A geomagnetic field is a significant factor dur-ing the growth and development of trees.Changes in the magnetic field(MF)will result in reactions at the biochemi-cal,molecular,cellular and gene levels.However,it is no...A geomagnetic field is a significant factor dur-ing the growth and development of trees.Changes in the magnetic field(MF)will result in reactions at the biochemi-cal,molecular,cellular and gene levels.However,it is not clear how a magnetic field affects metabolism and home-ostasis under stressful conditions such as salinity.In this study,a novel method was developed of a static magnetic field(SMF)to investigate magnetobiological changes in trees.The results show that pre-treatment of poplar(Popu-lus×euramericana‘Neva’)cuttings with a static magnetic field significantly mitigated the negative effects of salinity stress on their growth and physiological activities.Bio-chemical assays revealed that several chemical messengers,including hydrogen peroxide(H2O2)and O_(2)^(·-),were sig-nificantly improved in roots treated with salt,implying an increase reactive oxygen species.A static magnetic field also significantly increased proline concentrations,soluble protein contents,and CAT and SOD activities.Electrophysiological experiments further revealed that pre-treatment with a static magnetic field remarkably decreased salt-induced Na^(+)influx and H^(+)efflux which control plant salt tolerance.In pharmacological experiments,because the Na^(+)/H^(+)cor-relation was closely related to the SMF-activated plasma membrane and Na^(+)antiporter activity alleviated the mas-sive accumulation of salt-induced reactive oxygen spe-cies(ROS)within the roots.In addition,a static magnetic field dramatically increased the transcriptional activity of stress-responsive genes,including PtrRBOHD and PtrHA5.Together,these results indicate that SMF reduced Na^(+)influx by activating Na^(+)/H^(+)antiporters and plasma membrane H^(+)-ATPase to effectively maintain homeostasis by regu-lating the reactive oxygen species system and cytoplasmic osmotic potential.Ultimately,these static magnetic field methods improved salt tolerance in poplar cuttings,and,for future research,similar methods could be applied to other plants.展开更多
Salt stress severely limits rice growth and productivity.Auxin signaling has a well-documented role in development,but its role in rice salt stress responses is far from clear.In this study,we identified OsARF12,an au...Salt stress severely limits rice growth and productivity.Auxin signaling has a well-documented role in development,but its role in rice salt stress responses is far from clear.In this study,we identified OsARF12,an auxin response factor,as a critical positive regulator of salt tolerance in rice.Transcript analysis revealed salt-induced upregulation of OsARF12.More importantly,OsARF12 overexpression(OsARF12-OX)induced significantly increased survival rates and reduced biomass loss under 200 mmol L^(−1)NaCl treatment compared with wild-type(WT)plants,and OsARF12 knockout(OsARF12-KO)using CRISPR-Cas9 showed the opposite tendency.Physiological analyses revealed that OsARF12-OX plants mitigated salt-induced oxidative damage by enhancing ROS scavenging capacity and promoting Na^(+)/K^(+)homeostasis as well as through their superior photosynthetic efficiency under 200 mmol L^(−1)NaCl treatment,which was consistent with the upregulation of differentially expressed genes involved in ROS scavenging,photosynthesis and ion transport pathways.Furthermore,auxin receptor genes or transcription inhibitor genes were upregulated or downregulated in OsARF12-OX lines compared with WT plants under salt stress,respectively.Biochemical assays indicated that OsARF12 acts as a transcriptional activator,directly binding to TGTC-box motifs in the promoters of the key ion transporters OsSOS1 and OsHKT1;5 to reduce shoot Na^(+)content and the Na^(^(+))/K^(+)ratio,thereby increasing salt tolerance.These findings revealed the potential role of OsARF12 in increasing salt tolerance by integrating auxin signaling with ROS scavenging,ionic homeostasis and photosynthetic networks,offering valuable targets for breeding resilient rice varieties.展开更多
Global warming poses a severe threat to rice production and food security.We identified a heat-sensitive mutant hs1 through largescale screening of an established rice mutant library,and subsequently cloned the corres...Global warming poses a severe threat to rice production and food security.We identified a heat-sensitive mutant hs1 through largescale screening of an established rice mutant library,and subsequently cloned the corresponding gene HS1,which confers thermotolerance in rice.HS1 is localized to the chloroplast and functions by preserving chloroplast integrity under elevated temperatures through stabilizing the photosystem I subunit protein PsaC.Loss of HS1 function in the hs1 mutant leads to severe structural damage to the chloroplast under heat stress,accompanied by intracellular accumulation of reactive oxygen species(ROS),which in turn triggers DNA damage and leaf albinism,ultimately manifesting as a heat-sensitive phenotype.展开更多
