic stroke.

Extracting Microtubule Networks from Superresolution Single-Molecule Localization Microscopy Data

Molecular Biology of the Cell. Nov, 2016  |  Pubmed ID: 27852898

Microtubule filaments form ubiquitous networks that specify spatial organization in cells. However, quantitative analysis of the microtubule networks is hampered by their complex architecture, limiting insights into the interplay between their organization and cellular functions. Although superresolution microscopy has greatly facilitated high-resolution imaging of microtubule filaments, the extraction of the complete filament networks from such dataset remains challenging. Here, we describe a computational tool for the automated retrieval of microtubule filaments from single-molecule-localization-based superresolution microscopy images. We present a user-friendly graphically-interfaced implementation and demonstrate a quantitative analysis of microtubule network architecture phenotypes in fibroblasts.

3D Model for Rectangular Electrowetting Lens Structures

Applied Optics. Nov, 2016  |  Pubmed ID: 27857297

The electrowetting-on-dielectric (EWOD) lens is a good candidate for dynamic beam-shaping optics for advanced solid-state lighting systems. A geometric approximation model is described to predict the meniscus shape of a rectangular EWOD lens with arbitrary voltages and small Bond numbers. The model approximates the meniscus geometry as being a part of a compound toroidal surface. The model was compared with free-energy minimization simulations and experiments with the largest standard deviation between the geometric model and the simulation for a wide variety of bias voltages being less than 2%. The experimental validation compared the measured dynamic image shifts of a wire mesh produced with test EWOD cells with the predicted image obtained from the toroidal geometric model using a ray-tracing simulation. The optical performance of the experimental 3D electrowetting lens is described and was found to agree reasonably well with the predicted optical performance of the geometric model for a wide variety of operating conditions.

Mild Encephalopathy with a Reversible Splenial Lesion Mimicking Transient Ischemic Attack: A Case Report

Medicine. Nov, 2016  |  Pubmed ID: 27858890

Reversible splenial lesion syndrome (RESLES) is a newly recognized syndrome, and a reversible progress associated with transiently reduced diffusion lesion in the splenium of the corpus callosum (SCC) is the typical pathological finding. The routine clinical symptoms include mildly altered states of consciousness, delirium, and seizures.

Light-Controlled Ion Transport Through Biomimetic DNA-Based Channels

Angewandte Chemie (International Ed. in English). Dec, 2016  |  Pubmed ID: 27860091

Light-controlled nanochannels are fabricated through self-assembling azobenzene-incorporated DNA (Azo-DNA) strands to regulate ion transport. By switching between collapsed and relaxed states using visible and ultraviolet light alternately, the Azo-DNA channels can be opened and closed because the conformation of Azo-DNA changes, that is, Azo-DNA is used as switchable controlling unit. In addition to sharing short response time and reversibility with other photoresponsive apparatuses, the Azo-DNA-based nanochannel system has advantages in good biocompatibility and versatile design, which could potentially be applied in light-controlled drug release, optical information storage, and logic networks.

Expert Consensus on Perioperative Medications During Endoscopic Submucosal Dissection for Gastric Lesions (2015, Suzhou, China)

Journal of Digestive Diseases. Dec, 2016  |  Pubmed ID: 27860300

Do Invasive Alien Plants Benefit More from Global Environmental Change Than Native Plants?

Global Change Biology. Nov, 2016  |  Pubmed ID: 27888560

Invasive alien plant species threaten native biodiversity, disrupt ecosystem functions and can cause large economic damage. Plant invasions have been predicted to further increase under ongoing global environmental change. Numerous case studies have compared the performance of invasive and native plant species in response to global environmental change components (i.e. changes in mean levels of precipitation, temperature, atmospheric CO2 concentration or nitrogen deposition). Individually, these studies usually involve low numbers of species and therefore the results cannot be generalized. Therefore, we performed a phylogenetically controlled meta-analysis to assess whether there is a general pattern of differences in invasive and native plant performance under each component of global environmental change. We compiled a database of studies that reported performance measures for 74 invasive alien plant species and 117 native plant species in response to one of the above-mentioned global environmental change components. We found that elevated temperature and CO2 enrichment increased the performance of invasive alien plants more strongly than was the case for native plants. Invasive alien plants tended to also have a slightly stronger positive response to increased N deposition and increased precipitation than native plants, but these differences were not significant (N deposition: P = 0.051; increased precipitation: P = 0.679). Invasive alien plants tended to have a slightly stronger negative response to decreased precipitation than native plants, although this difference was also not significant (P = 0.060). So while drought could potentially reduce plant invasion, increases in the four other components of global environmental change considered, particularly global warming and atmospheric CO2 enrichment, may further increase the spread of invasive plants in the future.

Resveratrol Reverses P-glycoprotein-mediated Multidrug Resistance of U2OS/ADR Cells by Suppressing the Activation of the NF-κB and P38 MAPK Signaling Pathways

Oncology Letters. Nov, 2016  |  Pubmed ID: 27895784

The present study aimed to investigate the reversal effect of resveratrol on the phenomenon of multidrug resistance in U2OS/adriamycin (ADR) cells and to clarify the molecular mechanisms. To examine the cell survival and half-inhibitory concentration (IC50) of ADR in U2OS and U2OS/ADR cells, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used. The accumulation of ADR in U2OS and U2OS/ADR cells was investigated by flow cytometry. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were used to detect the expression of multidrug resistance protein 1 (MDR1), P-glycoprotein (P-gp), p65 and p38. Compared with U2OS cells, the IC50 value of ADR was significantly increased in U2OS/ADR cells, which exhibited high levels of MDR1/P-gp. However, resveratrol could drastically reduce the IC50 value of ADR and the expression of MDR1/P-gp, and increased the accumulation of ADR in U2OS/ADR cells. In addition, the expression levels of p38 (phosphorylated) and p65 (acetylated and total) in U2OS/ADR cells were also significantly suppressed by resveratrol. These results suggested that the nuclear factor (NF)-κB and p38 mitogen-activated protein kinase (MAPK) signaling pathways are correlated with ADR-induced drug resistance in U2OS/ADR cells. Furthermore, resveratrol could downregulate the expression of MDR1/P-gp and reverse the drug resistance phenomenon in U2OS/ADR cells partly at least by suppressing the activation of the NF-κB and p38 MAPK signaling pathways.

Differential Efficacy of Methylcobalamin and Alpha-lipoic Acid Treatment on Negative and Positive Symptoms of (type 2) Diabetic Peripheral Neuropathy

Minerva Endocrinologica. Nov, 2016  |  Pubmed ID: 27901334

Diabetic hyperglycemia damages peripheral nerves by triggering ischemia, oxidative stress, and inflammation. Alpha-lipoic acid (ALA) and methylcobalamin (MC) are known to improve signs of diabetic peripheral neuropathy (DPN), possibly by enhancing neural and vascular endothelial cell metabolism and antioxidant capacity. We evaluated differences in efficacy following short-term MC or ALA treatment on DPN symptoms to guide clinical drug selection.

An Increased Duplication of ZRS Region That Caused More Than One Supernumerary Digits Preaxial Polydactyly in a Large Chinese Family

Scientific Reports. Dec, 2016  |  Pubmed ID: 27922091

Preaxial polydactyly (PPD) is inherited in an autosomal dominant fashion and characterized by the presence of one or more supernumerary digits on the thumb side. It had been identified that point mutation or genomic duplications of the long-range limb-specific cis-regulator - zone of polarizing activity regulatory sequence (ZRS) cause PPD or other limb deformities such as syndactyly type IV (SD4) and Triphalangeal thumb-polysyndactyly syndrome (TPTPS). Most previously reported cases involved with no more than one extra finger; however, the role of the point mutation or genomic duplications of ZRS in the case of more than one redundant finger polydactyly remains unclear. In this article, we reported a family case of more than one redundant finger polydactyly on the thumb side for bilateral hands with a pedigree chart of the family. Results of quantitative PCR (qPCR) and sequence analysis suggested that the relative copy number (RCN) of ZRS but not point mutation (including insertion and deletion) was involved in all affected individuals.

Guideline for C1 Lateral Mass and C2 Pedicle Screw Choices in Children Younger Than 6 Years

Spine. Dec, 2016  |  Pubmed ID: 27926673

Prospective study.

Genome-wide Identification, Phylogeny, and Expression Analysis of Pectin Methylesterases Reveal Their Major Role in Cotton Fiber Development

BMC Genomics. Dec, 2016  |  Pubmed ID: 27927181

Pectin methylesterase (PME, EC is a hydrolytic enzyme that utilizes pectin as substrates, and plays a significant role in regulating pectin reconstruction thereby regulating plant growth. Pectin is one of the important components of the plant cell wall, which forms the main structural material of cotton fiber. In this research, cotton genome information was used to identify PMEs.

The Patterns and Timing of Recurrence After Curative Resection for Gastric Cancer in China

World Journal of Surgical Oncology. Dec, 2016  |  Pubmed ID: 27931221

The recurrence of gastric cancer after curative resection had adverse effects on patients' survival. The treatment presence varied from different countries. The aims of this study were to understand the recurrence incidence, patterns, and timing and to explore the risk factors in China.

Simulated Effects of Nitrogen Saturation on the Global Carbon Budget Using the IBIS Model

Scientific Reports. Dec, 2016  |  Pubmed ID: 27966643

Over the past 100 years, human activity has greatly changed the rate of atmospheric N (nitrogen) deposition in terrestrial ecosystems, resulting in N saturation in some regions of the world. The contribution of N saturation to the global carbon budget remains uncertain due to the complicated nature of C-N (carbon-nitrogen) interactions and diverse geography. Although N deposition is included in most terrestrial ecosystem models, the effect of N saturation is frequently overlooked. In this study, the IBIS (Integrated BIosphere Simulator) was used to simulate the global-scale effects of N saturation during the period 1961-2009. The results of this model indicate that N saturation reduced global NPP (Net Primary Productivity) and NEP (Net Ecosystem Productivity) by 0.26 and 0.03 Pg C yr(-1), respectively. The negative effects of N saturation on carbon sequestration occurred primarily in temperate forests and grasslands. In response to elevated CO2 levels, global N turnover slowed due to increased biomass growth, resulting in a decline in soil mineral N. These changes in N cycling reduced the impact of N saturation on the global carbon budget. However, elevated N deposition in certain regions may further alter N saturation and C-N coupling.

Shugan Xiaozhi Decoction Attenuates Nonalcoholic Steatohepatitis by Enhancing PPARα and L-FABP Expressions in High-Fat-Fed Rats

Evidence-based Complementary and Alternative Medicine : ECAM. 2016  |  Pubmed ID: 28003852

This study aimed to investigate the effects of Shugan Xiaozhi decoction (SX) on nonalcoholic steatohepatitis (NASH) induced by high-fat diet in rats. The rats were randomly divided into 6 groups, namely, control, model, fenofibrate, and three different dosage of SX (10, 20, and 40 g/kg/day, p.o.). After establishing the NASH model, at 8 weeks of the experiment, treatments were administrated intragastrically to the fenofibrate and SX groups. All rats were killed after 4 weeks of treatment. Compared with the model group, alanine aminotransferase (ALT), aspartate aminotransferase (AST), free fatty acid (FFA), total cholesterol (TC), triacylglycerol (TG), and low-density lipoprotein cholesterol (LDL) serum in the serum were significantly reduced in all SX treatment groups in a dose-dependent manner. Evidence showed that SX could protect the liver by upregulating the gene and protein expressions of peroxisome proliferator-activated receptor alpha (PPARα) and liver fatty acid binding protein (L-FABP) in a dose-dependent manner. Chemical constituents of SX were further analyzed by ultraperformance liquid chromatography coupled with electrospray ionization mass spectrometry (UPLC-ESI-MS) and 30 chemicals in the ethanolic extract were tentatively identified. To conclude, our results clearly indicated that SX could protect liver functions and relieve hepatic steatosis and inflammation.

