BACKGROUND:Xuebijing(XBJ)can alleviate the inflammatory response,improve organ function,and shorten the intensive care unit(ICU)stay in patients with pyogenic liver abscess(PLA)complicated with sepsis,but the molecula...BACKGROUND:Xuebijing(XBJ)can alleviate the inflammatory response,improve organ function,and shorten the intensive care unit(ICU)stay in patients with pyogenic liver abscess(PLA)complicated with sepsis,but the molecular mechanisms have not been elucidated.This study aimed to explore the molecular mechanism of XBJ in treating PLA complicated with sepsis using a network pharmacology approach.METHODS:The active ingredients and targets of XBJ were retrieved from the ETCM database.Potential targets related to PLA and sepsis were retrieved from the GeneCards,PharmGKB,DisGeNet,Online Mendelian Inheritance in Man(OMIM),Therapeutic Targets Database(TTD),and DrugBank databases.The targets of PLA complicated with sepsis were mapped to the targets of XBJ to identify potential treatment targets.Protein-protein interaction networks were analyzed using the STRING database.Potential treatment targets were imported into the Metascape platform for Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.Molecular docking was performed to validate the interactions between active ingredients and core targets.RESULTS:XBJ was found to have 54 potential treatment targets for PLA complicated with sepsis.Interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor(TNF)were identifi ed as core targets.KEGG enrichment analysis revealed important pathways,including the interleukin-17(IL-17)signaling pathway,the TNF signaling pathway,the nuclear factor-kappa B(NF-κB)signaling pathway,and the Toll-like receptor(TLR)signaling pathway.Molecular docking experiments indicated stable binding between XBJ active ingredients and core targets.CONCLUSION:XBJ may exert therapeutic eff ects on PLA complicated with sepsis by modulating signaling pathways,such as the IL-17,TNF,NF-κB,and TLR pathways,and targeting IL-1β,IL-6,and TNF.展开更多
BACKGROUND Extracellular vesicles(EVs)derived from hypoxia-preconditioned(HP)mesenchymal stem cells(MSCs)have better cardioprotective effects against myocardial infarction(MI)in the early stage than EVs isolated from ...BACKGROUND Extracellular vesicles(EVs)derived from hypoxia-preconditioned(HP)mesenchymal stem cells(MSCs)have better cardioprotective effects against myocardial infarction(MI)in the early stage than EVs isolated from normoxic(NC)-MSCs.However,the cardioprotective mechanisms of HP-EVs are not fully understood.AIM To explore the cardioprotective mechanism of EVs derived from HP MSCs.METHODS We evaluated the cardioprotective effects of HP-EVs or NC-EVs from mouse adipose-derived MSCs(ADSCs)following hypoxia in vitro or MI in vivo,in order to improve the survival of cardiomyocytes(CMs)and restore cardiac function.The degree of CM apoptosis in each group was assessed by the terminal deoxynucleotidyl transferase dUTP nick end-labeling and Annexin V/PI assays.MicroRNA(miRNA)sequencing was used to investigate the functional RNA diversity between HP-EVs and NC-EVs from mouse ADSCs.The molecular mechanism of EVs in mediating thioredoxin-interacting protein(TXNIP)was verified by the dual-luciferase reporter assay.Co-immunoprecipitation,western blotting,and immunofluorescence were performed to determine if TXNIP is involved in hypoxia-inducible factor-1 alpha(HIF-1α)ubiquitination and degradation via the chromosomal region maintenance-1(CRM-1)-dependent nuclear transport pathway.RESULTS HP-EVs derived from MSCs reduced both infarct size(necrosis area)and apoptotic degree to a greater extent than NC-EVs from CMs subjected to hypoxia in vitro and mice with MI in vivo.Sequencing of EV-associated miRNAs showed the upregulation of 10 miRNAs predicted to bind TXNIP,an oxidative stress-associated protein.We showed miRNA224-5p,the most upregulated miRNA in HP-EVs,directly combined the 3’untranslated region of TXNIP and demonstrated its critical protective role against hypoxia-mediated CM injury.Our results demonstrated that MI triggered TXNIP-mediated HIF-1αubiquitination and degradation in the CRM-1-mediated nuclear transport pathway in CMs,which led to aggravated injury and hypoxia tolerance in CMs in the early stage of MI.CONCLUSION The anti-apoptotic effects of HP-EVs in alleviating MI and the hypoxic conditions of CMs until reperfusion therapy may partly result from EV miR-224-5p targeting TXNIP.展开更多
