[Objectives]To assess the effects of endophytic bacteria on the growth,antioxidant responses,and the production of key secondary metabolites in Emilia prenanthoidea DC.[Methods]Three endophytic strains(H1,H2,L1)were i...[Objectives]To assess the effects of endophytic bacteria on the growth,antioxidant responses,and the production of key secondary metabolites in Emilia prenanthoidea DC.[Methods]Three endophytic strains(H1,H2,L1)were inoculated onto tissue-cultured seedlings and cultivated for 20 d under greenhouse conditions.Growth traits,reactive oxygen species(ROS)indicators,antioxidant enzyme activities,and the content of chlorogenic acid and quercetin were analyzed using one-way ANOVA followed by Tukey s test.[Results]Bacterial inoculation significantly enhanced plant performance.Treatment H2 increased plant height by 27%,chlorophyll content by 73%,and fresh weight by 31%.Levels of ROS(O^(-)_(2),H_(2)O_(2))and MDA decreased markedly,whereas the activities of POD and CAT increased.Additionally,the content of chlorogenic acid and quercetin increased by up to 67%and 64%,respectively,with both H2 and L1 treatments showing the most pronounced effects.[Conclusions]Endophytic bacteria markedly improve growth,redox balance,and phenolic accumulation in E.prenanthoidea.Strain H2 represents a promising bioinoculant for improving the medicinal quality of this species.展开更多
Objective:Glioblastoma(GB)therapy is challenged by tumor heterogeneity and multidrug resistance(MDR),highlighting the need for effective therapies.This study aimed to explore the combined anticancer effects of Sunitin...Objective:Glioblastoma(GB)therapy is challenged by tumor heterogeneity and multidrug resistance(MDR),highlighting the need for effective therapies.This study aimed to explore the combined anticancer effects of Sunitinib(SNB)and Fenofibrate(FEN)on U87 cells.Methods:U87 cells were exposed to SNB,FEN,or their combination for 24 h,followed by evaluations of cell viability,migration,and clonogenic survival using MTT,scratch,and colony formation assays.Intracellular reactive oxygen species(ROS)were quantified via the 2′,7′-dichlorofluorescein assay,while mitochondrial membrane potential(MMP)was assessed using JC-1 red/green fluorescence.Molecular docking was performed to investigate SNB and FEN interactions with multiple molecular targets,including topoisomerase II(TOP-II),c-Jun N-terminal kinase(JNK),histone deacetylase 2(HDAC2),cyclooxygenase-2(COX-2),matrix metalloproteinase-9(MMP-9),cytochrome P4503A4(CYP3A4),glutathione peroxidase 4(GPX4),glutathione Stransferase(GST),heme oxygenase-1(HO-1),and 5-lipoxygenase(5-LOX).Results:The results demonstrated that both SNB and FEN significantly reduced U87 cell viability,migration,and clonogenic potential,with the combination treatment exhibiting synergistic cytotoxicity.SNB alone markedly increased ROS levels,while FEN,individually or in combination,reduced oxidative stress.Although SNB diminished mitochondrial membrane potential,cotreatment with FEN restored MMP values close to control levels.Docking analyses revealed that SNB displayed strong affinities for TOP-II,JNK,and HDAC2,whereas FEN preferentially interacted with MMP-9,COX-2,CYP3A4,and GPX4,suggesting complementary mechanisms targeting oxidative stress,inflammation,and programmed cell death regulation.Conclusion:The combination of SNB and FEN represents a promising multi-targeted therapeutic approach against GB.SNB and FEN combination capable of modulating and reprogramming key molecular pathways involved in GB progression and MDR.展开更多
