Studies on Anti-Hepatoma Effect of Gan-Ai-Xiao Decoction

Purpose: To explore the anti-hepatoma effect of Gan-Ai-Xiao Decoction (GAXD), a folk remedy.Methods: High performance liquid chromatography (HPLC) was used to identify the major chemical components of GAXD ethanol extract (EE). The cytotoxic effect of GAXD EE against HepG2 cells was measured by methyl thiazolyl tetrazolium (MTT) assay. Flow cytometry and Western blot were used to study the effect of GAXD EE on apoptosis and apoptotic proteins (Bcl-2, Bax and caspase-3) in HepG2 cells. Xenograft assay was used to evaluate the anti-hepatoma effect of GAXD EE in vivo.Results: Four components were identified in GAXD EE by HPLC. The results of MTT and flow cytometry assays indicated that GAXD EE significantly reduced HepG2 cells viability (p < 0.05) and induced its apoptosis. The results of Western blot assay suggested that GAXD EE down-regulated the expression of anti-apoptotic protein (Bcl-2) and up-regulated the expression of pro-apoptotic proteins (Bax and caspase-3) in HepG2 cells. Furthermore, the results of xenograft assay showed that GAXD EE significantly inhibited the growth of HepG2 cells-induced tumor (p < 0.05) without any effect on the body weight of nude mice.Conclusion: GAXD has anti-hepatoma activity, and the mechanism is associated with apoptosis.Keywords: Gan-Ai-Xiao Decoction, Anti-hepatoma, Flow Cytometry, Western Blot, Xenograft, HepG2 cells, Apoptosi

Sampling constrained probability distributions using Spherical Augmentation

Statistical models with constrained probability distributions are abundant in machine learning. Some examples include regression models with norm constraints (e.g., Lasso), probit, many copula models, and latent Dirichlet allocation (LDA). Bayesian inference involving probability distributions confined to constrained domains could be quite challenging for commonly used sampling algorithms. In this paper, we propose a novel augmentation technique that handles a wide range of constraints by mapping the constrained domain to a sphere in the augmented space. By moving freely on the surface of this sphere, sampling algorithms handle constraints implicitly and generate proposals that remain within boundaries when mapped back to the original space. Our proposed method, called {Spherical Augmentation}, provides a mathematically natural and computationally efficient framework for sampling from constrained probability distributions. We show the advantages of our method over state-of-the-art sampling algorithms, such as exact Hamiltonian Monte Carlo, using several examples including truncated Gaussian distributions, Bayesian Lasso, Bayesian bridge regression, reconstruction of quantized stationary Gaussian process, and LDA for topic modeling.Comment: 41 pages, 13 figure

The gap in injury mortality rates between urban and rural residents of Hubei province, China

<p>Abstract</p> <p>Background</p> <p>Injury is a growing public health concern in China. Injury death rates are often higher in rural areas than in urban areas in general. The objective of this study is to compare the injury mortality rates in urban and rural residents in Hubei Province in central China by age, sex and mechanism of injury.</p> <p>Methods</p> <p>Using data from the Disease Surveillance Points (DSP) system maintained by the Hubei Province Centers for Disease Control and Prevention (CDC) from 2006 to 2008, injury deaths were classified according to the International Classification of Disease-10^thRevision (ICD-10). Crude and age-adjusted annual mortality rates were calculated for rural and urban residents of Hubei Province.</p> <p>Results</p> <p>The crude and age-adjusted injury death rates were significantly higher for rural residents than for urban residents (crude rate ratio 1.9, 95% confidence interval 1.8-2.0; adjusted rate ratio 2.4, 95% confidence interval 2.3-2.4). The age-adjusted injury death rate for males was 81.6/100,000 in rural areas compared with 37.0/100 000 in urban areas; for females, the respective rates were 57.9/100,000 and 22.4/100 000. Death rates for suicide (32.4 per 100 000 vs 3.9 per 100 000), traffic-related injuries (15.8 per 100 000 vs 9.5 per 100 000), drowning (6.9 per 100 000 vs 2.3 per 100 000) and crushing injuries (2.0 per 100 000 vs 0.7 per 100 000) were significantly higher in rural areas. Overall injury death rates were much higher in persons over 65 years, with significantly higher rates in rural residents compared with urban residents for suicide (279.8 per 100 000 vs 10.7 per 100 000), traffic-related injuries, and drownings in this age group. Death rates for falls, poisoning, and suffocation were similar in the two geographic groups.</p> <p>Conclusions</p> <p>Rates of suicide, traffic-related injury deaths and drownings are demonstrably higher in rural compared with urban locations and should be targeted for injury prevention activity. There is a need for injury prevention policies targeted at elderly residents, especially with regard to suicide prevention in rural areas in Central China.</p

Disparities and risks of sexually transmissible infections among men who have sex with men in China: a meta-analysis and data synthesis.