Sodium metal batteries(SMBs)are rising as viable alternatives to lithium-ion systems due to their superior energy density and sodium's relative abundance.However,SMBs face significant impediments,particularly the ...Sodium metal batteries(SMBs)are rising as viable alternatives to lithium-ion systems due to their superior energy density and sodium's relative abundance.However,SMBs face significant impediments,particularly the exceedingly high negative-to-positive capacity ratios(N/P ratios)which severely encumber energy density and hinder their practical application.Herein,a novel nucleophilic Na_(3)P interphase on aluminum foil has been designed to significantly lower the nucleation energy barrier for sodium atom deposition,resulting in a remarkable reduction of nucleation overpotential and efficient mitigation of dendritic growth at high sodium deposition of 5 mA h cm^(−2).The interphase promotes stable cycling in anode-less SMB configurations with a low N/P ratio of 1.4 and high cathode mass loading of 11.5 mg cm^(−2),and demonstrates a substantial increase in high capacity retention of 92.4%after 500 cycles even under 1 C rate condition.This innovation signifies a promising leap forward in the development of high-energy-density,anode-less SMBs,offering a potential solution to the longstanding issues of cycle stability and energy efficiency.展开更多
Lithium(Li)metal anodes have been regarded as the most promising candidates for high energy density second-ary lithium batteries due to their high specific capacity and low redox potential.However,the issues of Li den...Lithium(Li)metal anodes have been regarded as the most promising candidates for high energy density second-ary lithium batteries due to their high specific capacity and low redox potential.However,the issues of Li dendrites caused by nonuniform lithium deposition during battery cycling severely hinder the practical applications of Li metal anodes.Herein,a hybrid of black phosphorus-graphite(BP-G)is introduced to serve as an artificial protective layer for the Li met-al anode.The two-dimensional few-layer BP,which is lithophilic,combined with the high electronic conductive graphite can act as a regulator to adjust the migration of Li ions,delivering a uniform and stable lithium deposition.As the growth of lithium dendrites is inhibited,the utilization of Li metal achieves>98.5%for over 500 cycles in Li‖Cu half cells,and the life span is maintained over 2000 h in Li‖Li symmetric cells with a low voltage hysteresis of 50 mV.Moreover,the LiFePO_(4)‖Li full cell with a BP-G Li-ion regulator presents significantly better specific capacity and cycling stability than that with the bare Li metal anode.Therefore,the introduction of the BP-G Li-ion regulator is demonstrated to be an effect-ive approach to enable stable lithium deposition for rechargeable Li metal batteries.展开更多
BACKGROUND Myocardial ischemia-reperfusion injury(MIRI)poses a prevalent challenge in current reperfusion therapies,with an absence of efficacious interventions to address the underlying causes.AIM To investigate whet...BACKGROUND Myocardial ischemia-reperfusion injury(MIRI)poses a prevalent challenge in current reperfusion therapies,with an absence of efficacious interventions to address the underlying causes.AIM To investigate whether the extracellular vesicles(EVs)secreted by adipose mesenchymal stem cells(ADSCs)derived from subcutaneous inguinal adipose tissue(IAT)underγ-aminobutyric acid(GABA)induction(GABA-EVs^(IAT))demonstrate a more pronounced inhibitory effect on mitochondrial oxidative stress and elucidate the underlying mechanisms.METHODS We investigated the potential protective effects of EVs derived from mouse ADSCs pretreated with GABA.We assessed cardiomyocyte injury using terminal deoxynucleotidyl transferase dUTP nick end-labeling and Annexin V/propidium iodide assays.The integrity of cardiomyocyte mitochondria morphology was assessed using electron microscopy across various intervention backgrounds.To explore the functional RNA diversity between EVs^(IAT)and GABA-EVs^(IAT),we employed microRNA(miR)sequencing.Through a dual-luciferase reporter assay,we confirmed the molecular mechanism by which EVs mediate thioredoxin-interacting protein(TXNIP).Western blotting and immunofluorescence were conducted to determine how TXNIP is involved in mediation of oxidative stress and mitochondrial dysfunction.RESULTS