B-Cell Receptor-Associated Protein 31 Promotes Metastasis via AKT/β-Catenin/Snail Pathway in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most lethal cancer worldwide, characterized with high heterogeneity and inclination to metastasize. Emerging evidence suggests that BAP31 gets involved in cancer progression with different kinds. It still remains unknown whether and how BAP31 plays a role in HCC metastasis. Epithelial–mesenchymal transition (EMT) has been a common feature in tumor micro-environment, whose inducer TGF-β increased BAP31 expression in this research. Elevated expression of BAP31 was positively correlated with tumor size, vascular invasion and poor prognosis in human HCC. Ectopic expression of BAP31 promoted cell migration and invasion while BAP31 knockdown markedly attenuated metastatic potential in HCC cells and mice orthotopic xenografts. BAP31 induced EMT process, and enhanced the expression level of EMT-related factor Snail and decreased contents and membrane distribution of E-cadherin. BAP31 also activated AKT/β-catenin pathway, which mediated its promotional effects on HCC metastasis. AKT inhibitor further counteracted the activated AKT/β-catenin/Snail upon BAP31 over-expression. Moreover, silencing Snail in BAP31-overexpressed cells impaired enhanced migratory and invasive abilities of HCC cells. In HCC tissues, BAP31 expression was positively associated with Snail. In conclusion, BAP31 promotes HCC metastasis by activating AKT/β-catenin/Snail pathway. Thus, our study implicates BAP31 as potential prognostic biomarker, and provides valuable information for HCC prognosis and treatment

Reduction rules for the maximum parsimony distance on phylogenetic trees

In phylogenetics, distances are often used to measure the incongruence between a pair of phylogenetic trees that are reconstructed by different methods or using different regions of genome. Motivated by the maximum parsimony principle in tree inference, we recently introduced the maximum parsimony (MP) distance, which enjoys various attractive properties due to its connection with several other well-known tree distances, such as tbr and spr. Here we show that computing the MP distance between two trees, a NP-hard problem in general, is fixed parameter tractable in terms of the tbr distance between the tree pair. Our approach is based on two reduction rules – the chain reduction and the subtree reduction – that are widely used in computing tbr and spr distances. More precisely, we show that reducing chains to length 4 (but not shorter) preserves the MP distance. In addition, we describe a generalization of the subtree reduction which allows the pendant subtrees to be rooted in different places, and show that this still preserves the MP distance. On a slightly different note we also show that Monadic Second Order Logic (MSOL), posited over an auxiliary graph structure known as the display graph (obtained by merging the two trees at their leaves), can be used to obtain an alternative proof that computation of MP distance is fixed parameter tractable in terms of tbr-distance. We conclude with an extended discussion in which we focus on similarities and differences between MP distance and TBR distance and present a number of open problems. One particularly intriguing question, emerging from the MSOL formulation, is whether two trees with bounded MP distance induce display graphs of bounded treewidth

HBsAg seroprevalence in students for college entrance examination from 2006 to 2014 in Qidong of Jiangsu Province

