In JoVE (2)

Other Publications (200)

Articles by Jie Wu in JoVE

 JoVE Genetics

Detection of Copy Number Alterations Using Single Cell Sequencing

1Koch Institute for Integrative Cancer Research, Department of Biology, Massachusetts Institute of Technology, 2Howard Hughes Medical Institute, 3Division of Health Sciences and Technology, Harvard Medical School, 4The Barbara K. Ostrom (1978) Bioinformatics and Computing Facility in the Swanson Biotechnology Center, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 5BioMicro Center, Department of Biology, Massachusetts Institute of Technology


JoVE 55143

Other articles by Jie Wu on PubMed

Associations Between Sleep Duration and Overweight/Obesity: Results from 66,817 Chinese Adolescents

Scientific Reports. Nov, 2015  |  Pubmed ID: 26568253

The findings about the shapes of associations between sleep duration and overweight/obesity in adolescents were largely inconsistent in the existing literature. We examined the functional forms of the associations between sleep duration and overweight/obesity in 66,817 Chinese adolescents by modelling sleep duration categorically and continuously. The adjusted ORs (95% CI) of overweight (with 7.0-8.9 h of sleep being considered the reference group) for subjects reporting <5.0 hours, 5.0-6.9 hours and ≥9.0 hours of sleep were 1.26 (1.05-1.51), 1.06 (1.00-1.11) and 1.27 (1.14-1.42), respectively. The adjusted ORs (95% CI) of obesity (with 7.0-8.9 h of daily sleep being considered as the reference group) for adolescents reporting <5.0 hours, 5.0-6.9 hours and ≥9.0 hours of sleep were 1.24 (0.97-1.57), 0.94 (0.87-1.01) and 1.42 (1.24-1.63), respectively. Continuous splines regressions support non-linear U shape associations between sleep duration and overweight/obesity, with the bottom at around 7.0-8.0 hours sleep (overweight: likelihood ratio = 32.7 p < 0.01; obesity: likelihood ratio = 40.4 p < 0.01). U-shape associations were found between sleep duration and overweight/obesity in Chinese adolescents and an optimal sleep duration of 7.0-8.0 hours sleep may prevent overweight/obesity.

[The Effect of the Acupuncture Intervention of Dredging Governor Vessel and Regulating Mentality for the Medication Treatment of Post-stroke Depression]

Zhongguo Zhen Jiu = Chinese Acupuncture & Moxibustion. Aug, 2015  |  Pubmed ID: 26571884

To observe the differences in onset time and the overall efficacy of the acupuncture therapy of dredging Governor Vessel and regulating mentality combined with fluoxetine and the fluoxetine for post-stroke depression(PSD).

The Role, Mechanism and Potentially Novel Biomarker of MicroRNA-17-92 Cluster in Macrosomia

Scientific Reports. Nov, 2015  |  Pubmed ID: 26598317

Macrosomia is one of the most common perinatal complications of pregnancy and has life-long health implications for the infant. microRNAs (miRNAs) have been identified to regulate placental development, yet the role of miRNAs in macrosomia remains poorly understood. Here we investigated the role of miR-17-92 cluster in macrosomia. The expression levels of five miRNAs in miR-17-92 cluster were significantly elevated in placentas of macrosomia, which may due to the up-regulation of miRNA-processing enzyme Drosha and Dicer. Cell cycle pathway was identified to be the most relevant pathways regulated by miR-17-92 cluster miRNAs. Importantly, miR-17-92 cluster increased proliferation, attenuated cell apoptosis and accelerated cells entering S phase by targeting SMAD4 and RB1 in HTR8/SVneo cells. Furthermore, we found that expression of miR-17-92 cluster in serum had a high diagnostic sensitivity and specificity for macrosomia (AUC: 80.53%; sensitivity: 82.61%; specificity: 69.57%). Our results suggested that miR-17-92 cluster contribute to macrosomia development by targeting regulators of cell cycle pathway. Our findings not only provide a novel insight into the molecular mechanisms of macrosomia, but also the clinical value of miR-17-92 cluster as a predictive biomarker for macrosomia.

Clinical Characteristics and STK11 Gene Mutations in Chinese Children with Peutz-Jeghers Syndrome

BMC Gastroenterology. Nov, 2015  |  Pubmed ID: 26607058

Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant inherited disease characterized by gastrointestinal hamartomatous polyps and mucocutaneous melanin spots. Germline mutation of the serine/threonine kinase 11 (STK11) gene are responsible for PJS. In this study, we investigated the clinical characteristics and molecular basis of the disease in Chinese children with PJS.

Cyclovirobuxine D Inhibits Cell Proliferation and Induces Mitochondria-Mediated Apoptosis in Human Gastric Cancer Cells

Molecules (Basel, Switzerland). Nov, 2015  |  Pubmed ID: 26610442

Gastric cancer is one of the most common malignant cancers, with high death rates, poor prognosis and limited treatment methods. Cyclovirobuxine D (CVB-D) is the main active component of the traditional Chinese medicine Buxus microphylla. In the present study, we test the effects of CVB-D on gastric cancer cells and the underlying mechanisms of action. CVB-D reduced cell viability and colony formation ability of MGC-803 and MKN28 cells in a time- and concentration-dependent manner. Flow cytometry showed that cell cycle of CVB-D treated cells was arrested at the S-phase. CVB-D also induced apoptosis in MGC-803 and MKN28 cells, especially early stage apoptosis. Furthermore, mitochondria membrane potential (Δψm) was reduced and apoptosis-related proteins, cleaved Caspase-3 and Bax/Bcl-2, were up-regulated in CVB-D-treated MGC-803 and MKN28 cells. Taken together, our studies found that CVB-D plays important roles in inhibition of gastric tumorigenesis via arresting cell cycle and inducing mitochondria-mediated apoptosis, suggesting the potential application of CVB-D in gastric cancer therapy.

Pancreatic Neuroendocrine Carcinoma Diagnosed Using Endoscopic Ultrasound-guided Fine Needle Aspiration: A Case Report and Literature Review

Journal of Cancer Research and Therapeutics. Nov, 2015  |  Pubmed ID: 26612453

Pancreatic neuroendocrine carcinoma (NEC) is a rare pancreatic neoplasm. In this study, we report the case of a 67-year-old male who was admitted with epigastric pain, which began during the previous week. The planar imaging of the magnetic resonance imaging sequence detected oval shapes in the neck and tail of the pancreas. Endoscopic ultrasonography showed low-echo lumps at these sites. Endoscopic ultrasound-guided fine needle aspiration was performed on the pancreatic masses. Pathology results indicated that the tissue taken from the pancreas was consistent with small cell NEC. We also review the current published literature on pancreatic NEC.

Ginseng Alleviates Cyclophosphamide-induced Hepatotoxicity Via Reversing Disordered Homeostasis of Glutathione and Bile Acid

Scientific Reports. Dec, 2015  |  Pubmed ID: 26625948

Cyclophosphamide (CP), a chemotherapeutic agent, is restricted due to its side effects, especially hepatotoxicity. Ginseng has often been clinically used with CP in China, but whether and how ginseng reduces the hepatotoxicity is unknown. In this study, the hepatoprotective effects and mechanisms under the combined usage were investigated. It was found that ginseng could ameliorate CP-induced elevations of ALP, ALT, ALS, MDA and hepatic deterioration, enhance antioxidant enzymes' activities and GSH's level. Metabolomics study revealed that 33 endogenous metabolites were changed by CP, 19 of which were reversed when ginseng was co-administrated via two main pathways, i.e., GSH metabolism and primary bile acids synthesis. Furthermore, ginseng could induce expression of GCLC, GCLM, GS and GST, which associate with the disposition of GSH, and expression of FXR, CYP7A1, NTCP and MRP 3, which play important roles in the synthesis and transport of bile acids. In addition, NRF 2, one of regulatory elements on the expression of GCLC, GCLM, GS, GST, NTCP and MRP3, was up-regulated when ginseng was co-administrated. In conclusion, ginseng could alleviate CP-induced hepatotoxicity via modulating the disordered homeostasis of GSH and bile acid, which might be mediated by inducing the expression of NRF 2 in liver.

Epigenetic Regulation of CDH1 Exon 8 Alternative Splicing in Gastric Cancer

BMC Cancer. Dec, 2015  |  Pubmed ID: 26674321

The tumor suppressor gene CDH1 is critical for intercellular adhesion. In our previous work, we reported a nonfunctional CDH1 transcript that lacks the final 83 base pairs of exon 8 (1054del83). In this work, we probed the role of histone epigenetic modifications as well as DNA methylation in selection of this isoform.

Analysis of the Mitochondrial Maxicircle of Trypanosoma Lewisi, a Neglected Human Pathogen

Parasites & Vectors. Dec, 2015  |  Pubmed ID: 26715306

The haemoflagellate Trypanosoma lewisi is a kinetoplastid parasite which, as it has been recently reported to cause human disease, deserves increased attention. Characteristic features of all kinetoplastid flagellates are a uniquely structured mitochondrial DNA or kinetoplast, comprised of a network of catenated DNA circles, and RNA editing of mitochondrial transcripts. The aim of this study was to describe the kinetoplast DNA of T. lewisi.

Psychosocial Problems Syndemically Increase Adolescent Substance Use: Findings From a Cross-sectional Survey of 82,812 Chinese Adolescents

Medicine. Dec, 2015  |  Pubmed ID: 26717391

A growing body of studies have indicated the associations between substance use and psychosocial problems in adolescents. However, few of them have examined whether these psychosocial problems form a syndemic, which means the co-occurrence of psychosocial problems accompanied by additional effects on substance use.We conducted a cross-sectional survey with 82,812 Chinese adolescents who were selected using a multistage random procedure. Bivariate associations were estimated between selected syndemic indicators and adolescent substance use. Multivariate logistic regression was used to estimate the association between the syndemic indicator count score (the count of syndemic indicators) and adolescent substance use. In addition, cluster analysis was used to partition participants reporting at least one of syndemic indicators to assess associations between resolved cluster memberships and adolescent substance use.All selected syndemic indicators were associated with each other and with adolescent substance use. As the number of syndemic indicators increases, stronger associations with substance use were found in our analysis: the range of adjusted OR was from 1.57 (95% CI: 1.38-1.79) for 1 syndemic indicator to 9.45 (95% CI: 7.60-11.76) for 5 or 6 syndemic indicators. There was no effect modification of gender on these additive associations. The multivariate logistic regression indicated that the cluster membership of nonlow SES academic failures has the highest odds of using substance (OR = 2.26, 95% CI: 2.12-2.41), compared to students reporting none syndemic indicators.Our findings support the syndemic hypothesis that adolescents bearing multiple psychosocial problems experience additive risks of using substance. Our findings support that a comprehensive approach to substance use prevention in adolescents would necessitate the involvement of a variety of providers.

[Current Status and Clinical Progress of Capsule Retention]

Zhong Nan Da Xue Xue Bao. Yi Xue Ban = Journal of Central South University. Medical Sciences. Dec, 2015  |  Pubmed ID: 26739085

Small bowel capsule endoscopy has been now widely applied for patients who are highly suspected of small bowel disease with occult bleeding and unexplained abdominal pain. Capsule retention is a major complication, with an overall incidence of 1%-2%, commonly seen in the detection of Crohn's disease and small bowel tumors. Most cases run asymptomatically after retention, while intestinal obstruction or perforation can occur ralely. Conservative methods, endoscopic or surgical interventions are performed to deal with the retention. Patency capsule is currently used as a novel tool to reduce the risk of capsule retention.

Application of MSI in MRI-negative Focal Cortical Dysplasia Patients with Epilepsy

International Journal of Clinical and Experimental Medicine. 2015  |  Pubmed ID: 26770448

Focal cortical dysplasia (FCD) is the most common cause of intractable epilepsy in children and adolescent.

[Characteristics of Acupoint Application for the Sub-healthy Condition Treated with Ancient and Modern Acupuncture Based on Data Mining Exploration]

Zhongguo Zhen Jiu = Chinese Acupuncture & Moxibustion. Oct, 2015  |  Pubmed ID: 26790229

The acupoint selection was retrieved from the ancient and modern literature on the treatment of sub-healthy condition with acupuncture. The law of acupoint application was analyzed so as to provide a certain reference to the determination of acupoint prescription in clinical acupuncture. The ancient literature was retrieved from Chinese basic ancient literature database. The modern literature was retrieved from Cochrane Library, Medline, PubMed, Ovid evidence-based medicine database, Chinese biomedical literature database, China journal full-text database, VIP journal full-text database and Wanfang database. The database mining software was adopted to explore the law of acupoint application in treatment of sub-healthy conditions with ancient and modern acupuncture. The acupoint use frequency, compatibility association rule, law for meridian use and the use regularity of specific points were analyzed. In the ancient treatment for sub-healthy condition, the top five commonly used acupoints are Shenmen (HT 7), Zhaohai (KI 6), Taibai (SP 3), Daling (PC 7) and Taixi (KI 3). The most commonly combined points are Zhangmen (LR 13), Taibai (SP 3) and Zhaohai (KI 6). The most commonly used meridians are the bladder meridian of foot-taiyang, kidney meridian of foot-shaoyin and liver meridian of foot-jueyin. The most commonly used specific points are the five-shu points. The most commonly used acupoints are located in the lower limbs. In the modern treatment, the top five commonly used acupoints are Zusanli (ST 36), Sanyinjiao (SP 6), Baihui (GV 20), Shenshu (BL 23) and Guanyuan (CV 4). The most commonly supplemented points are Hegu (LI 4) and Taichong (LR 3). The most commonly used meridians are the bladder meridian of foot-taiyang, the conception vessel and the governor vessel. The most commonly used specific points are the back-shu points. The most commonly used acupoints are located in the lower limbs. After the systematic comprehension of the relevant ancient and modern literature, the most commonly used acupoints are selected along the bladder meridian of foot-taiyang, and the most commonly used specific points are the back-shu points, the five-shu points and the front-mu-points. the acupoints are mostly located in the lower limbs.

A Compact PET Detector Module Using SiPMs and MVT Digitizers

EJNMMI Physics. Dec, 2015  |  Pubmed ID: 26956330

Novel Hydrogel Adjuvant Based on Quaternized Chitosan for H5N1 Split Vaccine

Journal of Controlled Release : Official Journal of the Controlled Release Society. Sep, 2015  |  Pubmed ID: 27005183

A Coupled Mathematical Model of Cell Migration, Vessel Cooption and Tumour Microenvironment During the Initiation of Micrometastases

Molecular & Cellular Biomechanics : MCB. Dec, 2015  |  Pubmed ID: 27263259

We propose a coupled mathematical model for the detailed quantitative analyses of initial microtumour and micrometastases formation by including cancer cell migration, host vessel cooption and changes in microenvironment. Migrating cells are included as a new phenotype to describe the migration behaviour of malignant tumour cells. Migration probability of a migrating cell is assumed to be influenced by local chemical microenvironment. Pre-existing vessel cooption and remodelling are introduced according to the local haemodynamical microenvironment, such as interstitial pressure and vessel wall permeability. After the tumour cells and tumour vessels distribution are updated, the chemical substances are coupled calculated with the haemodynamical environment. The simulation results clearly reproduce the tumour cells migrate and proliferate along the pre-existing vessels at the very early stage of growth, which are consistent with many published experimental observations. In addition, the model demonstrates the interactions of tumour cells with the pre-existing vessels, which are believed to be essential for initial adhesion, proliferation, invasion, and micrometastases establishment. Quantitative analysis of tumour expansion in longitudinal and transverse directions shows that the cooption and migration along host vessels will be inhibited once angiogenesis phase occurs. The influences of the ability of cell migration and the inclusion of vessel cooption on the formation of micrometastases are discussed.

Perfluorooctanoic Acid-induced Toxicity in Primary Cultures of Chicken Embryo Cardiomyocytes

Environmental Toxicology. Nov, 2016  |  Pubmed ID: 26098785

Perfluorooctanoic acid (PFOA) is a widespread environmental contaminant that induces developmental cardiotoxicity. It is detectable in late stage chicken embryos and hatchling chickens. To investigate mechanism(s) of cardiotoxicity, primary cultures of cardiomyocytes were prepared from 10-day-old chicken embryos that were (A) pre-exposed to vehicle or 2 mg of PFOA/kg of egg weight in ovo or (B) incubated with PFOA in vitro at concentrations ranging from 0 to 100 µg/mL in medium for 1 or 36 h. When viability was assessed, survival of cardiomyocytes prepared from pre-exposed embryos did not differ from vehicle controls, even under conditions of serum starvation designed to challenge the cells. However, 1 h of exposure to 100 µg/mL of PFOA in vitro and 36 h of exposure to 75 and 100 µg/mL PFOA in vitro decreased viability. When contractility was evaluated, cardiomyocytes cultured from pre-exposed embryos exhibited decreases in time to maximum departure velocity and cell length at peak contraction, whereas cardiomyocytes exposed in vitro exhibited a reduction in the 50% relaxation time at a concentration of 1 µg/mL relative to vehicle controls. Morphological assessment revealed decreased cardiomyocytes axial length following in ovo PFOA exposure and 24 h in vitro PFOA 50 µg/mL exposure. Reactive oxygen species (ROS) generation, which was evaluated only in cardiomyocytes exposed to PFOA in vitro, was significantly elevated following incubation with 50 µg/mL of PFOA for 1 h. These data indicate that while in vitro exposure to relatively high concentrations of PFOA can induce cytotoxicity and ROS, developmental cardiotoxicity observed in ovo is not likely mediated via PFOA-induced overt cytotoxicity, but likely by altering early cardiac morphologic and function processes. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1580-1590, 2016.

Characterization of a Novel Purified Polysaccharide from the Flesh of Cipangopaludina Chinensis

Carbohydrate Polymers. Jan, 2016  |  Pubmed ID: 26572424

The purpose of this paper was to investigate the characterization of a novel polysaccharide from the flesh of Cipangopaludina chinensis, named CCPSn. The results found CCPSn was a white powder, readily soluble in hot water and slightly soluble in water. CCPSn was a homopolysaccharide composed of D-glucose (D-Glc) with molecular weight of 91.1 kDa. Based on analysis of UV-visible, FT-IR, periodic acid oxidation, Smith degradation, methylation, GM-MS and NMR, the structure of CCPSn was elucidated as follows: the backbone was composed of (1 → 3) linked α-D-Glc. The branches, consisting of a single (1 → 3) linked α-D-Glc units and terminal α-D-Glc-4-O-SO3(-), were attached to the main chain at C-4 positions. The degree of branching was calculated to be about 16.73%. The C-1 of terminal α-D-Glc-4-O-SO3(-) was linked to O-3 of (1 → 3) linked α-D-Glc in the branches. In addition, the results indicated CCPSn was a sulfated polysaccharide with the sulfate radical content of 9.12%.

DeepBase V2.0: Identification, Expression, Evolution and Function of Small RNAs, LncRNAs and Circular RNAs from Deep-sequencing Data

Nucleic Acids Research. Jan, 2016  |  Pubmed ID: 26590255

Small non-coding RNAs (e.g. miRNAs) and long non-coding RNAs (e.g. lincRNAs and circRNAs) are emerging as key regulators of various cellular processes. However, only a very small fraction of these enigmatic RNAs have been well functionally characterized. In this study, we describe deepBase v2.0 (http://biocenter.sysu.edu.cn/deepBase/), an updated platform, to decode evolution, expression patterns and functions of diverse ncRNAs across 19 species. deepBase v2.0 has been updated to provide the most comprehensive collection of ncRNA-derived small RNAs generated from 588 sRNA-Seq datasets. Moreover, we developed a pipeline named lncSeeker to identify 176 680 high-confidence lncRNAs from 14 species. Temporal and spatial expression patterns of various ncRNAs were profiled. We identified approximately 24 280 primate-specific, 5193 rodent-specific lncRNAs, and 55 highly conserved lncRNA orthologs between human and zebrafish. We annotated 14 867 human circRNAs, 1260 of which are orthologous to mouse circRNAs. By combining expression profiles and functional genomic annotations, we developed lncFunction web-server to predict the function of lncRNAs based on protein-lncRNA co-expression networks. This study is expected to provide considerable resources to facilitate future experimental studies and to uncover ncRNA functions.

Development and Characterization of a Novel Long-acting Recombinant Follicle Stimulating Hormone Agonist by Fusing Fc to an FSH-β Subunit

Human Reproduction (Oxford, England). Jan, 2016  |  Pubmed ID: 26621853

Does a novel long-acting recombinant human FSH, KN015, a heterodimer composed of FSHα and FSHβ-Fc/Fc, offer a potential FSH alternative?

A Plasmonic Colorimetric Strategy for Biosensing Through Enzyme Guided Growth of Silver Nanoparticles on Gold Nanostars

Biosensors & Bioelectronics. Apr, 2016  |  Pubmed ID: 26623511

A plasmonic colorimetric strategy was designed for sensitive detection of biomolecules through enzyme guided silver nanoparticles (AgNPs) growth on gold nanostars (AuNS). The growth of AgNPs on AuNS led to a substantial blue shift of the localized surface plasmon resonance (LSPR) peak and the color change of AuNS from blue to dark blue, purple and ultimately orange. Both the LSPR blueshift wavelength and the color of detection solution containing AuNS, Ag(+) and ascorbic acid 2-phosphate (AAP) depend on the amount of enzyme that catalyzed the dephosphorylation of AAP to reduce Ag(+) on AuNS surface. Thus this strategy could be used for LSPR and naked-eye detections of both the enzyme such as alkaline phosphatase (ALP) and other biomolecules involved in biorecognition events using ALP as a tag. The LSPR detection method for ALP showed a linear range from 1.0 pM to 25 nM with a detection limit of 0.5 pM. Using DNA as a mode target molecule, this technique showed a detection range from 10 fM to 50 pM DNA with a detection limit of 2.6 fM through the convenient combination with hybridization chain reaction amplification. The proposed plasmonic colorimetric strategy could be extended as a general analytical platform for design of immunosensors and aptasensors with ALP as a label.

Expression and Clinical Implication of S100A12 in Gastric Carcinoma

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine. May, 2016  |  Pubmed ID: 26638166

S100 protein family has been implicated in multiple stages of tumorigenesis and progression in which S100A12 is one of the subtypes. However, the role of S100A12 in gastric carcinoma (GC) has not been elucidated yet. This study was aimed to investigate the expression of S100A12 in GC tissues and evaluate the clinical significance of S100A12 in GC patients. S100A12 protein was detected in 207 GC and 52 paired non-cancerous mucosal tissues by immunohistochemistry, while messenger RNA (mRNA) was investigated by Oncomine database analysis. Moreover, survival analysis was performed and the correlation between S100A12 and ubiquitin-specific protease 10 (USP10) and p53 was determined. As for tumor cells, the expression of S100A12 protein and mRNA in GC was proved to be lower than that in non-cancerous mucosa tissues (p < 0.05). Clinicopathological analysis showed that S100A12 protein was negatively associated with tumor size (p = 0.004), depth of invasion (p = 0.022), tumor node metastasis (TNM) stage (p = 0.018), Lauren classification (p < 0.000), and cell differentiation (p < 0.000). In contrast, a positive correlation was found between S100A12 and USP10 protein (p < 0.000). However, no relationship was detected between S100A12 and p53. Moreover, the survival analysis indicated that S100A12 protein was a favorable factor of prognosis of GC (p < 0.05). Although the expression of S100A12 in the stromal cells was detected higher than that in the tumor cells, no relationship between S100A12 protein in stromal cells and the clinicopathological features described above was found (p > 0.05). Our findings suggested that low expression of S100A12 might be served as a new marker in the tumorigenesis and progression of GC.

Regulatory B Cells Contribute to the Impaired Antitumor Immunity in Ovarian Cancer Patients

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine. May, 2016  |  Pubmed ID: 26638169

Multiple factors in the tumor microenvironment were found to inhibit antitumor adaptive immune responses, allowing tumor persistence and growth. In this study, ascites from ovarian cancer patients were collected. We observed that a population of interleukin-10(+) B (IL-10(+) B) cells was preferentially enriched in the ascites. This population was associated with naive B cell phenotype or IgM or class-switched memory B cell phenotypes. The frequencies of IL-10(+) B cells were negatively correlated with the frequencies of interferon gamma-producing (IFN-g(+)) CD8(+) T cells and were positively correlated with the frequencies of Foxp3(+) CD4(+) T cells. To examine whether increased IL-10(+) B cells in ascites could directly result in increased suppression of IFN-g production by CD8(+) T cells, we cocultured CD8(+) T cells with autologous blood B cells or ascitic B cells and found that CD8(+) T cells cocultured with ascitic B cells demonstrated significantly suppressed IFN-g production. This suppression was in part mediated by IL-10 as well as low CD80/CD86 expression, since depletion of IL-10 and stimulation of CD28 partially reverted IL-10(+) B cell-mediated suppression. Together, these data demonstrated an additional regulatory mechanism in the tumor microenvironment, which utilizes IL-10(+) B cells.

A Palladium-catalyzed Coupling Reaction of Aryl Nonaflates, Sulfur Dioxide, and Hydrazines

Organic & Biomolecular Chemistry. Feb, 2016  |  Pubmed ID: 26700192

A facile route to synthesise N-aminosulfonamides through a palladium-catalyzed coupling reaction of aryl nonaflates, sulfur dioxide, and hydrazines is reported. This transformation proceeds in the presence of Pd(OAc)2/XantPhos, and TBAB in 1,4-dioxane at 80 °C, leading to the corresponding N-aminosulfonamides in moderate to good yields. The reaction scope has been demonstrated, and good functional tolerance is observed. A plausible mechanism is proposed through the insertion of sulfur dioxide.