Our study demonstrates that,under the influence of GABA,ADSCs exhibit an increased capacity to encapsulate a higher abundance of miR-21-5p within EVs.Consequently,this leads to a more pronounced inhibitory effect on mitochondrial oxidative stress compared to EVs from ADSCs without GABA intervention,ultimately resulting in myocardial protection.On a molecular mechanism level,EVs regulate the expression of TXNIP and mitigating excessive oxidative stress in mitochondria during MIRI process to rescue cardiomyocytes.CONCLUSION Administration of GABA leads to the specific loading of miR-21-5p into EVs by ADSCs,thereby regulating the expression of TXNIP.The EVs derived from ADSCs treated with GABA effectively ameliorates mitochondrial oxidative stress and mitigates cardiomyocytes damage in the pathological process of MIRI.展开更多
Doping strategies have been widely demonstrated as effective approaches to tailor microwave absorption properties in various material systems.However,achieving high-entropy doping(HED)in MoS_(2)while minimizing phase ...Doping strategies have been widely demonstrated as effective approaches to tailor microwave absorption properties in various material systems.However,achieving high-entropy doping(HED)in MoS_(2)while minimizing phase ratio interference,effectively integrating multiple transition metal element substitutions,and elucidating the underlying absorption mechanisms remain significant challenges.In this work,we develop a modular in situ/post solvothermal doping process to realize the cooperative incorporation of multiple dopants into a metallic-phase MoS_(2)(1T-MoS_(2))host.For the first time,we systematically investigate the effects of multiple-element codoping,including high-density lattice strain,crystalline defects,localized charge accumulation,and redistribution,which significantly increase dipole polarization loss.Owing to the balanced impedance characteristics and coordinated polarization/conductive losses enabled by HED engineering,the WVNbTaRu-MoS_(2)sample achieves a broadband effective absorption bandwidth of 7.65 GHz,which is more than double that of its undoped counterparts.Through combinatorial screening,we proposed 31 feasible doping configurations and experimentally validated 9 variants,establishing a foundational framework for designing advanced MoS_(2)-based absorbers with tailored electromagnetic properties.This study provides innovative insights and pathways for the rational design of high-performance transition metal dichalcogenide-based microwave absorbers.展开更多
基金supported by Hunan Province Key Research and Development Program(2020SKC2004).
文摘BACKGROUND:Xuebijing(XBJ)can alleviate the inflammatory response,improve organ function,and shorten the intensive care unit(ICU)stay in patients with pyogenic liver abscess(PLA)complicated with sepsis,but the molecular mechanisms have not been elucidated.This study aimed to explore the molecular mechanism of XBJ in treating PLA complicated with sepsis using a network pharmacology approach.METHODS:The active ingredients and targets of XBJ were retrieved from the ETCM database.Potential targets related to PLA and sepsis were retrieved from the GeneCards,PharmGKB,DisGeNet,Online Mendelian Inheritance in Man(OMIM),Therapeutic Targets Database(TTD),and DrugBank databases.The targets of PLA complicated with sepsis were mapped to the targets of XBJ to identify potential treatment targets.Protein-protein interaction networks were analyzed using the STRING database.Potential treatment targets were imported into the Metascape platform for Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.Molecular docking was performed to validate the interactions between active ingredients and core targets.RESULTS:XBJ was found to have 54 potential treatment targets for PLA complicated with sepsis.Interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor(TNF)were identifi ed as core targets.KEGG enrichment analysis revealed important pathways,including the interleukin-17(IL-17)signaling pathway,the TNF signaling pathway,the nuclear factor-kappa B(NF-κB)signaling pathway,and the Toll-like receptor(TLR)signaling pathway.Molecular docking experiments indicated stable binding between XBJ active ingredients and core targets.CONCLUSION:XBJ may exert therapeutic eff ects on PLA complicated with sepsis by modulating signaling pathways,such as the IL-17,TNF,NF-κB,and TLR pathways,and targeting IL-1β,IL-6,and TNF.