Controllable Terahertz Radiation from a Linear-Dipole Array Formed by a Two-Color Laser Filament in Air

Physical Review Letters. Dec, 2016  |  Pubmed ID: 28009219

We demonstrate effective control on the carrier-envelope phase and angular distribution as well as the peak intensity of a nearly single-cycle terahertz pulse emitted from a laser filament formed by two-color, the fundamental and the corresponding second harmonics, femtosecond laser pulses propagating in air. Experimentally, such control has been performed by varying the filament length and the initial phase difference between the two-color laser components. A linear-dipole-array model, including the descriptions of both the generation (via laser field ionization) and propagation of the emitted terahertz pulse, is proposed to present a quantitative interpretation of the observations. Our results contribute to the understanding of terahertz generation in a femtosecond laser filament and suggest a practical way to control the electric field of a terahertz pulse for potential applications.

Development and Evaluation of a Comprehensive Drought Index

Journal of Environmental Management. Oct, 2016  |  Pubmed ID: 28029478

Droughts are known as the world's costliest natural disasters impacting a variety of sectors. Despite their wide range of impacts, no universal drought definition has been defined. The goal of this study is to define a universal drought index that considers drought impacts on meteorological, agricultural, hydrological, and stream health categories. Additionally, predictive drought models are developed to capture both categorical (meteorological, hydrological, and agricultural) and overall impacts of drought. In order to achieve these goals, thirteen commonly used drought indices were aggregated to develop a universal drought index named MASH. The thirteen drought indices consist of four drought indices from each meteorological, hydrological, and agricultural categories, and one from the stream health category. Cluster analysis was performed to find the three closest indices in each category. Then the closest drought indices were averaged in each category to create the categorical drought score. Finally, the categorical drought scores were simply averaged to develop the MASH drought index. In order to develop predictive drought models for each category and MASH, the ReliefF algorithm was used to rank 90 variables and select the best variable set. Using the best variable set, the adaptive neuro-fuzzy inference system (ANFIS) was used to develop drought predictive models and their accuracy was examined using the 10-fold cross validation technique. The models' predictabilities ranged from R(2) = 0.75 for MASH to R(2) = 0.98 for the hydrological drought model. The results of this study can help managers to better position resources to cope with drought by reducing drought impacts on different sectors.

Bayesian Variable Selection in the Accelerated Failure Time Model with an Application to the Surveillance, Epidemiology, and End Results Breast Cancer Data

Statistical Methods in Medical Research. Jan, 2016  |  Pubmed ID: 28034170

Accelerated failure time model is a popular model to analyze censored time-to-event data. Analysis of this model without assuming any parametric distribution for the model error is challenging, and the model complexity is enhanced in the presence of large number of covariates. We developed a nonparametric Bayesian method for regularized estimation of the regression parameters in a flexible accelerated failure time model. The novelties of our method lie in modeling the error distribution of the accelerated failure time nonparametrically, modeling the variance as a function of the mean, and adopting a variable selection technique in modeling the mean. The proposed method allowed for identifying a set of important regression parameters, estimating survival probabilities, and constructing credible intervals of the survival probabilities. We evaluated operating characteristics of the proposed method via simulation studies. Finally, we apply our new comprehensive method to analyze the motivating breast cancer data from the Surveillance, Epidemiology, and End Results Program, and estimate the five-year survival probabilities for women included in the Surveillance, Epidemiology, and End Results database who were diagnosed with breast cancer between 1990 and 2000.

Effect of Small-Scale Turbulence on the Physiology and Morphology of Two Bloom-Forming Cyanobacteria

PloS One. 2016  |  Pubmed ID: 28036368

The main goal of the present work is to test the hypothesis that small-scale turbulence affected physiological activities and the morphology of cyanobacteria in high turbulence environments. Using quantified turbulence in a stirring device, we conducted one set of experiments on cultures of two strains of cyanobacteria with different phenotypes; i.e., unicellular Microcystis flos-aquae and colonial Anabaena flos-aquae. The effect of small-scale turbulence examined varied from 0 to 8.01×10-2 m2s-3, covering the range of turbulence intensities experienced by cyanobacteria in the field. The results of photosynthesis activity and the cellular chlorophyll a in both strains did not change significantly among the turbulence levels, indicating that the potential indirect effects of a light regime under the gradient of turbulent mixing could be ignored. However, the experiments demonstrated that small-scale turbulence significantly modulated algal nutrient uptake and growth in comparison to the stagnant control. Cellular N and C of the two stains showed approximately the same responses, resulting in a similar pattern of C/N ratios. Moreover, the change in the phosphate uptake rate was similar to that of growth in two strains, which implied that growth characteristic responses to turbulence may be dependent on the P strategy, which was correlated with accumulation of polyphosphate. Additionally, our results also showed the filament length of A. flos-aquae decreased in response to high turbulence, which could favor enhancement of the nutrient uptake. These findings suggested that both M. flos-aquae and A. flos-aquae adjust their growth rates in response to turbulence levels in the ways of asynchronous cellular stoichiometry of C, N, and P, especially the phosphorus strategy, to improve the nutrient application efficiency. The fact that adaptation strategies of cyanobacteria diversely to turbulence depending on their physiological conditions presents a good example to understand the direct cause-effect relationship between hydrodynamic forces and algae.

Spectral Assignment and Orientational Analysis in a Vibrational Sum Frequency Generation Study of DPPC Monolayers at the Air/water Interface

The Journal of Chemical Physics. Dec, 2016  |  Pubmed ID: 28049317

The interfacial behavior of the benchmark zwitterionic phospholipid molecule dipalmitoylphosphatidylcholine (DPPC) has been extensively investigated by surface-selective vibrational sum frequency generation spectroscopy (VSFG). However, there is still a lack of agreement between various orientational measurements of phospholipid monolayers at the air/water interface, mainly because of the difficulty in assigning congested VSFG features. In this study, polarization-dependent VSFG measurements reveal a frequency shift between the in-plane and out-of-plane antisymmetric stretching modes of the terminal methyl groups in the DPPC alkyl tails, favoring the model of Cs local symmetry rather than the previously assumed C3v symmetry. Further VSFG experiments of isotopically labeled DPPC successfully capture the vibrational signatures of the glycerol backbone. With the newly derived VSFG polarization selection rules for Cs symmetry and the refreshed spectral assignments, the average tilt angles of the alkyl tail groups, choline headgroup, and glycerol backbone of DPPC molecules can all be determined, showing the powerful capability of VSFG spectroscopy in revealing the structural details at interfaces. The VSFG polarization dependence rules and the orientational analysis procedures developed for Cs symmetry in this work are applicable to other bulky molecules in which the methyl group cannot freely rotate, and they therefore have general applications in future VSFG studies.

Genome Editing of Wnt-1, a Gene Associated with Segmentation, Via CRISPR/Cas9 in the Pine Caterpillar Moth, Dendrolimus Punctatus

Frontiers in Physiology. 2016  |  Pubmed ID: 28111552

The pine caterpillar moth, Dendrolimus punctatus, is a devastating forest pest. Genetic manipulation of this insect pest is limited due to the lack of genomic and functional genomic toolsets. Recently, CRISPR/Cas9 technology has been demonstrated to be a promising approach to modify the genome. To investigate gene functions during the embryogenesis, we introduced CRISPR/Cas9 system in D. punctatus to precisely and effectively manipulate gene expressions inmutant embryos. Compared to controls, knocking out of DpWnt-1, a gene well known for its role in the early body planning, led to high embryonic mortality. Among these mutants, 32.9% of the embryos and larvae showed an abnormal development. DpWnt-1 mutants predominantly exhibited abnormal posterior segments. In addition, multiple phenotypes were observed, including the loss of limbs and the head deformation, suggesting that DpWnt-1 signaling pathway is necessary for anterior segmentation and appendage development. Overall, our results demonstrate that CRISPR/Cas9 system is feasible and efficient in inducing mutations at a specific locus in D. punctatus. This study not only lays the foundation for characterizing gene functions in a non-model species, but also facilitates the future development of pest control alternatives for a major defoliator.

Protein Inference from the Integration of Tandem MS Data and Interactome Networks

IEEE/ACM Transactions on Computational Biology and Bioinformatics. Aug, 2016  |  Pubmed ID: 28113634

Since proteins are digested into mixture of peptides in the preprocessing step of tandem mass spectrometry(MS), it is difficult to determine which specific protein a shared peptide belongs to. In recent studies, besides tandem MS data and peptide identification information, some other information is exploited to infer proteins. Different from the methods which first use only tandem MS data to infer proteins and then use network information to refine them, this study proposes a protein inference method named TMSIN, which uses interactome networks directly. As two interacting proteins should co-exist, it is reasonable to assume that if one of interacting proteins is confidently inferred in a sample, its interacting partners should have a high probability in the same sample, too. Therefore, we can use the neighborhood information of a protein in an interactome network to adjust the probability that the shared peptide belongs to the protein. In TMSIN, a multi-weighted graph is constructed by incorporating the bipartite graph with interactome network information, where the bipartite graph is built with the peptide identification information. Based on multi-weighted graphs, TMSIN adopts an iterative workflow to infer proteins. At each iterative step, the probability that a shared peptide belongs to a specific protein is calculated by using the Bayes' law based on the neighbor protein support scores of each protein which are mapped by the shared peptides. We carried out experiments on yeast data and human data to evaluate the performance of TMSIN in terms of ROC, q-value, and accuracy. The experimental results show that AUC scores yielded by TMSIN are 0.742 and 0.874 in yeast dataset and human dataset, respectively, and TMSIN yields the maximum number of true positives when q-value less than or equal to 0.05. The overlap analysis shows that TMSIN is an effective complementary approach for protein inference.

Synthetic Biology Open Language (SBOL) Version 2.1.0

Journal of Integrative Bioinformatics. Dec, 2016  |  Pubmed ID: 28187407

Synthetic biology builds upon the techniques and successes of genetics, molecular biology, and metabolic engineering by applying engineering principles to the design of biological systems. The field still faces substantial challenges, including long development times, high rates of failure, and poor reproducibility. One method to ameliorate these problems would be to improve the exchange of information about designed systems between laboratories. The Synthetic Biology Open Language (SBOL) has been developed as a standard to support the specification and exchange of biological design information in synthetic biology, filling a need not satisfied by other pre-existing standards. This document details version 2.1 of SBOL that builds upon version 2.0 published in last year’s JIB special issue. In particular, SBOL 2.1 includes improved rules for what constitutes a valid SBOL document, new role fields to simplify the expression of sequence features and how components are used in context, and new best practices descriptions to improve the exchange of basic sequence topology information and the description of genetic design provenance, as well as miscellaneous other minor improvements.

Cadmium Stimulates Mouse Skin Fibroblast Apoptosis by Affecting Intracellular Homeostasis

Drug and Chemical Toxicology. Jan, 2017  |  Pubmed ID: 27147508

Cadmium (Cd(2+)) is an important industrial and environmental pollutant and has been shown to induce apoptosis in a variety of cell types and tissues.

