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 progr...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.展开更多
The aim of this study was to investigate the trend in testicular volume changes after orchiopexy in children with cryptorchidism.The clinical data of 854 children with cryptorchidism who underwent orchiopexy between J...The aim of this study was to investigate the trend in testicular volume changes after orchiopexy in children with cryptorchidism.The clinical data of 854 children with cryptorchidism who underwent orchiopexy between January 2013 and December 2016 in Shenzhen Children’s Hospital(Shenzhen,China)were retrospectively analyzed.The mean(standard deviation)age of the patients was 2.8(2.5)years,and the duration of follow-up ranged from 1 year to 5 years.Ultrasonography was conducted preoperatively and postoperatively.The variables analyzed included age at the time of surgery,type of surgical procedure,laterality,preoperative testicular position,preoperative and postoperative testicular volumes,and the testicular volume ratio of them.The average testicular volumes preoperatively and at 1 year,2 years,3 years,and 5 years postoperatively were 0.27 ml,0.38 ml,0.53 ml,0.87 ml,and 1.00 ml,respectively(P<0.001).The corresponding testicular volume ratios were 0.67,0.76,0.80,0.83,and 0.84(P<0.001).The mean volume of the undescended testes was significantly smaller than the mean normative value(P<0.001,lower than the 10th percentile).The postoperative testicular volumes in children with cryptorchidism were generally lower than those in healthy boys but were still greater than the 10th percentile and exhibited an increasing trend.The older the child is at the time of surgery,the larger the gap in volume between the affected and normal testes.Although testicular volume tends to gradually increase after orchiopexy for cryptorchidism,it could not normalizes.Earlier surgery results in affected testicular volumes closer to those of healthy boys.展开更多
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 ...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.展开更多
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 si...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.展开更多
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 ...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.展开更多
Hydrazine hydrate(DH)is a widely used chemical agent,but it is highly toxic.Thus,the development of low-cost and easy-to-prepare materials for the detection and adsorption of DH is very significant.Herein,a novel and ...Hydrazine hydrate(DH)is a widely used chemical agent,but it is highly toxic.Thus,the development of low-cost and easy-to-prepare materials for the detection and adsorption of DH is very significant.Herein,a novel and easy-to-prepare supramolecular smart material based on bisquinoline-functionalized naphthalene diimide(DQ8)has been designed and synthesized.In the DQ8,the synergistic effect between quinoline and naphthalene diimide groups has been employed to improve the selectivity and sensitivity for binding of DH.The DQ8-based crystalline porous material(DQ8-CPM)can simultaneously detect and adsorb DH and produce noticeable fluorescence color changes after adsorption of DH vapor.More significantly,the DQ8-CPM shows nice recycling performance on DH detection and adsorption.Meanwhile,a smart gel based on DQ8(DQ8-G)shows multi-channel response for DH through color,fluorescence,and state changes.The DQ8 shows high selectivity and sensitivity for DH.The detection limit of DQ8 for DH is 8.6×10^(-7) mol/L.According to the investigation of the DH binding and response mechanism,the synergistic effect between quinoline and naphthalene diimide groups plays an important role in the DH response process.It's a simple and feasible way to develop materials for detection and adsorption of DH through synergistic effects.展开更多
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 effici...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.展开更多
基金Supported by the Fundamental Research Program of Shanxi Province,No.202203021222418Research Program of Shanxi Provincial Health Commission,No.2023061+2 种基金Fundamental Research Cooperation Program of Beijing-Tianjin-Hebei Region of Natural Science Foundation of Tianjin,No.22JCZXJC00140Tianjin Major Science and Technology Project,No.21ZXJBSY00110Tianjin Health and Science and Technology Project,No.TJWJ2024ZK001.
文摘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.
基金This study was funded by the Guangdong High-level Hospital Construction Fund and Shenzhen Fund for Guangdong Provincial High-level Clinical Key Specialties(SZXK035).
文摘The aim of this study was to investigate the trend in testicular volume changes after orchiopexy in children with cryptorchidism.The clinical data of 854 children with cryptorchidism who underwent orchiopexy between January 2013 and December 2016 in Shenzhen Children’s Hospital(Shenzhen,China)were retrospectively analyzed.The mean(standard deviation)age of the patients was 2.8(2.5)years,and the duration of follow-up ranged from 1 year to 5 years.Ultrasonography was conducted preoperatively and postoperatively.The variables analyzed included age at the time of surgery,type of surgical procedure,laterality,preoperative testicular position,preoperative and postoperative testicular volumes,and the testicular volume ratio of them.The average testicular volumes preoperatively and at 1 year,2 years,3 years,and 5 years postoperatively were 0.27 ml,0.38 ml,0.53 ml,0.87 ml,and 1.00 ml,respectively(P<0.001).The corresponding testicular volume ratios were 0.67,0.76,0.80,0.83,and 0.84(P<0.001).The mean volume of the undescended testes was significantly smaller than the mean normative value(P<0.001,lower than the 10th percentile).The postoperative testicular volumes in children with cryptorchidism were generally lower than those in healthy boys but were still greater than the 10th percentile and exhibited an increasing trend.The older the child is at the time of surgery,the larger the gap in volume between the affected and normal testes.Although testicular volume tends to gradually increase after orchiopexy for cryptorchidism,it could not normalizes.Earlier surgery results in affected testicular volumes closer to those of healthy boys.
基金supported by the National Natural Science Foundation of China(No.21325416)
文摘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.
基金the Tianjin Municipal Education Commission Scientific Research Project,No.2018KJ055.
文摘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.
文摘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.
基金supported by the NSFC(Nos.22065031,22471222,22165027)the Key R&D Program of Gansu Province(No.21YF5GA066)+2 种基金the Top Leading Talents Project of Gansu Province,the Fundamental Research Funds for the Central Universities(No.31920230145)Gansu Province College Industry Support Plan Project(No.2022CYZC-18)Natural Science Foundation of Gansu Province(Nos.21JR1RA220,2020-0405-JCC-630,20JR10RA088).
文摘Hydrazine hydrate(DH)is a widely used chemical agent,but it is highly toxic.Thus,the development of low-cost and easy-to-prepare materials for the detection and adsorption of DH is very significant.Herein,a novel and easy-to-prepare supramolecular smart material based on bisquinoline-functionalized naphthalene diimide(DQ8)has been designed and synthesized.In the DQ8,the synergistic effect between quinoline and naphthalene diimide groups has been employed to improve the selectivity and sensitivity for binding of DH.The DQ8-based crystalline porous material(DQ8-CPM)can simultaneously detect and adsorb DH and produce noticeable fluorescence color changes after adsorption of DH vapor.More significantly,the DQ8-CPM shows nice recycling performance on DH detection and adsorption.Meanwhile,a smart gel based on DQ8(DQ8-G)shows multi-channel response for DH through color,fluorescence,and state changes.The DQ8 shows high selectivity and sensitivity for DH.The detection limit of DQ8 for DH is 8.6×10^(-7) mol/L.According to the investigation of the DH binding and response mechanism,the synergistic effect between quinoline and naphthalene diimide groups plays an important role in the DH response process.It's a simple and feasible way to develop materials for detection and adsorption of DH through synergistic effects.
基金This work was supported by National Key Research and Development Program(2016YFA0202500 and 2015CB932500)National Natural Science Foundation of China(21676160,21825501,and U1801257)the Tsinghua University Initiative Scientific Research Program.
文摘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.