基金Supported by National Natural Science Foundation of China,No. 81870264 and No. 81470546the Shanghai Committee of Science and Technology,No. 18411950500+1 种基金the Major Disease Joint Project of Shanghai Health System,No. 2014ZYJB0501Talent Cultivation Project of The Ninth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine,No. JC202005
文摘BACKGROUND Extracellular vesicles(EVs)derived from hypoxia-preconditioned(HP)mesenchymal stem cells(MSCs)have better cardioprotective effects against myocardial infarction(MI)in the early stage than EVs isolated from normoxic(NC)-MSCs.However,the cardioprotective mechanisms of HP-EVs are not fully understood.AIM To explore the cardioprotective mechanism of EVs derived from HP MSCs.METHODS We evaluated the cardioprotective effects of HP-EVs or NC-EVs from mouse adipose-derived MSCs(ADSCs)following hypoxia in vitro or MI in vivo,in order to improve the survival of cardiomyocytes(CMs)and restore cardiac function.The degree of CM apoptosis in each group was assessed by the terminal deoxynucleotidyl transferase dUTP nick end-labeling and Annexin V/PI assays.MicroRNA(miRNA)sequencing was used to investigate the functional RNA diversity between HP-EVs and NC-EVs from mouse ADSCs.The molecular mechanism of EVs in mediating thioredoxin-interacting protein(TXNIP)was verified by the dual-luciferase reporter assay.Co-immunoprecipitation,western blotting,and immunofluorescence were performed to determine if TXNIP is involved in hypoxia-inducible factor-1 alpha(HIF-1α)ubiquitination and degradation via the chromosomal region maintenance-1(CRM-1)-dependent nuclear transport pathway.RESULTS HP-EVs derived from MSCs reduced both infarct size(necrosis area)and apoptotic degree to a greater extent than NC-EVs from CMs subjected to hypoxia in vitro and mice with MI in vivo.Sequencing of EV-associated miRNAs showed the upregulation of 10 miRNAs predicted to bind TXNIP,an oxidative stress-associated protein.We showed miRNA224-5p,the most upregulated miRNA in HP-EVs,directly combined the 3’untranslated region of TXNIP and demonstrated its critical protective role against hypoxia-mediated CM injury.Our results demonstrated that MI triggered TXNIP-mediated HIF-1αubiquitination and degradation in the CRM-1-mediated nuclear transport pathway in CMs,which led to aggravated injury and hypoxia tolerance in CMs in the early stage of MI.CONCLUSION The anti-apoptotic effects of HP-EVs in alleviating MI and the hypoxic conditions of CMs until reperfusion therapy may partly result from EV miR-224-5p targeting TXNIP.
基金funding support from the National Natural Science Foundation of China (22125902, 22109150, 22279126, U2032202, and 21975243)the DNL cooperation Fund, CAS (DNL202020)+1 种基金the National Key R&D Program of China (no. 2022YFA1504101)the Anhui Provincial Natural Science Foundation (2108085QB65)
文摘Sodium metal batteries(SMBs)are rising as viable alternatives to lithium-ion systems due to their superior energy density and sodium's relative abundance.However,SMBs face significant impediments,particularly the exceedingly high negative-to-positive capacity ratios(N/P ratios)which severely encumber energy density and hinder their practical application.Herein,a novel nucleophilic Na_(3)P interphase on aluminum foil has been designed to significantly lower the nucleation energy barrier for sodium atom deposition,resulting in a remarkable reduction of nucleation overpotential and efficient mitigation of dendritic growth at high sodium deposition of 5 mA h cm^(−2).The interphase promotes stable cycling in anode-less SMB configurations with a low N/P ratio of 1.4 and high cathode mass loading of 11.5 mg cm^(−2),and demonstrates a substantial increase in high capacity retention of 92.4%after 500 cycles even under 1 C rate condition.This innovation signifies a promising leap forward in the development of high-energy-density,anode-less SMBs,offering a potential solution to the longstanding issues of cycle stability and energy efficiency.
基金supported by the National Natural Science Foundation of China(22109150)the Fundamental Research Funds for the Central Universities(YD3430002001)the Natural Science Foundation of Anhui Province(2108085QB65).