Cumulative Risk Impact of RET, SEMA3, and NRG1 Polymorphisms Associated With Hirschsprung Disease in Han Chinese

Journal of Pediatric Gastroenterology and Nutrition. Mar, 2017  |  Pubmed ID: 27203398

Hirschsprung disease (HSCR) is a congenital aganglionosis of myenteric and submucosal plexuses affecting a variable length of the intestine. The incidence of HSCR is approximately 1 of 5000 live births; however, the risk shows remarkable individual variation caused by single nucleotide polymorphisms (SNPs) at the RET, SEMA3, and NRG1 loci. The present study investigated the effects of these variants on the disease development and phenotype in a Chinese population.

Distinct Role of Heme Oxygenase-1 in Early- and Late-stage Intracerebral Hemorrhage in 12-month-old Mice

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism. Jan, 2017  |  Pubmed ID: 27317654

Intracerebral hemorrhage (ICH) is a devastating form of stroke with high morbidity and mortality. Heme oxygenase-1 (HO-1), the key enzyme in heme degradation, is highly expressed after ICH, but its role is still unclear. In this study, we used an HO-1 inducer and inhibitor to test the role of HO-1 in different stages of ICH in vivo and in vitro. In the early stage of ICH, high HO-1 expression worsened the outcomes of mice subjected to the collagenase-induced ICH model. HO-1 increased brain edema, white matter damage, neuronal death, and neurobehavioral deficits. Furthermore, elevated HO-1 increased inflammation, oxidative stress, matrix metalloproteinase-9/2 activity, and iron deposition. In the later stage of ICH, long-term induction of HO-1 increased hematoma absorption, angiogenesis, and recovery of neurologic function. We conclude that HO-1 activation mediates early brain damage after ICH but promotes neurologic function recovery in the later stage of ICH.

Gastric Bypass Procedure for Type 2 Diabetes Patients with BMI <28 kg/m(2)

Surgical Endoscopy. Mar, 2017  |  Pubmed ID: 27422245

To evaluate the Roux-en-Y gastric bypass (GBP) procedure for patients suffering from type 2 diabetes mellitus (T2DM) with body mass index (BMI) <28 kg/m(2).

BOSS: a Novel Scaffolding Algorithm Based on an Optimized Scaffold Graph

Bioinformatics (Oxford, England). Jan, 2017  |  Pubmed ID: 27634951

While aiming to determine orientations and orders of fragmented contigs, scaffolding is an essential step of assembly pipelines and can make assembly results more complete. Most existing scaffolding tools adopt scaffold graph approaches. However, due to repetitive regions in genome, sequencing errors and uneven sequencing depth, constructing an accurate scaffold graph is still a challenge task.

Identification of Three Selenoprotein T Paralogs in Goldfish (Carassius Auratus) and Expression Analysis in Response to Environmental Stressors

Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology. Jan, 2017  |  Pubmed ID: 27667707

Selenoproteins, which contain the selenocysteine (Sec), play crucial roles in antioxidant protection. In the present study, we have identified and characterized three selenoprotein T paralogs (designated as gfSelT1a, gfSelT1b and gfSelT2) in goldfish, Carassius auratus. The SECIS element was found in the 3'-UTRs of gfSelT1a, gfSelT1b and gfSelT2 mRNA. Sequence analysis showed that they all possess the CxxU motif (where U represents Sec) in the N-terminal. Constitutive expressions of gfSelT1a, gfSelT1b and gfSelT2 were observed in all tissues studied. In liver, gfSelT1a, gfSelT1b and gfSelT2 mRNA expression levels significantly decreased when fasting and increased after re-feeding. The expressions of gfSelT1a, gfSelT1b and gfSelT2 were all inducible by cadmium exposure and H2O2-mediated oxidative stress, except the transcripts of gfSelT1b decreasing with H2O2 stimulation in brain. Furthermore, the expressions of gfSelT1a, gfSelT1b and gfSelT2 consistently increased in spleen but decreased in brain in response to heat stress. However, in liver only gfSelT1a mRNA expression significantly increased. In a word, this is the first report of the presence of three SelT genes in goldfish and their distinct expression patterns in response to environmental stressors. Our results suggest a potential involvement of gfSelT1a, gfSelT1b and gfSelT2 in host protection against environmental stressors including heavy mental, oxidative stress and heat stress in goldfish.

An Artificial CO2 -Driven Ionic Gate Inspired by Olfactory Sensory Neurons in Mosquitoes

Advanced Materials (Deerfield Beach, Fla.). Jan, 2017  |  Pubmed ID: 27786377

A novel CO2 -driven ionic gate, mimicking the function of olfactory sensory neurons of mosquitoes, is successfully developed by functionalizing the walls of the nanochannels using 1-(4-amino-phenyl)-2,2,2-trifluoro-ethanone. This artificial nanochannel can switch between the ON-state and OFF-state in the presence and absence of CO2 , with an ultrahigh gating ratio of up to 1250, and has potential applications in CO2 -related sensing, gating, and nanofluidic systems.

In Vitro Antioxidative and Immunological Activities of Polysaccharides from Zizyphus Jujuba Cv. Muzao

International Journal of Biological Macromolecules. Feb, 2017  |  Pubmed ID: 27815124

Zizyphus jujuba has been used as a traditional Chinese medicinal herb since ancient time. Polysaccharides have been found to be important bioactive compounds in the jujube. This work was designed to investigate the physicochemical characteristics and bioactivities of polysaccharides purified from Zizyphus jujuba cv. Muzao. Water-soluble polysaccharides were extracted using an ultrasonically assisted extraction method. The purified polysaccharides (HJP) were obtained by deproteinization and decoloration. Three main fractions (HJP1, HJP2 and HJP3) were isolated using DEAE-Sepharose fast flow ion-exchange chromatography. The purified polysaccharides were found to consist of mannose, rhamnose, galactose, galacturonic acid, glucose and arabinose at various levels for different fractions. The HJP and its three main fractions displayed DPPH radical scavenging activities as well as relatively strong reducing power and HJP had stronger activities than homogeneous compositions. Moreover, the results from in vitro immunological activities studies indicated that HJP could improve the phagocytosis activity of THP-l cells and had effect on the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). In conclusion, the polysaccharides from Zizyphus jujuba cv. Muzao were discovered to have antioxidative and immunological activities.

Proteome Profiling Outperforms Transcriptome Profiling for Coexpression Based Gene Function Prediction

Molecular & Cellular Proteomics : MCP. Jan, 2017  |  Pubmed ID: 27836980

Coexpression of mRNAs under multiple conditions is commonly used to infer cofunctionality of their gene products despite well-known limitations of this "guilt-by-association" (GBA) approach. Recent advancements in mass spectrometry-based proteomic technologies have enabled global expression profiling at the protein level; however, whether proteome profiling data can outperform transcriptome profiling data for coexpression based gene function prediction has not been systematically investigated. Here, we address this question by constructing and analyzing mRNA and protein coexpression networks for three cancer types with matched mRNA and protein profiling data from The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumor Analysis Consortium (CPTAC). Our analyses revealed a marked difference in wiring between the mRNA and protein coexpression networks. Whereas protein coexpression was driven primarily by functional similarity between coexpressed genes, mRNA coexpression was driven by both cofunction and chromosomal colocalization of the genes. Functionally coherent mRNA modules were more likely to have their edges preserved in corresponding protein networks than functionally incoherent mRNA modules. Proteomic data strengthened the link between gene expression and function for at least 75% of Gene Ontology (GO) biological processes and 90% of KEGG pathways. A web application Gene2Net ( developed based on the three protein coexpression networks revealed novel gene-function relationships, such as linking ERBB2 (HER2) to lipid biosynthetic process in breast cancer, identifying PLG as a new gene involved in complement activation, and identifying AEBP1 as a new epithelial-mesenchymal transition (EMT) marker. Our results demonstrate that proteome profiling outperforms transcriptome profiling for coexpression based gene function prediction. Proteomics should be integrated if not preferred in gene function and human disease studies.

Curative Effects of Microneedle Fractional Radiofrequency System on Skin Laxity in Asian Patients: A Prospective, Double-blind, Randomized, Controlled Face-split Study

Journal of Cosmetic and Laser Therapy : Official Publication of the European Society for Laser Dermatology. Apr, 2017  |  Pubmed ID: 27849406

To date, no studies compared curative effects of thermal lesions in deep and superficial dermal layers in the same patient (face-split study).

Gemcitabine Treatment Enhanced the Anti-tumor Effect of Cytokine Induced Killer Cells by Depletion of CD4(+)CD25(bri) Regulatory T Cells

Immunology Letters. Jan, 2017  |  Pubmed ID: 27867030

Cytokine induced killer (CIK) cells have a powerful tumor cells killing activity both in vitro and in vivo and transfusion of these cells have become an adjuvant treatment for tumors. CIK cells are induced and amplified from peripheral blood mononuclear cells (PBMCs) with multiple cytokines. As CD4(+)CD25(bri) regulatory T cells can be also induced by high dose of interleukin 2 (IL-2) which is used for CIK cells amplification in the CIK cell culture system, the anti-tumor activity of CIK cells was suppressed to some extent. In order to overcome this unwanted suppressive factor, we found that low dose of gemcitabine could reduce the proportion of CD4(+)CD25(bri) regulatory T cells in the CIK cell culture system and significantly enhance the anti-tumor activity of CIK cells in vitro. The levels of interleukin-10 (IL-10) and transforming growth factor-β (TGF-β) were also reduced significantly following the depletion of CD4(+)CD25(bri) regulatory T cells in gemcitabine treated CIK cell culture system. In vivo experiment showed that low dose of gemcitabine treated CIK cells significantly suppressed tumor growth and prolonged their lifespan in tumor-bearing nude mice, with the proportion of CD4(+)CD25(bri) regulatory T cells reduced. Meanwhile, we detected lower levels of IL-10, TGF-β and a higher level of interferon-γ (IFN-γ) in tumor-bearing nude mice that received gemcitabine treated CIK cells transfusion than those in other groups. The possible mechanism involved in the enhanced anti-tumor activity in vivo was that gemcitabine treated CIK cells created a strengthened anti-tumor immune microenvironment with the changed levels of cytokines such as IL-10, TGF-β and IFN-γ. These results suggested a strategy to improve the adoptive immune therapy in recent use by removing the suppressive factors and a more effective tumor treatment combining chemotherapy and immunotherapy.

Increased Soluble Suppression of Tumorigenicity 2 Level Predicts All-Cause and Cardiovascular Mortality in Maintenance Hemodialysis Patients: A Prospective Cohort Study

Blood Purification. 2017  |  Pubmed ID: 27875808

Soluble suppression of tumorigenicity 2 (sST2) is a novel cardiovascular biomarker. This study aimed to evaluate the prognostic value of sST2 in hemodialysis patients.

On-treatment Markers As Predictors to Guide Anti-EGFR MoAb Treatment in Metastatic Colorectal Cancer: a Systematic Review with Meta-analysis

Cancer Chemotherapy and Pharmacology. Feb, 2017  |  Pubmed ID: 27878357

Skin toxicity (ST) and early tumor shrinkage (ETS) are early phenomenon during the anti-epidermal growth factor receptor (EGFR) monoclonal antibody (MoAb) treatment. We conducted a meta-analysis and included relevant studies that reported the impact of ST and ETS on survival- and life quality-based outcome of metastatic colorectal cancer (mCRC) patients treated with anti-EGFR MoAb.