ObjectiveTo investigate the HBsAg seroprevalence in the young generation in Qidong of Jiangsu Province, China. MethodsA total of 15 534 students for college entrance examination from 2006 to 2014 were randomly selected from three secondary schools in Qidong as student group. Some of them had hepatitis B vaccination at birth. A total of 1208 adults who had their routine checkups in our hospital from 2007 to 2013 were selected as adult group. It was confirmed that all of them did not have hepatitis B vaccination at birth. Serum HBsAg levels of the two groups were measured using enzyme-linked immunosorbent assay and the seroprevalence was analyzed. Comparison of data between the two groups was made by chi-square test. Results In the 9 years from 2007 to 2013, the seroprevalence rates of HBsAg in the student group were 4.2%(75/1794), 4.3%(77/1797), 4.4%(82/1858), 4.3%(82/1903), 3.4%(56/1627), 2.6%(46/1768), 1.6%(29/1778), 1.6%(27/1642), and 1.8%(24/1367), respectively. The mean HBsAg seroprevalence of the student group was 3.2%(498/15534), significantly lower compared with 7.1% (86/1208) of the adult group (χ2= 59.986, P＜0.001). In both of the student group and the adult group, the males had a significantly higher HBsAg seroprevalence than the females (χ2=10.521, P=0.001; χ2=8.452, P=0.004) and the values were 3.7%(266/7236) vs 2.8%(229/8298) and 8.8%(66/750) vs 4.4%(20/458), respectively. Among male subjects, the HBsAg seroprevalence of the adult group was 2.4 times that of the student group; among female subjects, the HBsAg seroprevalence of the adult group was 1.6 times that of the student group. ConclusionIn the recent 9 years from 2006 to 2014, the HBsAg seroprevalence in students for college entrance examination declined continuously. The goal set by the World Health Organization Western Pacific Region in 2010 had been achieved ahead of the schedule that the HBsAg seroprevalence should be controlled below 2% in children aged less than 5

Pre-S deletion and complex mutations of hepatitis B virus related to young age hepatocellular carcinoma in Qidong, China.

BACKGROUND/AIM: To investigate the roles of biomedical factors, hepatitis B virus (HBV) DNA levels, genotypes, and specific viral mutation patterns on the progression of hepatocellular carcinoma (HCC) patients below 40 years of age in Qidong, China. METHODS: We conducted a case-control study within a cohort of 2387 male HBV carriers who were recruited from August, 1996. The HBV DNA sequence was determined in 49 HCC and 90 chronic hepatitis (CH) patients below 40 years of age. Mutation exchanges during follow-up in 32 cases were compared with 65 controls with paired serum samples. In addition, a consecutive series of samples from 14 HCC cases were employed to compare the sequences before and after the occurrence of HCC. RESULTS: After adjustment for age, history of cigarette smoking and alcohol consumption, HBeAg positive, HBV DNA levels ≥4.00 log(10) copies/mL, pre-S deletion, T1762/A1764 double mutations, and T1766 and/or A1768 mutations were associated with risk of young age HCC. Moreover, the presence of an increasing number of HCC-related mutations (pre-S deletion, T1762/A1764, and T1766 and/or A1768 mutations) was associated with an increased risk of young age HCC. Paired samples analysis indicated that the increased HCC risk for at-risk sequence mutations were attributable to the persistence of these mutations, but not a single time point mutation. The longitudinal observation demonstrated a gradual combination of pre-S deletion, T1762/A1764 double mutations, and T1766 and/or A1768 mutations during the development of HCC. CONCLUSION: High HBV DNA levels and pre-S deletion were independent risk factors of young age HCC. Combination of pre-S deletion and core promoter mutations increased the risk and persistence of at-risk sequence mutations is critical for HCC development

AOSVSSNet: Attention-Guided Optical Satellite Video Smoke Segmentation Network

Smoke is more observable than open fires. Optical satellite video has the advantages of a wide monitoring range, fast response speed, and good economy in large-scale surface smoke monitoring tasks. It can be used in wide-area forest wildfire monitoring, battlefield dynamic monitoring, disaster relief decision-making. The smoke segmentation method based on traditional handcrafted features is easily limited by the scene and data. This article introduces the deep learning method to the optical satellite video smoke target segmentation. However, due to the lack of real smoke images and the blurred edges of smoke, there are currently few labeled datasets for smoke segmentation in high-resolution optical satellite imagery scenes, which cannot provide sufficient training data for deep learning models. The smoke image from the satellite perspective also has the characteristics of multiscale features and ground object background interference. To solve the abovementioned problems, we construct a set of high-resolution optical satellite imagery smoke synthesis datasets based on the optical imaging process of smoke targets, which saves the cost of manual labeling. In addition, we design an attention-guided optical satellite video smoke segmentation network model, which can effectively suppress the ground object background's false alarm and extract the smoke's multiscale features. Synthetic data faces the transferability problem in real-world applications, so the physical constraints of the smoke imaging process are introduced into the loss function to improve the generalization of the model in real smoke data. The comprehensive evaluation results show that the method outperforms representative semantic segmentation networks