The Genetics Underlying Acquired Long QT Syndrome: Impact for Genetic Screening

European Heart Journal. May, 2016  |  Pubmed ID: 26715165

Acquired long QT syndrome (aLQTS) exhibits QT prolongation and Torsades de Pointes ventricular tachycardia triggered by drugs, hypokalaemia, or bradycardia. Sometimes, QTc remains prolonged despite elimination of triggers, suggesting the presence of an underlying genetic substrate. In aLQTS subjects, we assessed the prevalence of mutations in major LQTS genes and their probability of being carriers of a disease-causing genetic variant based on clinical factors.

Promotion of Atherosclerosis in High Cholesterol Diet-fed Rabbits by Immunization with the P277 Peptide

Immunology Letters. Feb, 2016  |  Pubmed ID: 26730848

Previous evidence has proved the ability of immunization with heat shock protein (HSP) 60/65 to induce atherosclerosis. P277, a 24-residue peptide of human HSP60, is a promising peptide vaccine against autoimmune diabetes. But as a fragment of HSP60, its potential ability of promoting atherosclerosis has never been investigated yet. In the present study, the rabbits fed with normal standard diet or high cholesterol diet were immunized with P277 or PBS emulsified in incomplete Freund's adjuvant 4 times at 4-week intervals. Atherosclerotic lesions of the rabbits receiving P277 treatment and fed with high cholesterol diet increased significantly compared with those of the rabbits receiving PBS treatment and the same diet. However, no obvious lesions were found in the two groups of rabbits fed with the normal standard diet. Significant expression of P277 was detected in the high cholesterol diet-induced atherosclerotic lesions and heat-stressed endothelial cells. Surface exposure of P277 was also observed in the stressed cells. In the subsequent assay of endothelial cells in vitro, the purified anti-P277 antibodies mediated a noticeable cytotoxicity to the stressed cells with the participation of complement. In conclusion, subcutaneous immunization with P277 emulsified in IFA can aggravate the atherosclerosis in high cholesterol diet-fed rabbits. Surface expression of P277 was observed on stressed endothelial cells, and were suggested to mediate the autoimmune attack and promote the disease.

Relationships Between Root Diameter, Root Length and Root Branching Along Lateral Roots in Adult, Field-grown Maize

Annals of Botany. Mar, 2016  |  Pubmed ID: 26744490

Root diameter, especially apical diameter, plays an important role in root development and function. The variation in diameter between roots, and along roots, affects root structure and thus the root system's overall foraging performance. However, the effect of diameter variation on root elongation, branching and topological connections has not been examined systematically in a population of high-order roots, nor along the roots, especially for mature plants grown in the field.

Flavone Synthases from Lonicera Japonica and L. Macranthoides Reveal Differential Flavone Accumulation

Scientific Reports. Jan, 2016  |  Pubmed ID: 26754912

Flavones are important secondary metabolites found in many plants. In Lonicera species, flavones contribute both physiological and pharmaceutical properties. However, flavone synthase (FNS), the key enzyme responsible for flavone biosynthesis, has not yet been characterized in Lonicera species. In this study, FNSII genes were identified from Lonicera japonica Thunb. and L. macranthoides Hand.-Mazz. In the presence of NADPH, the recombinant cytochrome P450 proteins encoded by LjFNSII-1.1, LjFNSII-2.1, and LmFNSII-1.1 converted eriodictyol, naringenin, and liquiritigenin to the corresponding flavones directly. The different catalytic properties between LjFNSII-2.1 and LjFNSII-1.1 were caused by a single amino acid substitution at position 242 (glutamic acid to lysine). A methionine at position 206 and a leucine at position 381 contributed considerably to the high catalytic activity of LjFNSII-1.1. In addition, LjFNSII-1.1&2.1 and LmFNSII-1.1 also biosynthesize flavones that were further modified by O-glycosylation in transgenic tobacco. The expression levels of the FNSII genes were consistent with flavone accumulation patterns in flower buds. Our findings suggested that the weak catalytic activity of LmFNSII-1.1 and the relatively low expression of LmFNSII-1.1 in flowers might be responsible for the low levels of flavone accumulation in flower buds of L. macranthoides.

Erratum To: Analysis of the Mitochondrial Maxicircle of Trypanosoma Lewisi, a Neglected Human Pathogen

Parasites & Vectors. Jan, 2016  |  Pubmed ID: 26762513

Prediction of All-cause Death in Hemodialysis Patients Using Elevated Postdialysis Pulse Wave Velocity

Clinical Nephrology. Feb, 2016  |  Pubmed ID: 26772050

To identify the relationship between predialysis pulse wave velocity (PWV), postdialysis PWV during 1 hemodialysis (HD) session, and deaths in maintenance HD patients.

Assessment of Megabase-scale Somatic Copy Number Variation Using Single-cell Sequencing

Genome Research. Mar, 2016  |  Pubmed ID: 26772196

Megabase-scale copy number variants (CNVs) can have profound phenotypic consequences. Germline CNVs of this magnitude are associated with disease and experience negative selection. However, it is unknown whether organismal function requires that every cell maintain a balanced genome. It is possible that large somatic CNVs are tolerated or even positively selected. Single-cell sequencing is a useful tool for assessing somatic genomic heterogeneity, but its performance in CNV detection has not been rigorously tested. Here, we develop an approach that allows for reliable detection of megabase-scale CNVs in single somatic cells. We discover large CNVs in 8%-9% of cells across tissues and identify two recurrent CNVs. We conclude that large CNVs can be tolerated in subpopulations of cells, and particular CNVs are relatively prevalent within and across individuals.

Label-free Signal-on Aptasensor for Sensitive Electrochemical Detection of Arsenite

Biosensors & Bioelectronics. May, 2016  |  Pubmed ID: 26785310

A signal-on aptasensor was fabricated for highly sensitive and selective electrochemical detection of arsenite with a label-free Ars-3 aptamer self-assembled on a screen-printed carbon electrode (SPCE) via Au-S bond. The Ars-3 aptamer could adsorb cationic polydiallyldimethylammonium (PDDA) via electrostatic interaction to repel other cationic species. In the presence of arsenite, the change of Ars-3 conformation due to the formation of Ars-3/arsenite complex led to less adsorption of PDDA, and the complex could adsorb more positively charged [Ru(NH3)6](3+) as an electrochemically active indicator on the aptasensor surface, which produced a sensitive "turn-on" response. The target-induced structure switching could be used for sensitive detection of arsenite with a linear range from 0.2 nM to 100 nM and a detection limit down to 0.15 nM. Benefiting from Ars-3 aptamer, the proposed system exhibited excellent specificity against other heavy metal ions. The SPCE-based aptasensor exhibited the advantages of low cost and simple fabrication, providing potential application of arsenite detection in environment.

Developing a Model for Forecasting Gleason Score ≥7 in Potential Prostate Cancer Patients to Reduce Unnecessary Prostate Biopsies

International Urology and Nephrology. Apr, 2016  |  Pubmed ID: 26810323

The diagnosis of Gleason score (GS) ≥7 with distinction from GS < 7 remains a difficult problem instructing clinical decisions. Moreover, the present wide application of prostate biopsy to increase prostate cancer detection rate might cause unnecessary and excessive examination or treatment. Therefore, a risk assessment model for forecasting GS ≥ 7 in potential prostate cancer patients was established to reduce unnecessary prostate biopsies.

Dysmorphic Erythrocytes Are Superior to Hematuria for Indicating Non-diabetic Renal Disease in Type 2 Diabetics

Journal of Diabetes Investigation. Jan, 2016  |  Pubmed ID: 26812958

There are sparse and limited studies on erythrocyte morphology in renal biopsy identifying nephropathic patients among type 2 diabetics. The present study sought to clarify the predictive value of dysmorphic erythrocytes in type 2 diabetics with non-diabetic renal disease and influences on hematuria.

Comparison of the Effect of Recombinant Bovine Wild and Mutant Lipopolysaccharide-binding Protein in Lipopolysaccharide-challenged Bovine Mammary Epithelial Cells

Cell Stress & Chaperones. May, 2016  |  Pubmed ID: 26813383

Lipopolysaccharide (LPS)-binding protein (LBP) plays a crucial role in the recognition of bacterial components, such as LPS that causes an immune response. The aim of this study was to compare the different effects of recombinant bovine wild LBP and mutant LBP (67 Ala → Thr) on the LPS-induced inflammatory response of bovine mammary epithelial cells (BMECs). When BMECs were treated with various concentrations of recombinant bovine lipopolysaccharide-binding protein (RBLBP) (1, 5, 10, and 15 μg/mL) for 12 h, RBLBP of 5 μg/mL increased the apoptosis of BMECs induced by LPS without cytotoxicity, and mutant LBP resulted in a higher cell apoptosis than wild LBP did. By gene-chip microarray and bioinformatics, the data identified 2306 differentially expressed genes that were changed significantly between the LPS-induced inflamed BMECs treated with 5 μg/mL of mutant LBP and the BMECs only treated with 10 μg/mL of LPS (fold change ≥2). Meanwhile, 1585 genes were differently expressed between the inflamed BMECs treated with 5 μg/mL of wild LBP and 10 μg/mL of LPS-treated BMECs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that these differentially expressed genes were involved in different pathways that regulate the inflammation response. It predicted that carriers of this mutation increase the risk for a more severe inflammatory response. Our study provides an overview of the gene expression profile between wild LBP and mutant LBP on the LPS-induced inflammatory response of BMECs, which will lead to further understanding of the potential effects of LBP mutations on bovine mammary glands.

The Plasticity of Intrinsic Functional Connectivity Patterns Associated with Rehabilitation Intervention in Chronic Stroke Patients

Neuroradiology. Apr, 2016  |  Pubmed ID: 26820451

It has been demonstrated that rehabilitative interventions can promote motor function recovery in stroke patients. However, little is known regarding the neural mechanisms that underlie the rehabilitation treatments. The aim of this study was to investigate the plasticity of intrinsic functional connectivity patterns that are associated with rehabilitation intervention in chronic stroke patients.

A Simple Way to Prepare Reduced Graphene Oxide Nanosheets/Fe2O3-Pd/N-doped Carbon Nanosheets and Their Application in Catalysis

Journal of Colloid and Interface Science. Apr, 2016  |  Pubmed ID: 26828275

The catalysts with Pd and γ-Fe2O3 nanoparticles embedded between reduced graphene oxide nanosheets (rGS) and N-doped carbon nanosheets (NCS) were prepared through a two-step method. Firstly, graphene oxide nanosheets (GS)/prussian blue (PB)-Pd/polypyrrole (PPy) composites were synthesized by using pyrrole monomer as reductant, K3Fe(CN)6 and PdCl2 as oxidants in the presence of GS via a redox reaction. Subsequently, the as-obtained GS/PB-Pd/PPy composites were calcinated in N2 atmosphere. During the heat-treatment, carbonization of PPy to NCS, conversion of nonmagnetic PB to magnetic γ-Fe2O3 nanoparticles, and reduction of GS to rGS were finished, simultaneously. rGS/Fe2O3-Pd/NCS composites exhibited good catalytic activity toward reduction of 4-nitrophenol. The rate constant k and turnover frequency were calculated and compared with recent reports. Owing to γ-Fe2O3 nanoparticles, the rGS/Fe2O3-Pd/NCS composites could be quickly separated by magnet and reused without obvious decrease in activity.

Modulation of IL-1β Reprogrammes the Tumor Microenvironment to Interrupt Oral Carcinogenesis

Scientific Reports. Feb, 2016  |  Pubmed ID: 26831400

Head and neck squamous cell carcinoma (HNSCC) development is a multistage process includes the normal, dysplasia and squamous cell carcinoma (SCC) stages. Recently, increasing evidence has suggested that the tumor microenvironment (TME) is an integral part of malignant transformation. Exploring certain key node genes in TME for future intervention in dysplasia to interrupt oral carcinogenesis was the primary goal of this research. To achieve this goal, systems biology approaches were first applied to the epithelia and fibroblasts collected at sequential stages in a 4-nitroquinoline-1-oxide (4NQO) -induced rat oral carcinogenesis model. Through bioinformatics network construction, IL-1β was identified as one of the key node genes in TME during carcinogenesis. Immunohistochemical staining of human and rat samples demonstrated that IL-1β expression patterns were parallel to the stages of malignant transformation. Silencing IL-1β with lentivirus-delivered shRNA significantly inhibited oral squamous cell carcinoma cell growth both in vivo and in vitro. Based on these findings, we hypothesized that IL-1β may be a chemoprevention target in TME during oral carcinogenesis. Therefore, we targeted IL-1 in the TME by oral mucosal injection of an IL-1 receptor antagonist in 4NQO rats. The results demonstrated that targeting IL-1 could interrupt oral carcinogenesis by reprogramming the TME.

Expression of Functional Cannabinoid CB2 Receptor in VTA Dopamine Neurons in Rats

Addiction Biology. Feb, 2016  |  Pubmed ID: 26833913

We have recently reported the expression of functional cannabinoid CB2 receptors (CB2 Rs) in midbrain dopamine (DA) neurons in mice. However, little is known whether CB2 Rs are similarly expressed in rat brain because significant species differences in CB2 R structures and expression are found. In situ hybridization and immunohistochemical assays detected CB2 gene and receptors in DA neurons of the ventral tegmental area (VTA), which was up-regulated in cocaine self-administration rats. Electrophysiological studies demonstrated that activation of CB2 Rs by JWH133 inhibited VTA DA neuronal firing in single dissociated neurons. Systemic administration of JWH133 failed to alter, while local administration of JWH133 into the nucleus accumbens inhibited cocaine-enhanced extracellular DA and i.v. cocaine self-administration. This effect was blocked by AM630, a selective CB2 R antagonist. These data suggest that CB2 Rs are expressed in VTA DA neurons and functionally modulate DA neuronal activities and cocaine self-administration behavior in rats.

Quantitative Analysis of Ultrasound Images for Computer-aided Diagnosis

Journal of Medical Imaging (Bellingham, Wash.). Jan, 2016  |  Pubmed ID: 26835502

We propose an adaptable framework for analyzing ultrasound (US) images quantitatively to provide computer-aided diagnosis using machine learning. Our preliminary clinical targets are hepatic steatosis, adenomyosis, and craniosynostosis. For steatosis and adenomyosis, we collected US studies from 288 and 88 patients, respectively, as well as their biopsy or magnetic resonanceconfirmed diagnosis. Radiologists identified a region of interest (ROI) on each image. We filtered the US images for various texture responses and use the pixel intensity distribution within each ROI as feature parameterizations. Our craniosynostosis dataset consisted of 22 CT-confirmed cases and 22 age-matched controls. One physician manually measured the vectors from the center of the skull to the outer cortex at every 10 deg for each image and we used the principal directions as shape features for parameterization. These parameters and the known diagnosis were used to train classifiers. Testing with cross-validation, we obtained 72.74% accuracy and 0.71 area under receiver operating characteristics curve for steatosis ([Formula: see text]), 77.27% and 0.77 for adenomyosis ([Formula: see text]), and 88.63% and 0.89 for craniosynostosis ([Formula: see text]). Our framework is able to detect a variety of diseases with high accuracy. We hope to include it as a routinely available support system in the clinic.

Expression and Clinical Significance of IL-17 and IL-17 Receptor in Ulcerative Colitis

Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban. Feb, 2016  |  Pubmed ID: 26838737

The purpose of this study was to determine the expression levels of IL-17 in serum and IL-17 receptor (IL-17R) in intestinal mucosa tissue in patients with ulcerative colitis (UC) and controls, and evaluate their relationship with disease activity and explore the role of IL-17 in the patho-genesis of UC. A total of 36 Chinese UC patients and 60 healthy controls were enrolled in this study. Serum IL-17 and C-reactive protein (CRP) levels were determined by ELISA and immunonephelometry, respectively. The IL-17R mRNA expression levels were detected by quantitative PCR. Serum IL-17 levels were significantly elevated in UC patients as compared with those in the healthy controls (P<0.05). Among UC patients, serum IL-17 levels were significantly increased in active phase as compared with those in inactive phase (P<0.05), and correlated with CRP levels (r=0.578, P<0.01). IL-17R expression levels were higher in active UC patients than in healthy controls (P<0.05). It was concluded that IL-17 levels were highly expressed in UC, especially in active phase, and correlated with CRP levels in UC patients.

The Effect of Heat Stress on Gene Expression, Synthesis of Steroids, and Apoptosis in Bovine Granulosa Cells

Cell Stress & Chaperones. May, 2016  |  Pubmed ID: 26847372

Summer heat stress (HS) is a major contributing factor in low fertility in lactating dairy cows in hot environments. Heat stress inhibits ovarian follicular development leading to diminished reproductive efficiency of dairy cows during summer. Ovarian follicle development is a complex process. During follicle development, granulosa cells (GCs) replicate, secrete hormones, and support the growth of the oocyte. To obtain an overview of the effects of heat stress on GCs, digital gene expression profiling was employed to screen and identify differentially expressed genes (DEGs; false discovery rate (FDR) ≤ 0.001, fold change ≥2) of cultured GCs during heat stress. A total of 1211 DEGs including 175 upregulated and 1036 downregulated ones were identified, of which DEGs can be classified into Gene Ontology (GO) categories and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The results suggested that heat stress triggers a dramatic and complex program of altered gene expression in GCs. We hypothesized that heat stress could induce the apoptosis and dysfunction of GCs. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the expression of steroidogenic genes (steroidogenic acute regulatory protein (Star), cytochrome P-450 (CYP11A1), CYP19A1, and steroidogenic factor 1 (SF-1)) and apoptosis-related genes (caspase-3, BCL-2, and BAX). Radio immunoassay (RIA) was used to analyze the level of 17β-estradiol (E2) and progesterone (P4). We also assessed the apoptosis of GCs by flow cytometry. Our data suggested that heat stress induced GC apoptosis through the BAX/BCL-2 pathway and reduced the steroidogenic gene messenger RNA (mRNA) expression and E2 synthesis. These results suggest that the decreased function of GCs may cause ovarian dysfunction and offer an improved understanding of the molecular mechanism responsible for the low fertility in cattle in summer.

RNAi-mediated Ghrelin Affects Gastric H(+)-K(+)-ATPase Activity and Expression of GOAT-Ghrelin System in Vitro

General and Comparative Endocrinology. Mar, 2016  |  Pubmed ID: 26873629

Ghrelin has been implicated in the regulation of gastric functional development, and its physiological functions are mediated by Ghrelin-O-acyltransferase (GOAT) which is capable of generating the active form of this polypeptide hormone. However, whether and how ghrelin gene silencing may modify gastric acid secretion and GOAT-Ghrelin system is yet to be explored. The study was performed in gastric mucosal cells from weanling piglets in vitro. We evaluated the effect of ghrelin on gastric acid secretion, gene expression of GOAT and ghrelin as well as ghrelin levels by RNA interference assay. shGhrelin triggered the down-regulation of ghrelin mRNA expression (P<0.05) via an RNAi mechanism, as observed by real-time RT-PCR. In addition, shGhrelin showed reduced total ghrelin production and secretion (P<0.05) using ELISA in vitro. We also detected that GOAT mRNA expression was reduced in shGhrelin group (P<0.05), compared with control groups. In accordance with the GOAT expression, acylated ghrelin production and secretion were reduced in gastric mucosal cells and culture medium (P<0.05). Silencing of ghrelin gene achieved by RNAi-mediation inhibited the activity of H(+)-K(+)-ATPase and pepsin (P<0.05) in gastric mucosal cells. These results indicated that RNAi of Ghrelin gene inhibited the gastric acid secretion with decreased GOAT mRNA and acylated Ghrelin in gastric mucosal cells.

Optimal Modified Tracking Performance for MIMO Systems Under Bandwidth Constraint

ISA Transactions. May, 2016  |  Pubmed ID: 26874745

This paper investigates the optimal modified tracking performance of multi-input multi-output (MIMO) networked control systems (NCSs) with bandwidth and channel noise constraints. A new modified tracking performance index is proposed which prevents variations in the tracking error from leading to invalid data where there is no integrator in the plant. An expression for the optimal modified tracking performance is obtained using a method which includes co-prime factorization, partial factorization, spectral decomposition and H2 norm. The obtained results show that the optimal modified tracking performance is influenced by the non-minimum phase (NMP) zeros, unstable poles, and their directions. Furthermore, the characteristics of the input signal, the modification factor, the bandwidth and the channel noise are also shown to be closely related to the optimal modified tracking performance. Finally, the efficiency of the result is verified using some typical examples.

Epidermal Growth Factor and Prostaglandin E2 Levels in Helicobacter Pylori-positive Gastric Intraepithelial Neoplasia

The Journal of International Medical Research. Apr, 2016  |  Pubmed ID: 26880792

To investigate levels of epidermal growth factor (EGF) and prostaglandin E2 (PGE2) in Han Chinese patients with Helicobacter pylori-positive gastric low-grade intraepithelial neoplasia (LGIN).

Neuroprotective Oleanane Triterpenes from the Roots of Bupleurum Chinense

Bioorganic & Medicinal Chemistry Letters. Mar, 2016  |  Pubmed ID: 26883148

The discovery of new natural compounds with pharmacological properties is an increasingly important field, and a continuous phytochemical investigation of the roots of Bupleurum chinense D.C. has led to the isolation of 17 triterpenoids, including three new oleanane triterpenes (1-3) together with 14 known ones. Their structures were determined on the basis of 1D and 2D NMR spectra as well as HR-ESI-MS data. The cytotoxicities of all compounds against five selected human cancer cell lines were assayed. Only compounds 9 and 14 exhibited moderate activities. Recently, a number of investigations have focused on the neuroprotective properties of triterpenoids in B. chinense. In order to expand our knowledge about this herb, the neuroprotective effects of compounds 1-17 against hydrogen peroxide (H2O2)-induced neuronal cell damage in human neuroblastoma SH-SY5Y cells were evaluated. Compounds 1-3, 6-7 showed significant neuroprotective effects against H2O2-induced SH-SY5Y cell death. Preliminary structure-activity relationships (SARs) between neuroprotective effects and the isolates were also discussed.

Reassortment of Avian Influenza A/H6N6 Viruses from Live Poultry Markets in Guangdong, China

Frontiers in Microbiology. 2016  |  Pubmed ID: 26903958

Since early 2013, H7N9-subtype avian influenza virus (AIV) has caused human infection in eastern China. To evaluate AIV contamination and the public risk of infection, we systematically implemented environmental sampling from live poultry markets in Guangdong Province. Through real-time polymerase chain reaction assays and next-generation sequencing, we generated full nucleotide sequences of all 10 H6N6 AIVs isolated during sampling. Focusing on sequence analyses of hemagglutinin genes of the 10 H6N6 AIVs revealed that the viruses were low pathogenic AIVs with the typical hemagglutinin cleavage site of P-Q-I-E-T-R-G. The hemagglutinin, neuraminidase, and nucleocapsid genes of nine AIVs were of ST2853-like (H6-subtype) lineage, ST192-like (N6-subtype) lineage, and HN573-like (H6-subtype) lineage, respectively; whereas the other five genes were of ST339-like (H6-subtype) lineage. However, the polymerase PB2 and nucleocapsid genes of one strain (HZ057) were of GS/GD-like (H5N1-subtype) and ST339-like lineages. Phylogenic analysis revealed that all eight genes of the 10 viruses belonged to Eurasian avian lineage. Altogether, the 10 AIVs were reassortants of different genetic groups of exchanges with the same virus subtype, thus illustrating the genetic diversity and complexity of H6N6-subtype AIVs in Guangdong Province.

Genetic Features of Mycobacterium Tuberculosis Modern Beijing Sublineage

Emerging Microbes & Infections. Feb, 2016  |  Pubmed ID: 26905026

Mycobacterium tuberculosis (MTB) Beijing strains have caused a great concern because of their rapid emergence and increasing prevalence in worldwide regions. Great efforts have been made to investigate the pathogenic characteristics of Beijing strains such as hypervirulence, drug resistance and favoring transmission. Phylogenetically, MTB Beijing family was divided into modern and ancient sublineages. Modern Beijing strains displayed enhanced virulence and higher prevalence when compared with ancient Beijing strains, but the genetic basis for this difference remains unclear. In this study, by analyzing previously published sequencing data of 1082 MTB Beijing isolates, we determined the genetic changes that were commonly present in modern Beijing strains but absent in ancient Beijing strains. These changes include 44 single-nucleotide polymorphisms (SNPs) and two short genomic deletions. Through bioinformatics analysis, we demonstrated that these genetic changes had high probability of functional effects. For example, 4 genes were frameshifted due to premature stop mutation or genomic deletions, 19 nonsynonymous SNPs located in conservative codons, and there is a significant enrichment in regulatory network for all nonsynonymous mutations. Besides, three SNPs located in promoter regions were verified to alter downstream gene expressions. Our study precisely defined the genetic features of modern Beijing strains and provided interesting clues for future researches to elucidate the mechanisms that underlie this sublineage's successful expansion. These findings from the analysis of the modern Beijing sublineage could provide us a model to understand the dynamics of pathogenicity of MTB.