Graphene Oxide-based Fluorescent Sensor for Sensitive Turn-on Detection of Sinapine

Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy. Mar, 2017  |  Pubmed ID: 27886646

Sinapine (SP) has attracted extensive attention in food and medical field because it is a crucial component in many plants with unique physiological activities. Here, we reported a fluorescent sensor based on the unique properties of graphene oxide (GO) for rapid, sensitive detection of SP concentration. In this strategy, GO has stronger affinity toward SP and can be also served as a quencher for DNA fluorescence probe. The fluorescence can make a recovery by the addition of SP, which can competitively desorb probe from the surface of GO, and the SP can thus be monitored by recording the fluorescence change. Because of the low background assays and high quenching ability offered by GO, the developed method provides a great potential for plant-derived molecules research.

PSMC2 is Up-regulated in Osteosarcoma and Regulates Osteosarcoma Cell Proliferation, Apoptosis and Migration

Oncotarget. Jan, 2017  |  Pubmed ID: 27888613

Proteasome 26S subunit ATPase 2 (PSMC2) is a recently identified gene potentially associated with certain human carcinogenesis. However, the expressional correlation and functional importance of PSMC2 in osteosarcoma is still unclear. Current study was focused on elucidating the significance of PSMC2 on malignant behaviors in osteosarcoma including proliferation, apoptosis, colony formation, migration as well as invasion. The high protein levels of PSMC2 in osteosarcoma samples were identified by tissue microarrays analysis. Besides, its expression in the levels of mRNA and protein was also detected in four different osteosarcoma cell lines by real-time PCR and western blotting separately. Silencing PSMC2 by RNA interference in osteosarcoma cell lines (SaoS-2 and MG-63) would significantly suppress cell proliferation, enhance apoptosis, accelerate G2/M phase and/or S phase arrest, and decrease single cell colony formation. Similarly, pharmaceutical inhibition of proteasome with MG132 would mimic the PSMC2 depletion induced defects in cell cycle arrest, apoptosis and colonies formation. Silencing of PSMC2 was able to inhibit osteosarcoma cell motility, invasion as well as tumorigenicity in nude mice. Moreover, the gene microarray indicated knockdown of PSMC2 notably changed a number of genes, especially some cancer related genes including ITGA6, FN1, CCND1, CCNE2 and TGFβR2, and whose expression changes were further confirmed by western blotting. Our data suggested that PSMC2 may work as an oncogene for osteosarcoma and that inhibition of PSMC2 may be a therapeutic strategy for osteosarcoma treatment.

Selective Effect of Cytokine-induced Killer Cells on Survival of Patients with Early-stage Melanoma

Cancer Immunology, Immunotherapy : CII. Mar, 2017  |  Pubmed ID: 27889798

Adoptive immunotherapy using cytokine-induced killer (CIK) cells has shown potential antitumor ability against several kinds of cancers, including melanoma. However, little is known about the achievable outcome of CIK cells in melanoma patients at different pathological stages. Here we recruited 55 patients treated with conventional therapy plus CIK cells as the CIK group, and 49 patients treated with conventional therapy alone as the control group. The pathological characteristics were comparable between two groups, with a follow-up period up to 40 months. Survival data and immune responses were evaluated after CIK cell treatment. In this study, CIK cells were successfully generated from peripheral blood of melanoma patients after in vitro culture for 14 days. The cultured CIK cells not only produced high levels of pro-inflammatory cytokines upon in vitro stimulation but also efficiently killed human melanoma cell lines. No serious side events were observed in all patients treated with CIK cells. Furthermore, infusions of CIK cells improved the quality of life in some patients, including advanced cases. More importantly, the CIK group exhibited better survival rates compared to the control group among early-stage melanoma patients, in consistent with the increased frequency of peripheral CD4(+) T cells. However, the patients with advanced-stage melanoma did not benefit from the CIK cell therapy in terms of survival rate. In conclusion, CIK cells combined with conventional treatments may prolong the survival of early-stage melanoma patients and improve the quality of life for some advanced cases in a safe way.

Sequential Recognition of Zinc and Pyrophosphate Ions in a Terpyridine-Functionalized Single Nanochannel

Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry. Jan, 2017  |  Pubmed ID: 27897377

A highly selective recognition system for zinc(II) and pyrophosphate ions is constructed using a single conical nanochannel covalently functionalized with N'-{4-[(2,2':6',2''-terpyridine)-4-yl]benzyl}ethane-1,2-diamine (TPYD). The immobilized TPYD acts as a specific coordination site for Zn(2+) to form TPYD-Zn(2+) complexes in preference over other metal ions, and subsequently, the resulting Zn(2+) -coordinated nanochannel can be used as a selective recognition element for the pyrophosphate ion based on the coordination reaction between hydroxyl oxygen atoms of pyrophosphate and Zn(2+) . Ion recognition is monitored by measuring the current-voltage curves of the solutions. The ionic current of the TPYD-functionalized system at -2.0 V undergoes a clear decrease after exposure to Zn(2+) ions and is followed with an obvious increase after subsequent treatment with a pyrophosphate solution. The change of ionic current can be primarily attributed to the variation of charge density of the nanochannel. This functionalized single nanochannel might provide a simple and universal means to recognize other targets by modifying different functional molecules onto the inner surfaces of nanochannels.

Mutations in IL36RN Are Associated with Geographic Tongue

Human Genetics. Feb, 2017  |  Pubmed ID: 27900482

Geographic tongue (GT) is a benign inflammatory disorder of unknown etiology. Epidemiology and histopathology in previous studies found that generalized pustular psoriasis (GPP) is a factor associated with GT, but the molecular mechanism remains obscure. To investigate the mechanism of GT, with and without GPP, three cohorts were recruited to conduct genotyping of IL36RN, which is the causative gene of GPP. In a family spanning three generations and diagnosed with only GT ("GT alone"), GT was caused by the c.115+6T>C/p.Arg10ArgfsX1 mutation in the IL36RN gene. An autosomal dominant inheritance pattern with incomplete penetrance was observed. In the cohort consisting of sporadic cases of "GT alone" (n = 48), significant associations between GT and three IL36RN variants (c.115+6T>C/p.Arg10ArgfsX1, c.169G>A/p.Val57Ile and c.29G>A/p.Arg10Gln) were shown. In the GPP patient cohort (n = 56) and GPP family member cohort (n = 67), a significant association between the c.115+6T>C mutation and the simultaneous presence of GPP and GT was observed when compared to the presence of GPP without GT (P < 0.05). Biopsies revealed similarities among GT patients with different genotypes (AA, Aa and aa), with the neutrophils prominently infiltrating the epidermis. Western-blot analysis showed that the expression ratio of IL-36Ra/IL-36γ in lesioned tongues with individuals harboring different genotypes (AA, Aa and aa, n = 3, respectively) decreased significantly compared to controls (n = 3). We describe the mechanism of GT for the first time: some cases of GT are caused by IL36RN mutations, while those lacking mutations are associated with an imbalance in expression between IL-36Ra and IL-36γ proteins in tongue tissue.

Down Regulation of RNA Binding Motif, Single-stranded Interacting Protein 3, Along with Up Regulation of Nuclear HIF1A Correlates with Poor Prognosis in Patients with Gastric Cancer

Oncotarget. Jan, 2017  |  Pubmed ID: 27902480

Frequent loss of multiple regions in short arm of chromosome 3 is found in various tumors including gastric cancer (GC). RNA binding motif, single-stranded interacting protein 3 (RBMS3) is a tumor suppressor gene located in this region and mediates cancer angiogenesis. However, the role of RBMS3 in GC remains unclear.To evaluate whether RBMS3, together with HIF1A, another key regulator of angiogenesis, predicts GC prognosis, the levels of RBMS3 and HIF1A were first examined by quantitative PCR (qPCR) and western blot from 27 fresh frozen GC and paired normal gastric tissues and then tested by immunohistochemistry (IHC) from 191 GC and 46 normal controls. Moreover, uni- and multivariate analysis were employed to assess the correlations between their levels and microvessel density (MVD) and clinical prognosis. To further identify RBMS3 function in vitro, cell proliferation assay, clonogenic assay, flow cytometry analysis and endothelial cell tube formation assay were employed.We found that RBMS3 level was decreased, whereas HIF1A was elevated in GC. Furthermore, we demonstrated that RBMS3 was an independent prognostic factor and the levels of RBMS3 and HIF1A were associated with GC angiogenesis and histopathological differentiation: patients with lower RBMS3 level and higher nuclear HIF1A expression had poorer prognosis. Besides, gain- and loss-of-function study revealed RBMS3 regulation on G1/S progression, cell proliferation and the tube formation of human umbilical vein endothelial cells (HUVECs) in vitro. These findings implicated that RBMS3 and nuclear HIF1A could act as prognostic biomarkers and therapeutic targets for GC.

Puerarin Offsets the Anticoagulation Effect of Warfarin in Rats by Inducing RCyps, Upregulating Vitamin K Epoxide Reductase and Inhibiting Thrombomodulin

Biopharmaceutics & Drug Disposition. Jan, 2017  |  Pubmed ID: 27925234

The current study was conducted to investigate the potential pharmacokinetic and pharmacodynamic interactions between warfarin and puerarin which is the most abundant component in Pueraria lobata (Gegen). In vivo and ex vivo rat models were used to reveal the underlying mechanisms of such interactions.

Novel Copper Complexes As Potential Proteasome Inhibitors for Cancer Treatment (Review)

Molecular Medicine Reports. Jan, 2017  |  Pubmed ID: 27959411

The use of metal complexes in the pharmaceutical industry has recently increased and as a result, novel metal‑based complexes have initiated an interest as potential anticancer agents. Copper (Cu), which is an essential trace element in all living organisms, is important in maintaining the function of numerous proteins and enzymes. It has recently been demonstrated that Cu complexes may be used as tumor‑specific proteasome inhibitors and apoptosis inducers, by targeting the ubiquitin‑proteasome pathway (UPP). Cu complexes have demonstrated promising results in preclinical studies. The UPP is important in controlling the expression, activity and location of various proteins. Therefore, selective proteasome inhibition and apoptotic induction in cancer cells have been regarded as potential anticancer strategies. The present short review discusses recent progress in the development of Cu complexes, including clioquinol, dithiocarbamates and Schiff bases, as proteasome inhibitors for cancer treatment. A discussion of recent research regarding the understanding of metal inhibitors based on Cu and ligand platforms is presented.

A Novel Therapy for Ovarian Cancer Using Real‑time Imaging

Molecular Medicine Reports. Jan, 2017  |  Pubmed ID: 27959453

The present study was designed to develop an activable, dual‑targeted theranostic platform combining fluorescent and cytotoxic templates to provide a novel strategy for specific drug delivery and cellular imaging in ovarian cancer cells. Two compounds of a folic acid‑prodrug‑doxorubicin (Dox) scaffold were synthesized, and their antiproliferative activities were evaluated using 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide and flow cytometric analysis. The process of drug release was investigated using fluorescence emission spectra assay and confocal laser scanning microscopy. The results showed that the synthesized compounds exhibited potent antitumor activities against ovarian cell lines. Among them, compound 1e exhibited the most potent activity demonstrating half maximal inhibitory concentration values of 0.85±0.10, 8.64±0.37 and 0.81±0.03 µM against A2780, A2780/Dox and A2780/cisplatin cell lines. The fluorescence imaging of live cell lines also provided an easy and reliable method to monitor site‑specific drug activities through turn‑on systems induced by drug release. The results of the present study may assist in the treatment of ovarian cancer cells with strengthened efficiency and real‑time imaging, which may be used as a multifunctional system for the optimization of anticancer drugs.

Glucagon-like Peptide-1 Inhibits the Receptor for Advanced Glycation Endproducts to Prevent Podocyte Apoptosis Induced by Advanced Oxidative Protein Products

Biochemical and Biophysical Research Communications. Jan, 2017  |  Pubmed ID: 27965099

To investigate whether and how glucagon-like peptide-1 (GLP-1) can protect podocytes from apoptosis induced by advanced oxidative protein products (AOPPs).