BACKGROUND: Sexually transmitted infections (STIs), including Hepatitis B and C virus, are emerging public health risks in China, especially among men who have sex with men (MSM). This study aims to assess the magnitude and risks of STIs among Chinese MSM. METHODS: Chinese and English peer-reviewed articles were searched in five electronic databases from January 2000 to February 2013. Pooled prevalence estimates for each STI infection were calculated using meta-analysis. Infection risks of STIs in MSM, HIV-positive MSM and male sex workers (MSW) were obtained. This review followed the PRISMA guidelines and was registered in PROSPERO. RESULTS: Eighty-eight articles (11 in English and 77 in Chinese) investigating 35,203 MSM in 28 provinces were included in this review. The prevalence levels of STIs among MSM were 6.3% (95% CI: 3.5-11.0%) for chlamydia, 1.5% (0.7-2.9%) for genital wart, 1.9% (1.3-2.7%) for gonorrhoea, 8.9% (7.8-10.2%) for hepatitis B (HBV), 1.2% (1.0-1.6%) for hepatitis C (HCV), 66.3% (57.4-74.1%) for human papillomavirus (HPV), 10.6% (6.2-17.6%) for herpes simplex virus (HSV-2) and 4.3% (3.2-5.8%) for Ureaplasma urealyticum. HIV-positive MSM have consistently higher odds of all these infections than the broader MSM population. As a subgroup of MSM, MSW were 2.5 (1.4-4.7), 5.7 (2.7-12.3), and 2.2 (1.4-3.7) times more likely to be infected with chlamydia, gonorrhoea and HCV than the broader MSM population, respectively. CONCLUSION: Prevalence levels of STIs among MSW were significantly higher than the broader MSM population. Co-infection of HIV and STIs were prevalent among Chinese MSM. Integration of HIV and STIs healthcare and surveillance systems is essential in providing effective HIV/STIs preventive measures and treatments. TRIAL REGISTRATION: PROSPERO NO: CRD42013003721

Computational Models for Prediction of Yeast Strain Potential for Winemaking from Phenotypic Profiles

Saccharomyces cerevisiae strains from diverse natural habitats harbour a vast amount of phenotypic diversity, driven by interactions between yeast and the respective environment. In grape juice fermentations, strains are exposed to a wide array of biotic and abiotic stressors, which may lead to strain selection and generate naturally arising strain diversity. Certain phenotypes are of particular interest for the winemaking industry and could be identified by screening of large number of different strains. The objective of the present work was to use data mining approaches to identify those phenotypic tests that are most useful to predict a strain's potential for winemaking. We have constituted a S. cerevisiae collection comprising 172 strains of worldwide geographical origins or technological applications. Their phenotype was screened by considering 30 physiological traits that are important from an oenological point of view. Growth in the presence of potassium bisulphite, growth at 40 degrees C, and resistance to ethanol were mostly contributing to strain variability, as shown by the principal component analysis. In the hierarchical clustering of phenotypic profiles the strains isolated from the same wines and vineyards were scattered throughout all clusters, whereas commercial winemaking strains tended to co-cluster. Mann-Whitney test revealed significant associations between phenotypic results and strain's technological application or origin. Naive Bayesian classifier identified 3 of the 30 phenotypic tests of growth in iprodion (0.05 mg/mL), cycloheximide (0.1 mu g/mL) and potassium bisulphite (150 mg/mL) that provided most information for the assignment of a strain to the group of commercial strains. The probability of a strain to be assigned to this group was 27% using the entire phenotypic profile and increased to 95%, when only results from the three tests were considered. Results show the usefulness of computational approaches to simplify strain selection procedures.Ines Mendes and Ricardo Franco-Duarte are recipients of a fellowship from the Portuguese Science Foundation, FCT (SFRH/BD/74798/2010, SFRH/BD/48591/2008, respectively) and Joao Drumonde-Neves is recipient of a fellowship from the Azores government (M3.1.2/F/006/2008 (DRCT)). Financial support was obtained from FEDER funds through the program COMPETE and by national funds through FCT by the projects FCOMP-01-0124-008775 (PTDC/AGR-ALI/103392/2008) and PTDC/AGR-ALI/121062/2010. Lan Umek and Blaz Zupan acknowledge financial support from Slovene Research Agency (P2-0209). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

Strong enhancement of phonon scattering through nanoscale grains in lead sulfide thermoelectrics