IRE1α Signaling Pathways Involved in Mammalian Cell Fate Determination

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology. 2016  |  Pubmed ID: 26910807

A diverse array of cellular stresses can lead to accumulation of misfolded or unfolded proteins in endoplasmic reticulum (ER), which subsequently elicits ER stress. Inositol-requiring enzyme 1α (IRE1α) is the most sensitive of the three unfolded protein response (UPR) branches which are triggered to cope with ER stress in mammalian cells. IRE1α signaling is quite context-specific on account of many adaptor and modulator proteins that directly interact with it, including heat shock proteins (HSPs), RING finger protein 13 (RNF13), poly (ADP-ribose) polymerase 16 (PARP16), Bax/Bak, and Bax inhibitor-1 (BI-1). The activated IRE1α triggers different downstream pathways depending on the UPRosome formed by distinct modulator proteins. At the initial phase of ER stress, IRE1α-XBP1 axis functions as an adaptive response. While ER stress sustains or intensifies, signals shift to apoptotic responses. Furthermore, IRE1α signaling can be exploited to the development of a wide range of prevalent human diseases, with cancer the most characterized. Here we provide an overview of recent insights into the complex IRE1α signaling network which makes IRE1α an intriguing cell fate switch. Besides, the functional relevance is presented since IRE1α activation also participates in some other physiological processes beyond protein-folding status.

Ketones Block Amyloid Entry and Improve Cognition in an Alzheimer's Model

Neurobiology of Aging. Mar, 2016  |  Pubmed ID: 26923399

Sporadic Alzheimer's disease (AD) is responsible for 60%-80% of dementia cases, and the most opportune time for preventive intervention is in the earliest stage of its preclinical phase. As traditional mitochondrial energy substrates, ketone bodies (ketones, for short), beta-hydroxybutyrate, and acetoacetate, have been reported to provide symptomatic improvement and disease-modifying activity in epilepsy and neurodegenerative disorders. Recently, ketones are thought as more than just metabolites and also as endogenous factors protecting against AD. In this study, we discovered a novel neuroprotective mechanism of ketones in which they blocked amyloid-β 42, a pathologic hallmark protein of AD, entry into neurons. The suppression of intracellular amyloid-β 42 accumulation rescued mitochondrial complex I activity, reduced oxidative stress, and improved synaptic plasticity. Most importantly, we show that peripheral administration of ketones significantly reduced amyloid burden and greatly improved learning and memory ability in a symptomatic mouse model of AD. These observations provide us insights to understand and to establish a novel therapeutic use of ketones in AD prevention.

Gut Microbiota-involved Mechanisms in Enhancing Systemic Exposure of Ginsenosides by Coexisting Polysaccharides in Ginseng Decoction

Scientific Reports. Mar, 2016  |  Pubmed ID: 26932472

Oral decoctions of traditional Chinese medicines (TCMs) serve for therapeutic and prophylactic management of diseases for centuries. Small molecules and polysaccharides are the dominant chemicals co-occurred in the TCM decoction. Small molecules are well-studied by multidisciplinary elaborations, whereas the role of polysaccharides remains largely elusive. Here we explore a gut microbiota-involved mechanism by which TCM polysaccharides restore the homeostasis of gut microbiota and consequently promote the systemic exposure of concomitant small molecules in the decoction. As a case study, ginseng polysaccharides and ginsenosides in Du-Shen-Tang, the decoction of ginseng, were investigated on an over-fatigue and acute cold stress model. The results indicated that ginseng polysaccharides improved intestinal metabolism and absorption of certain ginsenosides, meanwhile reinstated the perturbed holistic gut microbiota, and particularly enhanced the growth of Lactobacillus spp. and Bacteroides spp., two major metabolic bacteria of ginsenosides. By exploring the synergistic actions of polysaccharides with small molecules, these findings shed new light on scientization and rationalization of the classic TCM decoctions in human health care.

Mathematical Modelling of a Brain Tumour Initiation and Early Development: A Coupled Model of Glioblastoma Growth, Pre-Existing Vessel Co-Option, Angiogenesis and Blood Perfusion

PloS One. 2016  |  Pubmed ID: 26934465

We propose a coupled mathematical modelling system to investigate glioblastoma growth in response to dynamic changes in chemical and haemodynamic microenvironments caused by pre-existing vessel co-option, remodelling, collapse and angiogenesis. A typical tree-like architecture network with different orders for vessel diameter is designed to model pre-existing vasculature in host tissue. The chemical substances including oxygen, vascular endothelial growth factor, extra-cellular matrix and matrix degradation enzymes are calculated based on the haemodynamic environment which is obtained by coupled modelling of intravascular blood flow with interstitial fluid flow. The haemodynamic changes, including vessel diameter and permeability, are introduced to reflect a series of pathological characteristics of abnormal tumour vessels including vessel dilation, leakage, angiogenesis, regression and collapse. Migrating cells are included as a new phenotype to describe the migration behaviour of malignant tumour cells. The simulation focuses on the avascular phase of tumour development and stops at an early phase of angiogenesis. The model is able to demonstrate the main features of glioblastoma growth in this phase such as the formation of pseudopalisades, cell migration along the host vessels, the pre-existing vasculature co-option, angiogenesis and remodelling. The model also enables us to examine the influence of initial conditions and local environment on the early phase of glioblastoma growth.

NADPH Oxidase: A Potential Target for Treatment of Stroke

Oxidative Medicine and Cellular Longevity. 2016  |  Pubmed ID: 26941888

Stroke is the third leading cause of death in industrialized nations. Oxidative stress is involved in the pathogenesis of stroke, and excessive generation of reactive oxygen species (ROS) by mitochondria is thought to be the main cause of oxidative stress. NADPH oxidase (NOX) enzymes have recently been identified and studied as important producers of ROS in brain tissues after stroke. Several reports have shown that knockout or deletion of NOX exerts a neuroprotective effect in three major experimental stroke models. Recent studies also confirmed that NOX inhibitors ameliorate brain injury and improve neurological outcome after stroke. However, the physiological and pathophysiological roles of NOX enzymes in the central nervous system (CNS) are not known well. In this review, we provide a comprehensive summary of our current understanding about expression and physiological function of NOX enzymes in the CNS and its pathophysiological roles in the three major types of stroke: ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.

A "building Block" Approach to the New Influenza A Virus Entry Inhibitors with Reduced Cellular Toxicities

Scientific Reports. Mar, 2016  |  Pubmed ID: 26952867

Influenza A virus (IAV) is a severe worldwide threat to public health and economic development that results in the emergence of drug-resistant or highly virulent strains. Therefore, it is imperative to develop potent anti-IAV drugs with different modes of action to currently available drugs. Herein, we show a new class of antiviral peptides generated by conjugating two known short antiviral peptides: part-1 (named Jp with the sequence of ARLPR) and part-2 (named Hp with the sequence of KKWK). The new peptides were thus created by hybridization of these two domains at C- and N- termini, respectively. The anti-IAV screening results identified that C20-Jp-Hp was the most potent peptide with IC50 value of 0.53 μM against A/Puerto Rico/8/34 (H1N1) strain. Interestingly, these new peptides display lower toxicities toward mammalian cells and higher therapeutic indices than their prototypes. In addition, the mechanism of action of C20-Jp-Hp was extensively investigated.

In Vitro Assembly of the Bacterial Actin Protein MamK from ' Candidatus Magnetobacterium Casensis' in the Phylum Nitrospirae

Protein & Cell. Apr, 2016  |  Pubmed ID: 26960409

Magnetotactic bacteria (MTB), a group of phylogenetically diverse organisms that use their unique intracellular magnetosome organelles to swim along the Earth's magnetic field, play important roles in the biogeochemical cycles of iron and sulfur. Previous studies have revealed that the bacterial actin protein MamK plays essential roles in the linear arrangement of magnetosomes in MTB cells belonging to the Proteobacteria phylum. However, the molecular mechanisms of multiple-magnetosome-chain arrangements in MTB remain largely unknown. Here, we report that the MamK filaments from the uncultivated 'Candidatus Magnetobacterium casensis' (Mcas) within the phylum Nitrospirae polymerized in the presence of ATP alone and were stable without obvious ATP hydrolysis-mediated disassembly. MamK in Mcas can convert NTP to NDP and NDP to NMP, showing the highest preference to ATP. Unlike its Magnetospirillum counterparts, which form a single magnetosome chain, or other bacterial actins such as MreB and ParM, the polymerized MamK from Mcas is independent of metal ions and nucleotides except for ATP, and is assembled into well-ordered filamentous bundles consisted of multiple filaments. Our results suggest a dynamically stable assembly of MamK from the uncultivated Nitrospirae MTB that synthesizes multiple magnetosome chains per cell. These findings further improve the current knowledge of biomineralization and organelle biogenesis in prokaryotic systems.

Prevalence and Clustering of Major Cardiovascular Risk Factors in China: A Recent Cross-Sectional Survey

Medicine. Mar, 2016  |  Pubmed ID: 26962771

Cardiovascular disease is the leading cause of death in the Chinese population. Although general prevalence estimates of cardiovascular risk factors (CVRFs) are available for Chinese adults, prevalence estimates covering all adult age groups by race/ethnicity have not been reported. The aim of this study is to estimate the current prevalence and clustering of major CVRFs in Chinese adults, including a plurality of ethnic minorities.A cross-sectional survey was conducted in a nationally representative sample of 23,010 adults aged 18 years and older from 2007 to 2011. Questionnaires and physical examinations were performed, and fasting blood was collected for laboratory measurements. The prevalence of traditional CVRFs, including hypertension, diabetes, dyslipidemia, overweight, and current smoking, were determined.The prevalence of the major CVRFs, including hypertension, diabetes, dyslipidemia, overweight, and current smoking were 24.3%, 4.3%, 49.3%, 32.0%, and 21.7%, respectively. These risk factors were significantly associated with sex, age, region, ethnicity, and education levels. Overall, 70.3%, 40.3%, and 16.7% of Chinese adults had ≥1, ≥2, or ≥3 CVRFs, respectively. Men, northern and rural residents were more likely to have clustered CVRFs compared with women, southern and urban residents, respectively. Compared with Han residents, Hui and Mongolian residents were more likely, and Tujia and Miao residents were less likely, to have ≥1, ≥2, or ≥3 risk factors. The prevalence of Chinese women having ≥1, ≥2, or ≥3 CVRFs decreased with increasing levels of education.The prevalence and clustering of CVRFs is still high in Chinese adults ≥18 years old, especially in men and in individuals living in the northern and rural areas. Of note, there are differences in cardiovascular risk among different ethnic groups. Therefore, targeted and enhanced intervention measures are required to reduce the risk of cardiovascular disease and the corresponding economic burden of disease in China.

Identification of Susceptibility Loci and Genes for Colorectal Cancer Risk

Gastroenterology. Jun, 2016  |  Pubmed ID: 26965516

Known genetic factors explain only a small fraction of genetic variation in colorectal cancer (CRC). We conducted a genome-wide association study to identify risk loci for CRC.

Shenhua Tablet Inhibits Mesangial Cell Proliferation in Rats with Chronic Anti-Thy-1 Nephritis

Biological Research. Mar, 2016  |  Pubmed ID: 26969153

In China, mesangial proliferative glomerulonephritis (MsPGN) is one of the most common kidney diseases. In this study, we treated a rat model of chronic anti-Thy-1 MsPGN with Shenhua Tablet and evaluated whether the tablet was able to protect the kidney function. Thirty-six Wistar rats were randomly divided into six groups: (1) Sham surgery (Sham); (2) anti-Thy-1 nephritis model (Thy-1); (3) anti-Thy-1 nephritis model + irbesartan-treated (Irb); (4) anti-Thy-1 nephritis model + low-dose of Shenhua Tablet (SHL); (5) anti-Thy-1 nephritis model + medium-dose of Shenhua Tablet (SHM); (6) anti-Thy-1 nephritis model + high-dose of Shenhua Tablet (SHH).

Resolution of Rac-Bambuterol Via Diastereoisomeric Salt Formation with O-Chloromandelic Acid and Differences in the Enantiomers' Pharmacodynamical Effects in Guinea Pigs and Beagles

Chirality. Apr, 2016  |  Pubmed ID: 26969816

In this study an enantioseparation method for rac-bambuterol (5-(2-(tert-butylamino)-1-hydroxyethyl)-1,3-phenylene bis(dimethylcarbamate)) via diastereoisomeric salt formation with o-chloromandelic acid was developed. The enantiomeric excess (ee) values and chemical purities of the desired products were confirmed by high-performance liquid chromatography (HPLC) using chiral stationary phase and reverse-phase HPLC analyses, respectively. The ee values and the chemical purities both exceeded 99%. Animal experiments showed that (R)-bambuterol was a potent inhibitor for histamine-induced asthma reactions. (S)-bambuterol was ineffective in relaxing the airways. Both enantiomers increased heart rates in beagles. Therefore, replacing rac-bambuterol with (R)-bambuterol could be beneficial for asthma patients.

Can Radiologic Evaluation Before Capsule Endoscopy Predict Capsule Retention?

Inflammatory Bowel Diseases. May, 2016  |  Pubmed ID: 26978726

Antioxidant Capacities and Anthocyanin Characteristics of the Black-red Wild Berries Obtained in Northeast China

Food Chemistry. Aug, 2016  |  Pubmed ID: 26988488

Various edible berries widely accessible in nature in Northeast China are poorly exploited. The compositions and contents of anthocyanins in black (Padus maackii, Padus avium, Lonicera caerulea, and Ribes nigrum) and red (Ribes rubrum, Sambucus williamsii, Rubus idaeus, and Ribes procumbens) wild berries in Northeast China were firstly characterized by HPLC-DAD/ESI-MS(2). Twenty-three anthocyanins were detected and identified. Cyanidin glycosides were dominant in both berries. Six anthocyanins were reported for the first time in P. avium, R. rubrum, and Sambucus. Total anthocyanin content (TAC) ranged from 10mg/100gfreshweight (FW) (R. procumbens) to 1058mg/100gFW (P. maackii) among berries. The TACs and antioxidant activities assessed by DPPH and FRAP assays were much higher in black than in red berries. Black-red berries, especially P. maackii and P. avium, can be used in developing functional foods and in improving breeding programs.

The Association Between Abnormal Long Noncoding RNA MALAT-1 Expression and Cancer Lymph Node Metastasis: A Meta-Analysis

BioMed Research International. 2016  |  Pubmed ID: 26989678

Previous studies have investigated that the expression levels of MALAT-1 were higher in cancerous tissues than matched histologically normal tissues. And, to some extent, overexpression of MALAT-1 was inclined to lymph node metastasis. This meta-analysis collected all relevant articles and explored the association between MALAT-1 expression levels and lymph node metastasis. We searched PubMed, EmBase, Web of Science, Cochrane Library, and OVID to address the level of MALAT-1 expression in cancer cases and noncancerous controls (accessed February 2015). And 8 studies comprising 696 multiple cancer patients were included to assess this association. The odds ratio (OR) and its corresponding 95% confidence interval (CI) were calculated to assess the strength of the association using Stata 12.0 version software. The results revealed there was a significant difference in the incidence of lymph node metastasis between high MALAT-1 expression group and low MALAT-1 expression group (OR = 1.94, 95% CI 1.15-3.28, P = 0.013 random-effects model). Subgroup analysis indicated that MALAT-1 high expression had an unfavorable impact on lymph node metastasis in Chinese patients (OR = 1.87, 95% CI 1.01-2.46). This study demonstrated that the incidence of lymph node metastasis in patients detected with high MALAT-1 expression was higher than that in patients with low MALAT-1 expression in China.

Facile Assembly of Benzo[b]naphtho[2,3-d]azocin-6(5 H)-ones by a Palladium-Catalyzed Double Carbometalation

Chemistry, an Asian Journal. May, 2016  |  Pubmed ID: 26991867

The palladium-catalyzed reaction of 2-alkynylanilines with 2-(2-bromobenzylidene)cyclobutanone as an efficient route to 7,8-dihydrobenzo[b]naphtho[2,3-d]azocin-6(5 H)-ones was developed. The fused eight-membered ring was constructed conveniently. During the reaction process, double carbometalation was involved, which resulted in excellent selectivity with the formation of three new bonds. This transformation is highly efficient and leads to fused polycycles in good to excellent yields with good functional group tolerance.

Surfactant-Assisted Nanocrystalline Zinc Coordination Polymers: Controlled Particle Sizes and Synergistic Effects in Catalysis

Chemistry (Weinheim an Der Bergstrasse, Germany). Apr, 2016  |  Pubmed ID: 26997347

Different morphologies and particle sizes of two crystalline zinc-based coordination polymers (CPs), [Zn(pytz)H2 O]n (1; H2 pytz=2,6-bis(tetrazole)pyridine) and [Zn2 (pytz)2 4 H2 O] (2), from the bulk scale to the nanoscale, could be obtained under solvothermal conditions with different surfactants (polyvinylpyrrolidone (PVP) or polyethylene glycol (PEG) 2000) as templates. PVP and PEG 2000 could act as capping and structure-directing agents, respectively, to influence the growth of crystalline particles and control their sizes. CP 1 exhibits a two-dimensional framework with window-like units and 2 shows a bimetallic structure. Nanocrystalline 1 and 2 were used as heterogeneous catalysts to study how adjacent catalytic active sites synergistically effected their catalytic reactivities in the direct catalytic conversion of aromatic dinitriles into oxazolines. The results showed that 1 produced bis-oxazolines as the sole products, whereas 2 gave the mono-oxazolines as the major products under the same reaction conditions.

Clinical Features, Endoscopic Polypectomy and STK11 Gene Mutation in a Nine-month-old Peutz-Jeghers Syndrome Chinese Infant

World Journal of Gastroenterology. Mar, 2016  |  Pubmed ID: 27004004

To investigate multiple polyps in a Chinese Peutz-Jeghers syndrome (PJS) infant.

Plasty of Human Bites Induced Full Thickness Large Area Eyelid Defects

Pakistan Journal of Pharmaceutical Sciences. Jan, 2016  |  Pubmed ID: 27005512

Large area eyelid defects induced by human biting was rare. A 43-year-old man was bited by a human. His Blepharocoloboma size was 60% percent of the upper eyelid, the horizontal defect length of defect area was 25mm, the vertical height was 5mm,a small mass like lateral eyelid tissue was left on the Lateralis lid margin. The toughness of this lateral eyelid tissue was enough to support the lateral canthus tissue transfered to the same area then the lateral eyelid tissue was sutured with the remaining sclera after which the sclera-conjunctiva was reconstructed. The skin tranfering from lateral canthus was sutured with conjunctiva without exposing. Eyelid defect was effectively repaired. The technique of lateralis cantholysis association with self remaining lateral eyelid tissue version was manifested an alternative and useful procedure for the reconstruction of large area upper full thickness eyelid defects.

Discovery of an Orally Active and Liver-Targeted Prodrug of 5-Fluoro-2'-Deoxyuridine for the Treatment of Hepatocellular Carcinoma

Journal of Medicinal Chemistry. Apr, 2016  |  Pubmed ID: 27022837

We report a series of novel O-(substituted benzyl) phosphoramidate prodrugs of 5-fluoro-2'-deoxyuridine for the treatment of hepatocellular carcinoma. Through structure optimization, the o-methylbenzyl analog (1t) was identified as an orally bioavailable and liver-targeted lead compound. This lead prodrug is well-tolerated at a dose up to 3 g/kg in Kuming mice via oral administration. An efficacy study demonstrated that it possesses good inhibitory effect (61.67% and 72.50%, respectively) on tumor growth in a mouse xenograft model. A metabolism study in Sprague-Dawley rats suggested that 1t can release the desired 5'-monophosphate in the liver with high liver-targeting index.

Rupture of Esophagus by Compressed Air

Revista Espanola De Enfermedades Digestivas : Organo Oficial De La Sociedad Espanola De Patologia Digestiva. Nov, 2016  |  Pubmed ID: 27022895

Currently, beverages containing compressed air such as cola and champagne are widely used in our daily life. Improper ways to unscrew the bottle, usually by teeth, could lead to an injury, even a rupture of the esophagus. This letter to editor describes a case of esophageal rupture caused by compressed air.

Activation of Sigma-1 Receptor Alleviates Postpartum Estrogen Withdrawal-Induced "Depression" Through Restoring Hippocampal NNOS-NO-CREB Activities in Mice

Molecular Neurobiology. Mar, 2016  |  Pubmed ID: 27032391

Postpartum depression affects approximately 15 % of mothers; however, its pathological mechanisms still remain unclear. Ovariectomized adult mice received the administration of estrogen (E2) and progesterone with a subsequent alone E2, termed hormone-simulated pregnancy (HSP). Affective behaviors as assessed by forced swim and tail suspension tests, hippocampal neuronal nitric oxide synthase (nNOS), nitric oxide (NO), cyclic AMP (cAMP) response element binding protein (CREB) phosphorylation (phosphor-CREB), and neurosteroidogenesis were examined before E2 withdrawal (EW; HSP mice) and on days 2-4 (early-EW mice) and days 8-10 (late-EW mice) after EW. Depressive-like behaviors were observed in early-EW mice but not in late-EW mice. Levels of nNOS, NO, and phosphor-CREB were increased in HSP mice followed by a significant decline in early-EW mice with a subsequent restoration in late-EW mice. The treatment of early-EW mice with NO donor alleviated depressive-like behaviors and decline of phosphor-CREB. The nNOS inhibitor and NO scavenger caused depressive-like behaviors and reduced phosphor-CREB in HSP mice and late-EW mice. Notably, the levels of steroidogenic enzymes StAR and P450scc were elevated in late-EW mice. The sigma-1 receptor (σ1R) agonist could alleviate depressive-like behaviors and decline of nNOS-NO-CREB in early-EW mice. The pharmacological blockade or deficiency of σ1R in late-EW mice caused depressive-like behaviors with decline of nNOS-NO-CREB. The reduction of hippocampal brain-derived neurotrophic factor (BDNF) or N-methyl-D-aspartic acid (NMDA) receptor NR2B phosphorylation in early-EW mice could recover in late-EW mice, which was sensitive to the blockade of σ1R. The NMDA receptor agonist, but not TrkB receptor activator, could correct the decline of nNOS-NO-CREB in early-EW mice. The findings indicate that the activation of σ1R can alleviate postpartum "depression" through increasing nNOS-NO-CREB activities.

Hall Effect in Quantum Critical Charge-cluster Glass

Proceedings of the National Academy of Sciences of the United States of America. Apr, 2016  |  Pubmed ID: 27044081

Upon doping, cuprates undergo a quantum phase transition from an insulator to a d-wave superconductor. The nature of this transition and of the insulating state is vividly debated. Here, we study the Hall effect in La2-xSrxCuO4(LSCO) samples doped near the quantum critical point atx∼ 0.06. Dramatic fluctuations in the Hall resistance appear belowTCG∼ 1.5 K and increase as the sample is cooled down further, signaling quantum critical behavior. We explore the doping dependence of this effect in detail, by studying a combinatorial LSCO library in which the Sr content is varied in extremely fine steps,Δx∼ 0.00008. We observe that quantum charge fluctuations wash out when superconductivity emerges but can be restored when the latter is suppressed by applying a magnetic field, showing that the two instabilities compete for the ground state.

Enhancer Activity of Helitron in Sericin-1 Gene Promoter from Bombyx Mori

Insect Science. Jun, 2016  |  Pubmed ID: 27067405

Sericin is a kind of water-soluble protein expressed specifically in the middle silk gland of Bombyx mori. When the sericin-1 gene promoter was cloned and a transgenic vector was constructed to express a foreign protein, a specific Helitron, Bmhel-8, was identified in the sericin-1 gene promoter sequence in some genotypes of Bombyx mori and Bombyx mandarina. Given that the Bmhel-8 Helitron transposon was present only in some genotypes, it could be the source of allelic variation in the sericin-1 promoter. The length of the sericin-1 promoter sequence is approximately 1063 or 643 bp. The larger size of the sequence or allele is ascribed to the presence of Bmhel-8. Silkworm genotypes can be homozygous for either the shorter or larger promoter sequence or heterozygous, containing both alleles. Bmhel-8 in the sericin-1 promoter exhibits enhancer activity, as demonstrated by a dual-luciferase reporter system in BmE cell lines. Furthermore, Bmhel-8 displays enhancer activity in a sericin-1 promoter-driven gene expression system but does not regulate the tissue-specific expression of sericin-1.

Chylothorax and Lymphedema As the Initial Manifestations of Gastric Carcinoma: A Case Report and Review of the Literature

Oncology Letters. Apr, 2016  |  Pubmed ID: 27073560

Chylothorax is the accumulation of lymph fluid in the pleura. Gastric carcinoma with chylothorax and lymphedema as the initial manifestations has rarely been reported, with only 14 cases reported to date. The mechanisms of gastric carcinoma generating chylothorax have not yet been determined. The current study reports the case of a 63-year-old woman presenting with chylothorax and lower extremity lymphedema, and reviews the existing literature. A chest radiograph performed on the present patient revealed large pleural effusion and chylothorax was diagnosed. Upper gastrointestinal endoscopy identified an irregular apophysis lesion and a biopsy confirmed poorly differentiated gastric adenocarcinoma. The patient was discharged at her request, and subsequently succumbed to the disease 4.5 months later. Based on the findings of the present study, as well as those of the literature, we proposed a novel form of gastric carcinoma infiltrating the body. Chylothorax and lymphedema may be a consequence of gastric carcinoma cells infiltrating the lymphatic circulatory system; therefore, the differential diagnosis of chylothorax and lymphedema of unknown cause should consider gastric carcinoma, regardless of gastrointestinal symptoms.