Prostate cancer(PCa)is a leading cause of cancer-related mortality among men.Radiotherapy is the cornerstone of PCa treatment.However,a major limitation of radiotherapy is the development of resistance,which compromis...Prostate cancer(PCa)is a leading cause of cancer-related mortality among men.Radiotherapy is the cornerstone of PCa treatment.However,a major limitation of radiotherapy is the development of resistance,which compromises treatment efficacy.Reactive oxygen species(ROS),which are generated by radiation,have a dual role in PCa by inducing DNA damage and apoptosis,while also promoting tumor progression and radioresistance.Elevated ROS levels enhance metabolic reprogramming,activate oncogenic pathways,and influence the tumor microenvironment by modulating immune responses and promoting the epithelial-mesenchymal transition(EMT).Key molecular mechanisms,including the Nrf2/Keap1 signaling axis,Bcl-2 mutations,and Speckle-type POZ protein alterations,contribute to radioresistance by enhancing antioxidant defenses and DNA repair capacity.Additionally,the interplay between hypoxia,androgen receptor variants(AR-Vs),and ferroptosis regulators further influence radiotherapy outcomes.Understanding these resistance mechanisms is crucial for developing targeted strategies to enhance radiosensitivity and improve therapeutic outcomes in PCa patients.展开更多
Atmospheric humic-like substances （HULIS） are not only an unresolved mixture of macro- organic compounds but also powerful chelating agents in atmospheric particulate matters （PMs）; impacting on both the propertie...Atmospheric humic-like substances （HULIS） are not only an unresolved mixture of macro- organic compounds but also powerful chelating agents in atmospheric particulate matters （PMs）; impacting on both the properties of aerosol particles and health effects by generating reactive oxygen spedes （ROS）. Currently, the interests of HULIS are intensively shifting to the investigations of HULIS-metal synergic effects and kinetics modeling studies, as well as the development of HULIS quantification, findings of possible HULIS sources and generation of ROS from HULIS. In light of HULIS studies, we comprehensively review the current knowledge of isolation and physicochemical characterization of HULIS from atmospheric samples as well as HULIS properties （hygroscopic, surface activity, and colloidal） and possible sources of HULIS. This review mainly highlights the generation of reactive oxygen species （ROS） from PMs, HULIS and transition metals, especially iron. This review also summarized the mechanism of iron-organic complexation and recent findings of OH formation from HULIS-metal complexes. This review will be helpful to carry out the modeling studies that concern with HULIS-transition metals and for further studies in the generation of ROS from HULIS-metal complexes,展开更多
Sepsis is a condition of severe organ failure caused by the maladaptive response of the host to an infection.It is a severe complication affecting critically ill patients,which can progress to severe sepsis,septic sho...Sepsis is a condition of severe organ failure caused by the maladaptive response of the host to an infection.It is a severe complication affecting critically ill patients,which can progress to severe sepsis,septic shock,and ultimately death.As a vital part of the human innate immune system,neutrophils are essential in resisting pathogen invasion,infection,and immune surveillance.Neutrophil-produced reactive oxygen species(ROS) play a pivotal role in organ dysfunction related to sepsis.In recent years,ROS have received a lot of attention as a major cause of sepsis,which can progress to severe sepsis and septic shock.This paper reviews the existing knowledge on the production mechanism of neutrophil ROS in human organ function impairment because of sepsis.展开更多
Age related defect of the osteogenic differentiation of mesenchymal stem cells（MSCs） plays a key role in osteoporosis. Mechanical loading is one of the most important physical stimuli for osteoblast differentiation....Age related defect of the osteogenic differentiation of mesenchymal stem cells（MSCs） plays a key role in osteoporosis. Mechanical loading is one of the most important physical stimuli for osteoblast differentiation.Here, we compared the osteogenic potential of MSCs from young and adult rats under three rounds of 2 h of cyclic stretch of 2.5% elongation at 1 Hz on 3 consecutive days. Cyclic stretch induced a significant osteogenic differentiation of MSCs from young rats, while a compromised osteogenesis in MSCs from the adult rats.Accordingly, there were much more reactive oxygen species（ROS） production in adult MSCs under cyclic stretch compared to young MSCs. Moreover, ROS scavenger N-acetylcysteine rescued the osteogenic differentiation of adult MSCs under cyclic stretch. Gene expression analysis revealed that superoxide dismutase 1（SOD1） was significantly downregulated in those MSCs from adult rats. In summary, our data suggest that reduced SOD1 may result in excessive ROS production in adult MSCs under cyclic stretch, and thus manipulation of the MSCs from the adult donors with antioxidant would improve their osteogenic ability.展开更多
