Goffchung5060

low-risk groups using seven and 14 AS genes in LUAD and LUSC, respectively. The LUAD risk signature was associated with gender and T, N, and TNM stages, but the LUSC risk signature was not associated with any clinical features. In addition, the risk signature and TNM stage were independent prognostic predictors in LUAD and the risk signature and T stage were independent prognostic predictors in LUSC after the multivariate Cox regression and receiver operating characteristic analyses. In conclusion, this study revealed the AS prognostic signature in the prediction of LUAD and LUSC prognosis.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.Lead (Pb) is among the deleterious heavy metal and has caused global health concerns due to its tendency to cause a detrimental effect on the development of the central nervous system (CNS). Despite being a serious health concern, treatment of Pb poisoning is not yet available, reflecting the pressing need for compounds that can relieve Pb-induced toxicity, especially neurotoxicity. In the quest of exploring protective strategies against Pb-induced developmental neurotoxicity, compounds from natural resources have gained increased attention. selleck chemical Chlorogenic acid (CGA) and its analogues neochlorogenic acid (NCGA) and cryptochlorogenic acid (CCGA) are the important phenolic compounds widely distributed in plants. Herein, utilizing zebrafish as a model organism, we modeled Pb-induced developmental neurotoxicity and investigated the protective effect of CGA, NCGA, and CCGA co-treatment. In zebrafish, Pb exposure (1,000 μg/L) for 5 days causes developmental malformation, loss of dopaminergic (DA) neurons, and brain vasculature, as well as disrupted neuron differentiation in the CNS. Additionally, Pb-treated zebrafish exhibited abnormal locomotion. Notably, co-treatment with CGA (100 µM), NCGA (100 µM), and CCGA (50 µM) alleviated these developmental malformation and neurotoxicity induced by Pb. Further underlying mechanism investigation revealed that these dietary phenolic acid compounds may ameliorate Pb-induced oxidative stress and autophagy in zebrafish, therefore protecting against Pb-induced developmental neurotoxicity. In general, our study indicates that CGA, NCGA, and CCGA could be promising agents for treating neurotoxicity induced by Pb, and CCGA shows the strongest detoxifying activity.4-O-β-tri-N-acetylchitotriosyl moranoline (GN3M) is a transition-state analogue for hen egg white lysozyme (HEWL) and identified as the most potent inhibitor till date. Isothermal titration calorimetry experiments provided the thermodynamic parameters for binding of GN3M to HEWL and revealed that the binding is driven by a favorable enthalpy change (ΔH° = -11.0 kcal/mol) with an entropic penalty (-TΔS° = 2.6 kcal/mol), resulting in a free energy change (ΔG°) of -8.4 kcal/mol [Ogata et al. (2013) 288, 6,072-6,082]. Dissection of the entropic term showed that a favorable solvation entropy change (-TΔS solv° = -9.2 kcal/mol) is its sole contributor. The change in heat capacity (ΔC p°) for the binding of GN3M was determined to be -120.2 cal/K·mol. These results indicate that the bound water molecules play a crucial role in the tight interaction between GN3M and HEWL.The severe acute respiratory syndrome (SARS)-like coronavirus disease (COVID-19) is caused by SARS-CoV-2 and has been a serious threat to global public health with limited treatment. Cellular heparan sulfate (HS) has been found to bind SARS-CoV-2 spike protein (SV2-S) and co-operate with cell surface receptor angiotensin-converting enzyme 2 (ACE2) to mediate SARS-CoV-2 infection of host cells. In this study, we determined that host cell surface SV2-S binding depends on and correlates with host cell surface HS expression. This binding is required for SARS-Cov-2 virus to infect host cells and can be blocked by heparin lyase, HS antagonist surfen, heparin, and heparin derivatives. The binding of heparin/HS to SV2-S is mainly determined by its overall sulfation with potential, minor contribution of specific SV2-S binding motifs. The higher binding affinity of SV2-S G614 mutant to heparin and upregulated HS expression may be one of the mechanisms underlying the higher infectivity of the SARS-CoV-2 G614 variant and the high vulnerability of lung cancer patients to SARS-CoV-2 infection, respectively. The higher host cell infection by SARS-CoV-2 G614 variant pseudovirus and the increased infection caused by upregulated HS expression both can be effectively blocked by heparin lyase and heparin, and possibly surfen and heparin derivatives too. Our findings support blocking HS-SV2-S interaction may provide one addition to achieve effective prevention and/treatment of COVID-19.