MicroRNA-155 Promotes the Directional Migration of Resident Smooth Muscle Progenitor Cells by Regulating Monocyte Chemoattractant Protein 1 in Transplant Arteriosclerosis

Arteriosclerosis, Thrombosis, and Vascular Biology. Jun, 2016  |  Pubmed ID: 27079875

Smooth muscle-like cells are major cell components of transplant arteriosclerosis lesions. This study investigated the origin of the smooth muscle-like cells, the mechanisms responsible for their accumulation in the neointima, and the factors that drive these processes.

Clinical, Pathological, and Prognostic Characteristics of Glomerulonephritis Related to Staphylococcal Infection

Medicine. Apr, 2016  |  Pubmed ID: 27082609

Staphylococcal infection has become a common cause of postinfectious glomerulonephritis in the past 3 decades. Because few investigations focus on this disease, the demographics and clinicopathological features of glomerulonephritis related to staphylococcal infection are not well characterized. We conducted a pooled analysis of published literature in electronic databases and analyzed the clinical features, laboratory findings, and histopathological changes. The patients were divided into 4 groups based on their prognosis: remission, persistent renal dysfunction, end-stage renal disease (ESRD), or death. A logistic regression model was used to identify the determinants of disease outcome. A total of 83 (64 men) patients with glomerulonephritis related to staphylococcal infection from 31 reports were analyzed. The mean age was 58 years (58 ± 17). Majority of the reports originated from Taiwan, Japan, and the United States. Clinical characteristics of the cases were hematuria (82/83), proteinuria (78/83), and acute kidney injury (75/83). Visceral abscesses (26/83) and skin infections (24/83) were the common sites of infection. Methicillin-resistant Staphylococcus aureus was the most common pathogen. The dominant or codominant deposition of IgA or C3 along the glomeruli was an important feature identified by immunofluorescence. There were 19 patients (22.9%) that progressed to dialysis-dependent ESRD. Twelve patients (14.5%) died. A univariate regression analysis indicated that diabetes mellitus (DM) (odds ratio [OR] 2.96; 95% confidence interval [CI] 1.03-8.48; P = 0.04) and age (OR 4.80; 95% CI 1.84-12.53; P = 0.001) were risk factors for ESRD or death. A multivariate regression analysis also revealed that age (OR 4.90; 95% CI 1.82-13.18; P = 0.002) and DM (OR 3.07; 95% CI 0.98-9.59; P = 0.05) were independent risk factors for unfavorable prognosis. Glomerulonephritis related to staphylococcal infection has different features than typical postinfectious glomerulonephritis. The diagnosis of glomerulonephritis related to staphylococcal infection relies on immunofluorescence and electron microscopy findings. Age and DM are independent risk factors of poor prognosis for glomerulonephritis related to staphylococcal infection.

Fusion Protein His-Hsp65-6IA2P2 Prevents Type 1 Diabetes Through Nasal Immunization in NOD Mice

International Immunopharmacology. Jun, 2016  |  Pubmed ID: 27082999

Human heat shock protein 60 (Hsp60), is an endogenous β-cells autoantigen, it could postpone the onset of insulitis and sooner type 1 diabetes mellitus. P277 is one of Hsp65 determinants at position 437-469 of amino acids cascaded. Meanwhile, it's already well-known that there were several better anti-diabetic B epitopes, such as insulinoma antigen-2 (IA-2). Currently, fusion protein IA2P2 has constructed in order to enhance its pharmacological efficacy. In addition, added homologous bacterial-derived Hsp65 and His tag were beneficial to protein immunogenicity and purification separately. So, finally we examined a fusion protein His-Hsp65-6IA2P2 could regulate Th2 immune response and reduce natural diabetic incidence in NOD mice. We constructed two express vector pET28a-His-Hsp65-6P277 and pET28a-His-Hsp65-6IA2P2. After purification, we observed that triple intranasal administration of these two fusion protein in 4-week-old NOD mice maintained normal blood glucose and weight, with a lower diabetic or insulitis incidence. Consistent with induced splenic T cells proliferation and tolerance, His-Hsp65-6IA2P2-treated mice performed reduced IFN-γ and increased IL-10 level. In conclusion, we suggested that fusion protein His-Hsp65-6IA2P2 could be reconstructed and purified successively. Furthermore, nasal administration of this fusion protein could rebalance T cells population and prevent T1DM.

Oral Administration of Lactococcus Lactis-expressing Heat Shock Protein 65 and Tandemly Repeated IA2P2 Prevents Type 1 Diabetes in NOD Mice

Immunology Letters. Jun, 2016  |  Pubmed ID: 27085380

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease characterized by the destruction of insulin-secreting β cells upon autoreactive T cell attack. Oral administration of autoantigens is an attractive approach to treating T1DM, but an effective carrier should be used in order to protect antigens. Lactococcus lactis, a safe engineering strain, was used for this task in the present study. Two recombinant L. lactis expressing protein HSP65-6IA2P2 were used and be investigated the effects and mechanisms against T1DM in NOD mice. Our findings demonstrate that recombinant L. lactis strains can successfully both deliver antigens to intestinal mucosa and maintain the epitopes for a long time in NOD mice. Oral administration of recombinant L. lactis could prevent hyperglycemia, improve glucose tolerance, and reduce insulitis by inhibiting antigen-specific proliferation of T cells, augmenting regulatory immune reactions, and balancing ratios of Th17/Tregs and Th1/Th2. These results prove that orally administrated L. lactis expressing HSP65-6IA2P2 is an effective approach for the prevention of T1DM in NOD mice.

Synthesis of Novel Imidazo[1,2-a]pyridin-2-amines from Arylamines and Nitriles Via Sequential Addition and I2 /KI-Mediated Oxidative Cyclization

Chemistry (Weinheim an Der Bergstrasse, Germany). May, 2016  |  Pubmed ID: 27112949

A novel and practical strategy for the construction of imidazo[1,2-a]pyridin-2-amine frameworks has been developed. The present sequential approach involves addition of arylamines to nitriles and I2 /KI-mediated oxidative C-N bond formation without purification of the intermediate amidines. This operationally simple synthetic process provides a facile access to a variety of new 2-amino substituted imidazo[1,2-a]pyridines and related heterocyclic compounds in an efficient and scalable fashion.

The Enlightenments from ITMIG Consensus on WHO Histological Classification of Thymoma and Thymic Carcinoma: Refined Definitions, Histological Criteria, and Reporting

Journal of Thoracic Disease. Apr, 2016  |  Pubmed ID: 27114842

The World Health Organization (WHO) histological classification of the thymoma and thymic carcinoma (TC) has been criticized for poor interobserver reproducibility or inconsistencies in the routine pathological diagnosis. The International Thymic Malignancy Interest Group (ITMIG) panel achieved an agreement to maintain the widely accepted WHO framework but to refine historic definitions and histological criteria, and further introduce some new terms with the aim to improve interobserver reproducibility. This review addresses the enlightenments we can get from the ITMIG consensus on the WHO histological classification of the thymoma and TC, which may be helpful for most pathologists.

Effect of Treatment with Geraniol on Ovalbumin-induced Allergic Asthma in Mice

Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. Jun, 2016  |  Pubmed ID: 27117312

Asthma, a complex highly prevalent airway disease, is a major public health problem for which current treatment options are inadequate.

Regioselective Synthesis of 3,4-disubstituted Isocoumarins Through the Pd-catalyzed Annulation of 2-iodoaromatic Acids with Ynamides

Chemical Communications (Cambridge, England). May, 2016  |  Pubmed ID: 27124602

A Pd(0)-catalyzed annulation reaction of ynamides is described for the efficient synthesis of 3,4-disubstituted isocoumarins. This novel methodology allows for the concomitant construction of O-C and C-C bonds between 2-iodoaromatic acids and ynamides, exhibiting excellent regioselectivities and a wide functional group tolerance.

Efficient Regioselective Synthesis of the Crotonyl Polydatin Prodrug by Thermomyces Lanuginosus Lipase: a Kinetics Study in Eco-friendly 2-Methyltetrahydrofuran

Applied Biochemistry and Biotechnology. Jul, 2016  |  Pubmed ID: 27125959

Bio-based solvents have recently been discussed as sustainable green and promising alternatives to conventional organic media for enzymatic processes. In this paper, highly regioselective synthesis of the 6″-O-crotonyl-polydatin catalyzed by Thermomyces lanuginosus lipase (TLL) in biomass-derived 2-methyltetrahydrofuran (2-MeTHF) was successfully performed for the first time. The results indicated that TLL lipase displayed significantly improved catalytic performance in 2-MeTHF than in other traditional solvents. Under the optimal conditions, the initial reaction rate, 6″-regioselectivity, and maximum substrate conversion were as high as 12.38 mM h(-1), 100 %, and 100 %, respectively. Moreover, further investigations on the operational stability, kinetic parameters like V max, K m, V max/K m, and E a revealed that 2-MeTHF exhibited excellent biocompatibility and rendered the greener process of the enzymatic acylation.

Microcrystalline Zinc Coordination Polymers As Single-site Heterogeneous Catalysts for the Selective Synthesis of Mono-oxazolines from Amino Alcohol and Dinitriles

Chemistry, an Asian Journal. Jun, 2016  |  Pubmed ID: 27136746

In our effort to develop coordination polymers (CPs)-based single-site catalysts for the selective synthesis of mono-oxazolines, two Zn-based CPs, [{Zn6 (idbt)4 (phen)4 } ⋅3 H2 O]n  (1) and [{Zn3 (idbt)2 (H2 O)4 }⋅2 H2 O]n  (2) (H3 idbt= 5,5'-(1H-imidazole-4,5-diyl)-bis-(2H-tetrazole), phen=1,10-phenanthroline) have been synthesized. They exhibit two-dimensional structure and contain isolated and accessible catalytically active sites, mimicking the site isolation of many catalytic enzymes. Micro CPs 1 and 2 are obtained by using surfactant-mediated hydrothermal methods, and an investigation is conducted to explore how different surfactants affect their morphologies and particle sizes. Furthermore, micro 1 and 2 have shown to be effective heterogeneous catalysts for the reaction of amino alcohols and aromatic dinitriles, and exerted a significant influence on the selectivity of the catalytic reactions, yielding mono-oxazolines as the major reaction product.

A Prospective Study of Autoantibodies to Ezrin and Pancreatic Cancer Risk

Cancer Causes & Control : CCC. 06, 2016  |  Pubmed ID: 27146838

No biomarker is available for pancreatic cancer early detection, but a small prospective European study involving 16 cases and 32 controls raised the possibility that anti-Ezrin autoantibodies may be associated with risk of pancreatic cancer. We aimed to validate this finding in a case-control study nested within a prospective study in the USA.

Continuing Reassortant of H5N6 Subtype Highly Pathogenic Avian Influenza Virus in Guangdong

Frontiers in Microbiology. 2016  |  Pubmed ID: 27148209

First identified in May 2014 in China's Sichuan Province, initial cases of H5N6 avian influenza virus (AIV) infection in humans raised great concerns about the virus's prevalence, origin, and development. To evaluate both AIV contamination in live poultry markets (LPMs) and the risk of AIV infection in humans, we have conducted surveillance of LPMs in Guangdong Province since 2013 as part of environmental sampling programs. With environmental samples associated with these LPMs, we performed genetic and phylogenetic analyses of 10 H5N6 AIVs isolated from different cities of Guangdong Province from different years. Results revealed that the H5N6 viruses were reassortants with hemagglutinin (HA) genes derived from clade 2.3.4.4 of H5-subtype AIV, yet neuraminidase (NA) genes derived from H6N6 AIV. Unlike the other seven H5N6 viruses isolated in first 7 months of 2014, all of which shared remarkable sequence similarity with the H5N1 AIV in all internal genes, the PB2 genes of GZ693, GZ670, and ZS558 more closely related to H6N6 AIV and the PB1 gene of GZ693 to the H3-subtype AIV. Phylogenetic analyses revealed that the environmental H5N6 AIV related closely to human H5N6 AIVs isolated in Guangdong. These results thus suggest that continued reassortment has enabled the emergence of a novel H5N6 virus in Guangdong, as well as highlight the potential risk of highly pathogenic H5N6 AIVs in the province.

Proximity Hybridization-regulated Chemiluminescence Resonance Energy Transfer for Homogeneous Immunoassay

Talanta. Jul, 2016  |  Pubmed ID: 27154699

Chemiluminescence resonance energy transfer (CRET) and the proximity ligation assay have been widely used in design of sensors for the bioanalysis. Here, a wash-free and homogeneous strategy was proposed to detect carcino-embryonic antigen (CEA) based on proximity hybridization-regulated CRET. The Cy5 demonstrated strong chemiluminescence (CL) via the oxidation of TCPO in the presence of H2O2 and energy transfer between excited TCPO and Cy5. Graphene oxide (GO) as an excellent quencher was used to produce the "Signal off" mode that little CL emission was observed through CRET between GO and the Cy5-labelled DNA3. Once CEA was introduced, the target-induced proximity hybridization occurred to form a proximate complex, which inhibited the CRET by preventing GO from absorbing Cy5-labelled DNA3. Furthermore, taking advantage of nicking endonuclease Nt.BbvCI for in situ recycling, the signal could be further amplified for highly sensitive CL detection. Our results showed that this strategy enabled a specific response to CEA with a detection range of 5 orders of magnitude, along with a detection limit of 3.2pg mL(-1). Apart from its easy operation, high sensitivity and acceptable accuracy, the proposed method needed only 0.3μL of sample, indicating its great opportunity for commercial application.

Prevalence and Transmission of Pyrazinamide Resistant Mycobacterium Tuberculosis in China

Tuberculosis (Edinburgh, Scotland). May, 2016  |  Pubmed ID: 27156619

Pyrazinamide (PZA) is an important first-line anti-tuberculosis drug, however, there are relatively few available data on PZA resistant (PZA-R) rate in China. From June 2009 to June 2012, we selected 493 isolates from five field settings in China to investigate PZA-R by pncA gene sequencing. The result showed that PZA-R rate was 1.0% (2/196) among pan-susceptible isolates, 3.1% (4/130) among isoniazid (INH) mono-resistant isolates, 14.0% (6/43) among rifampin (RIF) mono-resistant isolates and 43.5% (54/124) among multidrug resistant (MDR) isolates. MDR tuberculosis (TB), RIF mono-resistance, and retreatment were found to be risk factors for PZA-R. Newly diagnosed PZA-R TB patients and clustered isolates with identical pncA mutations indicate that transmission of PZA-R isolates plays an important role in emergence of PZA-R TB. The results suggest that, it is necessary to conduct PZA susceptibility test among MDR isolates and modify the treatment regimens accordingly.

IL-15 Signaling Promotes Adoptive Effector T-cell Survival and Memory Formation in Irradiation-induced Lymphopenia

Cell & Bioscience. 2016  |  Pubmed ID: 27158441

Lymphopenia promotes naïve T-cell homeostatic proliferation and adoptive effector T-cell survival and memory formation. IL-7 plays a critical role in homeostatic proliferation, survival and memory formation of naïve T-cells in lymphopenia, and its underlying molecular mechanism has also been well studied. However, the mechanism for adoptively transferred effector T-cell survival and memory formation is not fully understood. Here, we transferred in vitro-activated transgenic OT-I CD8(+) effector T-cells into irradiation (600 rads)-induced lymphopenic C57BL/6, IL-7 knockout (KO) and IL-15 KO mice, and investigated the survival and memory formation of transferred T-cells in lymphopenia.

Acellular Ostrich Corneal Stroma Used As Scaffold for Construction of Tissue-engineered Cornea

International Journal of Ophthalmology. 2016  |  Pubmed ID: 27158598

To assess acellular ostrich corneal matrix used as a scaffold to reconstruct a damaged cornea.

Effects of Nitric Oxide on the Biological Behavior of HepG2 Human Hepatocellular Carcinoma Cells

Experimental and Therapeutic Medicine. May, 2016  |  Pubmed ID: 27168820

Many studies have found the function of nitric oxide (NO) in cancer as a pro-neoplastic vs. an anti-neoplastic effector, but the role of NO in hepatocellular carcinoma (HCC) remains unclear. The present study aimed to investigate the effects of nitric oxide (NO) on the biological behavior of the human hepatocellular carcinoma cell line HepG2. HepG2 cell was cultured in vitro and treated with or without sodium nitroprusside (SNP), a NO donor. Subsequently, we evaluated the effects of NO in cell proliferation, cell cycle, apoptosis, migration and invasion by MTT assay, flow cytometry, wound healing assay and Matrigel invasion assay. We demonstrate that NO significantly inhibited HepG2 cell proliferation by inducing G0/G1 phase arrest in a dose-dependent manner. In addition, compared to the control group, cells treated with SNP showed obviously higher apoptosis ratios in a dose-dependent manner. Furthermore, we revealed that NO effectively inhibited the ability of migration and invasion of HepG2 cells. Taken together, our results suggested that NO has an important role in the regulation of biological behavior in HepG2 cells and the potential for use in the prevention and treatment of HCC.

TRF2Cancer: A Web Server to Detect TRNA-derived Small RNA Fragments (tRFs) and Their Expression in Multiple Cancers

Nucleic Acids Research. Jul, 2016  |  Pubmed ID: 27179031

tRNA-derived small RNA fragments (tRFs) are one class of small non-coding RNAs derived from transfer RNAs (tRNAs). tRFs play important roles in cellular processes and are involved in multiple cancers. High-throughput small RNA (sRNA) sequencing experiments can detect all the cellular expressed sRNAs, including tRFs. However, distinguishing genuine tRFs from RNA fragments generated by random degradation remains a major challenge. In this study, we developed an integrated web-based computing system, tRF2Cancer, to accurately identify tRFs from sRNA deep-sequencing data and evaluate their expression in multiple cancers. The binomial test was introduced to evaluate whether reads from a small RNA-seq data set represent tRFs or degraded fragments. A classification method was then used to annotate the types of tRFs based on their sites of origin in pre-tRNA or mature tRNA. We applied the pipeline to analyze 10 991 data sets from 32 types of cancers and identified thousands of expressed tRFs. A tool called 'tRFinCancer' was developed to facilitate the users to inspect the expression of tRFs across different types of cancers. Another tool called 'tRFBrowser' shows both the sites of origin and the distribution of chemical modification sites in tRFs on their source tRNA. The tRF2Cancer web server is available at http://rna.sysu.edu.cn/tRFfinder/.

Heteromeric α7β2 Nicotinic Acetylcholine Receptors in the Brain

Trends in Pharmacological Sciences. Jul, 2016  |  Pubmed ID: 27179601

The α7 nicotinic acetylcholine receptor (α7 nAChR) is highly expressed in the brain, where it maintains various neuronal functions including (but not limited to) learning and memory. In addition, the protein expression levels of α7 nAChRs are altered in various brain disorders. The classic rule governing α7 nAChR assembly in the mammalian brain was that it was assembled from five α7 subunits to form a homomeric receptor pentamer. However, emerging evidence demonstrates the presence of heteromeric α7 nAChRs in heterologously expressed systems and naturally in brain neurons, where α7 subunits are co-assembled with β2 subunits to form a novel type of α7β2 nAChR. Interestingly, the α7β2 nAChR exhibits distinctive function and pharmacology from traditional homomeric α7 nAChRs. We review recent advances in probing the distribution, function, pharmacology, pathophysiology, and stoichiometry of the heteromeric α7β2 nAChR, which have provided new insights into the understanding of a novel target of cholinergic signaling.

Long-term Soy Consumption and Tumor Tissue MicroRNA and Gene Expression in Triple-negative Breast Cancer

Cancer. Aug, 2016  |  Pubmed ID: 27183356

Soy food intake may have protective effects against the risk for breast cancer, including estrogen receptor (ER)-negative breast cancer. However, the underlying molecular mechanisms remain unclear.

[Distribution of Waist Circumference and Waist-to-height Ratio and Their Values in Obesity Screening Among 3-9 Years Old Han and Uygur Ethnic Children in Xinjiang Uygur Autonomous Region of China]

Zhonghua Liu Xing Bing Xue Za Zhi = Zhonghua Liuxingbingxue Zazhi. Jan, 2016  |  Pubmed ID: 27183665

To understand the distributions of waist circumference and waist-to-height ratio (WHtR) in Han and Uygur ethnic children aged 3-9 years in Xinjiang Uygur Autonomous Region (Xinjiang) and discuss their values in obesity screening in children.

MicroRNA-150 Inhibits the Activation of Cardiac Fibroblasts by Regulating C-Myb

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology. 2016  |  Pubmed ID: 27184887

Cardiac fibrosis is the primary cause of deteriorated cardiac function in various cardiovascular diseases. Numerous studies have demonstrated that microRNAs (miRNAs) are critical regulators of myocardial fibrosis. Specifically, many studies have reported that miR-150 is downregulated in cardiovascular diseases, such as acute myocardial infarction (AMI), myocardial hypertrophy and myocardial fibrosis. However, the exact role of miR-150 in these pathological processes remains unknown.

Steroids from the Rhizome of Anemarrhena Asphodeloides and Their Cytotoxic Activities

Bioorganic & Medicinal Chemistry Letters. Jul, 2016  |  Pubmed ID: 27189676

Cancer remains a major killer worldwide. To search for novel naturally occurring compounds that are cytotoxic to cancer cells to be used as lead structures for drug development, five new steroids (1-5) along with seven known ones (6-12) were isolated from the rhizome of Anemarrhena asphodeloides Bge. Their structures were established by detailed spectral studies, including 1D-NMR, 2D-NMR, HR-ESI-MS and by comparison with literature data. These compounds exhibited different levels of growth inhibition against A549, HepG2, Hep3B, Bcap37 and MCF7 cell lines in vitro. Compounds 9, 10 and 11 showed potent inhibitory against all the tested cell lines with IC50 values ranging from 0.35±0.15 to 25.53±0.31μM. The three compounds displayed stronger inhibitory activities against A549, HepG2 and Hep3B cell lines compared with the positive control 5-fluorouracil. The experimental data obtained permit us to identify the roles of the sugar moieties, hydroxyl group, double bond and F-ring with regard to their cytotoxic activities.

One-step Preparation of Fe3O4/Pd@polypyrrole Composites with Enhanced Catalytic Activity and Stability

Journal of Colloid and Interface Science. Aug, 2016  |  Pubmed ID: 27232537

Core/shell Fe3O4/Pd@polypyrrole (PPy) composites with a Fe3O4 core and a PPy shell embedding Pd nanoparticles were prepared in one-step. The diameter of highly dispersed Pd nanoparticles was as small as 2.9nm owing to coordination interaction generated between Pd(2+) ions and amino groups on PPy chains. The outer PPy shell was only 6.8nm: on one hand, the coverage was beneficial to improving the stability of resulting composites; on the other hand, the shell was thin enough to permit free contact between embedding Pd nanoparticles and reactants. Additionally, the as-prepared Fe3O4/Pd@PPy composites displayed good magnetic separation property due to incorporation of Fe3O4 nanospheres. Based on above merits, they served as suitable catalyst candidates. Their catalytic performance and reusability were evaluated by reduction of 4-nitrophenol with sodium borohydride as reducing agent. Compared with traditional Fe3O4/Pd composites, Fe3O4/Pd@PPy composites not only showed superior catalytic activity; but also exhibited much better stability in successive cycling tests.

Adjuvant Effect of Docetaxel on HPV16 L2E6E7 Fusion Protein Vaccine in a Mouse Model

International Immunopharmacology. Sep, 2016  |  Pubmed ID: 27233002

We previously demonstrated that the antineoplastic agent docetaxel enhanced the immune response to an influenza vaccine. This study evaluated the adjuvant effect of docetaxel (DOC) on the therapeutic efficacy of HPV16 L2E6E7 fusion protein (HPV-LFP) in mice inoculated with TC-1 cells. The results demonstrated that docetaxel significantly enhanced the therapeutic effect of HPV-LFP on TC-1 cell-induced tumors in mice. The injection of HPV-LFP in combination with docetaxel in TC-1 tumor-bearing mice significantly reduced tumor volume and weight, and a greater percent survival was detected than mice treated with HPV-LFP alone. The inhibition of tumors was associated with significantly increased serum antigen-specific IgG and isotypes, activated CTLs, increased IFN-γ-secreting T cells, and decreased Treg cells and IL-10-secreting cells in spleen. In addition, down-regulation of IL-10, VEGF and STAT3, up-regulation of IFN-γ and decreased Treg cells in the tumor microenvironment may also important contributing factors to the antitumor effect. It may be valuable to use a DOC-containing water to dilute HPV-LFP powder before injection in patients because of its excellent adjuvant effect on HPV-LFP and solubility in water.

P2Y1, P2Y2, and TRPV1 Receptors Are Increased in Diarrhea-Predominant Irritable Bowel Syndrome and P2Y2 Correlates with Abdominal Pain

Digestive Diseases and Sciences. Oct, 2016  |  Pubmed ID: 27250983

Previous studies indicated that P2Y1 and P2Y2 receptors, which are widely distributed in the enteric nervous system, are related to pain, while TRPV1 may contribute to visceral pain and hypersensitivity states in irritable bowel syndrome (IBS). Other studies showed that ATP activates the capsaicin-sensitive TRPV1 channel via P2Y receptors.