Tumor cell usually exhibits high levels of reactive oxygen species and adaptive antioxidant system due to the metabolic,genetic,and microenvironment-associated alterations.The altered redox homeostasis can promote tum...Tumor cell usually exhibits high levels of reactive oxygen species and adaptive antioxidant system due to the metabolic,genetic,and microenvironment-associated alterations.The altered redox homeostasis can promote tumor progression,development,and treatment resistance.Several membrane transporters are involved in the resetting redox homeostasis and play important roles in tumor progression.Therefore,targeting the involved transporters to disrupt the altered redox balance emerges as a viable strategy for cancer therapy.In addition,nanomedicines have drawn much attention in the past decades.Using nanomedicines to target or reset the redox homeostasis alone or combined with other therapies has brought convincing data in cancer treatment.In this review,we will introduce the altered redox balance in cancer metabolism and involved transporters,and highlight the recent advancements of redox-modulating nanomedicines for cancer treatment.展开更多
A number of studies have shown the existence of cross-tolerance in plants, but the physiological mechanism is poorly understood. In this study, we used the germination of barley seeds as a system to investigate the cr...A number of studies have shown the existence of cross-tolerance in plants, but the physiological mechanism is poorly understood. In this study, we used the germination of barley seeds as a system to investigate the cross-tolerance of low-temperature pretreatment to high-temperature stress and the possible involvement of reactive oxygen species （ROS） scavenging enzymes in the cross-tolerance. After pretreatment at 0 ℃ for different periods of time, barley seeds were germinated at 35 ℃, and the content of malondialdehyde （MDA） and the activities of ROS scavenging enzymes were measured by a spectrophotometer analysis. The results showed that barley seed germinated very poorly at 35 ℃, and this inhibitive effect could be overcome by pretreatment at 0 ℃. The MDA content varied, depending on the temperature at which seeds germinated, while barley seeds pretreated at 0 ℃ did not change the MDA content. Compared with seeds germinated directly at 35 ℃, the seeds pretreated first at 0 ℃ and then germinated at 35 ℃ had markedly increased activities of superoxide dismutase （SOD）, ascorbate peroxidase （APX）, catalase （CAT）, and glutathione reductase （GR）. The SOD and APX activities of seeds germinated at 35 ℃ after 0 ℃-pretreatment were even substantially higher than those at 25 ℃, and GR activity was similar to that at 25 ℃, at which the highest germination performance of barley seeds was achieved. These results indicate that low-temperature pretreatment can markedly increase the tolerance of barley seed to high temperature during germination, this being related to the increase in ROS scavenging enzyme activity. This may provide a new method for increasing seed germination under stress environments, and may be an excellent model system for the study of cross-tolerance.展开更多
Brain energy homeostasis is a vital physiological function in maintaining a balanced internal metabolic environment.The impairment of energy homeostasis is recognized as a key pathophysiological basis for brain metabo...Brain energy homeostasis is a vital physiological function in maintaining a balanced internal metabolic environment.The impairment of energy homeostasis is recognized as a key pathophysiological basis for brain metabolic disorders and related neurodegenerative diseases.Dendrobium species(‘Shihu’in Chinese)such as D.officinale,D.huoshanense,D.nobile,D.chrysanthum,D.loddigesii,D.moniliforme,D.gratiosissimum,D.candidum and D.caulis are widely used as traditional Chinese medicines/nutraceuticals to control and treat neurodegenerative disorders.These dietary herbs and their derived compounds possess a variety of biological properties,such as suppression of oxidative stress and neuroinflammation,regulation of energy homeostasis mainly through improving brain mitochondria function,insulin signaling and lipid metabolism.Furthermore,they reduce neurotoxicity,alleviate brain injury and neuropathy,and prevent neurodegenerative conditions including stroke,Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease in humans and/or rodents.Moreover,the nutraceuticals from Dendrobium species promote gut health and aid digestion,which appear to be associated with beneficial effects on brain energy homeostasis.Based on the above-mentioned health benefits associated with Dendrobium species,this work reviews their nutraceutical role in neurodegenerative disorders and further suggests the need to elucidate mechanisms of the underlying molecular actions.展开更多