ATF3 inhibits the tumorigenesis and progression of hepatocellular carcinoma cells via upregulation of CYR61 expression

Abstract Background Hepatocellular carcinoma (HCC) is one of the most common malignant cancers with a high incidence and high mortality in East Asia. Identifying biomarkers and clarifying the regulatory mechanisms of HCC are of great importance. Herein, we report the role and mechanism of activating transcription factor 3 (ATF3), a member of the ATF/cAMP-responsive element-binding protein family of transcription factors in HCC. Methods ATF3 overexpression vector and shRNAs were transfected into HCC cancer cells to upregulate or downregulate ATF3 expression. In vitro and in vivo assays were performed to investigate the functional role of ATF3 in hepatocellular carcinoma. RNA-Seq was performed to screen the differentially expressed genes downstream of ATF3. The dual-luciferase reporter assay, chromatin immunoprecipitation (Ch-IP) analysis and functional rescue experiments were used to confirm the target gene regulated by ATF3. Tissue microarrays (TMAs) comprising 236 human primary HCC tissues were obtained and immunohistochemical staining were carried out to analyze the clinical significance of ATF3. Results The results indicate that ATF3 significantly inhibited the proliferation and mobility of HCC cells both in vitro and in vivo. Cysteine-rich angiogenic inducer 61 (CYR61) is a key target for transcriptional regulation by ATF3. Both ATF3 and CYR61 were consistently downregulated in human HCC tissues, and their expression levels were significantly and positively correlated with each other. Conclusions Our findings indicate that ATF3 functions as a tumor suppressor in HCC through targeting and regulating CYR61

Cost-effectiveness analysis of hepatitis B vaccine booster in children born to HBsAg-positive mothers in rural China

Objective: In rural areas of China with highly endemic for hepatitis B virus (HBV) infection, protective efficacy was observed in adulthood when a one-dose HBV vaccine booster was administered to high-risk children born to mothers who were positive for hepatitis B surface antigen (HBsAg). The aim of this study was to estimate the cost-effectiveness of an HBV vaccine booster in this specific group of children when given at 10 years of age. Methods: Two potential strategies were considered: strategy 1 was a one-dose booster given if the child was negative on HBsAg screening; strategy 2 was a one-dose booster given if the child was negative on both HBsAg plus anti-HBs screening. A decision tree combined with a Markov model was developed to simulate the booster intervention process and to simulate the natural history of HBV infection in a cohort of 10-year-old children who were born to HBsAg-positive mothers. The model was calibrated based on multiple selected outcomes. Costs and quality-adjusted life years (QALYs) were measured from a societal perspective. Cost-effectiveness ratios (CERs) of the different strategies were compared in both base-case and one-way sensitivity analyses. Results: Compared to the current practice of ‘no screening and no booster’, both strategy 1 and strategy 2 were cost-saving, with CERs estimated at US$−6961 and US$ −6872 per QALY gained, respectively. In the one-way sensitivity analysis for strategy 1, all the CERs were found to be less than US$−5000 per QALY gained after considering the uncertainty of all the variables, including vaccination protective efficacy, natural history, behavior, and various costs and utility weights. In a ‘worst case’ scenario (all parameter values simultaneously being at the worst), the CER of strategy 1 increased to US$ 3263 per QALY gained, which was still less than the GDP per capita of China in 2016 (US$ 8126). Conclusions: A hepatitis B vaccine booster given to children born to HBsAg-positive mothers in rural China would be cost-effective and could be considered in HBV endemic areas. Keywords: Hepatitis B vaccine, Adolescent booster, Cost-effectiveness analysi