Biological impacts of 'hot-spot' mutations of hepatitis B virus X proteins are genotype B and C differentiated

AIM: To investigate the biological impacts of “hot-spot” mutations on genotype B and C HBV X proteins (HBx). METHODS: Five types of “hot-spot” mutations of genotype B or C HBV X genes, which sequentially lead to the amino acid substitutions of HBx as I127T, F132Y, K130M+V131I, I127T+K130M+V131I, or K130M+V131I+F132Y, respectively, were generated by means of site-directed mutagenesis. To evaluate the anti-proliferative effects, HBx or related mutants’ expression vectors were transfected separately to the Chang cells by lipofectamine, and the cells were cultured in hygromycin selective medium for 14 d, drug-resistant colonies were fixed with cold methanol, stained with Giemsa dyes and scored (increase of the colonies indicated the reduction of the anti-proliferation activity, and vice versa). Different types of HBx expression vectors were co-transfected separately with the reporter plasmid pCMVβ to Chang cells, which were lysed 48 h post-transfection and the intra-cellular β-galactosidase activities were monitored (increase of the β-galactosidase activities indicated the reduction of the transactivation activity, and vice versa). All data obtained were calculated by paired-samples t-test. RESULTS: As compared to standard genotype B HBx, mutants of I127T and I127T+K130M+V131I showed higher transactivation and anti-proliferative activities, while the mutants of F132Y, K130M+V131I, and K130M+V131I+F132Y showed lower activities. As compared to standard genotype C HBx, I127T mutant showed higher transactivation activity, while the other four types of mutants showed no differences. With regard to anti-proliferative activity, compared to standard genotype C HBx, F132Y and K130M+V131I mutants showed lower activities, and K130M+V131I +F132Y mutant, on the other hand, showed higher activity, while the mutants of I127T and I127T+K130M+V131I showed no differences. CONCLUSION: “Hot-spot” mutations affect the anti-proliferation and transactivation activities of genotype B and/or C HBx, and the biological impacts of most “hot-spot” mutations on HBx are genotype B and C differentiated.published_or_final_versio

Spatio-Temporal Characteristics of Global Warming in the Tibetan Plateau during the Last 50 Years Based on a Generalised Temperature Zone - Elevation Model

Temperature is one of the primary factors influencing the climate and ecosystem, and examining its change and fluctuation could elucidate the formation of novel climate patterns and trends. In this study, we constructed a generalised temperature zone elevation model (GTEM) to assess the trends of climate change and temporal-spatial differences in the Tibetan Plateau (TP) using the annual and monthly mean temperatures from 1961-2010 at 144 meteorological stations in and near the TP. The results showed the following: (1) The TP has undergone robust warming over the study period, and the warming rate was 0.318°C/decade. The warming has accelerated during recent decades, especially in the last 20 years, and the warming has been most significant in the winter months, followed by the spring, autumn and summer seasons. (2) Spatially, the zones that became significantly smaller were the temperature zones of -6°C and -4°C, and these have decreased 499.44 and 454.26 thousand sq km from 1961 to 2010 at average rates of 25.1% and 11.7%, respectively, over every 5-year interval. These quickly shrinking zones were located in the northwestern and central TP. (3) The elevation dependency of climate warming existed in the TP during 1961-2010, but this tendency has gradually been weakening due to more rapid warming at lower elevations than in the middle and upper elevations of the TP during 1991-2010. The higher regions and some low altitude valleys of the TP were the most significantly warming regions under the same categorizing criteria. Experimental evidence shows that the GTEM is an effective method to analyse climate changes in high altitude mountainous regions

EZH2 protein: A promising immunomarker for the detection of hepatocellular carcinomas in liver needle biopsies

Background and aims: A previous study of ours indicated that enhancer of zeste homologue 2 (EZH2) plays an important role in hepatocellular carcinoma (HCC) tumorigenesis. The aim of the present study was to investigate the potential diagnostic utility of EZH2 in HCC. Methods: Immunohistochemistry was performed to examine the expression dynamics of EZH2 in two independent surgical cohorts of HCC and non-malignant liver tissues to develop a diagnostic yield of EZH2, HSP70 and GPC3 for HCC detection. The diagnostic performances of EZH2 and a three-marker panel in HCC were re-evaluated by using an additional biopsy cohort. Results: Immunohistochemistry analysis demonstrated that the sensitivity and specificity of EZH2 for HCC detection was 95.8% and 97.8% in the testing cohort. Similar results were confirmed in the validation cohort. For diagnosis of well-differentiated HCCs, the sensitivity and specificity were 68.9% and 91.5% for EZH2, 62.5% and 98.5% for HSP70, 50.0% and 92.1% for GPC3, and 75.0% and 100% for a three-marker panel. In biopsies, positive cases for at least one marker increased from large regenerative nodule and hepatocellular adenoma (0/12) to focal nodular hyperplasia (2/20), dysplastic nodule (7/25), well-differentiated HCC (16/18) and moderately and poorly differentiated HCC (54/54). When at least two positive markers were considered, regardless of their identity, the positive cases were detected in 0/12 large regenerative nodules and hepatocellular adenomas, 0/20 focal nodular hyperplasias, 0/25 dysplastic nodules, 11/18 well-differentiated HCCs, 32/37 moderately differentiated HCCs and 15/17 poorly differentiated HCCs. Conclusion: Our findings suggest that EZH2 protein, as examined by immunohistochemistry, may serve as a promising diagnostic biomarker of HCCs, and the use of a three-marker panel (EZH2, HSP70 and GPC3) can improve the rate of detection of HCCs in liver biopsy tissues.published_or_final_versio