文摘Lithium(Li)metal anodes have been regarded as the most promising candidates for high energy density second-ary lithium batteries due to their high specific capacity and low redox potential.However,the issues of Li dendrites caused by nonuniform lithium deposition during battery cycling severely hinder the practical applications of Li metal anodes.Herein,a hybrid of black phosphorus-graphite(BP-G)is introduced to serve as an artificial protective layer for the Li met-al anode.The two-dimensional few-layer BP,which is lithophilic,combined with the high electronic conductive graphite can act as a regulator to adjust the migration of Li ions,delivering a uniform and stable lithium deposition.As the growth of lithium dendrites is inhibited,the utilization of Li metal achieves>98.5%for over 500 cycles in Li‖Cu half cells,and the life span is maintained over 2000 h in Li‖Li symmetric cells with a low voltage hysteresis of 50 mV.Moreover,the LiFePO_(4)‖Li full cell with a BP-G Li-ion regulator presents significantly better specific capacity and cycling stability than that with the bare Li metal anode.Therefore,the introduction of the BP-G Li-ion regulator is demonstrated to be an effect-ive approach to enable stable lithium deposition for rechargeable Li metal batteries.
基金Supported by the National Natural Science Foundation of China,No.82200270.
文摘BACKGROUND Myocardial ischemia-reperfusion injury(MIRI)poses a prevalent challenge in current reperfusion therapies,with an absence of efficacious interventions to address the underlying causes.AIM To investigate whether the extracellular vesicles(EVs)secreted by adipose mesenchymal stem cells(ADSCs)derived from subcutaneous inguinal adipose tissue(IAT)underγ-aminobutyric acid(GABA)induction(GABA-EVs^(IAT))demonstrate a more pronounced inhibitory effect on mitochondrial oxidative stress and elucidate the underlying mechanisms.METHODS We investigated the potential protective effects of EVs derived from mouse ADSCs pretreated with GABA.We assessed cardiomyocyte injury using terminal deoxynucleotidyl transferase dUTP nick end-labeling and Annexin V/propidium iodide assays.The integrity of cardiomyocyte mitochondria morphology was assessed using electron microscopy across various intervention backgrounds.To explore the functional RNA diversity between EVs^(IAT)and GABA-EVs^(IAT),we employed microRNA(miR)sequencing.Through a dual-luciferase reporter assay,we confirmed the molecular mechanism by which EVs mediate thioredoxin-interacting protein(TXNIP).Western blotting and immunofluorescence were conducted to determine how TXNIP is involved in mediation of oxidative stress and mitochondrial dysfunction.RESULTS Our study demonstrates that,under the influence of GABA,ADSCs exhibit an increased capacity to encapsulate a higher abundance of miR-21-5p within EVs.Consequently,this leads to a more pronounced inhibitory effect on mitochondrial oxidative stress compared to EVs from ADSCs without GABA intervention,ultimately resulting in myocardial protection.On a molecular mechanism level,EVs regulate the expression of TXNIP and mitigating excessive oxidative stress in mitochondria during MIRI process to rescue cardiomyocytes.CONCLUSION Administration of GABA leads to the specific loading of miR-21-5p into EVs by ADSCs,thereby regulating the expression of TXNIP.The EVs derived from ADSCs treated with GABA effectively ameliorates mitochondrial oxidative stress and mitigates cardiomyocytes damage in the pathological process of MIRI.
基金supported by the National Natural Science Foundation of China(Nos.52432002 and 52372041)the Central Guidance for Local Technology Development Special Fund(No.ZY25JD14)the Fundamental Research Funds for the Central Universities(No.HIT.DZJJ.2025002).
文摘Doping strategies have been widely demonstrated as effective approaches to tailor microwave absorption properties in various material systems.However,achieving high-entropy doping(HED)in MoS_(2)while minimizing phase ratio interference,effectively integrating multiple transition metal element substitutions,and elucidating the underlying absorption mechanisms remain significant challenges.In this work,we develop a modular in situ/post solvothermal doping process to realize the cooperative incorporation of multiple dopants into a metallic-phase MoS_(2)(1T-MoS_(2))host.For the first time,we systematically investigate the effects of multiple-element codoping,including high-density lattice strain,crystalline defects,localized charge accumulation,and redistribution,which significantly increase dipole polarization loss.Owing to the balanced impedance characteristics and coordinated polarization/conductive losses enabled by HED engineering,the WVNbTaRu-MoS_(2)sample achieves a broadband effective absorption bandwidth of 7.65 GHz,which is more than double that of its undoped counterparts.Through combinatorial screening,we proposed 31 feasible doping configurations and experimentally validated 9 variants,establishing a foundational framework for designing advanced MoS_(2)-based absorbers with tailored electromagnetic properties.This study provides innovative insights and pathways for the rational design of high-performance transition metal dichalcogenide-based microwave absorbers.