We present nanocrystalline PbS, which was prepared using a solvothermal method followed by spark plasma sintering, as a promising thermoelectric material. The effects of grains with different length scales on phonon scattering of PbS samples, and therefore on the thermal conductivity of these samples, were studied using transmission electron microscopy and theoretical calculations. We found that a high density of nanoscale grain boundaries dramatically lowered the thermal conductivity by effectively scattering long-wavelength phonons. The thermal conductivity at room temperature was reduced from 2.5 W m1K 1 for ingot-PbS (grain size 4200 lm) to 2.3 W m1K 1 for micro-PbS (grain size 40.4 lm); remarkably, thermal conductivity was reduced to 0.85 W m1 K 1 for nano-PbS (grain size B30 nm). Considering the full phonon spectrum of the material, a theoretical model based on a combination of first-principles calculations and semiempirical phonon scattering rates was proposed to explain this effective enhancement. The results show that the high density of nanoscale grains could cause effective phonon scattering of almost 61%. These findings shed light on developing high-performance thermoelectrics via nanograins at the intermediate temperature range.This contribution was supported primarily by the startup of the South University of Science and Technology of China, supported by the Shenzhen government, and the national 1000 plan for young scientists. This work was also partially supported by a grant-in-aid of ‘985 Project’ from Xi’an Jiaotong University, the National Natural Science Foundation of China (Grant No. 21201138 and 11204228), the National Basic Research Program of China (2012CB619402 and 2014CB644003) and the Fundamental Research Funds for the Central UniversitiesS

Human Hepatitis B Virus Production in Avian Cells Is Characterized by Enhanced RNA Splicing and the Presence of Capsids Containing Shortened Genomes

Experimental studies on hepatitis B virus (HBV) replication are commonly done with human hepatoma cells to reflect the natural species and tissue tropism of the virus. However, HBV can also replicate, upon transfection of virus coding plasmids, in cells of other species. In such cross-species transfection experiments with chicken LMH hepatoma cells, we previously observed the formation of HBV genomes with aberrant electrophoretic mobility, in addition to the those DNA species commonly seen in human HepG2 hepatoma cells. Here, we report that these aberrant DNA forms are mainly due to excessive splicing of HBV pregenomic RNA and the abundant synthesis of spliced DNA products, equivalent to those also made in human cells, yet at much lower level. Mutation of the common splice acceptor site abolished splicing and in turn enhanced production of DNA from full-length pgRNA in transfected LMH cells. The absence of splicing made other DNA molecules visible, that were shortened due to the lack of sequences in the core protein coding region. Furthermore, there was nearly full-length DNA in the cytoplasm of LMH cells that was not protected in viral capsids. Remarkably, we have previously observed similar shortened genomes and non-protected viral DNA in human HepG2 cells, yet exclusively in the nucleus where uncoating and final release of viral genomes occurs. Hence, two effects reflecting capsid disassembly in the nucleus in human HepG2 cells are seen in the cytoplasm of chicken LMH cells

Serine Phosphoacceptor Sites within the Core Protein of Hepatitis B Virus Contribute to Genome Replication Pleiotropically

The core protein of hepatitis B virus can be phosphorylated at serines 155, 162, and 170. The contribution of these serine residues to DNA synthesis was investigated. Core protein mutants were generated in which each serine was replaced with either alanine or aspartate. Aspartates can mimic constitutively phosphorylated serines while alanines can mimic constitutively dephosphorylated serines. The ability of these mutants to carry out each step of DNA synthesis was determined. Alanine substitutions decreased the efficiency of minus-strand DNA elongation, primer translocation, circularization, and plus-strand DNA elongation. Aspartate substitutions also reduced the efficiency of these steps, but the magnitude of the reduction was less. Our findings suggest that phosphorylated serines are required for multiple steps during DNA synthesis. It has been proposed that generation of mature DNA requires serine dephosphorylation. Our results suggest that completion of rcDNA synthesis requires phosphorylated serines

Mimicking immune signatures of flavivirus infection with targeted adjuvants improves dengue subunit vaccine immunogenicity.

Neutralizing antibodies (nAbs) are a critical component for protection against dengue virus (DENV) infection, but little is known about the immune mechanisms governing their induction and whether such mechanisms can be harnessed for vaccine development. In this study, we profiled the early immune responses to flaviviruses in human peripheral blood mononuclear cells and screened a panel of toll-like receptor (TLR) agonists that stimulate the same immune signatures. Monocyte/macrophage-driven inflammatory responses and interferon responses were characteristics of flavivirus infection and associated with induction of nAbs in humans immunized with the yellow fever vaccine YF-17D. The signatures were best reproduced by the combination of TLR agonists Pam3CSK4 and PolyI:C (PP). Immunization of both mice and macaques with a poorly immunogenic recombinant DENV-2 envelope domain III (EDIII) induced more consistent nAb and CD4+ T-cell responses with PP compared to alum plus monophosphoryl lipid A. Induction of nAbs by PP required interferon-mediated signals in macrophages in mice. However, EDIII + PP vaccination only provided partial protection against viral challenge. These results provide insights into mechanisms underlying nAb induction and a basis for further improving antigen/adjuvant combinations for dengue vaccine development