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

Van der Waals epitaxy between the highly lattice mismatched Cu-doped FeSe and Bi₂Te₃

We present a structural and density functional theory study of FexCu1−xSe within the three-dimensional topological insulator Bi2Te3. The FexCu1−xSe inclusions are single-crystalline and epitaxially oriented with respect to the Bi2Te3 thin film. Aberration-corrected scanning transmission electron microscopy and electron energy loss spectroscopy show an atomically sharp FeICu1−xSe/Bi2Te3 interface. The FexCu1−xSe/Bi2Te3 interface is determined by Se–Te bonds and no misfit dislocations are observed, despite the different lattice symmetries and large lattice mismatch of ∼19%. First-principle calculations show that the large strain at the FexCu1−xSe/Bi2Te3 interface can be accommodated by van der Waals-like bonding between Se and Te atoms

Measurements of the branching fraction and polarization in B+->rho K-+(*0) decays

We present the results of a study of the charmless vector-vector decay B+->rho K-+(*0), based on 253 fb(-1) of data collected with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider. We obtain the branching fraction B(B+->rho K-+(*0))=[8.9 +/- 1.7(stat)+/- 1.2(syst)]x10(-6). We also perform a helicity analysis of the rho and K-* vector mesons, and obtain the longitudinal polarization fraction f(L)(B+->rho K-+(*0))=0.43 +/- 0.11(stat)(-0.02)(+0.05)(syst)

Human breast cancer-derived soluble factors facilitate CCL19-induced chemotaxis of human dendritic cells

Breast cancer remains as a challenging disease with high mortality in women. Increasing evidence points the importance of understanding a crosstalk between breast cancers and immune cells, but little is known about the effect of breast cancer-derived factors on the migratory properties of dendritic cells (DCs) and their consequent capability in inducing T cell immune responses. Utilizing a unique 3D microfluidic device, we here showed that breast cancers (MCF-7, MDA-MB-231, MDA-MB-436 and SK-BR-3)-derived soluble factors increase the migration of DCs toward CCL19. The enhanced migration of DCs was mainly mediated via the highly activated JNK/c-Jun signaling pathway, increasing their directional persistence, while the velocity of DCs was not influenced, particularly when they were co-cultured with triple negative breast cancer cells (TNBCs or MDA-MB-231 and MDA-MB-436). The DCs up-regulated inflammatory cytokines IL-1?? and IL-6 and induced T cells more proliferative and resistant against activation-induced cell death (AICD), which secret high levels of inflammatory cytokines IL-1??, IL-6 and IFN-??. This study demonstrated new possible evasion strategy of TNBCs utilizing their soluble factors that exploit the directionality of DCs toward chemokine responses, leading to the building of inflammatory milieu which may support their own growth.ope

Evidence for direct CP violation in B-0 -> K+pi(-) decays

We report evidence for direct CP violation in the decay B-0-->K(+)pi(-) with 253 fb(-1) of data collected with the Belle detector at the KEKB e(+)e(-) collider. Using 275x10(6) B(B) over bar pairs we observe a B-->K(+/-)pi(-/+) signal with 2140+/-53 events. The measured CP violating asymmetry is A(CP)(K(+)pi(-))=-0.101+/-0.025(stat)+/-0.005(syst), corresponding to a significance of 3.9sigma including systematics. We also search for CP violation in the decays B+-->K(+)pi(0) and B+-->pi(+)pi(0). The measured CP violating asymmetries are A(CP)(K(+)pi(0))=0.04+/-0.05(stat)+/-0.02(syst) and A(CP)(pi(+)pi(0))=-0.02+/-0.10(stat)+/-0.01(syst), corresponding to the intervals -0.05< A(CP)(K(+)pi(0))<0.13 and -0.18< A(CP)(pi(+)pi(0))<0.14 at 90% confidence level

Measurement of forward-backward asymmetry and wilson coefficients in B -> K(*)l(+)l(-)

We report the first measurement of the forward-backward asymmetry and the ratios of Wilson coefficients A(9)/A(7) and A(10)/A(7) in B -> K(*)l(+)l(-), where l represents an electron or a muon. We find evidence for the forward-backward asymmetry with a significance of 3.4 sigma. The results are obtained from a data sample containing 386x10(6) (B) over bar pairs that were collected on the Upsilon(4S) resonance with the Belle detector at the KEKB asymmetric-energy e(+)e(-) collider