视觉同步定位与建图(simultaneous localization and mapping,SLAM)是实现移动机器人自主定位并构建环境地图的关键环节。SLAM技术虽能精确重建环境几何结构,却难以为机器人提供执行复杂任务所需的语义理解能力;建筑信息模型(building i...视觉同步定位与建图(simultaneous localization and mapping,SLAM)是实现移动机器人自主定位并构建环境地图的关键环节。SLAM技术虽能精确重建环境几何结构,却难以为机器人提供执行复杂任务所需的语义理解能力;建筑信息模型(building information model,BIM)包含丰富的建筑信息,但与机器人操作系统(robot operating system,ROS)之间存在显著的数据格式和表达方式差异,且现有研究多采用人工方式进行转换,效率低下难以规模化应用,且室内环境并非静态不变,从而会影响机器人的导航决策。因此,提出一种集成BIM数据的ROS室内语义地图构建与动态更新方法。通过研发工业基础类(industry foundation classes,IFC)到统一机器人描述格式(unified robot description format,URDF)自动转换器,实现从BIM到机器人仿真环境的自动化建模;融合YOLOv8与随机采样一致性(random sample consensus,RANSAC)算法,建立视觉驱动的语义地图动态更新机制。结果表明,静态建筑元素还原准确率达98%以上,动态物体识别精度达0.9以上,显著提升了语义地图的自动化程度、知识丰富度及环境适应性。展开更多
Hepatic fibrosis is regulated by the synergistic actions of various cells and cytokines,with the activation and proliferation of hepatic stellate cells(HSCs) being considered the central event in this process.To achie...Hepatic fibrosis is regulated by the synergistic actions of various cells and cytokines,with the activation and proliferation of hepatic stellate cells(HSCs) being considered the central event in this process.To achieve specific targeting of activated hepatic stellate cells(a HSCs) and precise treatment of hepatic fibrosis,this study developed a dual-functional drug delivery system(SIL/c RGD-PEG-PPS PMs) with both targeting and responsive release capabilities.It aims to target the αvβ 3 receptor specifically expressed on the surface of a HSCs using the cyclic peptide c(RGDyk),and to exploit the high reactive oxygen species(ROS) level in the cellular microenvironment to achieve concentrated burst release of drugs at the pathological sites of hepatic fibrosis.Based on multiple assessments,SIL/c RGD-PEG-PPS PMs specifically enhanced the targeted delivery of silybin(SIL) to a HSCs,inhibited the proliferation and migration of a HSCs,and exhibited good biosafety.Additionally,it demonstrated excellent anti-fibrotic activity in fibrotic mice.In summary,this study shows great potential in targeted treatment of hepatic fibrosis and provides a multifunctional tool for advancing the research and therapeutic strategies of hepatic fibrosis.展开更多
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
文摘[Objectives]To assess the effects of endophytic bacteria on the growth,antioxidant responses,and the production of key secondary metabolites in Emilia prenanthoidea DC.[Methods]Three endophytic strains(H1,H2,L1)were inoculated onto tissue-cultured seedlings and cultivated for 20 d under greenhouse conditions.Growth traits,reactive oxygen species(ROS)indicators,antioxidant enzyme activities,and the content of chlorogenic acid and quercetin were analyzed using one-way ANOVA followed by Tukey s test.[Results]Bacterial inoculation significantly enhanced plant performance.Treatment H2 increased plant height by 27%,chlorophyll content by 73%,and fresh weight by 31%.Levels of ROS(O^(-)_(2),H_(2)O_(2))and MDA decreased markedly,whereas the activities of POD and CAT increased.Additionally,the content of chlorogenic acid and quercetin increased by up to 67%and 64%,respectively,with both H2 and L1 treatments showing the most pronounced effects.[Conclusions]Endophytic bacteria markedly improve growth,redox balance,and phenolic accumulation in E.prenanthoidea.Strain H2 represents a promising bioinoculant for improving the medicinal quality of this species.
基金funding program(ORF-2025-1037)at King Saud University,Riyadh,Saudi Arabia.