Molecularly Imprinted Polymer Grafted Paper-based Method for the Detection of 17β-estradiol

Food Chemistry. Apr, 2017  |  Pubmed ID: 27979279

17β-estradiol (17β-E2) usually is used to promote the growth of animal. Abuse of 17β-E2 has become a global food security problem, because the residues in foods can cause endocrine disorder through the food chain. A novel molecularly imprinted polymer (MIP) grafted paper-based method for the sensitive and specific detection of 17β-E2 was reported in this work. Results showed that the MIP's optimum synthetic conditions were as follows: 12 mL of acetonitrile was chosen as the solvent; the molar ratio of template molecule, functional monomer and cross linker was 1:12:12. MIP synthesized had a good recognition ability, the limit of detection (LOD) of established detection method for milk and human urine samples could reach 0.25μgL(-1).

A Highly Sensitive Signal-amplified Gold Nanoparticle-based Electrochemical Immunosensor for Dibutyl Phthalate Detection

Biosensors & Bioelectronics. May, 2017  |  Pubmed ID: 28011415

A simple and signal-amplified, label-free electrochemical impedimetric immunosensor for dibutyl phthalate (DBP), a type of phthalate ester, was developed using gold nanoparticles (AuNPs) induced signal amplification. The approach was based on an indirectly competitive binding system of coating antigen that coated on antigen/chitosan/MWCNTs@GONRs/GCE (modified electrodes), target (DBP) and anti-DBP antibody. Signal amplification was performed via the enlargement of AuNPs through NADH-promoted catalytic precipitation, which caused a marked increase in the electron-transfer resistance and electrostatic repulsion after an AuNP-labeled second antibody conjugated to anti-DBP. Under the optimized conditions, this method displayed: (i) low detection limits (7ng/mL, 10 times lower than the traditional ELISA method using the same antibody); (ii) satisfactory accuracy (recoveries, 86.0-120.4%) and agreement with corresponding ELISA method; (iii) high tolerance to some environmental interferents; and (iv) low cost and low sample consumption (6µL). Our results demonstrate the great potential and high efficiency of this immunosensor in practical applications for the cost-effective and sensitive monitoring of DBP in aquatic environments.

Efficacy and Safety of the Absorb Everolimus-Eluting Bioresorbable Scaffold for Treatment of Patients With Diabetes Mellitus: Results of the Absorb Diabetic Substudy

JACC. Cardiovascular Interventions. Jan, 2017  |  Pubmed ID: 28017311

The study sought to evaluate the efficacy and safety of the Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) (Abbott Vascular, Abbott Park, Illinois) in patients with diabetes mellitus.

Protective Effects of Resveratrol Against Mancozeb Induced Apoptosis Damage in Mouse Oocytes

Oncotarget. Jan, 2017  |  Pubmed ID: 28031523

Mancozeb, a mixture of ethylene-bis-dithiocarbamate manganese and zinc salts, is one of the most widely used fungicides in agriculture. Mancozeb could lead to mitochondria dysfunction, cellular anti-oxidation enzymes depletion and apoptotic pathways activation. Previous studies indicated the exposure of mancozeb through mother would lead to irregular estrous cycles, decreased progesterone levels, reduced litter sizes, and more frequent delivery of dead fetuses. In this study, we investigated mancozeb inducing reproductive toxicity, especially focusing on its apoptotic effect and epigenetic modifications. We also showed that resveratrol, a kind of phytoalexin found in peanuts and grapes, can alleviate mancozeb's adverse effects, such as declined fertility, decreased ovary weight and primary follicles. Besides, mancozeb treated oocytes displayed suboptimal developmental competence and this can also be improved by treatment of resveratrol. More detailed investigation of these processes revealed that mancozeb increased reactive oxygen species, causing cell apoptosis and abnormal epigenetic modifications, and resveratrol can block these cytotoxic changes. Collectively, our results showed that resveratrol can alleviate mancozeb induced infertility and this was mainly through the correction of apoptotic tendency and the abnormity of cellular epigenetic modification.

A Validator and Converter for the Synthetic Biology Open Language

ACS Synthetic Biology. Feb, 2017  |  Pubmed ID: 28033703

This paper presents a new validation and conversion utility for the Synthetic Biology Open Language (SBOL). This utility can be accessed directly in software using the libSBOLj library, through a web interface, or using a web service via RESTful API calls. The validator checks all required and best practice rules set forth in the SBOL specification document, and it reports back to the user the location within the document of any errors found. The converter is capable of translating from/to SBOL 1, GenBank, and FASTA formats to/from SBOL 2. The SBOL Validator/Converter utility is released freely and open source under the Apache 2.0 license. The online version of the validator/converter utility can be found here: . The source code for the validator/converter can be found here: .

Electron Microscopy Studies of the Coronavirus Ribonucleoprotein Complex

Protein & Cell. Mar, 2017  |  Pubmed ID: 28044277

Data on Taxonomic Status and Phylogenetic Relationship of Tits

Data in Brief. Feb, 2017  |  Pubmed ID: 28050581

The data in this paper are related to the research article entitled "Taxonomic status and phylogenetic relationship of tits based on mitogenomes and nuclear segments" (X.J. Li et al., 2016) [1]. The mitochondrial genomes and nuclear segments of tits were sequenced to analyze mitochondrial characteristics and phylogeny. In the data, the analyzed results are presented. The data holds the resulting files of mitochondrial characteristics, heterogeneity, best schemes, and trees.

Ingroup/outgroup Membership Modulates Fairness Consideration: Neural Signatures from ERPs and EEG Oscillations

Scientific Reports. Jan, 2017  |  Pubmed ID: 28051156

Previous studies have shown that ingroup/outgroup membership influences individual's fairness considerations. However, it is not clear yet how group membership influences brain activity when a recipient evaluates the fairness of asset distribution. In this study, subjects participated as recipients in an Ultimatum Game with alleged members of both an experimentally induced ingroup and outgroup. They either received extremely unequal, moderately unequal, or equal offers from proposers while electroencephalogram was recorded. Behavioral results showed that the acceptance rates for unequal offers were higher when interacting with ingroup partners than with outgroup partners. Analyses of event related potentials revealed that proposers' group membership modulated offer evaluation at earlier processing stages. Feedback-related negativity was more negative for extremely and moderately unequal offers compared to equal offers in the ingroup interaction whereas it did not show differential responses to different offers in the outgroup interaction. Analyses of event related oscillations revealed that the theta power (4-6 Hz) was larger for moderately unequal offers than equal offers in the ingroup interaction whereas it did not show differential responses to different offers in the outgroup interaction. Thus, early mechanisms of fairness evaluation are strongly modulated by the ingroup/outgroup membership of the interaction partner.

Vincristine Alleviates Adriamycin-induced Nephropathy Through Stabilizing Actin Cytoskeleton

Cell & Bioscience. 2017  |  Pubmed ID: 28053698

Antimicrotubule agent vincristine (VCR) has long been known as an alternative treatment for frequent relapse nephrotic syndrome and steroid-dependent nephrotic syndrome (SDNS). However, the mechanism is unknown. Here we found that VCR at a dosage much lower than that as an antimicrotubule agent can alleviate adriamycin (ADR)-induced proteinuria and podocyte foot process effacement. In cultured podocytes, VCR prevents ADR-induced actin fiber disorganization. In both in vitro and in vivo models, VCR suppresses ADR-induced overexpression of α3β1 integrin and focal adhesion kinase (FAK). These data suggest that VCR may relieve ADR-induced nephropathy through inhibiting injury-induced activation of integrin outside-in signaling to prevent actin cytoskeleton remodeling. Hence, our work reveals a novel role of VCR in regulating actin fiber assembly and provides first evidence on the therapeutic mechanism of VCR on nephrotic syndrome.

Coupling of C(sp(3))-H Bonds with C(sp(2))-O Electrophiles: Mild, General and Selective

Chemical Communications (Cambridge, England). Jan, 2017  |  Pubmed ID: 28059403

Herein is reported the mild and general coupling of amine/ether C(sp(3))-H bonds with various kinds of C(sp(2))-O electrophiles with high selectivity and efficiency. Valuable allylic/benzylic amines are generated in moderate to excellent yields. The utility of this transformation is demonstrated by a broad substrate scope (>50 examples), good functional group tolerance and facile product modification.

Transition-Metal-Free Lactonization of Sp(2) C-H Bonds with CO2

Organic Letters. Jan, 2017  |  Pubmed ID: 28060515

The transition-metal-free lactonization of heteroaryl and alkenyl C-H bonds with carbon dioxide is reported to synthesize important coumarin derivatives in moderate to excellent yields. These redox-neutral reactions feature a broad substrate scope, good functional group tolerance, facile scalability, and easy product derivatization.

High-Carbohydrate/Low-Fat Diet-Induced Gender-Specific Serum Lipid Profile Changes Are Associated with LEPR Polymorphisms in Chinese Youth

Annals of Nutrition & Metabolism. Jan, 2017  |  Pubmed ID: 28064282

The study aimed to investigate the interactions of genetic variants in the leptin receptor (LEPR) gene with lipid profile changes following a high-carbohydrate/low-fat (HC/LF) diet in a Chinese Han population.

Questionnaire to Assess Quality of Life in Patients with Breast Cancer - Validation of the Chinese Version of the EORTC QLQ-BR 53

Breast (Edinburgh, Scotland). Apr, 2017  |  Pubmed ID: 28068605

To evaluate the reliability and validity of the Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Breast Cancer (EORTC QLQ-BR53) questionnaire firstly in north of China.

Micro-electromechanical Film Bulk Acoustic Sensor for Plasma and Whole Blood Coagulation Monitoring

Biosensors & Bioelectronics. May, 2017  |  Pubmed ID: 28068607

Monitoring blood coagulation is an important issue in the surgeries and the treatment of cardiovascular diseases. In this work, we reported a novel strategy for the blood coagulation monitoring based on a micro-electromechanical film bulk acoustic resonator. The resonator was excited by a lateral electric field and operated under the shear mode with a frequency of 1.9GHz. According to the apparent step-ladder curves of the frequency response to the change of blood viscoelasticity, the coagulation time (prothrombin time) and the coagulation kinetics were measured with the sample consumption of only 1μl. The procoagulant activity of thromboplastin and the anticoagulant effect of heparin on the blood coagulation process were illustrated exemplarily. The measured prothrombin times showed a good linear correlation with R(2)=0.99969 and a consistency with the coefficient of variation less than 5% compared with the commercial coagulometer. The proposed film bulk acoustic sensor, which has the advantages of small size, light weight, low cost, simple operation and little sample consumption, is a promising device for miniaturized, online and automated analytical system for routine diagnostics of hemostatic status and personal health monitoring.

Predictive Factors of Depression Symptoms Among Adolescents in the 18-month Follow-up After Wenchuan Earthquake in China

Journal of Mental Health (Abingdon, England). Feb, 2017  |  Pubmed ID: 28079406

It is unclear about the change and risk factors of depression among adolescent survivors after earthquake.

Experience of Mowat-Wilson Syndrome Prenatal Diagnosis for a Chinese Family

Clinical Case Reports. Jan, 2017  |  Pubmed ID: 28096981

Mowat-Wilson syndrome (MWS) is a complex developmental disorder. We report the first prenatal diagnosis provided for a family in mainland China after identifying the causal mutation for the proband. Special focus on MWS-related organs during prenatal ultrasound scan is described which is extremely important for genetic counseling of parents.

