Background:Cardiac fibrosis following myocardial infarction(MI)drives adverse ventricular remodeling and heart failure,with cardiac fibroblasts(CFs)playing a central role.Glutathione S-transferase mu 1(GSTM1)is an imp...Background:Cardiac fibrosis following myocardial infarction(MI)drives adverse ventricular remodeling and heart failure,with cardiac fibroblasts(CFs)playing a central role.Glutathione S-transferase mu 1(GSTM1)is an important member of the glutathione S-transferase(GSTs)family,which plays an important role in maintaining cell homeostasis and detoxification.This study investigated the role and mechanism of GSTM1 in post-MI fibrosis.Methods:Multi-omics approaches(proteomics/scRNA-seq)identified GSTM1 as a dysregulated target in post-MI fibroblasts.Using a murine coronary ligation model,we assessed GSTM1 dynamics via molecular profiling,such as Western blotting,immunofluorescence,and real-time quantitative polymerase chain reaction.Adeno-associated virus serotype 9(AAV9)-mediated cardiac-specific GSTM1 overexpression was achieved through systemic delivery.In vitro studies employed transforming growth factor-β(TGF-β)-stimulated primary fibroblasts with siRNA/plasmid interventions.Mechanistic insights were derived from transcriptomics and lipid peroxidation assays.Results:The expression of GSTM1 in mouse CFs after MI was significantly down-regulated at both transcriptional and protein levels.In human dilated cardiomyopathy(DCM)patients with severe heart failure,GSTM1 expression was decreased alongside aggravated fibrosis.Overexpression of GSTM1 in post-MI mice improved cardiac function,while significantly reducing infarct size and fibrosis compared with the control group.In vitro models demonstrated that GSTM1 markedly attenuated collagen secretion and activation of fibroblasts,as well as suppressed their proliferation and migration.Further studies revealed that GSTM1 overexpression significantly inhibited the generation of intracellular and mitochondrial reactive oxygen species(ROS)under pathological conditions,suggesting that GSTM1 exerts an antioxidative stress effect in post-infarction fibroblasts.Further investigation of molecular mechanisms indicated that GSTM1 may suppress the initiation and progression of fibrosis by modulating lipid metabolism and ferroptosis-related pathways.Overexpression of GSTM1 significantly reduced lipid peroxidation and free ferrous iron levels in fibroblasts and mitochondria,markedly decreased ferroptosis-related indicators,and alleviated oxidative lipid levels[such as 12-hydroxyeicosapentaenoic acid(HEPE)and 9-,10-dihydroxy octadecenoic acid(DHOME)]under fibrotic conditions.GSTM1 enhanced the phosphorylation of signal transducer and activator of transcription 3(STAT3),thereby upregulating the downstream expression of glutathione peroxidase 4(GPX4),reducing ROS production,and mitigating fibroblast activation and phenotypic transformation by inhibiting lipid peroxidation.Conclusions:This study identifies GSTM1 as a key inhibitor of fibroblast activation and cardiac fibrosis,highlighting its ability to target ferroptosis through redox regulation.AAV-mediated GSTM1 therapy demonstrates significant therapeutic potential for improving outcomes post-MI.展开更多
A recent study published in Science by Engleman et al.uncovered that erythropoietin(EPO)secreted by tumor cells can mediate the formation of a noninflamed immune microenvironment and promote tumor progression.1 Specif...A recent study published in Science by Engleman et al.uncovered that erythropoietin(EPO)secreted by tumor cells can mediate the formation of a noninflamed immune microenvironment and promote tumor progression.1 Specifically,in hepatocellular carcinoma(HCC),tumor cell-derived EPO binds to the erythropoietin receptor(EPOR)on tumor-associated macrophages(TAMs),thereby inhibiting the production of pro-inflammatory cytokines and reactive oxygen species(ROS)by Kupffer cells(KCs)and monocyte-derived macrophages(MDMs).This interaction facilitates the shift of macrophages from an inflamed to a noninflamed phenotype,ultimately promoting the progression of HCC.展开更多