Transcription factors(TFs)regulate diverse stress defensive-associated physiological processes and plant stress responses.We characterized TaNF-YB11,a gene of the NF-YB TF family in Triticum aestivum,in mediating plan...Transcription factors(TFs)regulate diverse stress defensive-associated physiological processes and plant stress responses.We characterized TaNF-YB11,a gene of the NF-YB TF family in Triticum aestivum,in mediating plant drought tolerance.TaNF-YB11 harbors the conserved domains specified by its NF-YB partners and targets the nucleus after the endoplasmic reticulum(ER)assortment.Yeast two-hybrid assay indicated the interactions of TaNF-YB11 with TaNF-YA2 and TaNF-YC3,two proteins encoded by genes in the NF-YA and NF-YC families,respectively.These results suggested that the heterotrimer established among them further regulated downstream genes at the transcriptional level.The transcripts of TaNF-YB11 were promoted in roots and leaves under a 27-h drought regime.Moreover,its upregulated expression levels under drought were gradually restored following a recovery treatment,suggesting its involvement in plant drought response.TaNF-YB11 conferred improved drought tolerance on plants;the lines overexpressing target gene displayed improved phenotype and biomass compared with wild type(WT)under drought treatments due to enhancement of stomata closing,osmolyte accumulation,and cellular reactive oxygen species(ROS)homeostasis.Knockdown expression of TaP5CS2,a P5CS family gene modulating proline biosynthesis that showed upregulated expression in drought-challenged TaNF-YB11 lines,alleviated proline accumulation of plants treated by drought.Likewise,TaSOD2 and TaCAT3,two genes encoding superoxide dismutase(SOD)and catalase(CAT)that were upregulated underlying TaNF-YB11 regulation,played critical roles in ROS homeostasis via regulating SOD and CAT activities.RNA-seq analysis revealed that numerous genes associated with processes of‘cellular processes',‘environmental information processing',‘genetic information processing',‘metabolism',and‘organismal systems'modified transcription under drought underlying control of TaNF-YB11.These results suggested that the TaNF-YB11-mediated drought response is possibly accomplished through the target gene in modifying gene transcription at the global level,which modulates complicated biological processes related to drought response.TaNF-YB11 is essential in plant drought adaptation and a valuable target for molecular breeding of drought-tolerant cultivars in T.aestivum.展开更多
The Beijing“Coal to Electricity”program provides a unique opportunity to explore air quality impacts by replacing residential coal burning with electrical appliances.In this study,the atmospheric ROS(Gas-phase ROS a...The Beijing“Coal to Electricity”program provides a unique opportunity to explore air quality impacts by replacing residential coal burning with electrical appliances.In this study,the atmospheric ROS(Gas-phase ROS and Particle-phase ROS,abbreviated to G-ROS and P-ROS)were measured by an online instrument in parallel with concurrent PM_(2.5) sample collections analyzed for chemical composition and cellular ROS in a baseline year(Coal Use Year-CUY)and the first year following implementation of the“Coal to Electricity”program(Coal Ban Year-CBY).The results showed PM_(2.5) concentrations had no significant difference between the two sampling periods,but the activities of G-ROS,P-ROS,and cellular ROS in CBY were 8.72 nmol H_(2)O_(2)/m^(3),9.82 nmol H 2 O 2/m 3,and 2045.75μg UD/mg PM higher than in CUY.Six sources were identified by factor-analysis from the chemical components of PM_(2.5).Secondary sources(SECs)were the dominant source of PM_(2.5) in the two periods,with 15.90%higher contribution in CBY than in CUY.Industrial Emission&Coal Combustion sources(Ind.&CCs),mainly from regional transport,also increased significantly in CBY.The contributions of Aged Sea Salt&Residential Burning sources to PM_(2.5) decreased 5.31% from CUY to CBY.The correlation results illustrated that Ind.&CCs had significant positive correlations with atmospheric ROS,and SECs significantly associated with cellular ROS,especially nitrates(r=0.626,p=0.000).Therefore,the implementation of the“Coal to Electricity”program reduced PM_(2.5) contributions from coal and biomass combustion,but had little effect on the improvement of atmospheric and cellular ROS.展开更多
The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs ...The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with iron.The constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial effects.Attractively,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading SACs.Consequently,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/C.In addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)depletion.Both in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound healing.This work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.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
基金supported by the the National Natural Science Foundation of China(32071751).