In Vitro DNA-Binding, Anti-Oxidant and Anticancer Activity of Indole-2-Carboxylic Acid Dinuclear Copper(II) Complexes

Molecules (Basel, Switzerland). Jan, 2017  |  Pubmed ID: 28117677

Indole-2-carboxylic acid copper complex (ICA-Cu) was successfully prepared and characterized through elemental analysis, IR, UV-Vis, ¹H-NMR, TG analysis, and molar conductance, and its molecular formula was [Cu₂(C₉H₆O₂N)₄(H₂O)₂]·2H₂O. The binding ability of ICA-Cu to calf thymus DNA (CT-DNA) was examined by fluorescence spectrometry and the viscosity method. The results indicated that, upon the addition of increasing amounts of CT-DNA, the excitation and emission intensity of ICA-Cu decreased obviously and the excitation spectra shifted towards a long wavelength. ICA-Cu could displace ethidium bromide (EB) from the EB-DNA system, making the fluorescence intensity of the EB-DNA system decrease sharply; the quenching constant KSV value was 3.99 × 10⁴ M(-1). The emission intensity of the ICA-Cu-DNA system was nearly constant, along with the addition of Na⁺ in a series of concentrations. The fluorescence of the complex could be protected after the complex interacted with DNA. A viscosity measurement further supported the result that the ICA-Cu complex may interact with DNA in an intercalative binding mode. The antioxidant activities of ICA-Cu were evaluated by a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, a hydroxyl radical (OH) scavenging assay, and a 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assay. The ICA-Cu exhibited the highest inhibitory effects on the ABTS radical (94% inhibition at 60 µM), followed by OH and DPPH radicals (the degrees of inhibition being 71% and 56%, respectively). The in vitro cytotoxicity activity of ICA-Cu against two human breast cancer cell lines, MDA-MB-231 and MCF-7, was investigated by 3-[4,5-dimethyltiazol2-yl]-2.5-diphenyl-tetrazolium bromide (MTT) assay and cellular morphological analysis. The results showed that, upon increasing the concentration of ICA-Cu, an increase was observed in growth-inhibitory activity and the inhibition percentage were greater than 90% at 20 µM in both cell lines. Also, cellular morphological changes in the two cell lines agreed with the cytotoxicity results.

Presenilin 2 Deficiency Facilitates Aβ-induced Neuroinflammation and Injury by Upregulating P2X7 Expression

Science China. Life Sciences. Feb, 2017  |  Pubmed ID: 28120269

Accumulating evidence suggests that β-amyloid (Aβ)-induced neuroinflammation plays a prominent and early role in Alzheimer's disease (AD). In this study, we demonstrated that Presenilin 2 (PS2) deficiency facilitates Aβ-induced neuroinflammation and injury by upregulating P2X7 expression both in vitro and in vivo. PS2 knockout mice demonstrated increased cognitive impairments and cerebral injury. PS2 deficiency increased the expression of P2X7 both in neurons and microglial cells. Furthermore, extracellular ATP also increased in both Aβ-treated and untreated PS2 knockout microglial cells. Notably, Aβ-induced classical proinflammatory cytokines such as IL-1β, IL-1α and TNF-α were increased in PS2 knockout microglial cells, suggesting a potential role for PS2 in the regulation of neuroinflammation. The expression of P2X7 clearly increased in PS2 knockdown BV2 cells. Consistent with in vivo data, Aβ-induced IL-1β production was also clearly enhanced in PS2 knockdown BV2 cells. Additionally, expression of the transcription factor Sp1 was increased in PS2 knockdown cells. When we treated PS2 knockdown cells with the specific Sp1 inhibitor MIT, we observed that enhanced P2X7 expression was significantly rescued. Taken together, these data suggests that PS2 plays a protective role during Aβ-induced neuroinflammation and injury through down-regulation of P2X7 expression.

Rabies Transmission Following Organ Transplantation in China

The Journal of Infection. Apr, 2017  |  Pubmed ID: 28143755

Dual Tuning in Creative Processes: Joint Contributions of Intrinsic and Extrinsic Motivational Orientations

The Journal of Applied Psychology. Feb, 2017  |  Pubmed ID: 28150986

Intrinsic and extrinsic motivational orientations often coexist and can serve important functions. We develop and test a model in which intrinsic and extrinsic motivational orientations interact positively to influence personal creativity goal. Personal creativity goal, in turn, has a positive relationship with incremental creativity and an inverted U-shaped relationship with radical creativity. In a pilot study, we validated the personal creativity goal measure using 180 (Sample 1) and 69 (Sample 2) employees from a consulting firm. In the primary study, we tested the overall model using a sample of 657 research and development employees and their direct supervisors from an automobile firm. The results support the hypothesized model and yield several new insights. Intrinsic and extrinsic motivational orientations synergize with each other to strengthen personal creativity goal. Personal creativity goal in turn benefits incremental and radical creativity, but only up to a certain point for the latter. In addition to its linear indirect relationship with incremental creativity, intrinsic motivational orientation has an inverted U-shaped indirect relationship with radical creativity via personal creativity goal. (PsycINFO Database Record

Defective Branched-Chain Amino Acid Catabolism Disrupts Glucose Metabolism and Sensitizes the Heart to Ischemia-Reperfusion Injury

Cell Metabolism. Feb, 2017  |  Pubmed ID: 28178567

Elevated levels of branched-chain amino acids (BCAAs) have recently been implicated in the development of cardiovascular and metabolic diseases, but the molecular mechanisms are unknown. In a mouse model of impaired BCAA catabolism (knockout [KO]), we found that chronic accumulation of BCAAs suppressed glucose metabolism and sensitized the heart to ischemic injury. High levels of BCAAs selectively disrupted mitochondrial pyruvate utilization through inhibition of pyruvate dehydrogenase complex (PDH) activity. Furthermore, downregulation of the hexosamine biosynthetic pathway in KO hearts decreased protein O-linked N-acetylglucosamine (O-GlcNAc) modification and inactivated PDH, resulting in significant decreases in glucose oxidation. Although the metabolic remodeling in KO did not affect baseline cardiac energetics or function, it rendered the heart vulnerable to ischemia-reperfusion injury. Promoting BCAA catabolism or normalizing glucose utilization by overexpressing GLUT1 in the KO heart rescued the metabolic and functional outcome. These observations revealed a novel role of BCAA catabolism in regulating cardiac metabolism and stress response.

Identification of TAZ Mutations in Pediatric Patients with Cardiomyopathy by Targeted Next-generation Sequencing in a Chinese Cohort

Orphanet Journal of Rare Diseases. Feb, 2017  |  Pubmed ID: 28183324

Barth syndrome (BTHS) is a rare X-linked recessive disease characterized by cardiomyopathy, neutropenia, skeletal myopathy and growth delay. Early diagnosis and appropriate treatment may improve the prognosis of this disease. The purpose of this study is to determine the role of targeted next-generation sequencing (NGS) in the early diagnosis of BTHS in children with cardiomyopathy.

Long Non-coding RNA TUG1 Promotes Migration and Invasion by Acting As a CeRNA of MiR-335-5p in Osteosarcoma Cells

Cancer Science. Feb, 2017  |  Pubmed ID: 28205334

Long non-coding RNAs (lncRNAs) have now become the new hotspots in an ocean of diseases including osteosarcoma. The function of taurine up-regulated gene 1 (TUG1) and its working mechanism in osteosarcoma remain unclear. In our research, we found that TUG1 was elevated and correlated with a poor prognosis in osteosarcoma patients. Also, the following functional experiment showed that decreased TUG1 could remarkably inhibit osteosarcoma cell migration and invasion, indicating that TUG1 functioned as an oncogene in osteosarcoma. Moreover, we elucidated that TUG1 and Rho associated coiled-coil containing protein kinase 1 (ROCK1) - a metastasis-related gene targeted by microRNA-335-5p (miR-335-5p) had the same miR-335-5p combining site. The subsequent luciferase assay verified TUG1 was a target of miR-335-5p. Furthermore, the results of a qRT-PCR showed TUG1 and miR-335-5p could affect each other's expression respectively. Finally, we affirmed that TUG1 affected ROCK1 expression and ROCK1 mediated migration/invasion by working as a competitive endogenous RNAs (ceRNA) manner via miR-335-5p. In summary, the findings of this study basing on the ceRNA theory, combining the research foundation of miR-335-5p and ROCK1, taking TUG1 as a new study point, provided new insights into molecular level reversing migration and invasion of osteosarcoma. This article is protected by copyright. All rights reserved.

Ultrasensitive Surface-Enhanced Raman Scattering Sensor of Gaseous Aldehydes As Biomarkers of Lung Cancer on Dendritic Ag Nanocrystals

Analytical Chemistry. Feb, 2017  |  Pubmed ID: 28208308

Surface-enhanced Raman scattering (SERS) is expected as a technique that even theoretically detected chemicals at the single molecule level by surface plasmon phenomena of noble metal nanostructures. Insensitivity of detecting Raman weak-intensity molecules and low adsorptivity of gaseous molecules on solid substrates are two main factors hindering the application of SERS in gas detectors. In this manuscript, we demonstrated an operational SERS strategy to detect gaseous Raman weak-intensity aldehydes that have been considered as a biomarker of lung cancer for abnormal content was measured in volatile organic compounds (VOCs) of lung cancer patients. To enhance the adsorption of gaseous molecules, dendritic Ag nanocrystals mimicking the structural feature (dendritic) of moth's antennae were formed, wherein the existence of numerous cavity traps in Ag dendritic nanocrystals prolonged reaction time of the gaseous molecules on the surface of solid surface through the "cavity-vortex" effect. By the nucleophilic addition reaction with the Raman-active probe molecule p-aminothiophenol (4-ATP) pregrafted on dendritic Ag nanocrystals, the gaseous aldehyde molecules were sensitively captured to detect at the ppb (parts per billion) level. Additionally, the sensitivity of this operational SERS strategy to detection of lung cancer biomarkers was not affected by the humidity, which represented a great potential in fast, easy, cost-effective, and noninvasive recognition of lung malignancies.

Long-term Results of Paclitaxel Plus Cisplatin with Concurrent Radiotherapy for Loco-regional Esophageal Squamous Cell Carcinoma

World Journal of Gastroenterology. Jan, 2017  |  Pubmed ID: 28210091

To evaluate the long-term effectiveness and late toxicities of paclitaxel (PTX) plus cisplatin (DDP) with concurrent radiotherapy for locally advanced esophageal squamous cancer.

Immunotoxin Therapy for Lung Cancer

Chinese Medical Journal. 03, 2017  |  Pubmed ID: 28229994

Effects of Microcystis on Hypothalamic-Pituitary-Gonadal-Liver Axis in Nile Tilapia (Oreochromis Niloticus)

Bulletin of Environmental Contamination and Toxicology. Apr, 2017  |  Pubmed ID: 28236009

In the present study, Nile tilapia (Oreochromis niloticus) were used to assess the endocrine disruption potential of Microcytis aeruginosa. Male Nile tilapia were exposed to lyophilized M. aeruginosa or purified microcystin-LR (8.3 μg/L) for 28 days. The levels of serum hormones (17β-estradiol and testosterone) and transcripts of selected genes in the hypothalamus-pituitary-gonadal-liver axis were analyzed. The results showed that serum hormones were significantly up-regulated, and transcripts of 13 genes (GHRH, PACAP, GH, GHR1, GHR2, IGF1, IGF2, CYP19a, CYP19b, 3β-HSD1, 20β-HSD, 17β-HSD1 and 17β-HSD8) were significantly altered after Microcytis exposure. These results indicate that fish reproduction can be altered in a Microcystis bloom-contaminated aquatic environment.