Recently,reactive oxygen species(ROS)-independent mimetics of oxidase with Au nanoclusters(NCs)as the catalysts and MnO_(2)as electron acceptor have gained attention.In this study,we aim to explore the oxidase-mimicki...Recently,reactive oxygen species(ROS)-independent mimetics of oxidase with Au nanoclusters(NCs)as the catalysts and MnO_(2)as electron acceptor have gained attention.In this study,we aim to explore the oxidase-mimicking potential of bovine serum albumin(BSA)-templated metal nanoclusters(BSA-M NCs,where M=Ag,Pt,Cu,or Cd)beyond Au NCs in boosting the oxidation of 3,3',5,5'-tetramethylbenzidine(TMB)by MnO_(2),denoted as BM@Metal.The oxidase-mimetic activity of BM@Metal is independent of ROS and generally enhanced by the incorporation of metal nanoclusters.Notably,this enhancement varies with the metal species,with BSA-Cd exhibiting the highest activity.The X-ray photoelectron spectroscopy(XPS)analysis confirms mixed valence states(Mn(Ⅳ)/Mn(Ⅱ))in BM@Cd.Given that the catalytic activity is closely linked to the substrate adsorption,the label-free isothermal titration calorimetry was employed to probe the affinity between TMB and BSA-M NCs,which provides a robust approach for probing the interface adsorption.The results reveal that the superior catalytic performance of BSA-Cd correlates with enhanced TMB adsorption,likely facilitated by coordination and hydrophobic interactions.Finally,the superior catalytic performance of BSA-M NCs on the oxidation of TMB by MnO_(2)has inspired us to fabricate the assay for analyzing α-glucosidase’s activity.This work not only demonstrates the versatility of metal NCs in constructing ROS-independent oxidase mimetics but also provides interfacial adsorption engineered strategy for the rational design of superior ROS independent mimetics of natural oxidase.展开更多
Bisphenol A(BPA)is an industrial pollutant that can cause immune impairment.Selenium acts as an antioxidant,as selenium deficiency often accompanies oxidative stress,resulting in organ damage.This study is the first t...Bisphenol A(BPA)is an industrial pollutant that can cause immune impairment.Selenium acts as an antioxidant,as selenium deficiency often accompanies oxidative stress,resulting in organ damage.This study is the first to demonstrate that BPA and/or selenium deficiency induce pyroptosis and ferroptosis-mediated thymic injury in chicken and chicken lymphoma cell(MDCC-MSB-1)via oxidative stress-induced endoplasmic reticulum(ER)stress.We established a broiler chicken model of BPA and/or selenium deficiency exposure and collected thymus samples as research subjects after 42 days.The results demonstrated that BPA or selenium deficiency led to a decrease in antioxidant enzyme activities(T-AOC,CAT,and GSH-Px),accumulation of peroxides(H2O2 and MDA),significant upregulation of ER stress-relatedmarkers(GRP78,IER 1,PERK,EIF-2α,ATF4,and CHOP),a significant increase in iron ion levels,significant upregulation of pyroptosis-related gene(NLRP3,ASC,Caspase1,GSDMD,IL-18 and IL-1β),significantly increase ferroptosis-related genes(TFRC,COX2)and downregulate GPX4,HO-1,FTH,NADPH.In vitro experiments conducted in MDCC-MSB-1 cells confirmed the results,demonstrating that the addition of antioxidant(NAC),ER stress inhibitor(TUDCA)and pyroptosis inhibitor(Vx765)alleviated oxidative stress,endoplasmic reticulum stress,pyroptosis,and ferroptosis.Overall,this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.展开更多
Teucrifarides A-D(1-4),four previously unreported neo-clerodane-type diterpenoids,combined with sixteen known analogs(5-20),were purified from Teucrium quadrifarium.The absolute forma of compounds 1-4 were determined ...Teucrifarides A-D(1-4),four previously unreported neo-clerodane-type diterpenoids,combined with sixteen known analogs(5-20),were purified from Teucrium quadrifarium.The absolute forma of compounds 1-4 were determined via spectroscopic and ECD calculation methods,together with X-ray crystallography experiments.Among them,compound 1 possessed a 5,20-epoxy ring featuring a unique cage-like 12-oxatricyclo[5.3.2.0^(1,6)]undecane skeleton.Meanwhile,2 incorporated a 6,20-epoxy ring with a novel 12-oxatricyclo[6.2.2.0^(2,7)]undecane skeleton.Compounds 1 and 12 exhibited significant inhibitory effects against HT-22 cells ferroptosis induced by RSL3,with EC_(50)values of 11.8±1.0μM,and 4.52±1.24μM,respectively.Moreover,ROS accumulation in HT22 cells treated with compound 1 was also observed.展开更多
With the growing application of intelligent robots in service,manufacturing,and medical fields,efficient and natural interaction between humans and robots has become key to improving collaboration efficiency and user ...With the growing application of intelligent robots in service,manufacturing,and medical fields,efficient and natural interaction between humans and robots has become key to improving collaboration efficiency and user experience.Gesture recognition,as an intuitive and contactless interaction method,can overcome the limitations of traditional interfaces and enable real-time control and feedback of robot movements and behaviors.This study first reviews mainstream gesture recognition algorithms and their application on different sensing platforms(RGB cameras,depth cameras,and inertial measurement units).It then proposes a gesture recognition method based on