BIRC3 induces the phosphoinositide 3-kinase-Akt pathway activation to promote trastuzumab resistance in human epidermal growth factor receptor 2-positive gastric cancer

BACKGROUND Trastuzumab-targeted therapy is currently the standard of care for advanced human epidermal growth factor receptor 2(HER2)-positive gastric cancer.However,the emergence of resistance to trastuzumab poses significant challenges.AIM To identify the key genes associated with trastuzumab resistance.These results provide a basis for the development of interventions to address drug resistance and improve patient outcomes.METHODS High-throughput sequencing and bioinformatics were used to identify the differentially expressed pivotal gene BIRC3 and delineate its potential function and pathway regulation.Tumor samples were collected from patients with HER2-positive gastric cancer to evaluate the correlation between BIRC3 expression and trastuzumab resistance.We established gastric cancer cell lines with both highly expressed and suppressed levels of BIRC3,followed by comprehensive in vitro and in vivo experiments to confirm the involvement of BIRC3 in trastuzumab resistance and to elucidate its underlying mechanisms.RESULTS In patients with HER2-positive gastric cancer,there is a significant correlation between elevated BIRC3 expression in tumor tissues and higher T stage,tumor node metastasis stage,as well as poor overall survival and progressionfree survival.BIRC3 is highly expressed in trastuzumab-resistant gastric cancer cell lines,where it inhibits tumor cell apoptosis and enhances trastuzumab resistance by promoting the phosphorylation and activation of the phosphoinositide 3-kinase-Akt(PI3K-AKT)pathway in HER2-positive gastric cancer cells,both in vivo and in vitro.CONCLUSION This study revealed a robust association between high BIRC3 expression and an unfavorable prognosis in patients with HER2-positive gastric cancer.Thus,the high expression of BIRC3 stimulated PI3K-AKT phosphorylation and activation,stimulating the proliferation of HER2-positive tumor cells and suppressing apoptosis,ultimately leading to trastuzumab resistance.

A method for automated development of model and fragility inventories of nonductile reinforced concrete buildings

The nonductile reinforced concrete building(NDRCB)stock-typically,pre-1974 structures in the U.S.-is a well-known high-risk group for seismic hazards.Prior studies indicate that there are approximately 1500 NDRCBs in Los Angeles.Through various ordinances,the owners are currently required to choose between demolition and,when appropriate,seismic retrofitting.Because fulfilling these ordinances will take decades,the potential risk of major losses will persist.In this study,a method for automated development of structural analysis models and damage fragilities for non-ductile moment-resisting frames is established.This capability enables seismic risk assessment at a regional scale using relatively limited building metadata and the era-specific seismic design code.The approach is used first to develop archetypal models in OpenSees,verified through static pushover and nonlinear time-history analyses against prior detailed studies.Fragility curves for discrete damage states are developed through a probabilistic seismic demand model.Additional investigations are carried out to consider the influence of soil-structural interaction effects and to determine the most suitable seismic intensity measures to quantify the seismic damage levels of NDRCB frames.The sensitivity of the proposed modeling method to variations/uncertainties in building configurations and properties is also examined through parametric studies.The method is limited to a particular subcategory of NDRBCs-namely,moment-resisting frames-but extensions to other types appear straightforward.

电子导电水凝胶电极在柔性储能系统中的应用研究进展

电子导电水凝胶是一类将导电材料与水凝胶基体结合的新型水凝胶,具有高导电性、优异的柔韧性以及结构易于调控等优势,在柔性超级电容器和电池等领域表现出广阔的应用前景.迄今为止,各种电子导电水凝胶电极已经被开发出来,用于制备具有优异机械和电化学性能的柔性储能设备.本文回顾了近年来柔性超级电容器及电池中电子导电水凝胶电极的研究进展,讨论了提高导电水凝胶电极在柔性储能应用中的关键因素,系统地总结了基于导电聚合物水凝胶、石墨烯水凝胶及复合水凝胶电极的柔性超级电容器及基于硅基水凝胶和过渡金属氧化物水凝胶电极的柔性锂离子电池.最后,探讨了在该领域中导电水凝胶电极面临的挑战和机遇.

RGS4 promotes the progression of gastric cancer through the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and epithelial-mesenchymal transition

BACKGROUND Regulator of G protein signaling(RGS)proteins participate in tumor formation and metastasis by acting on theα-subunit of heterotrimeric G proteins.The speci-fic effect of RGS,particularly RGS4,on the progression of gastric cancer(GC)is not yet clear.AIM To explore the role and underlying mechanisms of action of RGS4 in GC develop-ment.METHODS The prognostic significance of RGS4 in GC was analyzed using bioinformatics based public databases and verified by immunohistochemistry and quantitative polymerase chain reaction in 90 patients with GC.Function assays were employed to assess the carcinogenic impact of RGS4,and the mechanism of its possible influence was detected by western blot analysis.A nude mouse xenograft model was established to study the effects of RGS4 on GC growth in vitro.RESULTS RGS4 was highly expressed in GC tissues compared with matched adjacent normal tissues.Elevated RGS4 expression was correlated with increased tumor-node-metastasis stage,increased tumor grade as well as poorer overall survival in patients with GC.Cell experiments demonstrated that RGS4 knockdown suppressed GC cell proliferation,migration and invasion.Similarly,xenograft experiments confirmed that RGS4 silencing significantly inhibited tumor growth.Moreover,RGS4 knockdown resulted in reduced phosphorylation levels of focal adhesion kinase,phosphatidyl-inositol-3-kinase,and protein kinase B,decreased vimentin and N-cadherin,and elevated E-cadherin.CONCLUSION High RGS4 expression in GC indicates a worse prognosis and RGS4 is a prognostic marker.RGS4 influences tumor progression via the focal adhesion kinase/phosphatidyl-inositol-3-kinase/protein kinase B pathway and epithelial-mesenchymal transition.

A compact inorganic layer for robust anode protection in lithium-sulfur batteries

Lithium-sulfur(Li-S)batteries are one of the most promising candidates for high energy density rechargeable batteries beyond current Li-ion batteries.However,severe corrosion of Li metal anode and low Coulombic efficiency(CE)induced by the unremitting shuttle of Li polysulfides immensely hinder the practical applications of Li-S batteries.Herein,a compact inorganic layer(CIL)formed by ex situ reactions between Li anode and ionic liquid emerged as an effective strategy to block Li polysulfides and suppress shuttle effect.A CE of 96.7%was achieved in Li-S batteries with CIL protected Li anode in contrast to 82.4%for bare Li anode while no lithium nitrate was employed.Furthermore,the corrosion of Li during cycling was effectively inhibited.While applied to working batteries,80.6%of the initial capacity after 100 cycles was retained in Li-S batteries with CIL-protected ultrathin(33μm)Li anode compared with 58.5%for bare Li anode,further demonstrating the potential of this strategy for practical applications.This study presents a feasible interfacial regulation strategy to protect Li anode with the presence of Li polysulfides and opens avenues for Li anode protection in Li-S batteries under practical conditions.

The Design of Second-order Nonlinear Optical Dendrimers:From"Branch Only"to"Root Containing"

Dendrimers are considered as a promising family of organic second-order nonlinear optical （NLO） polymers because of their well-defined structures, easily modified peripheral functional groups, interior branches and central cores. In order to obtain NLO materials with high performance, dendrimer structures have been optimized in the past years, such as the ＂branch only＂ and the ＂root containing＂ type dendrimers. This feature article highlights the achievements in exploring the rational design of dendrimers, partially marked by their macroscopic NLO performance.