Carbenoxolone Inhibits TRPV4 Channel-initiated Oxidative Urothelial Injury and Ameliorates Cyclophosphamide-induced Bladder Dysfunction

Journal of Cellular and Molecular Medicine. Feb, 2017  |  Pubmed ID: 28244642

Carbenoxolone (CBX) is a clinically prescribed drug for the treatment of digestive ulcer and inflammation. It is also a widely used pharmacological inhibitor of several channels in basic research. Given that the overactivity of several channels, including those inhibitable by CBX, underlies bladder dysfunction, we tested the potential therapeutic application and mechanism of CBX in the treatment of voiding dysfunction. In a mouse model of cystitis induced by cyclophosphamide (CYP), CBX administration prevented the CYP-elicited increase in bladder weight, oedema, haemorrhage, and urothelial injury. CBX also greatly improved micturition pattern, as manifested by the apparently decreased micturition frequency and increased micturition volume. Western blot results showed that CBX suppressed CYP-induced increase in protein carbonyls, COX-2, and iNOS. Further analysis using cultured urothelial cells revealed that acrolein, the major metabolite of CYP, caused protein oxidation, p38 activation, and urothelial injury. These effects of acrolein were reproduced by TRPV4 agonists and significantly prevented by antioxidant NAC, p38 inhibitor SB203580, TRPV4 antagonist RN-1734, and CBX. Further studies showed that CBX potently suppressed TRPV4 agonist-initiated calcium influx and subsequent cell injury. CBX attenuated CYP-induced cystitis in vivo and reduced acrolein-induced cell injury in vitro, through mechanisms involving inhibition of TRPV4 channels and attenuation of the channel-mediated oxidative stress. CBX might be a promising agent for the treatment of bladder dysfunction.

Modulation of N-Methyl-D-Aspartate Receptors (NMDAR), Bcl-2 and C-Fos Gene Expressions on Exposure to Individual and Mixtures of Low Concentration Metals in Zebrafish (Danio Rerio)

Archives of Environmental Contamination and Toxicology. Apr, 2017  |  Pubmed ID: 28255683

Currently, there is limited information on the toxicity of low concentration of metal mixtures in the environment. Of particular interest is the effect of low levels of metal mixtures on neurodevelopment of aquatic organisms. This study reports the neurological gene expressions after exposing zebrafish embryos to low concentration toxic heavy metals, 120 h post fertilization (hpf). Embryos were exposed to low concentration individual and mixtures of lead (Pb), mercury (Hg), arsenic (As), and cadmium (Cd). Quantitative real-time PCR was used to assess gene expressions. The findings of this study confirmed that exposure to low concentration heavy metals upregulated N-methyl-D-aspartate (NMDA) receptor subunits NMDAR2A (NR2A), NMDAR2B (NR2B), and NMDAR2D (NR2D) and B cell lymphoma (Bcl-2) genes. NR2A genes were significantly upregulated by 90 and 74%, respectively, on exposure to Pb + As and Pb + Cd. NR2B genes were upregulated by 85.3, 68.6, 62.7, and 62.7% on exposure to As, Pb + Hg, Pb + As, and Pb + Cd, respectively. Exposure to As, Pb + Cd, and Pb + Hg + As significantly upregulated Bcl-2 genes by 2.01-, 1.84-, and 1.80-fold, respectively. NR1A and C-fos gene expressions were not significantly different from control. Upregulation of NMDAR subunits and Bcl-2 genes in this study was largely a counter measure against insults from exposure to low concentration heavy metals. Principal component analysis confirmed the influence of low concentration individual and mixtures of Pb, Hg, As, and Cd on gene expression of NMDAR subunits and Bcl-2. These data suggest that altered expression of NMDA receptor subunits and Bcl-2 genes may explain toxicity of low concentration individual and mixtures of Pb, Hg, As, and Cd.

A Potent Peptide As Adiponectin Receptor 1 Agonist to Against Fibrosis

Journal of Enzyme Inhibition and Medicinal Chemistry. Dec, 2017  |  Pubmed ID: 28260395

Fibrotic diseases have become a major cause of death in the developed world. AdipoR1 agonists are potent inhibitors of fibrotic responses. Here, we focused on the in silico identification of novel AdipoR1 peptide agonists. A homology model was constructed to predict the 3D structure of AdipoR1. By docking to known active peptides, the putative active site of the model was further explored. A virtual screening study was then carried out with a set of manually designed peptides using molecular docking. Peptides with high docking scores were then evaluated for their anti-fibrotic properties. The data indicated that the novel peptide Pep70 significantly inhibited the proliferation of hepatic stellate cells (HSC) and NIH-3T3 cells (18.33% and 27.80%) and resulted in favouring cell-cycle arrest through increasing the accumulation of cells in the G0/G1 phase by 17.08% and 15.86%, thereby reducing the cell population in the G2/M phase by 11.25% and 15.95%, respectively. Additionally, Pep70 exhibited the most marked suppression on the expression of α-smooth muscle actin (α-SMA), collagen type I alpha1 (COL1A1) and TGF-β1. Therefore, the peptide Pep70 was ultimately identified as an inhibitor of fibrotic responses and as a potential AdipoR1 agonist.

A Study on the Temperature Field of a Bronze-bonded Diamond Wheel Dressed Using a Laser/ultrasonic Vibration Combined Method

Proceedings. Mathematical, Physical, and Engineering Sciences. Jan, 2017  |  Pubmed ID: 28265189

To solve problems in dressings for metal-bonded super-hard abrasive wheels, such as low efficiency and rapid wear, this article introduces a laser-assisted ultrasonic vibration dressing technique. Firstly, finite-element simulations were conducted on the dressing process of a bronze-bonded diamond wheel, and the wheel's temperature field distributions under different laser parameters were simulated. By analysing the simulation results of temperature fields and the melting point of the bronze bond, the laser parameters for laser-assisted ultrasonic vibration dressing tests were optimized, and then actual tests were carried out on the bronze-bonded diamond wheel. Results showed that, with appropriate technology parameters, the laser-assisted ultrasonic vibration dressing technique achieved desirable dressing results; specifically, the dressing force was low, the abrasive particles had high protrusions and the wheel had a large chip space and favourable surface topography.

Role of Clavicle Chest Cage Angle Difference in Predicting Postoperative Shoulder Balance in Lenke 5C Adolescent Idiopathic Scoliosis Patients After Selective Posterior Fusion

Orthopaedic Surgery. Mar, 2017  |  Pubmed ID: 28276642

To evaluate the role of preoperative clavicle chest cage angle difference (CCAD) on postoperative radiographic shoulder imbalance, patient's satisfaction and surgeon's fulfillment in Lenke 5 adolescent idiopathic scoliosis (AIS). CCAD, as a novel radiographic parameter, has proven to be a reliable predictor for postoperative shoulder imbalance in Lenke 1 AIS patients. However, the value of CCAD in predicting shoulder balance has never been evaluated in Lenke 5 AIS patients.

Finite Element Analysis of the Three Different Posterior Malleolus Fixation Strategies in Relation to Different Fracture Sizes

Injury. Feb, 2017  |  Pubmed ID: 28279427

Appropriate fixation method for the posterior malleolar fractures (PMF) according to the fracture size is still not clear. Aim of this study was to evaluate the outcomes of the different fixation methods used for fixation of PMF by finite element analysis (FEA) and to compare the effect of fixation constructs on the size of the fracture computationally.

Germ Cell Apoptosis and Expression of Bcl-2 and Bax in Porcine Testis Under Normal and Heat Stress Conditions

Acta Histochemica. Mar, 2017  |  Pubmed ID: 28279507

The aim of this study was to examine whether an elevated ambient temperature (37-40°C) had an effect on the apoptosis of germ cells and the expression of Bcl-2 and Bax in porcine testis. Six boars were used. Three boars were subjected to an elevated ambient temperature (37-40°C, 7days, 3h per day) as a heat stress (HS) group. The other 3 boars were kept in a room temperature house (20-27°C) as a control group. All boars were castrated and the testes were harvested. TUNEL assay was used for the detection of apoptotic cells. Immunohistochemistry, Western blotting and quantitative real-time PCR were used to analyze protein and mRNA levels of Bcl-2 and Bax in response to heat treatment. The results showed that apoptotic signals increased under heat stress conditions compared with the control (P<0.01), and the cell types most affected by heat treatment were spermatocytes and spermatids. In both the control and experimental groups, Bcl-2 was expressed in the cytoplasm and nucleus of spermatogonia, spermatocytes and differentiating spermatids and Bcl-2 preferentially localized close to the seminiferous tubule's luminal surface in late spermatocytes and spermatids. Compared with the control group, the expression levels of Bcl-2 protein and mRNA significantly increased in heat treatment group, while the expression levels of Bax protein and mRNA did not show significant changes between the control and experimental group. Low to moderate Bax immunoreactivity staining was observed in all kinds of germ cells in the control group. Strong staining was observed in spermatogonia, and low to moderate Bax staining was observed in spermatocytes and spermatids. A redistribution of Bax from a cytoplasmic to perinuclear or nuclear localization could be observed in the spermatogonia, spermatocytes and spermatids obtained in the heat treated group. These results showed that elevated ambient temperatures induced germ cell apoptosis. In response to heat stress, the expression of Bcl-2 increased and a redistribution of Bax from a cytoplasmic to a perinuclear or nuclear localization. This indicates that Bcl-2 and Bax may be involved in regulation of germ cell apoptosis induced by heat stress in boars.

Gambogic Acid-loaded Biomimetic Nanoparticles in Colorectal Cancer Treatment

International Journal of Nanomedicine. 2017  |  Pubmed ID: 28280328

Gambogic acid (GA) is expected to be a potential new antitumor drug, but its poor aqueous solubility and inevitable side effects limit its clinical application. Despite these inhe rent defects, various nanocarriers can be used to promote the solubility and tumor targeting of GA, improving antitumor efficiency. In addition, a cell membrane-coated nanoparticle platform that was reported recently, unites the customizability and flexibility of a synthetic copolymer, as well as the functionality and complexity of natural membrane, and is a new synthetic biomimetic nanocarrier with improved stability and biocompatibility. Here, we combined poly(lactic-co-glycolic acid) (PLGA) with red blood-cell membrane (RBCm), and evaluated whether GA-loaded RBCm nanoparticles can retain and improve the antitumor efficacy of GA with relatively lower toxicity in colorectal cancer treatment compared with free GA. We also confirmed the stability, biocompatibility, passive targeting, and few side effects of RBCm-GA/PLGA nanoparticles. We expect to provide a new drug carrier in the treatment of colorectal cancer, which has strong clinical application prospects. In addition, the potential antitumor drug GA and other similar drugs could achieve broader clinical applications via this biomimetic nanocarrier.