multimodal feature fusion and a lightweight deep neural network that balances recognition accuracy with computational efficiency.At system level,a modular human-robot interaction architecture is constructed,comprising perception,decision,and execution layers,and gesture commands are transmitted and mapped to robot actions in real time via the ROS communication protocol.Through multiple comparative experiments on public gesture datasets and a self-collected dataset,the proposed method’s superiority is validated in terms of accuracy,response latency,and system robustness,while user-experience tests assess the interface’s usability.The results provide a reliable technical foundation for robot collaboration and service in complex scenarios,offering broad prospects for practical application and deployment.展开更多
During cellular proliferation DNA undergoes frequent rep-lication cycles in which errors inevitably accumulate.DNA simultaneously faces continuous damage from endogenous sources[e.g.,reactive oxygen species(ROS)]and e...During cellular proliferation DNA undergoes frequent rep-lication cycles in which errors inevitably accumulate.DNA simultaneously faces continuous damage from endogenous sources[e.g.,reactive oxygen species(ROS)]and environmen-tal stressors,such as ultraviolet(UV)and ionizing radiation(IR).Such lesions compromise genomic stability and may escalate into DNA double-strand breaks(DSBs).Failure to repair DSBs can ultimately trigger cell death1.展开更多
基金supported by the National Natural Science Foundation of China(82270386,82070252,and 8207025)the Zhejiang Provincial Medical and Health Science and Technology Plan(2023RC020)the Zhejiang Provincial Natural Science Foundation(LR21H020001).
文摘Background:Cardiac fibrosis following myocardial infarction(MI)drives adverse ventricular remodeling and heart failure,with cardiac fibroblasts(CFs)playing a central role.Glutathione S-transferase mu 1(GSTM1)is an important member of the glutathione S-transferase(GSTs)family,which plays an important role in maintaining cell homeostasis and detoxification.This study investigated the role and mechanism of GSTM1 in post-MI fibrosis.Methods:Multi-omics approaches(proteomics/scRNA-seq)identified GSTM1 as a dysregulated target in post-MI fibroblasts.Using a murine coronary ligation model,we assessed GSTM1 dynamics via molecular profiling,such as Western blotting,immunofluorescence,and real-time quantitative polymerase chain reaction.Adeno-associated virus serotype 9(AAV9)-mediated cardiac-specific GSTM1 overexpression was achieved through systemic delivery.In vitro studies employed transforming growth factor-β(TGF-β)-stimulated primary fibroblasts with siRNA/plasmid interventions.Mechanistic insights were derived from transcriptomics and lipid peroxidation assays.Results:The expression of GSTM1 in mouse CFs after MI was significantly down-regulated at both transcriptional and protein levels.In human dilated cardiomyopathy(DCM)patients with severe heart failure,GSTM1 expression was decreased alongside aggravated fibrosis.Overexpression of GSTM1 in post-MI mice improved cardiac function,while significantly reducing infarct size and fibrosis compared with the control group.In vitro models demonstrated that GSTM1 markedly attenuated collagen secretion and activation of fibroblasts,as well as suppressed their proliferation and migration.Further studies revealed that GSTM1 overexpression significantly inhibited the generation of intracellular and mitochondrial reactive oxygen species(ROS)under pathological conditions,suggesting that GSTM1 exerts an antioxidative stress effect in post-infarction fibroblasts.Further investigation of molecular mechanisms indicated that GSTM1 may suppress the initiation and progression of fibrosis by modulating lipid metabolism and ferroptosis-related pathways.Overexpression of GSTM1 significantly reduced lipid peroxidation and free ferrous iron levels in fibroblasts and mitochondria,markedly decreased ferroptosis-related indicators,and alleviated oxidative lipid levels[such as 12-hydroxyeicosapentaenoic acid(HEPE)and 9-,10-dihydroxy octadecenoic acid(DHOME)]under fibrotic conditions.GSTM1 enhanced the phosphorylation of signal transducer and activator of transcription 3(STAT3),thereby upregulating the downstream expression of glutathione peroxidase 4(GPX4),reducing ROS production,and mitigating fibroblast activation and phenotypic transformation by inhibiting lipid peroxidation.Conclusions:This study identifies GSTM1 as a key inhibitor of fibroblast activation and cardiac fibrosis,highlighting its ability to target ferroptosis through redox regulation.AAV-mediated GSTM1 therapy demonstrates significant therapeutic potential for improving outcomes post-MI.