Novel Exosome-targeted T-cell-based Vaccine Counteracts T-cell Anergy and Converts CTL Exhaustion in Chronic Infection Via CD40L Signaling Through the MTORC1 Pathway

Cellular & Molecular Immunology. Jun, 2016  |  Pubmed ID: 27264687

CD8(+) cytotoxic T lymphocyte (CTL) exhaustion is a chief issue for ineffective virus elimination in chronic infectious diseases. We generated novel ovalbumin (OVA)-specific OVA-Texo and HIV-specific Gag-Texo vaccines inducing therapeutic immunity. To assess their therapeutic effect in chronic infection, we developed a new chronic infection model by i.v. infecting C57BL/6 mice with the OVA-expressing adenovirus AdVova. During chronic AdVova infection, mouse CTLs were found to express the inhibitory molecules programmed cell-death protein-1 (PD-1) and lymphocyte-activation gene-3 (LAG-3) and to be functionally exhausted, showing a significant deficiency in T-cell proliferation, IFN-γ production and cytolytic effects. Naive CD8(+) T cells upregulated inhibitory PD-ligand 1 (PD-L1), B- and T-lymphocyte attenuator and T-cell anergy-associated molecules (Grail and Itch) while down-regulating the proliferative response upon stimulation in mice with chronic infection. Remarkably, the OVA-Texo vaccine counteracted T-cell anergy and converted CTL exhaustion. The latter was associated with (i) the upregulation of a marker for CTL functionality, diacetylated histone-H3 (diAcH3), (ii) a fourfold increase in CTLs, occurring independent of host DCs or CD4(+) T cells, and (iii) the restoration of CTL IFN-γ production and cytotoxicity. In vivo OVA-Texo-stimulated CTLs upregulated the activities of the mTORC1 pathway-related molecules Akt, S6, eIF4E and T-bet, and treatment of the CTLs with an mTORC1 inhibitor, rapamycin, significantly reduced the OVA-Texo-induced increase in CTLs. Interestingly, OVA-Texo-mediated CD40L signaling played a critical role in the observed immunological effects. Importantly, the Gag-Texo vaccine induced Gag-specific therapeutic immunity in chronic infection. Therefore, this study should have a serious impact on the development of new therapeutic vaccines for human immunodeficiency virus (HIV-1) infection.Cellular & Molecular Immunology advance online publication, 6 June 2016; doi:10.1038/cmi.2016.23.

A Diffusional Kurtosis Imaging Study of Idiopathic Generalized Epilepsy with Unilateral Interictal Epileptiform Discharges in Children

Journal of Neuroradiology. Journal De Neuroradiologie. Oct, 2016  |  Pubmed ID: 27269387

To investigate brain abnormalities in children with a clinical diagnosis of idiopathic generalized epilepsy (IGE) and unilateral interictal epileptiform discharges (IED) demonstrated on electroencephalography (EEG) by diffusional kurtosis imaging (DKI).

In Vivo Metabolism Study of (R)-bambuterol in Humans Using Ultra High Performance Liquid Chromatography with Tandem Mass Spectrometry

Journal of Separation Science. Aug, 2016  |  Pubmed ID: 27273913

(R)-Bambuterol, a selective β2-adrenoceptor agonist, has been approved as a new drug for the treatment of asthma and chronic obstructive pulmonary disease by the China Food and Drug Administration and is currently under phase I clinical trials. In this study, a combined method based on ultra high performance liquid chromatography with triple quadrupole mass spectrometry and ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry was employed for the identification of the major metabolites of (R)-bambuterol in human plasma and urine after an oral dose of 10 mg. The metabolites were separated by gradient elution program and different sample preparation methods were compared. Totally, 12 metabolites of (R)-bambuterol were identified, including four metabolites in plasma and all 12 metabolites in urine. Among these, four metabolites are reported for the first time. The possible metabolic pathways of (R)-bambuterol were subsequently proposed. The results indicated that (R)-bambuterol was metabolized via hydrolysis, demethylation, oxygenation, glucuronidation, and sulfation pathways in vivo. This study revealed that this combined method was accurate and sensitive to identify the possible metabolites and to better understand the metabolism of (R)-bambuterol in vivo.

Impact of Aortocaval Shunt Flow on Cardiac and Renal Function in Unilateral Nephrectomized Rats

Scientific Reports. Jun, 2016  |  Pubmed ID: 27279232

We previously reported significantly enhanced cardiac remodeling post aortocaval fistula (AV) in unilateral nephrectomized (UNX) rats. However, the relationship between the size of the AV and the cardiorenal effects in UNX rats remains unknown. In the present study, AV was induced by 20, 18 and 16 gauge needles in UNX rats to see if larger shunt would definitely induce heavier cardiac and renal damage in UNX rats. Our results demonstrated that bigger shunt size is linked with proportional more significant cardiorenal remodeling and dysfunction in UNX rats. Expression of inflammatory biomarkers including CRP, TNF-α, IL-6, IL-1β, TGF-β and MCP-1 in left kidney and heart was significantly increased in all UNX + AV groups compared to Sham rats. Inflammation might thus participate in the worsening cardiorenal functions and remodeling processes in this model.

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

Theranostics. 2016  |  Pubmed ID: 27279914

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

A Spermine Conjugated Stearic Acid-g-chitosan Oligosaccharide Polymer with Different Types of Amino Groups for Efficient P53 Gene Therapy

Colloids and Surfaces. B, Biointerfaces. Sep, 2016  |  Pubmed ID: 27289311

The effect of various amino groups on gene vector is different. In order to combine their effect in one vector and finally promote the transfection efficiency, a biogenic tetra-amine spermine was introduced to modify the stearic acid-grafted chitosan oligosaccharide (CSOSA) polymer to build a new gene delivery system. The spermine linked CSOSA (SP-CSOSA) polymer consists two types of amino groups with 73.3%, 19.3% of all nitrogen atoms for primary and secondary amine groups, respectively. The SP modified CSOSA showed strong DNA condensation capability and obviously enhanced proton binding ability especially at about pH 5.0, which significantly promoted the escape of SP-CSOSA/pDNA complexes from endo-lysosoms. Moreover, the transfection efficiency at the N/P ratio of 10 could compete with that of Lipofectamine 2000 and PEI 25K, but with lower cytotoxicities. The therapeutic wild type p53 gene transfected by the SP-CSOSA polymer restored the function of aberrant p53 gene and induced obvious cell apoptosis and G1 phase arrest. We concluded that the new vector SP-CSOSA polymer proved to be a potential delivery system for gene therapy.

Overexpression of Arabidopsis NLP7 Improves Plant Growth Under Both Nitrogen-limiting and -sufficient Conditions by Enhancing Nitrogen and Carbon Assimilation

Scientific Reports. Jun, 2016  |  Pubmed ID: 27293103

Nitrogen is essential for plant survival and growth. Excessive application of nitrogenous fertilizer has generated serious environment pollution and increased production cost in agriculture. To deal with this problem, tremendous efforts have been invested worldwide to increase the nitrogen use ability of crops. However, only limited success has been achieved to date. Here we report that NLP7 (NIN-LIKE PROTEIN 7) is a potential candidate to improve plant nitrogen use ability. When overexpressed in Arabidopsis, NLP7 increases plant biomass under both nitrogen-poor and -rich conditions with better-developed root system and reduced shoot/root ratio. NLP7-overexpressing plants show a significant increase in key nitrogen metabolites, nitrogen uptake, total nitrogen content, and expression levels of genes involved in nitrogen assimilation and signalling. More importantly, overexpression of NLP7 also enhances photosynthesis rate and carbon assimilation, whereas knockout of NLP7 impaired both nitrogen and carbon assimilation. In addition, NLP7 improves plant growth and nitrogen use in transgenic tobacco (Nicotiana tabacum). Our results demonstrate that NLP7 significantly improves plant growth under both nitrogen-poor and -rich conditions by coordinately enhancing nitrogen and carbon assimilation and sheds light on crop improvement.

Alpha-asarone Improves Striatal Cholinergic Function and Locomotor Hyperactivity in Fmr1 Knockout Mice

Behavioural Brain Research. Oct, 2016  |  Pubmed ID: 27316341

Hyperactivity is a symptom found in several neurological and psychiatric disorders, including Fragile X syndrome (FXS). The animal model of FXS, fragile X mental retardation gene (Fmr1) knockout (KO) mouse, exhibits robust locomotor hyperactivity. Alpha (α)-asarone, a major bioactive component isolated from Acorus gramineus, has been shown in previous studies to improve various disease conditions including central nervous system disorders. In this study, we show that treatment with α-asarone alleviates locomotor hyperactivity in Fmr1 KO mice. To elucidate the mechanism underlying this improvement, we evaluated the expressions of various cholinergic markers, as well as acetylcholinesterase (AChE) activity and acetylcholine (ACh) levels, in the striatum of Fmr1 KO mice. We also analyzed the AChE-inhibitory activity of α-asarone. Striatal samples from Fmr1 KO mice showed decreased m1 muscarinic acetylcholine receptor (m1 mAChR) expression, increased AChE activity, and reduced ACh levels. Treatment with α-asarone improved m1 mAChR expression and ACh levels, and attenuated the increased AChE activity. In addition, α-asarone dose-dependently inhibited AChE activity in vitro. These results indicate that direct inhibition of AChE activity and up-regulation of m1 mAChR expression in the striatum might contribute to the beneficial effects of α-asarone on locomotor hyperactivity in Fmr1 KO mice. These findings might improve understanding of the neurobiological mechanisms responsible for locomotor hyperactivity.

Novel Reassortant Avian Influenza A(H5N6) Viruses in Humans, Guangdong, China, 2015

Emerging Infectious Diseases. Aug, 2016  |  Pubmed ID: 27331418

Recent Studies of Pickering Emulsions: Particles Make the Difference

Small (Weinheim an Der Bergstrasse, Germany). Sep, 2016  |  Pubmed ID: 27337222

In recent years, emulsions stabilized by micro- or nanoparticles (known as Pickering emulsions) have attracted much attention. Micro- or nanoparticles, as the main components of the emulsion, play a key role in the preparation and application of Pickering emulsions. The existence of particles at the interface between the oil and aqueous phases affects not only the preparation, but also the properties of Pickering emulsions, affording superior stability, low toxicity, and stimuli-responsiveness compared to classical emulsions stabilized by surfactants. These advantages of Pickering emulsions make them attractive, especially in biomedicine. In this review, the effects of the characteristics of micro- and nanoparticles on the preparation and properties of Pickering emulsions are introduced. In particular, the preparation methods of Pickering emulsions, especially uniform-sized emulsions, are listed. Uniform Pickering emulsions are convenient for both mechanistic research and applications. Furthermore, some biomedical applications of Pickering emulsions are discussed and the problems hindering their clinical application are identified.

Progressive Aortic Dilation Is Regulated By miR-17-Associated MiRNAs

Journal of the American College of Cardiology. Jun, 2016  |  Pubmed ID: 27339495

Patients with a bicuspid aortic valve (BAV) are at increased risk for progressive aortic dilation associated with extracellular matrix (ECM) degradation by matrix metalloproteinases (MMP). However, the mechanisms responsible for initiating this process are unknown. In the heart, MMP activity is regulated by micro-ribonucleic acid-17 (miR-17)-related downregulation of tissue inhibitors of metalloproteinases (TIMP); a similar process may exist in the aorta.

Metabolic Labeling and Imaging of N-Linked Glycans in Arabidopsis Thaliana

Angewandte Chemie (International Ed. in English). Aug, 2016  |  Pubmed ID: 27346875

Molecular imaging of glycans has been actively pursued in animal systems for the past decades. However, visualization of plant glycans remains underdeveloped, despite that glycosylation is essential for the life cycle of plants. Metabolic glycan labeling in Arabidopsis thaliana by using N-azidoacetylglucosamine (GlcNAz) as the chemical reporter is reported. GlcNAz is metabolized through the salvage pathway of N-acetylglucosamine (GlcNAc) and incorporated into N-linked glycans, and possibly intracellular O-GlcNAc. Click-labeling with fluorescent probes enables visualization of newly synthesized N-linked glycans. N-glycosylation in the root tissue was discovered to possess distinct distribution patterns in different developmental zones, suggesting that N-glycosylation is regulated in a developmental stage-dependent manner. This work shows the utility of metabolic glycan labeling in elucidating the function of N-linked glycosylation in plants.

An Efficient Implementation of Fixed Failure-Rate Ratio Test for GNSS Ambiguity Resolution

Sensors (Basel, Switzerland). Jun, 2016  |  Pubmed ID: 27347949

Ambiguity Resolution (AR) plays a vital role in precise GNSS positioning. Correctly-fixed integer ambiguities can significantly improve the positioning solution, while incorrectly-fixed integer ambiguities can bring large positioning errors and, therefore, should be avoided. The ratio test is an extensively used test to validate the fixed integer ambiguities. To choose proper critical values of the ratio test, the Fixed Failure-rate Ratio Test (FFRT) has been proposed, which generates critical values according to user-defined tolerable failure rates. This contribution provides easy-to-implement fitting functions to calculate the critical values. With a massive Monte Carlo simulation, the functions for many different tolerable failure rates are provided, which enriches the choices of critical values for users. Moreover, the fitting functions for the fix rate are also provided, which for the first time allows users to evaluate the conditional success rate, i.e., the success rate once the integer candidates are accepted by FFRT. The superiority of FFRT over the traditional ratio test regarding controlling the failure rate and preventing unnecessary false alarms is shown by a simulation and a real data experiment. In the real data experiment with a baseline of 182.7 km, FFRT achieved much higher fix rates (up to 30% higher) and the same level of positioning accuracy from fixed solutions as compared to the traditional critical value.

Temperature Dependence of Aggregated Structure of β-carotene by Absorption Spectral Experiment and Simulation

Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy. Dec, 2016  |  Pubmed ID: 27348046

β-carotene can self-assemble to form J- or H-type aggregate in hydrophilic environments, which is crucial for the proper functioning of biological system. Although several ways controlling the formation of the two types of aggregate in hydrated ethanol have been investigated in recent years, our study provided another way to control whether J- or H- β-carotene was formed and presented a method to investigate the aggregated structure. For this purpose, the aggregates of β-carotene formed at different temperatures were studied by UV-Vis spectra and a computational method based on Frenkel exciton was applied to simulate the absorption spectra to obtain the aggregated structure of the β-carotene. The analysis showed that β-carotene formed weakly coupled H-aggregate at 15°C in 1:1 ethanol-water solvent, and with the increase of temperature it tended to form J-type of aggregate. The absorption spectral simulation based on one-dimensional Frenkel exciton model revealed that good fit with the experiment was obtained with distance between neighbor molecules r=0.82nm, disorder of the system D=1500cm(-1) for H-type and r=1.04nm, D=1800cm(-1) for J-type.

Metal-Free [2 + 2 + 2] Cycloaddition of Ynamides with Nitriles to Construct 2,4-Diaminopyridines

Organic Letters. Jul, 2016  |  Pubmed ID: 27366955

We present a metal-free [2 + 2 + 2] cycloaddition of ynamides with nitriles that enables highly efficient access to 2,4-diaminopyridines. This catalytic protocol is more environmentally friendly and allows for a concomitant construction of C-C and C-N bonds between ynamides and nitriles, exhibiting excellent chemoselectivity, regioselectivity, and wide functional groups tolerance.

Prognostic and Predictive Significance of Tumor Length in Patients with Esophageal Squamous Cell Carcinoma Undergoing Radical Resection

BMC Cancer. Jul, 2016  |  Pubmed ID: 27387460

The objective of this study was to investigate the prognostic and predictive significance of tumor length in patients with esophageal squamous cell carcinoma undergoing radical resection.

Gap Junctions Contribute to Ictal/Interictal Genesis in Human Hypothalamic Hamartomas

EBioMedicine. Jun, 2016  |  Pubmed ID: 27428422

Human hypothalamic hamartoma (HH) is a rare subcortical lesion associated with treatment-resistant epilepsy. Cellular mechanisms responsible for epileptogenesis are unknown. We hypothesized that neuronal gap junctions contribute to epileptogenesis through synchronous activity within the neuron networks in HH tissue. We studied surgically resected HH tissue with Western-blot analysis, immunohistochemistry, electron microscopy, biocytin microinjection of recorded HH neurons, and microelectrode patch clamp recordings with and without pharmacological blockade of gap junctions. Normal human hypothalamus tissue was used as a control. Western blots showed increased expression of both connexin-36 (Cx36) and connexin-43 (Cx43) in HH tissue compared with normal human mammillary body tissue. Immunohistochemistry demonstrated that Cx36 and Cx43 are expressed in HH tissue, but Cx36 was mainly expressed within neuron clusters while Cx43 was mainly expressed outside of neuron clusters. Gap-junction profiles were observed between small HH neurons with electron microscopy. Biocytin injection into single recorded small HH neurons showed labeling of adjacent neurons, which was not observed in the presence of a neuronal gap-junction blocker, mefloquine. Microelectrode field recordings from freshly resected HH slices demonstrated spontaneous ictal/interictal-like discharges in most slices. Bath-application of gap-junction blockers significantly reduced ictal/interictal-like discharges in a concentration-dependent manner, while not affecting the action-potential firing of small gamma-aminobutyric acid (GABA) neurons observed with whole-cell patch-clamp recordings from the same patient's HH tissue. These results suggest that neuronal gap junctions between small GABAergic HH neurons participate in the genesis of epileptic-like discharges. Blockade of gap junctions may be a new therapeutic strategy for controlling seizure activity in HH patients.

Changes in Expression and Production of Heme Oxygenase-1 in Rats with Acute Liver Injury Induced by Lipopolysaccharide

The Journal of Toxicological Sciences. 2016  |  Pubmed ID: 27432233

To investigate the changes of heme oxygenase-1 (HO-1) expression and production in rats with acute liver injury induced by lipopolysaccharide (LPS), and explore the role of HO-1 in the pathogenesis of liver injury. Liver injury was assessed histologically and the serum level of alanine transaminase (ALT) and aspartate transaminase (AST) were examined. The activity of super oxide dismutase (SOD) and the content of malondialdehyde (MDA) and carbon monoxide (CO) in liver tissues were also examined at the same time. HO-1 mRNA expression was examined at different time points following LPS treatment and the expression of HO-1 protein was determined by immunohistochemical staining. Administration of LPS caused severe hepatic damage, characterized by significant elevation of serum ALT and AST levels and hepatic MDA content as well as a remarkable reduction of liver SOD activity at 24 hr as compared with those in the control group. HO-1 activity was elevated significantly after modeling, showing a time-dependent manner from 6 to 24 hr, while expression of HO-1 protein was increased remarkably from 6 to 24 hr. Endogenous CO concentration in the liver of control rats remained very low but was elevated significantly after LPS treatment (6, 12, 24 hr), which was in accordance with the changes of HO-1. HO-1 activity and protein are increased significantly in rats with acute liver injury induced by LPS, suggesting that HO-1 plays an important role in the pathogenesis of acute hepatic damage.

Cannabinoid Receptor Subtype 2 (CB2R) Agonist, GW405833 Reduces Agonist-induced Ca(2+) Oscillations in Mouse Pancreatic Acinar Cells

Scientific Reports. Jul, 2016  |  Pubmed ID: 27432473

Emerging evidence demonstrates that the blockade of intracellular Ca(2+) signals may protect pancreatic acinar cells against Ca(2+) overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB2Rs modulate intracellular Ca(2+) signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R agonist, GW405833 (GW) in agonist-induced Ca(2+) oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB1R-knockout (KO), and CB2R-KO mice. Immunohistochemical labeling revealed that CB2R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB2Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca(2+) oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca(2+) oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB2Rs eliminates ACh-induced Ca(2+) oscillations and L-arginine-induced enhancement of Ca(2+) signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis.

The Potential Adjuvanticity of Quaternized Chitosan Hydrogel Based Microparticles for Porcine Reproductive and Respiratory Syndrome Virus Inactivated Vaccine

International Immunopharmacology. Oct, 2016  |  Pubmed ID: 27449471

Infectious diseases possess a big threat to the livestock industry worldwide. Currently, inactivated veterinary vaccines have attracted much attention to prevent infection due to their safer profile compared to live attenuated vaccine. However, its intrinsic poor immunogenicity demands the incorporation of an adjuvant. Mineral oil based adjuvant (Montanide™ ISA206) was usually used to potentiate the efficacy of veterinary vaccines. However, ISA206 could not induce robust cellular immune responses, which was very important in controlling virus replication and clearing the infected cells. Moreover, mineral oil would result in severe side effects. To improve both the humoral and cellular immune responses of porcine reproductive and respiratory syndrome virus (PRRSV) inactivated vaccine, we developed pH-sensitive and size-controllable quaternized chitosan hydrogel microparticles (Gel MPs) without using chemical cross linking agent. Gel MPs, ionic cross-linked with glycerophosphate (GP), were biocompatible and could efficiently adsorb the inactivated PRRSV vaccine with a loading capacity of 579.05μg/mg. After intramuscular immunization in mice, results suggested that Gel MPs elicited significantly higher cell-mediated immune responses and comparable humoral immune responses compared to ISA 206. Regarding the biocompatibility, safety and effectiveness, Gel MPs would be a promising candidate to enhance the efficacy of veterinary vaccine.

Use of Patency Capsules in Patients with Established Crohn's Disease

Endoscopy. Aug, 2016  |  Pubmed ID: 27459215

HIV/STIs Risks Between Migrant MSM and Local MSM: a Cross-sectional Comparison Study in China

PeerJ. 2016  |  Pubmed ID: 27478695

Background. Internal migration plays a significant role in China's HIV epidemic. However, few studies have directly compared migrant men who have sex with men (MSM) with local MSM with regard to HIV/sexually transmitted infections (STIs) risks. Methods. We conducted a study in Guangzhou, China, with the aim of understanding the differences in HIV/STIs risks between migrant MSM and local MSM. A cross-sectional study was conducted among 273 migrant MSM and 249 local MSM in Guangzhou, China. Their behavioral and serologic data on HIV/syphilis were collected and compared between the two groups. A multivariate logistic regression was used to estimate the associations between HIV/STIs risks and migratory status. Results. Migrant MSM, compared to local MSM, have higher odds of reporting unprotected anal intercourse (UAI) (OR = 1.4; 95% CI [0.9-2.0]) and having multiple homosexual partners (OR = 1.2; 95% CI [0.8-1.8]). A lower rate of condom use at homosexual debut was reported in migrant MSM than in local MSM (OR = 0.7; 95% CI [0.5-0.9]). Migrant MSM have less odds of reporting HIV/STIs testing in the previous 6 months relative to local MSM (OR = 0.5; 95% CI [0.4-0.8]). In addition, migrant MSM demonstrated a lower level of HIV knowledge than local MSM (OR = 0.4; 95% CI [0.2-0.8]). Conclusion. Migrant MSM are more likely to engage in sexual risk behaviors, report a lower level of HIV knowledge and have less access to HIV/STIs testing. Further comprehensive interventions targeting migrant MSM are urged.

Base-controlled [3+3] Cycloaddition of Isoquinoline N-oxides with Azaoxyallyl Cations

Chemical Communications (Cambridge, England). Aug, 2016  |  Pubmed ID: 27484327

A base-controlled [3+3] cycloaddition reaction of isoquinoline N-oxides with azaoxyallyl cations is developed. 1,11b-dihydro-[1,2,4]oxadiazino[3,2-a]isoquinolin-2(3H)-ones are obtained when isoquinoline N-oxides are treated with α-halohydroxamates in the presence of sodium carbonate, while 2-(isoquinolin-1-yloxy)acetamides are unexpectedly produced when the base is changed to cesium carbonate. This transformation proceeds through an azaoxyallyl cation generated in situ from α-bromohydroxamate, and the [3+3] cycloaddition reaction is the key step for the final outcome.

Optimal Modified Tracking Performance for Networked Control Systems with QoS Constraint

ISA Transactions. Nov, 2016  |  Pubmed ID: 27491894

This paper investigates the optimal modified tracking performance of networked control systems with a constraint on quality of service (QoS). The QoS is characterized by two parameters of the system, viz. data dropout and the additive white Gaussian noise. The proposed modified tracking performance index prevents the probability of invalid data arising from the variations in the tracking error in the absence of an integrator in the plant. The derived optimal filter eliminates the influence of channel noise in the feedback channel. The optimal modified tracking performance expression is obtained by using the co-prime factorization. Results indicate that the optimal modified tracking performance is influenced by the non-minimum phase zeros, modification factor, packet dropout probability, and the characteristics of the reference signals. The obtained results will give some guidance for the design of networked control systems. The efficiency of the model is verified using some typical examples.

Comparative Genomics and Transcriptomics of Pichia Pastoris

BMC Genomics. Aug, 2016  |  Pubmed ID: 27495311

Pichia pastoris has emerged as an important alternative host for producing recombinant biopharmaceuticals, owing to its high cultivation density, low host cell protein burden, and the development of strains with humanized glycosylation. Despite its demonstrated utility, relatively little strain engineering has been performed to improve Pichia, due in part to the limited number and inconsistent frameworks of reported genomes and transcriptomes. Furthermore, the co-mingling of genomic, transcriptomic and fermentation data collected about Komagataella pastoris and Komagataella phaffii, the two strains co-branded as Pichia, has generated confusion about host performance for these genetically distinct species. Generation of comparative high-quality genomes and transcriptomes will enable meaningful comparisons between the organisms, and potentially inform distinct biotechnological utilies for each species.