Effect of MiR-106b on Invasiveness of Pituitary Adenoma Via PTEN-PI3K/AKT

Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. Mar, 2017  |  Pubmed ID: 28288092

BACKGROUND Pituitary adenomas are mostly benign tumors, although certain cases have invasiveness, which might be related with high expression of miR-106b. The PTEN-PI3K/AKT signal pathway is known to be related with cell migration and invasion. Among these, PTEN is the target gene for miR-106b. Whether miR-106b affects invasiveness of pituitary adenoma via PTEN-PI3K/AKT is unclear. MATERIAL AND METHODS Both invasive and non-invasive pituitary adenoma tissue samples were collected from our Neurosurgery Department, in parallel with brain tissues after head contusion surgery. Pituitary adenoma cell line HP75 was cultured in vitro and divided into NC and miR-106b inhibitor groups for measuring cell cycle/proliferation. Malignant growth of cells was measured by agarose gel clonal assay, while cell migration and invasion were reflected by starch assay and Transwell assay, respectively. The expression of PTEN, PI3K/AKT, and MMP-9 was measured. RESULTS MiR-106b was significantly up-regulated in pituitary adenoma but PTEN was down-regulated, especially in invasive tumors. The inhibition of miR-106b remarkably suppressed proliferation and anchorage-independent growth of HP75 cells, with major arrest of cell cycles. The inhibition of miR-106b significantly depressed starch healing and invasive potency of cells. A negative targeted regulation existed between miR-106b and PTEN, as the inhibition of miR-106b significantly enhanced PTEN expression, affecting the activity of downstream PI3K/AKT signaling pathway, thus affecting migration and invasion of pituitary adenoma. CONCLUSIONS MiR-106b can affect migration and invasion of pituitary adenoma cells via regulating PTEN and further activity of the PI3K/AKT signaling pathway and MMP-9 expression.

A Novel Laparoscopic Technique for Anorectal Malformation with Low Recto-bulbar Fistulae

Surgical Endoscopy. Mar, 2017  |  Pubmed ID: 28289973

The repair of anorectal malformation (ARM) with low recto-bulbar fistula (bowel-to-skin distance: 1-1.5 cm) is contraindicated for laparoscopy due to the difficulty in exposing the fistulae. Posterior or anterior sagittal anorectoplasty is thus conventionally carried out for low recto-bulbar fistula repair. However, these procedures carry the potential risk of wound infection/dehiscence and incontinence. We have developed a single-incision laparoscopic-assisted perineal anorectoplasty (SILPARP) technique. The current study aims to evaluate the safety and efficacy of this novel procedure.

Injectable Polypeptide Hydrogel As Biomimetic Scaffolds with Tunable Bioactivity and Controllable Cell Adhesion

Biomacromolecules. Mar, 2017  |  Pubmed ID: 28292176

Injectable hydrogels have been widely investigated for applications in biomedical fields, for instance, as biomimetic scaffolds mimicking the extracellular matrix (ECM). In addition to as scaffolds for mechanical support and transferring of nutrients, the dynamic bioactivity of ECM is another critical factor that affects cell behavior. In this work, a novel injectable poly(l-glutamic acid)-based hydrogel decorated with RGD was fabricated. The presentation of RGD significantly enhanced the cell-matrix interaction and promoted cell adhesion and proliferation. Moreover, the cell-adhesive RGD was conjugated to the network via a disulfide bond, so that the density of RGD and the bioactivity of hydrogel can be well controlled by tuning the RGD content through treating with glutathione. As a result, the cell behaviors on the hydrogel can be tuned on demand. The injectable hydrogel with controllable bioactivity may provide an interesting strategy to develop a scaffold mimicking ECM that can regulate cell adhesion dynamically.

Chemotherapy in Combination with Cytokine-induced Killer Cell Transfusion: An Effective Therapeutic Option for Patients with Extensive Stage Small Cell Lung Cancer

International Immunopharmacology. Mar, 2017  |  Pubmed ID: 28292730

In the past decade of clinical studies, the combination of chemotherapy with cytokine induced killer (CIK) cell transfusion has confirmed a promised efficacy in several types of cancer. CIK cells are a mixture of T lymphocytes, generated from peripheral blood mononuclear cells induced by multiple cytokines. This study was aimed to evaluate the clinical efficacy of chemotherapy combined with CIK- cell therapy in patients with extensive stage small cell lung cancer (ES SCLC).

The Circular RNA CiRS-7 Promotes APP and BACE1 Degradation in an NF-κB-dependent Manner

The FEBS Journal. Mar, 2017  |  Pubmed ID: 28296235

The aberrant accumulation of β-amyloid peptide (Aβ) in the brain is a key feature of Alzheimer's disease (AD), and enhanced cleavage of β-amyloid precursor protein (APP) by β-site APP-cleaving enzyme 1 (BACE1) has a major causative role in AD. Despite their prominence in AD pathogenesis, the regulation of BACE1 and APP is incompletely understood. In this study, we report that the circular RNA circular RNA sponge for miR-7 (ciRS-7) has an important role in regulating BACE1 and APP protein levels. Previous studies have shown that ciRS-7, which is highly expressed in the human brain, is down-regulated in the brain of people with AD but the relevance of this finding was not clear. We have found that ciRS-7 is not involved in the regulation of APP and BACE1 gene expression, but instead reduces the protein levels of APP and BACE1 by promoting their degradation via the proteasome and lysosome. Consequently, overexpression of ciRS-7 reduces the generation of Aβ, indicating a potential neuroprotective role of ciRS-7. Our data also suggest that ciRS-7 modulates APP and BACE1 levels in a nuclear factor-κB (NF-κB)-dependent manner: ciRS-7 expression inhibits translation of NF-κB and induces its cytoplasmic localization, thus derepressing expression of UCHL1, which promotes APP and BACE1 degradation. Additionally, we demonstrated that APP reduces the level of ciRS-7, revealing a mutual regulation of ciRS-7 and APP. Taken together, our data provide a molecular mechanism implicating reduced ciRS-7 expression in AD, suggesting that ciRS-7 may represent a useful target in the development of therapeutic strategies for AD.

Diagnostic Value of CYFRA 21-1 in the Cerebrospinal Fluid for Leptomeningeal Metastasis

Disease Markers. 2017  |  Pubmed ID: 28298807

Cerebrospinal fluid (CSF) cytology has low sensitivity for leptomeningeal metastasis (LM); thus, new markers are needed to improve the diagnostic accuracy of LM. We measured carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) in paired samples of CSF and serum from patients with LM and patients with nonmalignant neurological diseases (NMNDs) as controls. Receiver operating curve analysis was performed to assess their diagnostic accuracy for LM. In patients with NMNDs, CEA and CYFRA 21-1 levels in the CSF were significantly lower than the serum levels. In patients with LM, there was no significant difference between the CSF and serum CEA levels, whereas the CYFRA 21-1 levels were significantly higher in the CSF than the serum. CSF/serum quotients of CYFRA 21-1 were higher than those of CEA in patients with LM and patients with NMNDs. CSF CYFRA 21-1 and CSF/serum quotient of CYFRA 21-1 had high accuracy for differentiating LM from NMNDs that was similar to CSF CEA and CSF/serum quotient of CYFRA 21-1, whereas serum CYFRA 21-1 is of poor diagnostic value. Measurement of CSF CYFRA 21-1 should not be overlooked in patients with suspected LM, even if the serum CYFRA 21-1 level is within normal limits.

Nuclear-Shell Biopolymers Initiated by Telomere Elongation for Individual Cancer Cell Imaging and Drug Delivery

Analytical Chemistry. Mar, 2017  |  Pubmed ID: 28301132

Here, we propose a strategy for unique nuclear-shell biopolymers initiated by telomere elongation for telomerase activity detection and precise drug delivery to individual cancer cells. Telomerase-triggered DNA rolling-circle amplification (RCA) is used to assemble nuclear-shell biopolymers with signal molecules for selective cancer cell recognition and efficient drug delivery to targeted individual cells. This strategy not only should allow the creation of clustered 5-carboxyfluorescein (FAM)-fluorescence spots in response to human-telomerase activity in individual cancer cells but also could efficiently deliver drugs to reduce the undesired death of healthy cells. These findings offer new opportunities to improve the efficacy of cancer cell imaging and therapy.

Spinal Epidural Lipomatosis - an Easily Ignored Secondary Intraspinal Disorder in Spinal Kyphotic Deformities

BMC Musculoskeletal Disorders. Mar, 2017  |  Pubmed ID: 28302104

A previous study reported a high prevalence of spinal epidural lipomatosis (SEL) in patients with Scheuermann kyphosis (SK) and suggested that it may play a role in the pathogenesis of this disease. According to our observation, however, SEL occurs in other spinal kyphotic deformities as well. The aim of this study was to test the hypothesis that SEL commonly occurs in patients with different types of kyphotic deformities as a secondary intraspinal disorder.

Microsomal Glutathione Transferase 1 Attenuated ROS-induced Lipid Peroxidation in Apostichopus Japonicus

Developmental and Comparative Immunology. Mar, 2017  |  Pubmed ID: 28302499

Microsomal glutathione transferase (mGST) is a membrane bound glutathione transferase in multifunctional detoxification isoenzymes family and also plays crucial roles in innate immunity. In the present study, a novel microsomal GST homology was identified from Apostichopus japonicus (designated as AjmGST1) by RACE approaches. The full-length cDNA of AjmGST1 was of 1296 bp encoded a protein of 169 amino acids residues. Multiple sequence alignment and phylogenetic analysis together supported that AjmGST1 belonged to a new member in invertebrates mGST family. Spatial expression analysis revealed that AjmGST1was ubiquitously expressed in all examined tissues with the larger magnitude in tentacle. Time-course expression of AjmGST1 mRNA in coelomocytes was up-regulated after Vibrio splendidus challenge from 6 h until 72 h with the peak expression in 24 h, compared with that in the control group. Similarly, the induced expression of AjmGST1 expression was also detected in lipopolysaccharide (LPS) exposed primary coelomocytes. The purified recombinant protein of AjmGST1 showed high activity with GST substrate at pH of 7.0 and temperature of 35 °C. Meantime, the recombinant AjmGST1 depressed H2O2-induced MDA production both in vivo and in vitro. All of these results indicated that AjmGST1 was an important regulator in elimination of lipid peroxidation under immune response.

Tandem Coupling of Azide with Isonitrile and Boronic Acid: Facile Access to Functionalized Amidines

Angewandte Chemie (International Ed. in English). Mar, 2017  |  Pubmed ID: 28319297

Amidine is a notable nitrogen-containing structural motif found in bioactive natural products and pharmaceuticals. Herein, a novel rhodium(I)-catalyzed tandem reaction of readily accessible azides with isonitriles and boronic acids via a carbodiimide intermediate is achieved. This protocol offers an alternative approach toward N-sulfonyl-, N-acyl-, and N- phosphoryl-functionalized, as well as general N-aryl and N-alkyl amidines with broad substrate scope. In addition, functionalized guanidines can also been synthesized when amines are used instead. The accomplishment of estrone-derived amidine and glibenclamide bioisosteres further reveals the practical utility of this strategy.

Tandem SN2' Nucleophilic Substitution/oxidative Radical Cyclization of Aryl Substituted Allylic Alcohols with 1,3-dicarbonyl Compounds

Organic & Biomolecular Chemistry. Mar, 2017  |  Pubmed ID: 28332678

A novel and efficient tandem SN2' nucleophilic substitution/oxidative radical cyclization reaction of aryl substituted allylic alcohols with 1,3-dicarbonyl compounds has been developed by using Mn(OAc)3 as an oxidant, which enables the expeditious synthesis of polysubstituted dihydrofuran (DHF) derivatives in moderate to high yields. The use of weakly acidic hexafluoroisopropanol (HFIP) as the solvent rather than AcOH has successfully improved the yields and expanded the substrate scope of this type of radical cyclization reactions. Mechanistic studies confirmed the cascade reaction process involving a final radical cyclization.

Iterative Dataset Optimization in Automated Planning: Implementation for Breast and Rectal Cancer Radiotherapy

Medical Physics. Mar, 2017  |  Pubmed ID: 28339103

To develop a new automated treatment planning solution for breast and rectal cancer radiotherapy.

simple hit counter