基金supported by the National Natural Science Foundation of China(32000799 to J.Zhang)Zhejiang Province Key Research and Development Program(2025C02058 to G.Ding)Zhejiang Association of Rehabilitation Medicine Foundation(ZKKY2024003 to G.Ding).
文摘A recent study published in Science by Engleman et al.uncovered that erythropoietin(EPO)secreted by tumor cells can mediate the formation of a noninflamed immune microenvironment and promote tumor progression.1 Specifically,in hepatocellular carcinoma(HCC),tumor cell-derived EPO binds to the erythropoietin receptor(EPOR)on tumor-associated macrophages(TAMs),thereby inhibiting the production of pro-inflammatory cytokines and reactive oxygen species(ROS)by Kupffer cells(KCs)and monocyte-derived macrophages(MDMs).This interaction facilitates the shift of macrophages from an inflamed to a noninflamed phenotype,ultimately promoting the progression of HCC.
基金the financial support from the National Natural Science Foundation of China(Nos.22073025,21603067,and U23A2089)the Program of Science and Technology Plan of the City of Tianjin(No.24JRRCRC00040)+1 种基金Opening Fund of Hubei Key Laboratory of Bioinorganic Chemistry&Materia Medica(No.BCMM202507)the Open Fund of Hubei Key Laboratory of Resources and Chemistry of Chinese Medicine(No.KLRCCM2404).
文摘Recently,reactive oxygen species(ROS)-independent mimetics of oxidase with Au nanoclusters(NCs)as the catalysts and MnO_(2)as electron acceptor have gained attention.In this study,we aim to explore the oxidase-mimicking potential of bovine serum albumin(BSA)-templated metal nanoclusters(BSA-M NCs,where M=Ag,Pt,Cu,or Cd)beyond Au NCs in boosting the oxidation of 3,3',5,5'-tetramethylbenzidine(TMB)by MnO_(2),denoted as BM@Metal.The oxidase-mimetic activity of BM@Metal is independent of ROS and generally enhanced by the incorporation of metal nanoclusters.Notably,this enhancement varies with the metal species,with BSA-Cd exhibiting the highest activity.The X-ray photoelectron spectroscopy(XPS)analysis confirms mixed valence states(Mn(Ⅳ)/Mn(Ⅱ))in BM@Cd.Given that the catalytic activity is closely linked to the substrate adsorption,the label-free isothermal titration calorimetry was employed to probe the affinity between TMB and BSA-M NCs,which provides a robust approach for probing the interface adsorption.The results reveal that the superior catalytic performance of BSA-Cd correlates with enhanced TMB adsorption,likely facilitated by coordination and hydrophobic interactions.Finally,the superior catalytic performance of BSA-M NCs on the oxidation of TMB by MnO_(2)has inspired us to fabricate the assay for analyzing α-glucosidase’s activity.This work not only demonstrates the versatility of metal NCs in constructing ROS-independent oxidase mimetics but also provides interfacial adsorption engineered strategy for the rational design of superior ROS independent mimetics of natural oxidase.
基金supported by the National Natural Science Foundation of China Regional Joint Innovation Fund (No.U22A20524)the Heilongjiang Province Natural Science Foundation Key projects (No.ZD2023C002).