Preclinical Modeling of KIF5B-RET Fusion Lung Adenocarcinoma

Molecular Cancer Therapeutics. Oct, 2016  |  Pubmed ID: 27496134

RET fusions have been found in lung adenocarcinoma, of which KIF5B-RET is the most prevalent. We established inducible KIF5B-RET transgenic mice and KIF5B-RET-dependent cell lines for preclinical modeling of KIF5B-RET-associated lung adenocarcinoma. Doxycycline-induced CCSP-rtTA/tetO-KIF5B-RET transgenic mice developed invasive lung adenocarcinoma with desmoplastic reaction. Tumors regressed upon suppression of KIF5B-RET expression. By culturing KIF5B-RET-dependent BaF3 (B/KR) cells with increasing concentrations of cabozantinib or vandetanib, we identified cabozantinib-resistant RET(V804L) mutation and vandetanib-resistant-RET(G810A) mutation. Among cabozantinib, lenvatinib, ponatinib, and vandetanib, ponatinib was identified as the most potent inhibitor against KIF5B-RET and its drug-resistant mutants. Interestingly, the vandetanib-resistant KIF5B-RET(G810A) mutant displayed gain-of-sensitivity (GOS) to ponatinib and lenvatinib. Treatment of doxycycline-induced CCSP-rtTA/tetO-KIF5B-RET bitransgenic mice with ponatinib effectively induced tumor regression. These results indicate that KIF5B-RET-associated lung tumors are addicted to the fusion oncogene and ponatinib is the most effective inhibitor for targeting KIF5B-RET in lung adenocarcinoma. Moreover, this study finds a novel vandetanib-resistant RET(G810A) mutation and identifies lenvatinib and ponatinib as the secondary drugs to overcome this vandetanib resistance mechanism. Mol Cancer Ther; 15(10); 2521-9. ©2016 AACR.

The Molecular Mechanisms of Action of PPAR-γ Agonists in the Treatment of Corneal Alkali Burns (Review)

International Journal of Molecular Medicine. Oct, 2016  |  Pubmed ID: 27499172

Corneal alkali burns (CAB) are characterized by injury-induced inflammation, fibrosis and neovascularization (NV), and may lead to blindness. This review evaluates the current knowledge of the molecular mechanisms responsible for CAB. The processes of cytokine production, chemotaxis, inflammatory responses, immune response, cell signal transduction, matrix metalloproteinase production and vascular factors in CAB are discussed. Previous evidence indicates that peroxisome proliferator-activated receptor γ (PPAR-γ) agonists suppress immune responses, inflammation, corneal fibrosis and NV. This review also discusses the role of PPAR-γ as an anti-inflammatory, anti-fibrotic and anti-angiogenic agent in the treatment of CAB, as well as the potential role of PPAR-γ in the pathological process of CAB. There have been numerous studies evaluating the clinical profiles of CAB, and the aim of this systematic review was to summarize the evidence regarding the treatment of CAB with PPAR-γ agonists.

Efficacy of Leflunomide, Telmisartan, and Clopidogrel for Immunoglobulin A Nephropathy: A Randomized Controlled Trial

Chinese Medical Journal. Aug, 2016  |  Pubmed ID: 27503012

The efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for immunoglobulin A nephropathy (IgAN) are unclear. This study was designed to evaluate the efficacy and safety of telmisartan combined with clopidogrel, leflunomide, or both drugs for IgAN.

Effects of the Combination of Aeration and Biofilm Technology on Transformation of Nitrogen in Black-odor River

Water Science and Technology : a Journal of the International Association on Water Pollution Research. 2016  |  Pubmed ID: 27508370

Excess nitrogen in urban river networks leading to eutrophication has become one of the most urgent environmental problems. Combinations of different aeration and biofilm techniques was designed to remove nitrogen from rivers. In laboratory water tank simulation experiments, we assessed the removal efficiency of nitrogen in both the overlying water and sediments by using the combination of the aeration and biofilm techniques, and then analyzed the transformation of nitrogen during the experiments. Aeration (especially sediment aeration) combined with the biofilms techniques was proved efficient in removing nitrogen from polluted rivers. Results indicated that the combination of sediment aeration and biofilms, with the highest nitrogen removal rate from the overlying water and sediments, was the most effective combined process, which especially inhibited the potential release of nitrogen from sediments by reducing the enzyme activity. It was found that the content of dissolved oxygen in water could be restored on the basis of the application of aeration techniques ahead, and the biofilm technique would be effective in purifying water in black-odor rivers.

Cadmium-induced Immune Abnormality is a Key Pathogenic Event in Human and Rat Models of Preeclampsia

Environmental Pollution (Barking, Essex : 1987). Nov, 2016  |  Pubmed ID: 27511439

With increased industrial development, cadmium is an increasingly important environmental pollutant. Studies have identified various adverse effects of cadmium on human beings. However, the relationships between cadmium pollution and the pathogenesis of preeclampsia remain elusive. The objective of this study is to explore the effects of cadmium on immune system among preeclamptic patients and rats. The results showed that the cadmium levels in the peripheral blood of preeclamptic patients were significantly higher than those observed in normal pregnancy. Based on it, a novel rat model of preeclampsia was established by the intraperitoneal administration of cadmium chloride (CdCl2) (0.125 mg of Cd/kg body weight) on gestational days 9-14. Key features of preeclampsia, including hypertension, proteinuria, placental abnormalities and small foetal size, appeared in pregnant rats after the administration of low-dose of CdCl2. Cadmium increased immunoglobulin production, mainly angiotensin II type 1-receptor-agonistic autoantibodies (AT1-AA), by increasing the expression of activation-induced cytosine deaminase (AID) in B cells. AID is critical for the maturation of antibody and autoantibody responses. In addition, angiotensin II type 1-receptor-agonistic autoantibody, which emerged recently as a potential pathogenic contributor to PE, was responsible for the deposition of complement component 5 (C5) in kidneys of pregnant rats via angiotensin II type 1 receptor (AT1R) activation. C5a is a fragment of C5 that is released during C5 activation. Selectively interfering with C5a signalling by a complement C5a receptor-specific antagonist significantly attenuated hypertension and proteinuria in Cd-injected pregnant rats. Our results suggest that cadmium induces immune abnormalities that may be a key pathogenic contributor to preeclampsia and provide new insights into treatment strategies of preeclampsia.

Total Synthesis of Nuclear Factor of Activated T-Cells-68 (NFAT-68): Sequential Use of Chiral Allenylsilane and Titanium Alkoxide-Mediated Reductive Coupling Bond Construction

Organic Letters. Sep, 2016  |  Pubmed ID: 27513364

Highly enantioenriched chiral allenylsilanes 4 were prepared in high yield through a scalable synthetic sequence, employing a modified copper-catalyzed SN2' reaction. These reagents were used for the production of enantioenriched homoproparglylic ethers 5, which were subjected to titanium alkoxide-mediated reductive coupling with acetylenic esters to produce (E,E)-dienes 6 bearing α,β,γ,δ-unsaturated esters. Both enantiomers of nuclear factor of activated T-cells-68 (NFAT-68) were synthesized in five steps with the sequential use of the two methods.

Investigation of Synergistic Mechanism and Identification of Interaction Site of Aldose Reductase with the Combination of Gigantol and Syringic Acid for Prevention of Diabetic Cataract

BMC Complementary and Alternative Medicine. Aug, 2016  |  Pubmed ID: 27520089

Gigantol and syringic acid (SA) have been shown to synergistically prevent formation of diabetic cataract (DC). However, the exact mechanism of this effect is unknown. Here, we investigate the effect of these compounds on the activity of aldose reductase (AR) and cataract formation.

Contact Tracing for Imported Case of Middle East Respiratory Syndrome, China, 2015

Emerging Infectious Diseases. Sep, 2016  |  Pubmed ID: 27532887

Confirmation of an imported case of infection with Middle East respiratory syndrome coronavirus in China triggered intensive contact tracing and mandatory monitoring. Using a hotline and surveillance video footage was effective for tracing all 110 identified contacts. Contact monitoring detected no secondary transmission of infection in China.

AC Electrokinetic Drug Delivery in Dentistry Using an Interdigitated Electrode Assembly Powered by Inductive Coupling

Biomedical Microdevices. Oct, 2016  |  Pubmed ID: 27565821

AC electrokinetics (ACEK) has been shown to deliver certain drugs into human teeth more effectively than diffusion. However, using electrical wires to power intraoral ACEK devices poses risks to patients. The study demonstrates a novel interdigitated electrode arrays (IDE) assembly powered by inductive coupling to induce ACEK effects at appropriate frequencies to motivate drugs wirelessly. A signal generator produces the modulating signal, which multiplies with the carrier signal to produce the amplitude modulated (AM) signal. The AM signal goes through the inductive link to appear on the secondary coil, then rectified and filtered to dispose of its carrier signal, and the positive half of the modulating signal appears on the load. After characterizing the device, the device is validated under light microscopy by motivating carboxylate-modified microspheres, tetracycline, acetaminophen, benzocaine, lidocaine and carbamide peroxide particles with induced ACEK effects. The assembly is finally tested in a common dental bleaching application. After applying 35 % carbamide peroxide to human teeth topically or with the IDE at 1200 Hz, 5 Vpp for 20 min, spectrophotometric analysis showed that compared to diffusion, the IDE enhanced whitening in specular optic and specular optic excluded modes by 215 % and 194 % respectively. Carbamide peroxide absorbance by the ACEK group was two times greater than diffusion as measured by colorimetric oxidation-reduction and UV-Vis spectroscopy at 550 nm. The device motivates drugs of variable molecular weight and structure wirelessly. Wireless transport of drugs to intraoral targets under ACEK effects may potentially improve the efficacy and safety of drug delivery in dentistry.

Evolution and Transmission of Respiratory Syncytial Group A (RSV-A) Viruses in Guangdong, China 2008-2015

Frontiers in Microbiology. 2016  |  Pubmed ID: 27574518

Respiratory syncytial viruses (RSVs) including subgroups A (RSV-A) and B (RSV-B) are an important cause of acute respiratory tract infections worldwide. RSV-A include major epidemic strains. Fundamental questions concerning the evolution, persistence and transmission of RSV-A are critical for disease control and prevention, yet remain unanswered. In this study, we generated 64 complete G gene sequences of RSV-A strains collected between 2008 and 2015 in Guangdong, China. Phylogenetic analysis was undertaken by incorporating 572 publicly available RSV-A sequences. Current data indicate that genotypes GA1, GA4, and GA5 are endemic with limited epidemic activity. In contrast, the GA2 genotype which likely originated in 1980 has spread rapidly and caused epidemics worldwide. By analyzing GA2 genotype sequences across epidemic seasons within Guangdong, we find that RSV-A epidemics in Guangdong are caused by a combination of virus importation and local persistence, although the magnitude of the latter is likely overestimated due to infrequent sampling in other regions. Our results provide new insights into RSV-A evolution and transmission at global and local scales and highlights the rapid and wide spread of genotype GA2 compared to other genotypes. In order to control RSV transmission and outbreak, both local persistence and external introduction should be taken into account when designing optimal strategies.

Simplified Deployment of Health Informatics Applications by Providing Docker Images

Studies in Health Technology and Informatics. 2016  |  Pubmed ID: 27577463

Due to the specific needs of biomedical researchers, in-house development of software is widespread. A common problem is to maintain and enhance software after the funded project has ended. Even if many tools are made open source, only a couple of projects manage to attract a user basis large enough to ensure sustainability. Reasons for this include complex installation and configuration of biomedical software as well as an ambiguous terminology of the features provided; all of which make evaluation of software laborious. Docker is a para-virtualization technology based on Linux containers that eases deployment of applications and facilitates evaluation. We investigated a suite of software developments funded by a large umbrella organization for networked medical research within the last 10 years and created Docker containers for a number of applications to support utilization and dissemination.

Mechanism of Intestinal Mucosal Barrier Dysfunction in a Rat Model of Chronic Obstructive Pulmonary Disease: An Observational Study

Experimental and Therapeutic Medicine. Sep, 2016  |  Pubmed ID: 27588054

The aim of the present study was to investigate intestinal mucosal barrier dysfunction in a rat model of chronic obstructive pulmonary disease (COPD). Male Sprague Dawley rats (n=40) were evenly randomized into control and COPD groups and the COPD model was established by regulated exposure to cigarette smoke for 6 months. Histopathological changes of the lung and intestinal tissues were detected by hematoxylin and eosin staining. Expression of the tight junction proteins occludin and zona occludens-1 (ZO-1) in the intestinal tissues were analyzed by western blotting, serum diamine oxidase (DAO) activity was detected by spectrophotometry, the urinary lactulose to mannitol ratio (L/M) was evaluated by high performance liquid chromatography, and intestinal tissue secretion of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-8 were detected by ELISA. Lung histopathology revealed thinned alveolar walls, ruptured alveolar septa, enlarged and deformed alveoli, and the formation of bullae and emphysema due to alveolar fusion in the COPD group, while intestinal histopathology indicated clearly swollen intestines with darkened and gray mucosa, neutrophil infiltration of the intestinal mucosal and regional epithelial shedding. The occludin and ZO-1 expression levels were significantly lower in the COPD group compared with those in the corresponding control group (P<0.05), while the urinary L/M ratio was significantly higher (P<0.05). Furthermore, the serum DAO activity and secretion of TNF-α, IFN-γ and IL-8 in the intestinal tissues were significantly higher in the COPD group than in the control group (each P<0.05). Dysfunctional and structural changes were observed in the intestinal mucosal barrier in COPD model rats, which may be associated with the increased intestinal inflammatory responses.

Nicotine Regulates Activity of Lateral Habenula Neurons Via Presynaptic and Postsynaptic Mechanisms

Scientific Reports. Sep, 2016  |  Pubmed ID: 27596561

There is much interest in brain regions that drive nicotine intake in smokers. Interestingly, both the rewarding and aversive effects of nicotine are probably critical for sustaining nicotine addiction. The medial and lateral habenular (LHb) nuclei play important roles in processing aversion, and recent work has focused on the critical involvement of the LHb in encoding and responding to aversive stimuli. Several neurotransmitter systems are implicated in nicotine's actions, but very little is known about how nicotinic acetylcholine receptors (nAChRs) regulate LHb activity. Here we report in brain slices that activation of nAChRs depolarizes LHb cells and robustly increases firing, and also potentiates glutamate release in LHb. These effects were blocked by selective antagonists of α6-containing (α6*) nAChRs, and were absent in α6*-nAChR knockout mice. In addition, nicotine activates GABAergic inputs to LHb via α4β2-nAChRs, at lower concentrations but with more rapid desensitization relative to α6*-nAChRs. These results demonstrate the existence of diverse functional nAChR subtypes at presynaptic and postsynaptic sites in LHb, through which nicotine could facilitate or inhibit LHb neuronal activity and thus contribute to nicotine aversion or reward.

Switchable PDT for Reducing Skin Photosensitization by a NIR Dye Inducing Self-assembled and Photo-disassembled Nanoparticles

Biomaterials. Nov, 2016  |  Pubmed ID: 27598652

Photodynamic therapy (PDT) is the combination of light and photosensitizer (PS) to kill tumor cells, which has the potential to meet many currently unmet medical needs. However, the whole body distribution and activatability by sunlight of photosensitizers to induce skin photosensitivity have limited the extensive clinic application of PDT. Herein, a novel strategy is presented to overcome these limitations by using a hydrophobic Near-infared (NIR) dye IR-780 iodide (IR780) to induce the self-assembly of albumin-PS conjugates, as a switchable PDT (Switch-PDT) agent. The PDT effect of PS is effectively inhibited by IR780 and recovered by NIR light irradiation in vitro. This quench/recovery strategy dose not sacrifice the anti-tumor ability in vivo, and the combined PDT and PTT (photothermal) effect contributes a very effective tumor inhibition rate of 100%. More importantly, the PDT effect is significantly suppressed after intravenous administration in mice or subcutaneous administration in rabbits as exhibited by the negligible skin response, while traditional PDT agent arouses severe skin erythema and edema. To the best of our knowledge, the switchable PDT is the first time to be used to eradicate the skin photosensitization of PS in vivo.

In Vitro Inhibition of UGT1A3, UGT1A4 by Ursolic and Oleanolic Acid and Drug-drug Interaction Risk Prediction

Xenobiotica; the Fate of Foreign Compounds in Biological Systems. Sep, 2016  |  Pubmed ID: 27600106

1. Ursolic acid (UA) and oleanolic acid (OA) may have important activity relevant to health and disease prevention. Thus, we studied the activity of UA and OA on UDP-glucuronosyltransferases (UGTs) and used trifluoperazine as a probe substrate to test UGT1A4 activity. Recombinant UGT-catalyzed 4-methylumbelliferone (4-MU) glucuronidation was used as a probe reaction for other UGT isoforms. 2. UA and OA inhibited UGT1A3 and UGT1A4 activity but did not inhibit other tested UGT isoforms. 3. UA-mediated inhibition of UGT1A3 catalyzed 4-MU-β-D-glucuronidation was via competitive inhibition (IC50 0.391 ± 0.013 μM; Ki 0.185 ± 0.015 μM). UA also competitively inhibited UGT1A4-mediated trifluoperazine-N-glucuronidation (IC50 2.651 ± 0.201 μM; Ki 1.334 ± 0.146 μM). 4. OA offered mixed inhibition of UGT1A3-mediated 4-MU-β-D-glucuronidation (IC50 0.336 ± 0.013 μM; Ki 0.176 ± 0.007 μM;) and competitively inhibited UGT1A4-mediated trifluoperazine-N-glucuronidation (IC50 5.468 ± 0.697 μM; Ki 6.298 ± 0.891 μM). 5. Co-administering OA or UA with drugs or products that are substrates of UGT1A3 or UGT1A4 may produce drug-mediated side effects.

Generation of Sulfonyl Radicals from Aryldiazonium Tetrafluoroborates and Sulfur Dioxide: The Synthesis of 3-Sulfonated Coumarins

Angewandte Chemie (International Ed. in English). Sep, 2016  |  Pubmed ID: 27603499

A catalyst-free approach for the generation of sulfonyl radicals from aryldiazonium tetrafluoroborates in the presence of DABCO⋅(SO2 )2 is realized. The combination of aryldiazonium tetrafluoroborates, DABCO⋅(SO2 )2 , and aryl propiolates affords 3-sulfonated coumarins in good to excellent yields. This tandem reaction process involves radical addition, spirocyclization, and 1,2-migration of esters. Additionally, the in situ diazotization of a number of anilines allows the directional synthesis of desired 3-sulfonated coumarins in a one-pot, two-step process.

Molecular Engineering of Mechanochromic Materials by Programmed C-H Arylation: Making a Counterpoint in Chromism Trend

Journal of the American Chemical Society. Sep, 2016  |  Pubmed ID: 27603792

The development of facile accesses for screening organic functional molecules through the C-H bond activation is a revolutionary trend in material research. The prediction of mechanochromism as well as mechanochromic trend of luminogens is an appealing, yet challenging puzzle. Here, we present the design strategy of mechanochromic luminogens on the basis of the dipole moment of donor-acceptor (D-A) molecules. For this purpose, a highly efficient route to 2,7-diaryl [1,2,4]triazolo[1,5-a]pyrimidines (2,7-diaryl TAPs) has been established through the programmed C-H arylation, which unlocks a great opportunity to rapidly assemble a library of fluorophores for the discovery of the mechanochromic regularity. The molecular dipole moment can be employed to explain and further predict the mechanochromic trend. The 2,7-diaryl TAPs with electron-donating groups (EDGs) on 2-aryl and electron-withdrawing groups (EWGs) on 7-aryl possess a relatively small dipole moment and exhibit a red-shifted mechanochromism. While the two aryls are interchanged, the resulting luminogens have a relatively large dipole moment and display a blue-shifted mechanochromism. Seven pairs of isomers with an opposite mechanochromic trend have been given as illustrative examples. The aryl-interchanged congeners with a bidirectional emission shift are structurally similar, which would provide an avenue for deeply understanding the mechanochromic mechanism.

Isolation of H5N6, H7N9 and H9N2 Avian Influenza A Viruses from Air Sampled at Live Poultry Markets in China, 2014 and 2015

Euro Surveillance : Bulletin Europeen Sur Les Maladies Transmissibles = European Communicable Disease Bulletin. Sep, 2016  |  Pubmed ID: 27608369

Zoonotic infections by avian influenza viruses occur at the human-poultry interface, but the modes of transmission have not been fully investigated. We assessed the potential for airborne and fomite transmission at live poultry markets in Guangzhou city and in Hong Kong Special Administrative Region (SAR), China, during 2014 and 2015. Viral genome and infectious avian influenza A viruses of H5N6, H7N9, and H9N2 subtypes were detected predominantly from particles larger or equal to 1 μm in diameter in the air sampled with cyclone-based bioaerosol samplers at the live poultry markets in Guangzhou. Influenza A(H9N2) viruses were ubiquitously isolated every month during the study period from air and environmental swabs, and different lineages of H9N2 virus were isolated from markets where chickens and minor land-based poultry were sold. The use of de-feathering devices increased the quantity of virus-laden airborne particles while market closure reduced the amount of such particles. The results highlight the possibility of airborne transmission of avian influenza viruses among poultry or from poultry to humans within such settings. This may explain epidemiological observations in which some patients with H7N9 infection reported being in markets but no direct contact with live poultry or poultry stalls.

Route for the Generation of Trifluoromethyl-Substituted Pyrrplo[3,2-c]quinolines

The Journal of Organic Chemistry. Oct, 2016  |  Pubmed ID: 27611327

Generation of trifluoromethyl-substituted pyrrolo[3,2-c]quinolines via a copper(II)-catalyzed tandem reaction of N-(σ-iodoaryl)alkynylimines with 2-isocyanoacetates is reported. The process involves a [3 + 2] cycloaddition and intramolecular C-C bond coupling, leading to the fluorine-containing N-heterocycles under mild conditions with high efficiency.

Silica Nanoparticles Induce Alpha-synuclein Induction and Aggregation in PC12-cells

Chemico-biological Interactions. Oct, 2016  |  Pubmed ID: 27613482

Silica nanoparticles (SiO2-NPs) are widely applied in diagnosis, imaging, and drug delivery of central nervous diseases. Previously, we found that SiO2-NPs enter the brain and, more specifically, the dopaminergic neurons in the striatum. Whether SiO2-NPs have neurotoxicity and contribute to development of Parkinson's disease (PD) remains unclear. In this study, we investigated the effect of SiO2-NPs on PC12 cells, a dopaminergic neuron-like cell line. We showed that SiO2-NPs up-regulated α-synuclein expression, and N-acetyl cysteine reduced α-synuclein. SiO2-NPs inhibited 20S proteasome activity and decreased ubiquitin, Parkin, and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) protein levels in the ubiquitin-proteasome system (UPS). SiO2-NPs induced autophagy as shown by transmission electron microscopy, and elevated LC3-II and Beclin 1 levels in PC12 cells. SiO2-NPs inhibited phosphorylation of PI3K, Akt, mTOR, and P70S6. These data suggest that SiO2-NPs induce oxidative stress and α-synuclein aggregation by inhibiting the UPS. SiO2-NPs also induce autophagy through inhibiting PI3K-Akt-mTOR signaling, which is known to negatively regulate autophagy. Amyloid aggregates of α-synuclein in dopaminergic neurons of the midbrain are considered the hallmark of PD. Our findings indicate that SiO2-NPs exposure induces neurotoxicity and may be a significant risk factor for the development of PD.

Iodine/Copper Iodide-Mediated C-H Functionalization: Synthesis of Imidazo[1,2-a]pyridines and Indoles from N-Aryl Enamines

The Journal of Organic Chemistry. Oct, 2016  |  Pubmed ID: 27617346

A practical intramolecular C-H functionalization reaction of N-aryl enamines has been carried out with molecular iodine (I2) as the sole oxidant in the presence of copper iodide (CuI). The efficient and versatile synthetic method described here is compatible with both N-heteroaryl and N-aryl substituted enamines and produces diverse imidazo[1,2-a]pyridine and indole derivatives via I2-mediated oxidative C-N and C-C bond formation, respectively. This ligand-free C-H functionalization methodology also works well with crude enamines, which allows for the sequential synthesis of the products directly from arylamines and ketones (or alkynes) without purification of the enamine intermediates.

Developing a New Score System for Patients with PSA Ranging from 4 to 20 ng/mL to Improve the Accuracy of PCa Detection

SpringerPlus. 2016  |  Pubmed ID: 27652058

To develop a new score system for patients with prostate specific antigen (PSA) ranging from 4 to 20 ng/mL to improve the accuracy of prostate cancer (PCa) detection, and to evaluate it with receiver operating characteristic curve.