文摘A geomagnetic field is a significant factor dur-ing the growth and development of trees.Changes in the magnetic field(MF)will result in reactions at the biochemi-cal,molecular,cellular and gene levels.However,it is not clear how a magnetic field affects metabolism and home-ostasis under stressful conditions such as salinity.In this study,a novel method was developed of a static magnetic field(SMF)to investigate magnetobiological changes in trees.The results show that pre-treatment of poplar(Popu-lus×euramericana‘Neva’)cuttings with a static magnetic field significantly mitigated the negative effects of salinity stress on their growth and physiological activities.Bio-chemical assays revealed that several chemical messengers,including hydrogen peroxide(H2O2)and O_(2)^(·-),were sig-nificantly improved in roots treated with salt,implying an increase reactive oxygen species.A static magnetic field also significantly increased proline concentrations,soluble protein contents,and CAT and SOD activities.Electrophysiological experiments further revealed that pre-treatment with a static magnetic field remarkably decreased salt-induced Na^(+)influx and H^(+)efflux which control plant salt tolerance.In pharmacological experiments,because the Na^(+)/H^(+)cor-relation was closely related to the SMF-activated plasma membrane and Na^(+)antiporter activity alleviated the mas-sive accumulation of salt-induced reactive oxygen spe-cies(ROS)within the roots.In addition,a static magnetic field dramatically increased the transcriptional activity of stress-responsive genes,including PtrRBOHD and PtrHA5.Together,these results indicate that SMF reduced Na^(+)influx by activating Na^(+)/H^(+)antiporters and plasma membrane H^(+)-ATPase to effectively maintain homeostasis by regu-lating the reactive oxygen species system and cytoplasmic osmotic potential.Ultimately,these static magnetic field methods improved salt tolerance in poplar cuttings,and,for future research,similar methods could be applied to other plants.
基金funded by National Natural Science Foundation of China(NSFC 32272014)Program for Innovative Research Team(in Science and Technology)in University of Henan Province(25IRTSTHN030)+2 种基金Henan Provincial Science and Technology Research Project(252102111144)the Key Laboratory of Functional Agriculture of Guizhou Province([2023]007)the Key Laboratory of Molecular Breeding for Grain and Oil Crops of Guizhou Province([2023]008).
文摘Salt stress severely limits rice growth and productivity.Auxin signaling has a well-documented role in development,but its role in rice salt stress responses is far from clear.In this study,we identified OsARF12,an auxin response factor,as a critical positive regulator of salt tolerance in rice.Transcript analysis revealed salt-induced upregulation of OsARF12.More importantly,OsARF12 overexpression(OsARF12-OX)induced significantly increased survival rates and reduced biomass loss under 200 mmol L^(−1)NaCl treatment compared with wild-type(WT)plants,and OsARF12 knockout(OsARF12-KO)using CRISPR-Cas9 showed the opposite tendency.Physiological analyses revealed that OsARF12-OX plants mitigated salt-induced oxidative damage by enhancing ROS scavenging capacity and promoting Na^(+)/K^(+)homeostasis as well as through their superior photosynthetic efficiency under 200 mmol L^(−1)NaCl treatment,which was consistent with the upregulation of differentially expressed genes involved in ROS scavenging,photosynthesis and ion transport pathways.Furthermore,auxin receptor genes or transcription inhibitor genes were upregulated or downregulated in OsARF12-OX lines compared with WT plants under salt stress,respectively.Biochemical assays indicated that OsARF12 acts as a transcriptional activator,directly binding to TGTC-box motifs in the promoters of the key ion transporters OsSOS1 and OsHKT1;5 to reduce shoot Na^(+)content and the Na^(^(+))/K^(+)ratio,thereby increasing salt tolerance.These findings revealed the potential role of OsARF12 in increasing salt tolerance by integrating auxin signaling with ROS scavenging,ionic homeostasis and photosynthetic networks,offering valuable targets for breeding resilient rice varieties.