文摘Bisphenol A(BPA)is an industrial pollutant that can cause immune impairment.Selenium acts as an antioxidant,as selenium deficiency often accompanies oxidative stress,resulting in organ damage.This study is the first to demonstrate that BPA and/or selenium deficiency induce pyroptosis and ferroptosis-mediated thymic injury in chicken and chicken lymphoma cell(MDCC-MSB-1)via oxidative stress-induced endoplasmic reticulum(ER)stress.We established a broiler chicken model of BPA and/or selenium deficiency exposure and collected thymus samples as research subjects after 42 days.The results demonstrated that BPA or selenium deficiency led to a decrease in antioxidant enzyme activities(T-AOC,CAT,and GSH-Px),accumulation of peroxides(H2O2 and MDA),significant upregulation of ER stress-relatedmarkers(GRP78,IER 1,PERK,EIF-2α,ATF4,and CHOP),a significant increase in iron ion levels,significant upregulation of pyroptosis-related gene(NLRP3,ASC,Caspase1,GSDMD,IL-18 and IL-1β),significantly increase ferroptosis-related genes(TFRC,COX2)and downregulate GPX4,HO-1,FTH,NADPH.In vitro experiments conducted in MDCC-MSB-1 cells confirmed the results,demonstrating that the addition of antioxidant(NAC),ER stress inhibitor(TUDCA)and pyroptosis inhibitor(Vx765)alleviated oxidative stress,endoplasmic reticulum stress,pyroptosis,and ferroptosis.Overall,this study concludes that the combined effects of oxidative stress and ER stress mediate pyroptosis and ferroptosis in chicken thymus induced by BPA exposure and selenium deficiency.
基金supported by the National Natural Science Foundation of China(32100322,32460112,32060100)and the Science and Technology Department of Guizhou Province(QKHZC[2022]019).
文摘Teucrifarides A-D(1-4),four previously unreported neo-clerodane-type diterpenoids,combined with sixteen known analogs(5-20),were purified from Teucrium quadrifarium.The absolute forma of compounds 1-4 were determined via spectroscopic and ECD calculation methods,together with X-ray crystallography experiments.Among them,compound 1 possessed a 5,20-epoxy ring featuring a unique cage-like 12-oxatricyclo[5.3.2.0^(1,6)]undecane skeleton.Meanwhile,2 incorporated a 6,20-epoxy ring with a novel 12-oxatricyclo[6.2.2.0^(2,7)]undecane skeleton.Compounds 1 and 12 exhibited significant inhibitory effects against HT-22 cells ferroptosis induced by RSL3,with EC_(50)values of 11.8±1.0μM,and 4.52±1.24μM,respectively.Moreover,ROS accumulation in HT22 cells treated with compound 1 was also observed.
文摘With the growing application of intelligent robots in service,manufacturing,and medical fields,efficient and natural interaction between humans and robots has become key to improving collaboration efficiency and user experience.Gesture recognition,as an intuitive and contactless interaction method,can overcome the limitations of traditional interfaces and enable real-time control and feedback of robot movements and behaviors.This study first reviews mainstream gesture recognition algorithms and their application on different sensing platforms(RGB cameras,depth cameras,and inertial measurement units).It then proposes a gesture recognition method based on multimodal feature fusion and a lightweight deep neural network that balances recognition accuracy with computational efficiency.At system level,a modular human-robot interaction architecture is constructed,comprising perception,decision,and execution layers,and gesture commands are transmitted and mapped to robot actions in real time via the ROS communication protocol.Through multiple comparative experiments on public gesture datasets and a self-collected dataset,the proposed method’s superiority is validated in terms of accuracy,response latency,and system robustness,while user-experience tests assess the interface’s usability.The results provide a reliable technical foundation for robot collaboration and service in complex scenarios,offering broad prospects for practical application and deployment.
基金supported by grants fromthe Shenzhen Medical Research Fund(Grant No.A2302040).
文摘During cellular proliferation DNA undergoes frequent rep-lication cycles in which errors inevitably accumulate.DNA simultaneously faces continuous damage from endogenous sources[e.g.,reactive oxygen species(ROS)]and environmen-tal stressors,such as ultraviolet(UV)and ionizing radiation(IR).Such lesions compromise genomic stability and may escalate into DNA double-strand breaks(DSBs).Failure to repair DSBs can ultimately trigger cell death1.