Resistance to Second-Line Antituberculosis Drugs and Delay in Drug Susceptibility Testing Among Multidrug-Resistant Tuberculosis Patients in Shanghai

BioMed Research International. 2016  |  Pubmed ID: 27652260

Introduction. Second-line antituberculosis drugs (SLDs) are used for treating multidrug-resistant tuberculosis (MDR-TB). Prolonged delays before confirming MDR-TB with drug susceptibility testing (DST) could result in transmission of drug-resistant strains and inappropriate use of SLDs, thereby increasing the risk of resistance to SLDs. This study investigated the diagnostic delay in DST and prevalence of baseline SLD resistance in Shanghai and described the distribution of SLD resistance with varied delays to DST. Methods. All registered patients from 2011 to 2013 in Shanghai were enrolled. Susceptibility to ofloxacin, amikacin, kanamycin, and capreomycin was tested. Total delay in DST completion was measured from the onset of symptoms to reporting DST results. Results. Resistance to SLDs was tested in 217 of the 276 MDR-TB strains, with 118 (54.4%) being resistant to at least one of the four SLDs. The median total delay in DST was 136 days. Patients with delay longer than median days were roughly twice more likely to have resistance to at least one SLD (OR 2.22, 95% CI 1.19-4.11). Conclusions. During prolonged delay in DST, primary and acquired resistance to SLDs might occur more frequently. Rapid diagnosis of MDR-TB, improved nosocomial infection controls, and regulated treatment are imperative to prevent SLD resistance.

AlCl3-Catalyzed Annulations of Ynamides Involving a Torquoselective Process for the Simultaneous Control of Central and Axial Chirality

Organic Letters. Oct, 2016  |  Pubmed ID: 27653170

A highly torquoselective process for simultaneous control of central and axial chirality by the annulation of terminally substituted ynamides with o-quinone methides is reported. In the presence of AlCl3, a sequence comprising a [2 + 2] cycloaddition followed by the torquoselective 4π-electrocyclic ring opening and 6π-electrocyclic ring closure leads to highly stereoselective formation of diastereoisomeric 4-amino-2H-chromenes. Terminally unsubstituted ynamides undergo AlCl3-catalyzed [4 + 2] cycloaddition with o-quinone methides providing 2-amino-4H-chromenes.

Microbial HSP70 Peptide Epitope 407-426 As Adjuvant in Tumor-derived Autophagosome Vaccine Therapy of Mouse Lung Cancer

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine. Nov, 2016  |  Pubmed ID: 27662838

Tumor-derived autophagome (DRibble) is an effective therapeutic cancer vaccine inducing T cell recognition and death of tumor cells in mice. However, the potential for improved anti-tumor response still remains. Our previous study demonstrated that two repeats of a mycobacterial HSP70407-426 (M2) peptide acted as adjuvant in improving anti-tumor efficacy of human umbilical vein endothelial cell (HUVEC) vaccine. Here, a DRibble vaccine conjugated with M2 (DRibble-M2) was designed as a novel vaccine to enhance anti-tumor activity. Compared with DRibble alone, DRibble-M2 vaccination more significantly inhibited the growth of mouse Lewis lung cancer both in a subcutaneous tumor model and in a lung metastasis model. Higher expression of antigen-specific CTL was induced by DRibble-M2. DRibble-M2 induced higher CD83 and CD86 expression in DC2.4 and also improved the internalization of DRibble antigen into DC2.4. Our data indicated that DRibble-M2 is a potential vaccine for clinical cancer therapy.

Erratum To: Comparative Genomics and Transcriptomics of Pichia Pastoris

BMC Genomics. Sep, 2016  |  Pubmed ID: 27681084

Clinical Predictors Differentiating Non-diabetic Renal Diseases from Diabetic Nephropathy in a Large Population of Type 2 Diabetes Patients

Diabetes Research and Clinical Practice. Nov, 2016  |  Pubmed ID: 27693840

Non-diabetic renal diseases (NDRDs) are associated with better renal outcomes than diabetic nephropathy (DN). This study was conducted to determine the common clinical markers predicting NDRDs in type 2 diabetes patients.

Improving Adjuvanticity of Quaternized Chitosan-based Microgels for H5N1 Split Vaccine by Tailoring the Particle Properties to Achieve Antigen Dose Sparing Effect

International Journal of Pharmaceutics. Dec, 2016  |  Pubmed ID: 27697632

In this study, we developed the quaternized chitosan microgels without chemical crosslinking as an adjuvant of H5N1 split vaccine. The microgels with pH-sensitivity, positive surface charge and good biocompatibility, have been demonstrated in favor of enhancing both humoral and cellular immune response. However, the detailed mechanism of the chitosan-based microgels to enhance antigen specific immune responses remains unclear. Therefore, we prepared the quaternized chitosan microgels with well defined quaternization degrees (QDs, 20-80%) and particle sizes (800nm-5μm) by the premix membrane emulsification technique, and investigated the effect of quaternization degree (QD) and size on the adjuvanticity of microgels. Results suggested that microgels with relatively smaller size (807nm) and moderate quaternization degree (QD 41% and 60%) were favorable for a maximum immune response. The mechanism was studied and explained by examining the characteristics of microgels and investigating the stimulation of bone-marrow derived dendritic cells (BMDCs). Moreover, they induced significantly stronger immune responses at lower antigen doses (known as antigen sparing effect) compared to aluminum adjuvant. These data indicated that a maximum immune response can be achieved by controlling properties of chitosan microgels, which also could serve as a significant guidance for rational design of chitosan-based particle adjuvant.

Erratum To: P2Y1, P2Y2, and TRPV1 Receptors Are Increased in Diarrhea-Predominant Irritable Bowel Syndrome and P2Y2 Correlates with Abdominal Pain

Digestive Diseases and Sciences. Dec, 2016  |  Pubmed ID: 27709366

A Binary Catalyst System of a Cationic Ru-CNC Pincer Complex with an Alkali Metal Salt for Selective Hydroboration of Carbon Dioxide

Chemical Communications (Cambridge, England). Sep, 2016  |  Pubmed ID: 27711420

Binary catalyst systems comprising a cationic Ru-CNC pincer complex and an alkali metal salt were developed for selective hydroboration of CO2 utilizing pinacolborane at r.t. and 1 atm CO2, with the combination of [Ru(CNCBn)(CO)2(H)][PF6] and KOCO2(t)Bu producing formoxyborane in 76% yield. A bicyclic catalytic mechanism was proposed and discussed.

Preparation of Raspberry-like γ-Fe2O3/crackled Nitrogen-doped Carbon Capsules and Their Application As Supports to Improve Catalytic Activity

Nanoscale. Nov, 2016  |  Pubmed ID: 27734999

In this manuscript, we have introduced a novel method to improve the catalytic activity of metal nanoparticles via optimizing the support structure. To this end, raspberry-like γ-Fe2O3/crackled nitrogen-doped carbon (CNC) capsules were prepared by a two-step method. Compared with traditional magnetic capsules, in γ-Fe2O3/CNC capsules, the γ-Fe2O3 nanoparticles were embedded in a CNC shell; therefore, they neither occupied the anchoring sites for metal nanoparticles nor came into contact with them, which was beneficial for increasing the metal nanoparticle loading. Numerous tiny cracks appeared on the porous CNC shell, which effectively improved the mass diffusion and transport in catalytic reactions. Additionally, the coordination interaction could be generated between the precursor metal ions and doped-nitrogen atoms in the capsule shell. With the help of these structural merits, γ-Fe2O3/CNC capsules were ideal supports for Pd nanoparticles, because they were beneficial for improving the Pd loading, reducing the nanoparticle size, increasing their dispersity and maximizing the catalytic performance of Pd nanoparticles anchored on the inner shell surface. As expected, γ-Fe2O3/CNC@Pd catalysts exhibited a dramatically enhanced catalytic activity towards hydrophilic 4-nitrophenol and hydrophobic nitrobenzene. The reaction rate constant k was compared with recent work and the corresponding reference samples. Moreover, they could be easily recycled by using a magnet and reused without an obvious loss of catalytic activity.

Magnetic Resonance Enterography or Patency Capsule to Predict Capsule Retention

Gastrointestinal Endoscopy. Nov, 2016  |  Pubmed ID: 27742047

Molecular Pathogenesis of Long QT Syndrome Type 1

Journal of Arrhythmia. Oct, 2016  |  Pubmed ID: 27761162

Long QT syndrome type 1 (LQT1) is a subtype of a congenital cardiac syndrome caused by mutation in the KCNQ1 gene, which encodes the α-subunit of the slow component of delayed rectifier K(+) current (IKs) channel. Arrhythmias in LQT1 are characterized by prolongation of the QT interval on ECG, as well as the occurrence of life-threatening cardiac events, frequently triggered by adrenergic stimuli (e.g., physical or emotional stress). During the past two decades, much advancement has been made in understanding the molecular pathogenesis underlying LQT1. Uncovering the genotype-phenotype correlations in LQT1 is of clinical importance to better understand the gene-specific differences that may influence the propensity for developing life-threatening arrhythmias under specific conditions. Elucidation of these mechanisms will also help to improve the diagnosis and management of this cardiac disorder based on gene-specific considerations. This review describes the current medical consensus and recent developments regarding the molecular pathogenesis of LQT1 and provides a novel insight into the adrenergic regulation of this disease.

Engineering Escherichia Coli to Bind to Cyanobacteria

Journal of Bioscience and Bioengineering. Oct, 2016  |  Pubmed ID: 27773604

We engineered Escherichia coli cells to bind to cyanobacteria by heterologously producing and displaying lectins of the target cyanobacteria on their surface. To prove the efficacy of our approach, we tested this design on Microcystis aeruginosa with microvirin (Mvn), the lectin endogenously produced by this cyanobacterium. The coding sequence of Mvn was C-terminally fused to the ice nucleation protein NC (INPNC) gene and expressed in E. coli. Results showed that E. coli cells expressing the INPNC::Mvn fusion protein were able to bind to M. aeruginosa and the average number of E. coli cells bound to each cyanobacterial cell was enhanced 8-fold. Finally, a computational model was developed to simulate the binding reaction and help reconstruct the binding parameters. To our best knowledge, this is the first report on the binding of two organisms in liquid culture mediated by the surface display of lectins and it may serve as a novel approach to mediate microbial adhesion.

RNA Sequencing of Formalin-Fixed, Paraffin-Embedded Specimens for Gene Expression Quantification and Data Mining

International Journal of Genomics. 2016  |  Pubmed ID: 27774452

Background. Proper rRNA depletion is crucial for the successful utilization of FFPE specimens when studying gene expression. We performed a study to evaluate two major rRNA depletion methods: Ribo-Zero and RNase H. RNAs extracted from 4 samples were treated with the two rRNA depletion methods in duplicate and sequenced (N = 16). We evaluated their reducibility, ability to detect RNA, and ability to molecularly subtype these triple negative breast cancer specimens. Results. Both rRNA depletion methods produced consistent data between the technical replicates. We found that the RNase H method produced higher quality RNAseq data as compared to the Ribo-Zero method. In addition, we evaluated the RNAseq data generated from the FFPE tissue samples for noncoding RNA, including lncRNA, enhancer/super enhancer RNA, and single nucleotide variation (SNV). We found that the RNase H is more suitable for detecting high-quality, noncoding RNAs as compared to the Ribo-Zero and provided more consistent molecular subtype identification between replicates. Unfortunately, neither method produced reliable SNV data. Conclusions. In conclusion, for FFPE specimens, the RNase H rRNA depletion method performed better than the Ribo-Zero. Neither method generates data sufficient for SNV detection.

ZFX Modulates the Growth of Human Leukemic Cells Via B4GALT1

Acta Biochimica Et Biophysica Sinica. Dec, 2016  |  Pubmed ID: 27797721

Zinc finger protein X-linked (ZFX) is a key regulator of both embryonic stem cells (ESCs) and hematopoietic stem cells (HSCs), which is required for both Notch intracellular domain (NotchIC)-induced acute T-cell leukemia and MLL-AF9-induced myeloid leukemia in mouse models. However, the role of ZFX and its underlying mechanism in human leukemic cells remain unclear yet, though accumulating data have demonstrated that ZFX is aberrantly expressed in various human tumors and plays an important role. Herein, we found that ZFX was aberrantly expressed in various human leukemic cell lines and primary cells from leukemia patients compared with control cells. The silence of ZFX led to the growth suppression through either the deregulated cell cycle or the induction of apoptosis in various cells including K562, Jurkat, Namalwa, and THP-1 cells. The gene expression analysis revealed that UDP-Gal:βGlcNAc β 1,4-galactosyltransferase, polypeptide 1 (B4GALT1) was significantly down-regulated upon ZFX silencing, which is implicated in the response of K562 cells to the treatment of imatinib mesylate (IM). In addition, lectin blot assay showed that the galactosylation of glycoproteins in K562 cells was suppressed upon ZFX silencing. Interestingly, overexpression of B4GALT1 restored the growth and conferred drug resistance to ZFX-silenced cells. Taken together, we have demonstrated that ZFX is aberrantly expressed in multiple human leukemic cells and it modulates the growth and drug response of leukemic cells partially via B4GALT1, which suggests that ZFX is a new regulator of leukemic cells and warrants intensive investigations on this 'stemness' regulator in these deadly diseases.

BPTF Is Essential for T Cell Homeostasis and Function

Journal of Immunology (Baltimore, Md. : 1950). Dec, 2016  |  Pubmed ID: 27799308

Bromodomain PHD finger transcription factor (BPTF), a ubiquitously expressed ATP-dependent chromatin-remodeling factor, is critical for epigenetically regulating DNA accessibility and gene expression. Although BPTF is important for the development of thymocytes, its function in mature T cells remains largely unknown. By specifically deleting BPTF from late double-negative 3/double-negative 4 stage of developing T cells, we found that BPTF was critical for the homeostasis of T cells via a cell-intrinsic manner. In addition, BPTF was essential for the maintenance and function of regulatory T (Treg) cells. Treg cell-specific BPTF deletion led to reduced Foxp3 expression, increased lymphocyte infiltration in the nonlymphoid organs, and a systemic autoimmune syndrome. These findings therefore reveal a vital role for BPTF in T and Treg cell function and immune homeostasis.

Transcriptome Sequencing and Metabolite Analysis for Revealing the Blue Flower Formation in Waterlily

BMC Genomics. Nov, 2016  |  Pubmed ID: 27829354

Waterlily (Nymphaea spp.), a perennial herbaceous aquatic plant, is divided into two ecological groups: hardy waterlily and tropical waterlily. Although the hardy waterlily has no attractive blue flower cultivar, its adaptability is stronger than tropical waterlily because it can survive a cold winter. Thus, breeding hardy waterlily with real blue flowers has become an important target for breeders. Molecular breeding may be a useful way. However, molecular studies on waterlily are limited due to the lack of sequence data.

Altered Effective Connectivity of the Primary Motor Cortex in Stroke: A Resting-State FMRI Study with Granger Causality Analysis

PloS One. 2016  |  Pubmed ID: 27846290

The primary motor cortex (M1) is often abnormally recruited in stroke patients with motor disabilities. However, little is known about the alterations in the causal connectivity of M1 following stroke. The purpose of the present study was to investigate whether the effective connectivity of the ipsilesional M1 is disturbed in stroke patients who show different outcomes in hand motor function. 23 patients with left-hemisphere subcortical stroke were selected and divided into two subgroups: partially paralyzed hands (PPH) and completely paralyzed hands (CPH). Further, 24 matched healthy controls (HCs) were recruited. A voxel-wise Granger causality analysis (GCA) on the resting-state fMRI data between the ipsilesional M1 and the whole brain was performed to explore differences between the three groups. Our results showed that the influence from the frontoparietal cortices to ipsilesional M1 was diminished in both stroke subgroups and the influence from ipsilesional M1 to the sensorimotor cortices decreased greater in the CPH group than in the PPH group. Moreover, compared with the PPH group, the decreased influence from ipsilesional M1 to the contralesional cerebellum and from the contralesional superior parietal lobe to ipsilesional M1 were observed in the CPH group, and their GCA values were positively correlated with the FMA scores; Conversely, the increased influence from ipsilesional M1 to the ipsilesional middle frontal gyrus and middle temporal gyrus were observed, whose GCA values were negatively correlated with the FMA scores. This study suggests that the abnormalities of casual flow in the ipsilesional M1 are related to the severity of stroke-hand dysfunction, providing valuable information to understand the deficits in resting-state effective connectivity of motor execution and the frontoparietal motor control network during brain plasticity following stroke.

Effect of Live Poultry Market Interventions on Influenza A(H7N9) Virus, Guangdong, China

Emerging Infectious Diseases. Dec, 2016  |  Pubmed ID: 27869613

Since March 2013, three waves of human infection with avian influenza A(H7N9) virus have been detected in China. To investigate virus transmission within and across epidemic waves, we used surveillance data and whole-genome analysis of viruses sampled in Guangdong during 2013-2015. We observed a geographic shift of human A(H7N9) infections from the second to the third waves. Live poultry market interventions were undertaken in epicenter cities; however, spatial phylogenetic analysis indicated that the third-wave outbreaks in central Guangdong most likely resulted from local virus persistence rather than introduction from elsewhere. Although the number of clinical cases in humans declined by 35% from the second to the third waves, the genetic diversity of third-wave viruses in Guangdong increased. Our results highlight the epidemic risk to a region reporting comparatively few A(H7N9) cases. Moreover, our results suggest that live-poultry market interventions cannot completely halt A(H7N9) virus persistence and dissemination.

A DNA Dual Lock-and-key Strategy for Cell-subtype-specific SiRNA Delivery

Nature Communications. Nov, 2016  |  Pubmed ID: 27882923

The efficient and precise delivery of siRNA to target cells is critical to successful gene therapy. While novel nanomaterials enhance delivery efficiency, it still remains challenging for precise gene delivery to overcome nonspecific adsorption and off-target effect. Here we design a dual lock-and-key system to perform cell-subtype-specific recognition and siRNA delivery. The siRNA is self-assembled in an oligonucleotide nano vehicle that is modified with a hairpin structure to act as both the 'smart key' and the delivery carrier. The auto-cleavable hairpin structure can be activated on site at target cell membrane by reacting with two aptamers as 'dual locks' sequentially, which leads to cell-subtype discrimination and precise siRNA delivery for high efficient gene silencing. The success of this strategy demonstrates the precise delivery of siRNA to specific target cells by controlling multiple parameters, thus paving the way for application of RNAi in accurate diagnosis and intervention.

PD-1/PD-Ls: A New Target for Regulating the Immunopathogenesis in Central Nervous System Disorders

Current Drug Delivery. Nov, 2016  |  Pubmed ID: 27889994

The central nervous system (CNS) was traditionally thought to tolerate inflammatory responses. However, CNS is not completely immune-privileged in recent researches. These responses including Microglia and macrophage activation and peripheral immune cells infiltration have been founded successively. Thus, the traditional view of the adult brain as an immune-privileged organ has been changed. Increasing evidence indicated that the PD-1(programmed cell death-1)/PD-Ls signal pathway plays an important role in regulating the immunopathogenesis of brain following injury. So we view the relevant knowledge about PD-1/PD-Ls signal pathway, and potential effect with immune cells, cerebral ischemia, brain tumors and Multiple sclerosis. Two electronic databases (PubMed and EMBASE) were used without any limitations. In the review, the cited works mainly focused on basic researches.

Inhibitory Effect of Hesperetin and Naringenin on Human UDP-Glucuronosyltransferase Enzymes: Implications for Herb-Drug Interactions

Biological & Pharmaceutical Bulletin. 2016  |  Pubmed ID: 27904048

Hesperetin (HET) and naringenin (NGR) are flavanones found in citrus (oranges and grapefruit) and Aurantii Fructus Immaturus. The present study aims to investigate the inhibition potential of HET and NGR derivatives towards one of the most important phase II drug-metabolizing enzymes-uridine diphosphate (UDP)-glucuronosyltransferases (UGTs). We used trifluoperazine as a probe substrate to test UGT1A4 activity, and recombinant UGT-catalyzed 4-methylumbelliferone glucuronidation was used as a probe reaction for other UGT isoforms. Data show that HET and NGR displayed broad-spectrum inhibition against human UGTs. Besides, HET exhibited strong inhibitory effects on UGT1A1, 1A3 and 1A9 (both IC50 and Ki values lower than 10 µM), and the inhibitory effects of NGR against three major UGTs, including UGT1A1, 1A3 and 2B7. In a combination of inhibition parameters (Ki) and in vivo concentration of HET and NGR, the potential in vivo inhibition magnitude was predicted. Based on the reported maximum plasma concentration of HET and NGR in vivo, these findings indicate the potential herb-drug interactions (HDI) between HET or NGR and the drugs mainly undergoing UGT1A3 or UGT2B7 catalyzed metabolic elimination. Considering the variety of citrus that contains HET and NGR, so caution should be applied when taking drugs that utilize UGTs for metabolism and clearance with citrus fruits.

Transmission of Multidrug-resistant Mycobacterium Tuberculosis in Shanghai, China: a Retrospective Observational Study Using Whole-genome Sequencing and Epidemiological Investigation

The Lancet. Infectious Diseases. Dec, 2016  |  Pubmed ID: 27919643

Multidrug-resistance is a substantial threat to global elimination of tuberculosis. Understanding transmission patterns is crucial for control of the disease. We used a genomic and epidemiological approach to assess recent transmission of multidrug-resistant (MDR) tuberculosis and identify potential risk factors for transmission.

Prognostic Value of Circulating Tumor Cells in Castration Resistant Prostate Cancer: A Meta-analysis

Urology Journal. 12, 2016  |  Pubmed ID: 27928807

The prognostic value of circulating tumor cells (CTC) detected in castration-resistant prostate cancer(CRPC) is currently under debate. The aim of our meta-analysis was to evaluate the prognostic effect of CTC andto elucidate whether the detection of CTC in the peripheral blood (PB) of patients diagnosed with CRPC can beused as an independent prognostic factor for survival.

Correction: A Binary Catalyst System of a Cationic Ru-CNC Pincer Complex with an Alkali Metal Salt for Selective Hydroboration of Carbon Dioxide

Chemical Communications (Cambridge, England). Dec, 2016  |  Pubmed ID: 27942620

Correction for 'A binary catalyst system of a cationic Ru-CNC pincer complex with an alkali metal salt for selective hydroboration of carbon dioxide' by Chee Koon Ng et al., Chem. Commun., 2016, 52, 11842-11845.

The Preoperative Neutrophil-To-Lymphocyte Ratio Is a Novel Immune Parameter for the Prognosis of Esophageal Basaloid Squamous Cell Carcinoma

PloS One. 2016  |  Pubmed ID: 27959959

The pretreatment neutrophil-to-lymphocyte ratio (NLR) is an independent predictor of prognosis in various malignancies, but its predictive capacity in basaloid squamous cell carcinoma of the esophagus (BSCCE) remains unclear. We aim to determine the value of the inflammation-related factors, including the NLR, neutrophil-to-monocyte ratio (NMR), and albumin levels, in predicting BSCCE prognosis.

Corneal Collagen Cross-linking and Liposomal Amphotericin B Combination Therapy for Fungal Keratitis in Rabbits

International Journal of Ophthalmology. 2016  |  Pubmed ID: 27990355

To observe the therapeutic effect of corneal collagen cross-linking (CXL) in combination with liposomal amphotericin B in fungal corneal ulcers.

Review of Clinical and Basic Approaches of Fungal Keratitis

International Journal of Ophthalmology. 2016  |  Pubmed ID: 27990375

Fungal keratitis (FK) is a serious disease which can cause blindness. This review has current information about the pathogenesis, limitations of traditional diagnosis and therapeutic strategies, immune recognition and the diagnosis and therapy of FK. The information of this summary was reviewed regularly and updated as what we need in the diagnosis and therapy of FK nowadays.

The Pathogenic Spectrum of Fungal Keratitis in Northwestern China

International Journal of Ophthalmology. 2016  |  Pubmed ID: 28003991

A Cluster of Coxsackievirus A21 Associated Acute Respiratory Illness: the Evidence of Efficient Transmission of CVA21

Archives of Virology. Dec, 2016  |  Pubmed ID: 28025712

In March 2016, a cluster of unexplained respiratory illnesses was reported by the acute respiratory infections (ARI) surveillance system of Guangdong Province, China. Twenty-three high school students and one teacher from the four neighboring classes were admitted to a hospital. CVA21 was found in eight of fourteen patients. Phylogenetic analysis suggested that the CVA21 outbreak was most likely caused by transmission of the virus from person to person. This is the first report of an ARI outbreak caused by CVA21, which suggests that CVA21 has the potential to be transmitted efficiently from person to person and should be closely monitored by clinicians and public health agencies.

Knockout of MicroRNA-155 Ameliorates the Th1/Th17 Immune Response and Tissue Injury in Chronic Rejection

The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. Feb, 2017  |  Pubmed ID: 27296836

MicroRNAs (miRNAs) are integral for maintaining immune homeostasis and self-tolerance. The influence of miRNAs on T-cell differentiation and plasticity are critical in the development of chronic rejection of transplanted hearts. In this study, we sought to determine whether the knockout of miR-155 affects the development of cardiac allograft vasculopathy (CAV) in a murine model.

Motor-based Microprobe Powered by Bio-assembled Catalase for Motion Detection of DNA

Biosensors & Bioelectronics. Jan, 2017  |  Pubmed ID: 27517735

A motor-based microprobe is proposed using a tubular microengine powered by bio-assembled enzyme as catalyst and exploited for washing-free detection of DNA through motion readout. The microprobe is fabricated by assembling a catalase layer on the inner surface of poly(3,4-ethylenedioxythiophene)/Au (PEDOT/Au) microtube through DNA conjugate, which is responsible for the biocatalytic bubble propulsion. The sensing concept of the microprobe relies on the target-induced release of catalase through the DNA strand-replacement hybridization, which decreases the amount of enzyme assembled on microtube to slow down the movement of the microprobe. Therefore, the motion speed is negatively correlated with the target concentration. At the optimal conditions, the microprobe can conveniently distinguish the concentration of specific DNA in a range of 0.5-10µM without any washing and separation step. This microprobe can be prepared in batch with good reproducibility and stability, and its motion speed can be conveniently visualized by optical microscope. The proposed motor-based microprobe and its dynamic sensing method provide a novel platform for the development of intelligent microprobe and clinical diagnostic strategy.