基金supported by the National Natural Science Foundation of China(Grant Nos.32372118 and 32188102)the Zhejiang Natural Science Foundation,China(Grant No.LZ25C130010)+1 种基金the Qian Qian Academician Workstation,and the specific research fund of the Innovation Platform for Academicians of Hainan Province,China(Grant No.YSPTZX202303)the Central Public-Interest Scientific Institution Basal Research Fund from Chinese Academy of Agricultural Sciences(Grant No.Y2025YC93)。
文摘Global warming poses a severe threat to rice production and food security.We identified a heat-sensitive mutant hs1 through largescale screening of an established rice mutant library,and subsequently cloned the corresponding gene HS1,which confers thermotolerance in rice.HS1 is localized to the chloroplast and functions by preserving chloroplast integrity under elevated temperatures through stabilizing the photosystem I subunit protein PsaC.Loss of HS1 function in the hs1 mutant leads to severe structural damage to the chloroplast under heat stress,accompanied by intracellular accumulation of reactive oxygen species(ROS),which in turn triggers DNA damage and leaf albinism,ultimately manifesting as a heat-sensitive phenotype.
基金supported by grants from Ningbo Yongjiang Talent programme-Project for Innovative Talents(Grant No.20240340)Jinhua Science and Technology Bureau(Grant No.2022-4-258)2022 Shandong Medical Association Clinical Research Special Fund for Dynamic Monitoring of Lymphocyte Subpopulations by Flow Cytometry(Grant No.YXH2022ZX03227)。
文摘Prostate cancer(PCa)is a leading cause of cancer-related mortality among men.Radiotherapy is the cornerstone of PCa treatment.However,a major limitation of radiotherapy is the development of resistance,which compromises treatment efficacy.Reactive oxygen species(ROS),which are generated by radiation,have a dual role in PCa by inducing DNA damage and apoptosis,while also promoting tumor progression and radioresistance.Elevated ROS levels enhance metabolic reprogramming,activate oncogenic pathways,and influence the tumor microenvironment by modulating immune responses and promoting the epithelial-mesenchymal transition(EMT).Key molecular mechanisms,including the Nrf2/Keap1 signaling axis,Bcl-2 mutations,and Speckle-type POZ protein alterations,contribute to radioresistance by enhancing antioxidant defenses and DNA repair capacity.Additionally,the interplay between hypoxia,androgen receptor variants(AR-Vs),and ferroptosis regulators further influence radiotherapy outcomes.Understanding these resistance mechanisms is crucial for developing targeted strategies to enhance radiosensitivity and improve therapeutic outcomes in PCa patients.
基金the Natural Science Foundation of China under NSFC Grant No. 21477073, 41273127 for support to conduct this research
文摘Atmospheric humic-like substances （HULIS） are not only an unresolved mixture of macro- organic compounds but also powerful chelating agents in atmospheric particulate matters （PMs）; impacting on both the properties of aerosol particles and health effects by generating reactive oxygen spedes （ROS）. Currently, the interests of HULIS are intensively shifting to the investigations of HULIS-metal synergic effects and kinetics modeling studies, as well as the development of HULIS quantification, findings of possible HULIS sources and generation of ROS from HULIS. In light of HULIS studies, we comprehensively review the current knowledge of isolation and physicochemical characterization of HULIS from atmospheric samples as well as HULIS properties （hygroscopic, surface activity, and colloidal） and possible sources of HULIS. This review mainly highlights the generation of reactive oxygen species （ROS） from PMs, HULIS and transition metals, especially iron. This review also summarized the mechanism of iron-organic complexation and recent findings of OH formation from HULIS-metal complexes. This review will be helpful to carry out the modeling studies that concern with HULIS-transition metals and for further studies in the generation of ROS from HULIS-metal complexes,
文摘Sepsis is a condition of severe organ failure caused by the maladaptive response of the host to an infection.It is a severe complication affecting critically ill patients,which can progress to severe sepsis,septic shock,and ultimately death.As a vital part of the human innate immune system,neutrophils are essential in resisting pathogen invasion,infection,and immune surveillance.Neutrophil-produced reactive oxygen species(ROS) play a pivotal role in organ dysfunction related to sepsis.In recent years,ROS have received a lot of attention as a major cause of sepsis,which can progress to severe sepsis and septic shock.This paper reviews the existing knowledge on the production mechanism of neutrophil ROS in human organ function impairment because of sepsis.