文摘Objective:Glioblastoma(GB)therapy is challenged by tumor heterogeneity and multidrug resistance(MDR),highlighting the need for effective therapies.This study aimed to explore the combined anticancer effects of Sunitinib(SNB)and Fenofibrate(FEN)on U87 cells.Methods:U87 cells were exposed to SNB,FEN,or their combination for 24 h,followed by evaluations of cell viability,migration,and clonogenic survival using MTT,scratch,and colony formation assays.Intracellular reactive oxygen species(ROS)were quantified via the 2′,7′-dichlorofluorescein assay,while mitochondrial membrane potential(MMP)was assessed using JC-1 red/green fluorescence.Molecular docking was performed to investigate SNB and FEN interactions with multiple molecular targets,including topoisomerase II(TOP-II),c-Jun N-terminal kinase(JNK),histone deacetylase 2(HDAC2),cyclooxygenase-2(COX-2),matrix metalloproteinase-9(MMP-9),cytochrome P4503A4(CYP3A4),glutathione peroxidase 4(GPX4),glutathione Stransferase(GST),heme oxygenase-1(HO-1),and 5-lipoxygenase(5-LOX).Results:The results demonstrated that both SNB and FEN significantly reduced U87 cell viability,migration,and clonogenic potential,with the combination treatment exhibiting synergistic cytotoxicity.SNB alone markedly increased ROS levels,while FEN,individually or in combination,reduced oxidative stress.Although SNB diminished mitochondrial membrane potential,cotreatment with FEN restored MMP values close to control levels.Docking analyses revealed that SNB displayed strong affinities for TOP-II,JNK,and HDAC2,whereas FEN preferentially interacted with MMP-9,COX-2,CYP3A4,and GPX4,suggesting complementary mechanisms targeting oxidative stress,inflammation,and programmed cell death regulation.Conclusion:The combination of SNB and FEN represents a promising multi-targeted therapeutic approach against GB.SNB and FEN combination capable of modulating and reprogramming key molecular pathways involved in GB progression and MDR.
文摘视觉同步定位与建图(simultaneous localization and mapping,SLAM)是实现移动机器人自主定位并构建环境地图的关键环节。SLAM技术虽能精确重建环境几何结构,却难以为机器人提供执行复杂任务所需的语义理解能力;建筑信息模型(building information model,BIM)包含丰富的建筑信息,但与机器人操作系统(robot operating system,ROS)之间存在显著的数据格式和表达方式差异,且现有研究多采用人工方式进行转换,效率低下难以规模化应用,且室内环境并非静态不变,从而会影响机器人的导航决策。因此,提出一种集成BIM数据的ROS室内语义地图构建与动态更新方法。通过研发工业基础类(industry foundation classes,IFC)到统一机器人描述格式(unified robot description format,URDF)自动转换器,实现从BIM到机器人仿真环境的自动化建模;融合YOLOv8与随机采样一致性(random sample consensus,RANSAC)算法,建立视觉驱动的语义地图动态更新机制。结果表明,静态建筑元素还原准确率达98%以上,动态物体识别精度达0.9以上,显著提升了语义地图的自动化程度、知识丰富度及环境适应性。
基金supported by the financial assistance from Natural Science Fund Project of Science and Technology Department of Jilin Province (Nos.YDZJ202301ZYTS141,YDZJ202501ZYTS793)。
文摘Hepatic fibrosis is regulated by the synergistic actions of various cells and cytokines,with the activation and proliferation of hepatic stellate cells(HSCs) being considered the central event in this process.To achieve specific targeting of activated hepatic stellate cells(a HSCs) and precise treatment of hepatic fibrosis,this study developed a dual-functional drug delivery system(SIL/c RGD-PEG-PPS PMs) with both targeting and responsive release capabilities.It aims to target the αvβ 3 receptor specifically expressed on the surface of a HSCs using the cyclic peptide c(RGDyk),and to exploit the high reactive oxygen species(ROS) level in the cellular microenvironment to achieve concentrated burst release of drugs at the pathological sites of hepatic fibrosis.Based on multiple assessments,SIL/c RGD-PEG-PPS PMs specifically enhanced the targeted delivery of silybin(SIL) to a HSCs,inhibited the proliferation and migration of a HSCs,and exhibited good biosafety.Additionally,it demonstrated excellent anti-fibrotic activity in fibrotic mice.In summary,this study shows great potential in targeted treatment of hepatic fibrosis and provides a multifunctional tool for advancing the research and therapeutic strategies of hepatic fibrosis.
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.