Effect of Se Treatment on the Volatile Compounds in Broccoli

Food Chemistry. Feb, 2017  |  Pubmed ID: 27596413

Broccoli contains high levels of bioactive compounds but deteriorates and senesces easily. In the present study, freshly harvested broccoli was treated with selenite and stored at two different temperatures. The effect of selenite treatment on sensory quality and postharvest physiology were analyzed. Volatile components were assessed by HS-SPME combined with GC-MS and EN. The metabolism of Se and S was also examined. Results indicated that Se treatment had a significant effect on maintaining the sensory quality, suppressing the respiration intensity and ethylene production, as well as increasing the content of Se and decreasing the content of S. In particular, significant differences in the composition of volatile compounds were present between control and Se-treated. The differences were mainly due to differences in alcohols and sulfide compounds. These results demonstrate that Se treatment can have a positive effect on maintaining quality and enhancing its sensory quality through the release of volatile compounds.

Removal of Artificial Sweetener Aspartame from Aqueous Media by Electrochemical Advanced Oxidation Processes

Chemosphere. Jan, 2017  |  Pubmed ID: 27728881

The degradation and mineralization of aspartame (ASP) in aqueous solution were investigated, for the first time, by electrochemical advanced oxidation processes (EAOPs) in which hydroxyl radicals were formed concomitantly in the bulk from Fenton reaction via in situ electrogenerated Fenton's reagent and at the anode surface from the water oxidation. Experiments were performed in an undivided cylindrical glass cell with a carbon-felt cathode and a Pt or boron-doped diamond (BDD) anode. The effect of Fe(2+) concentration and applied current on the degradation and mineralization kinetics of ASP was evaluated. The absolute rate constant for the reaction between ASP and OH was determined as (5.23 ± 0.02) × 10(9) M(-1) s(-1) by using the competition kinetic method. Almost complete mineralization of ASP was achieved with BDD anode at 200 mA constant current electrolysis. The formation and generation of the formed carboxylic acids (as ultimate end products before complete mineralization) and released inorganic ion were monitored by ion-exclusion high performance liquid chromatography (HPLC) and ion chromatography techniques, respectively. The global toxicity of the treated ASP solution during treatment was assessed by the Microtox(®) method using V. fischeri bacteria luminescence inhibition.

Design, Synthesis and Biological Evaluation of Bambuterol Analogues As Novel Inhibitors of Butyrylcholinesterase

European Journal of Medicinal Chemistry. Jan, 2017  |  Pubmed ID: 27744187

An increase activity of butyrylcholinesterase is believed to contribute to Alzheimer's disease. Bambuterol is a known potent inhibitor of butyrylcholinesterase, but it has undesired cardiac effects and less lipophilicity. Thirteen bambuterol analogues were synthesized using 1-(3, 5-dihydroxyphenyl) ethanone as a starting material. In-vitro cholinesterase assay established that the majority of the compounds are specific butyrylcholinesterase inhibitors. Out of the 13 compounds, two bambuterol derivatives, BD-6 and BD-11 exhibited similar efficacies in inhibiting butyrylcholinesterase with fewer effects on heart and enhanced possibilities of permeating through the blood-brain barrier as compared to bambuterol. These bambuterol analogues may provide better alternatives for treatments of Alzheimer's disease.

Highly Selective and Sensitive Detection of Nitroaromatic Compounds and Metal Ions by Supramolecular Assemblies of 3,3',5,5'-Azobenzenetetracarboxylic Acid and 4,4'-Bipyridine

Journal of Fluorescence. Jan, 2017  |  Pubmed ID: 27785650

A supramolecular compound, (H4L)(4,4'-bpy)2 (1) (H4L = 1,2-bis(3,5-dicarboxyphenyl)diazene oxide, 4,4'-bpy = 4,4'-bipyridine) with 2D + 2D → 2D 3-fold parallel interpenetrated layer feature, has been prepared which was investigated as selective sensing material for detection of nitroaromatic compounds (NACs) and metal ions, and exhibits significant fluorescence quenching toward NACs and high selectivity for detection of Fe(3+) ion. The result indicates that 1 is a promising multi-functional fluorescence probe for detecting and recognizing NACs and metal ions with high sensitivity and selectivity.

Enhanced Antibacterial and Wound Healing Activities of Microporous Chitosan-Ag/ZnO Composite Dressing

Carbohydrate Polymers. Jan, 2017  |  Pubmed ID: 27842847

Nano Ag/ZnO hybrid material has been considered to be a promising nanocomposites for biomedical application because it has enhanced antibacterial activity and low cytotoxicity. Here a sponge-like nano Ag/ZnO-loaded chitosan composite dressing was first synthesized via preparing a chitosan sponge by lyophilization process, followed by the incorporation of Ag/ZnO nanocomposites into chitosan sponge. The porosity, swelling, blood clotting and in vitro antibacterial activity against drug-sensitive and drug-resistant pathogenic bacteria were evaluated. The results demonstrate that the prepared composite dressing shows high porosity and swelling as well as enhanced blood clotting and antibacterial activity. Cytocompatibility test evaluated in vitro illustrates the very low toxic nature of the composite dressing. Furthermore, the in vivo evaluation in mice reveals that the chitosan-Ag/ZnO composite dressing enhances the wound healing and promotes re-epithelialization and collagen deposition. These results strongly support the possibility of using this novel chitosan-AgZnO composite dressing for wound care application.

Vicinal Difluoroalkylation and Aminosulfonylation of Alkynes Under Photoinduced Conditions

Chemistry (Weinheim an Der Bergstrasse, Germany). Jan, 2017  |  Pubmed ID: 27900780

A photoinduced vicinal difluoroalkylation and aminosulfonylation of alkynes under photocatalysis was realized. The combination of ethyl 2-bromo-2,2-difluoroacetate, alkynes, and DABCO⋅(SO2 )2 with hydrazines, catalyzed by 9-mes-10-methyl acridinium perchlorate in the presence of visible light, afforded (E)-ethyl 2,2-difluoro-4-aryl-4-sulfamoylbut-3-enoates in good yields with high stereoselectivity. This four-component reaction proceeds through radical addition with the insertion of sulfur dioxide.

The First Example of Palladium-catalyzed Cascade Amidine Arylation-intramolecular Ester Amidation for the Synthesis of Hypoxanthines: Application to the Synthesis of 8-azanebularine Analogues

Organic & Biomolecular Chemistry. Jan, 2017  |  Pubmed ID: 27910976

8-Azanebularine analogues display interesting antiviral, antitumour and biochemical activities. However, typical glycosylation of 8-azapurines always resulted in the desired products in low yields due to the lack of stereo- and regioselectivity of the glycosylation reaction. Herein, a concise synthetic route toward 8-azanebularine analogues has been developed. Key steps involve a copper-catalyzed 1,3-dipolar cycloaddition of a 1-β-azido sugar moiety with ethyl 3-bromopropiolate and a palladium-catalyzed cascade amidine arylation-intramolecular ester amidation reaction to build the hypoxanthine structural motif. This protocol affords a facile methodology for the synthesis of a series of novel 8-azanebularine analogues from the readily accessible 1-β-azido sugar moiety under mild conditions.

Targeted Myocardial Delivery of GDF11 Gene Rejuvenates the Aged Mouse Heart and Enhances Myocardial Regeneration After Ischemia-reperfusion Injury

Basic Research in Cardiology. Jan, 2017  |  Pubmed ID: 28004242

Ischemic cardiac injury is the main contributor to heart failure, and the regenerative capacity of intrinsic stem cells plays an important role in tissue repair after injury. However, stem cells in aged individuals have reduced regenerative potential and aged tissues lack the capacity to renew. Growth differentiation factor 11 (GDF11), from the activin-transforming growth factor β superfamily, has been shown to promote stem cell activity and rejuvenation. We carried out non-invasive targeted delivery of the GDF11 gene to the heart using ultrasound-targeted microbubble destruction (UTMD) and cationic microbubble (CMB) to investigate the ability of GDF11 to rejuvenate the aged heart and improve tissue regeneration after injury. Young (3 months) and old (21 months) mice were used to evaluate the expression of GDF11 mRNA in the myocardium at baseline and after ischemia/reperfusion (I/R) and myocardial infarction. GDF11 expression decreased with age and following myocardial injury. UTMD-mediated delivery of the GDF11 plasmid to the aged heart after I/R injury effectively and selectively increased GDF11 expression in the heart, and improved cardiac function and reduced infarct size. Over-expression of GDF11 decreased senescence markers, p16 and p53, as well as the number of p16(+) cells in old mouse hearts. Furthermore, increased proliferation of cardiac stem cell antigen 1 (Sca-1(+)) cells and increased homing of endothelial progenitor cells and angiogenesis in old ischemic hearts occurred after GDF11 over-expression. Repetitive targeted delivery of the GDF11 gene via UTMD can rejuvenate the aged mouse heart and protect it from I/R injury.

Synergistic Antibacterial Effect of Bi2S3 Nanospheres Combined with Ineffective Antibiotic Gentamicin Against Methicillin-resistant Staphylococcus Aureus

Journal of Inorganic Biochemistry. Mar, 2017  |  Pubmed ID: 28011210

In this paper, Bi2S3 nanospheres with size of 212nm were prepared by a simple hydrothermal process. The selectively enhanced antibacterial effects of Bi2S3 nanospheres with three classes of ineffective antibiotics, β-lactam (cefuroxime, CXM; cefotaxime, CTX and piperacillin, PIP), quinolone (ciprofloxacin, CIP) and aminoglycoside (gentamicin, GEN) against clinical isolated methicillin-resistant Staphylococcus aureus (MRSA) were investigated for the first time. GEN shows significantly synergistic growth inhibition against MRSA when combined with Bi2S3 nanospheres, while CXM, CTX, PIP and CIP do not. Raman spectroscopy and Z potential studies reveal that Bi2S3 could interact with GEN and the combination showed small electronegativity, which probably induced the increase of GEN content in cytoplasm of bacteria. Furthermore, the combination of Bi2S3 nanospheres and GEN can destroy the bacterial membrane function and induce more bactericidal reactive oxygen generation than that of Bi2S3 or GEN alone. The cytotoxicity test indicates that the combination of Bi2S3 and GEN presented low toxicity to human normal hepatocyte L02. This work shows that Bi2S3 nanospheres can be used to enhance the action of ineffective antibiotic GEN against MRSA, thus strengthening the antibiotic capacity for fighting MRSA infections.

Traditional Chinese Medicine Jianpi Bushen Therapy Suppresses the Onset of Pre-metastatic Niche in a Murine Model of Spontaneous Lung Metastasis

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie. Feb, 2017  |  Pubmed ID: 28012398

Distinct metastasis accounts for the leading cause of mortality among patients with gastric cancer. The formation of pre-metastatic niche in the target organs provides permissive environments for the adhesion and subsequent growth of metastasized cancer cells. Targeting the pre-metastatic niche is a potential approach to prevent metastasis. Traditional Chinese medicine regimen called Jianpi Bushen therapy (JPBS) has been widely used in clinics to strengthen patients' abilities to fight cancer. The present work is aimed to study the modulating effect of JPBS on the lungs expressions of Rac1, Cdc42, SDF-1, and FN in a murine gastric cancer model showing spontaneous lung metastasis.

One-step Preparation of Magnetic Recyclable Quinary Graphene Hydrogels with High Catalytic Activity

Journal of Colloid and Interface Science. Apr, 2017  |  Pubmed ID: 28012915

Metal nanoparticles (NPs) displayed overwhelming superiority in catalysis towards the corresponding bulk-phase materials; nevertheless, how to further improve catalytic activity was still an ongoing subject. Herein, we have combined one-step redox reaction and following freeze-dried technology to construct the quinary reduced graphene oxide nanosheets (rGS)/Fe2O3-PdPt/polypyrrole (PPy) hydrogels. Compared with traditional catalysts, their catalytic property was improved via two ways: construction of three-dimensional (3D) rGS hydrogels instead of two-dimensional rGS and synthesis of bimetallic alloys instead of monometallic NPs. The highly dispersed PdPt with diameter as small as 3.2nm uniformly loaded on hydrogel surface. Due to special interconnected and porous structure, the reactants were easily adsorbed in hydrogels and contacted with PdPt alloys. To explain the contributions of bimetallic alloys and 3D rGS structure on enhanced catalytic activity, the catalytic property of quinary hydrogels was compared with reference samples. Besides superior activity, they also displayed good reusability, since hydrogels could be magnetically recycled owing to the existence of Fe2O3 NPs.

Antibacterial Activity and Mechanism of Ag/ZnO Nanocomposite Against Anaerobic Oral Pathogen Streptococcus Mutans

Journal of Materials Science. Materials in Medicine. Jan, 2017  |  Pubmed ID: 28044252

Dental caries is a widespread disease mainly caused by the anaerobic oral pathogen Streptococcus mutans (S. mutans). Ag/ZnO nanocomposite is an efficient antibacterial agent because of its high antibacterial activity and low cytotoxicity. In this study, rod-like Ag/ZnO nanocomposite was synthesized through a deposition-precipitation method and characterized by X-ray diffraction, scanning electron microscopy and transmission electron microscopy. The activity of Ag/ZnO nanocomposite against S. mutans was evaluated by determining the minimal inhibitory concentration, minimum bactericidal concentration and growth inhibition curve. The results showed that Ag/ZnO nanocomposite displayed higher activity against S. mutans compared with pure ZnO nanorods. Moreover, the antibacterial mechanism was investigated by determining the bacterial membrane potential, release of K(+), intracellular reactive oxygen generation and lipid peroxidation. Disruption of membrane function and oxidation of biomacromolecules played important role in the antibacterial action of Ag/ZnO nanocomposite. This work proposes a potentially effective dental antibacterial agent against the dental caries-causing S. mutans.

Synthesis of β-Keto Sulfones by a Catalyst-Free Reaction of Aryldiazonium Tetrafluoroborates, Sulfur Dioxide, and Silyl Enol Ethers

Chemistry, an Asian Journal. Jan, 2017  |  Pubmed ID: 28052596

A green approach for the generation of β-keto sulfones through a reaction of aryldiazonium tetrafluoroborates and sulfur dioxide with silyl enol ether under catalyst- and additive-free conditions has been realized. This reaction proceeds efficiently at room temperature and goes to completion in half an hour. During the reaction process, aryldiazonium tetrafluoroborate is treated with DABCO⋅(SO2 )2 (DABCO=1,4-diazabicyclo[2.2.2]octane) to provide a sulfonyl radical as the key intermediate, which then initiates the transformation. Oxidants or metal catalysts are avoided, and the presence of DABCO also plays an important role in the reaction.

Urinary Mitochondrial DNA Levels Identify Acute Kidney Injury in Surgical Critical Illness Patients

Shock (Augusta, Ga.). Jan, 2017  |  Pubmed ID: 28060212

Recent studies showed that mitochondrial injury and mitochondrial DNA (mtDNA) damage are associated with the initiation and progression of acute kidney injury (AKI). However, practical limitations of existing assays of mitochondrial function have limited our ability to study the link between mitochondrial dysfunction and renal injury. Therefore, we evaluated urinary mtDNA (UmtDNA) as a biomarker of AKI in critical illness patients.

Brain Cannabinoid Receptor 2: Expression, Function and Modulation

Acta Pharmacologica Sinica. Jan, 2017  |  Pubmed ID: 28065934

Cannabis sativa (marijuana) is a fibrous flowering plant that produces an abundant variety of molecules, some with psychoactive effects. At least 4% of the world's adult population uses cannabis annually, making it one of the most frequently used illicit drugs in the world. The psychoactive effects of cannabis are mediated primarily through cannabinoid receptor (CBR) subtypes. The prevailing view is that CB1Rs are mainly expressed in the central neurons, whereas CB2Rs are predominantly expressed in peripheral immune cells. However, this traditional view has been challenged by emerging strong evidence that shows CB2Rs are moderately expressed and function in specific brain areas. New evidence has demonstrated that brain CB2Rs modulate animal drug-seeking behaviors, suggesting that these receptors may exist in brain regions that regulate drug addiction. Recently, we further confirmed that functional CB2Rs are expressed in mouse ventral tegmental area (VTA) dopamine (DA) neurons and that the activation of VTA CB2Rs reduces neuronal excitability and cocaine-seeking behavior. In addition, CB2R-mediated modulation of hippocampal CA3 neuronal excitability and network synchronization has been reported. Here, we briefly summarize recent lines of evidence showing how CB2Rs modulate function and pathophysiology in the CNS.

Bacterial Genome Editing Via a Designed Toxin-Antitoxin Cassette

ACS Synthetic Biology. Jan, 2017  |  Pubmed ID: 28094982

Manipulating the bacterial genomes in an efficient manner is essential to biological and biotechnological research. Here, we reprogrammed the bacterial TA systems as the toxin counter-selectable cassette regulated by an antitoxin switch (TCCRAS) for genetic modifications in the extensively studied and utilized Gram-positive bacteria, B. subtilis and Corynebacterium glutamicum. In the five characterized type II TA systems, the RelBE complex can specifically and efficiently regulate cell growth and death by the conditionally controlled antitoxin RelB switch, thereby serving as a novel counter-selectable cassette to establish the TCCRAS system. Using a single vector, such a system has been employed to perform in-frame deletion, functional knock-in, gene replacement, precise point mutation, large-scale insertion, and especially, deletion of the fragments up to 194.9 kb in B. subtilis. In addition, the biosynthesis of lycopene was first achieved in B. subtilis using TCCRAS to integrate a 5.4-kb fusion cluster (Pspac-crtI-crtE-crtB). The system was further adapted for gene knockdown and replacement, and large-scale deletion of the fragments up to 179.8 kb in C. glutamicum, with the mutation efficiencies increased by 0.8-1.0-fold compared to the conventional SacB method. TCCRAS thus holds promise as an effective and versatile genome-scale engineering technology for metabolic engineering and synthetic genomics research in a broad range of the Gram-positive bacteria.

Gigantol from Dendrobium Chrysotoxum Lindl. Binds and Inhibits Aldose Reductase Gene to Exert Its Anti-cataract Activity: an in Vitro Mechanistic Study

Journal of Ethnopharmacology. Jan, 2017  |  Pubmed ID: 28104409

Dendrobium. chrysotoxum Lindl is a commonly used species of medicinal Dendrobium which belongs to the family of Orchidaceae, locally known as "Shihu" or "Huangcao". D. chrysotoxum Lindl is widely known for medicinal values in traditional Chinese medicine as it possesses anti-inflammatory, anti-hyperglycemic induction, antitumor and antioxidant properties.

Human Infection with an Avian Influenza A/H9N2 Virus in Guangdong in 2016

The Journal of Infection. Jan, 2017  |  Pubmed ID: 28109675

Identification of CD4(+) T-cell-derived CD161(+) CD39(+) and CD39(+)CD73(+) Microparticles As New Biomarkers for Rheumatoid Arthritis

Biomarkers in Medicine. Feb, 2017  |  Pubmed ID: 28111965

This study aimed to identify CD4(+) T-cell-derived microparticles (MPs) and investigate their roles in rheumatoid arthritis (RA).

A Novel Role for Transcription-coupled Nucleotide Excision Repair for the in Vivo Repair of 3,N4-ethenocytosine

Nucleic Acids Research. Jan, 2017  |  Pubmed ID: 28115629

Etheno (ε) DNA base adducts are highly mutagenic lesions produced endogenously via reactions with lipid peroxidation (LPO) products. Cancer-promoting conditions, such as inflammation, can induce persistent oxidative stress and increased LPO, resulting in the accumulation of ε-adducts in different tissues. Using a recently described fluorescence multiplexed host cell reactivation assay, we show that a plasmid reporter bearing a site-specific 3,N(4)-ethenocytosine (εC) causes transcriptional blockage. Notably, this blockage is exacerbated in Cockayne Syndrome and xeroderma pigmentosum patient-derived lymphoblastoid and fibroblast cells. Parallel RNA-Seq expression analysis of the plasmid reporter identifies novel transcriptional mutagenesis properties of εC. Our studies reveal that beyond the known pathways, such as base excision repair, the process of transcription-coupled nucleotide excision repair plays a role in the removal of εC from the genome, and thus in the protection of cells and tissues from collateral damage induced by inflammatory responses.

Electroacupuncture Regulates Hippocampal Synaptic Plasticity Via MiR-134-Mediated LIMK1 Function in Rats with Ischemic Stroke

Neural Plasticity. 2017  |  Pubmed ID: 28116173

MircoRNAs (miRs) have been implicated in learning and memory, by regulating LIM domain kinase (LIMK1) to induce synaptic-dendritic plasticity. The study aimed to investigate whether miRNAs/LIMK1 signaling was involved in electroacupuncture- (EA-) mediated synaptic-dendritic plasticity in a rat model of middle cerebral artery occlusion induced cognitive deficit (MICD). Compared to untreatment or non-acupoint-EA treatment, EA at DU20 and DU24 acupoints could shorten escape latency and increase the frequency of crossing platform in Morris water maze test. T2-weighted imaging showed that the MICD rat brain lesions were located in cortex, hippocampus, corpus striatum, and thalamus regions and injured volumes were reduced after EA. Furthermore, we found that the density of dendritic spine and the number of synapses in the hippocampal CA1 pyramidal cells were obviously reduced at Day 14 after MICD. However, synaptic-dendritic loss could be rescued after EA. Moreover, the synaptic-dendritic plasticity was associated with increases of the total LIMK1 and phospho-LIMK1 levels in hippocampal CA1 region, wherein EA decreased the expression of miR-134, negatively regulating LIMK1 to enhance synaptic-dendritic plasticity. Therefore, miR-134-mediated LIMK1 was involved in EA-induced hippocampal synaptic plasticity, which served as a contributor to improving learning and memory during the recovery stage of ischemic stroke.

Germacrone Derivatives: Synthesis, Biological Activity, Molecular Docking Studies and Molecular Dynamics Simulations

Oncotarget. Jan, 2017  |  Pubmed ID: 28148897

Germacrone is one of the major bioactive components in the Curcuma zedoaria oil product, which is extracted from Curcuma zedoaria Roscoe, known as zedoary. The present study designed some novel germacrone derivatives based on combination principles, synthesized these compounds, and investigated their inhibitions on Bel-7402, HepG2, A549 and HeLa cells. Meanwhile, the study evaluated inhibitions of these derivatives on c-Met kinase, which has been detected in a number of cancers. The results suggested that the majority of the compounds showed stronger inhibitory effect on cancers and c-Met kinase than germacrone. Furthermore, our docking experiments analyzed the results and explained the molecular mechanism. Molecular dynamics simulations were then applied to perform further evaluation of the binding stabilities between compounds and their receptors.

Ex-PRESS Implantation with Phacoemulsification in POAG Versus CPACG

International Journal of Ophthalmology. 2017  |  Pubmed ID: 28149776

To compare the long-term outcomes of the Ex-PRESS miniature glaucoma device implanted under a scleral flap in combination of phacoemulsification with intraocular lens implantation in primary open angle glaucoma (POAG) and chronic primary angle-closure glaucoma (CPACG).

Interleukin-17A Promotes Esophageal Adenocarcinoma Cell Invasiveness Through ROS-dependent, NF-κB-mediated MMP-2/9 Activation

Oncology Reports. Mar, 2017  |  Pubmed ID: 28184939

Interleukin-17A (IL-17A), a pro-inflammatory cytokine secreted primarily by Th17 cells, has been proved to be involved in the microenvironment of certain inflammation-related tumors. However, the role of IL-17A in cancer development has always been controversial. In this study, we investigated the effect of IL-17A on the regulation of esophageal adenocarcinoma (EAC) cell invasiveness and related molecular mechanism. Surface IL-17 receptor (IL-17R) expression on human EAC cell line OE19 was examined using flow cytometry. The effect of IL-17A on cell proliferation was measured by MTT assay. Cell migration and invasive ability in vitro were assessed by wound-healing and Matrigel-coated Transwell invasion assay. Intracellular reactive oxygen species (ROS) levels were determined by flow cytometry and fluorescence microscope. The protein expression levels of MMP-2, MMP-9, NF-κB and p-IκB-α were detected by western blotting. Our results showed that IL-17A promoted migration and invasion of OE19 cells in a dose-dependent manner, however it had less effect on OE19 cell proliferation. Furthermore, IL-17A treatment significantly upregulated the expression of MMP-2 and MMP-9, stimulated intracellular ROS production, increased IκB-α phosphorylation and NF-κB nuclear translocation. Nevertheless, IL-17A-induced expression of MMP-2/9 and OE19 cell invasiveness were both inhibited by pretreatment with N-acetyl-L-cysteine (NAC, a ROS scavenger) or pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor). In conclusion, these findings demonstrate that IL-17A can promote the migration and invasiveness of EAC cells through ROS/NF-κB/MMP-2/9 signaling pathway activation, indicating that IL-17A may be a potential therapeutic target for EAC.

Waiting
simple hit counter