基金financially supported by National Natural Science Foundation of China (81100240)‘985’ project of Sun Yat-Sen University grant+2 种基金Sun Yat-Sen university young teachers training project (13YKPY42)Natural Science Foundation of Guangdong Province,China(S2012010009495)Science and Technology Planning Project of Guangdong Province,China(2012B031800185)
文摘Age related defect of the osteogenic differentiation of mesenchymal stem cells（MSCs） plays a key role in osteoporosis. Mechanical loading is one of the most important physical stimuli for osteoblast differentiation.Here, we compared the osteogenic potential of MSCs from young and adult rats under three rounds of 2 h of cyclic stretch of 2.5% elongation at 1 Hz on 3 consecutive days. Cyclic stretch induced a significant osteogenic differentiation of MSCs from young rats, while a compromised osteogenesis in MSCs from the adult rats.Accordingly, there were much more reactive oxygen species（ROS） production in adult MSCs under cyclic stretch compared to young MSCs. Moreover, ROS scavenger N-acetylcysteine rescued the osteogenic differentiation of adult MSCs under cyclic stretch. Gene expression analysis revealed that superoxide dismutase 1（SOD1） was significantly downregulated in those MSCs from adult rats. In summary, our data suggest that reduced SOD1 may result in excessive ROS production in adult MSCs under cyclic stretch, and thus manipulation of the MSCs from the adult donors with antioxidant would improve their osteogenic ability.
基金This work was financially supported by the National Natural Science Foundation of China(81803443,81903551)the Natural Science Foundation of Zhejiang Province(LQ19H300001)+1 种基金the Wenzhou Science and Technology Bureau(ZY2019007,Y20180180,Y20180208,Y20190177)the start-up funds from the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University.
文摘Tumor cell usually exhibits high levels of reactive oxygen species and adaptive antioxidant system due to the metabolic,genetic,and microenvironment-associated alterations.The altered redox homeostasis can promote tumor progression,development,and treatment resistance.Several membrane transporters are involved in the resetting redox homeostasis and play important roles in tumor progression.Therefore,targeting the involved transporters to disrupt the altered redox balance emerges as a viable strategy for cancer therapy.In addition,nanomedicines have drawn much attention in the past decades.Using nanomedicines to target or reset the redox homeostasis alone or combined with other therapies has brought convincing data in cancer treatment.In this review,we will introduce the altered redox balance in cancer metabolism and involved transporters,and highlight the recent advancements of redox-modulating nanomedicines for cancer treatment.
基金Project (No. 30870223) supported by the National Natural Science Foundation of China
文摘A number of studies have shown the existence of cross-tolerance in plants, but the physiological mechanism is poorly understood. In this study, we used the germination of barley seeds as a system to investigate the cross-tolerance of low-temperature pretreatment to high-temperature stress and the possible involvement of reactive oxygen species （ROS） scavenging enzymes in the cross-tolerance. After pretreatment at 0 ℃ for different periods of time, barley seeds were germinated at 35 ℃, and the content of malondialdehyde （MDA） and the activities of ROS scavenging enzymes were measured by a spectrophotometer analysis. The results showed that barley seed germinated very poorly at 35 ℃, and this inhibitive effect could be overcome by pretreatment at 0 ℃. The MDA content varied, depending on the temperature at which seeds germinated, while barley seeds pretreated at 0 ℃ did not change the MDA content. Compared with seeds germinated directly at 35 ℃, the seeds pretreated first at 0 ℃ and then germinated at 35 ℃ had markedly increased activities of superoxide dismutase （SOD）, ascorbate peroxidase （APX）, catalase （CAT）, and glutathione reductase （GR）. The SOD and APX activities of seeds germinated at 35 ℃ after 0 ℃-pretreatment were even substantially higher than those at 25 ℃, and GR activity was similar to that at 25 ℃, at which the highest germination performance of barley seeds was achieved. These results indicate that low-temperature pretreatment can markedly increase the tolerance of barley seed to high temperature during germination, this being related to the increase in ROS scavenging enzyme activity. This may provide a new method for increasing seed germination under stress environments, and may be an excellent model system for the study of cross-tolerance.
基金funded by the National Key Research and Development Program of China(2018YFC1706105)the National Natural Science Foundation of China(81872961)+1 种基金Key Project at Central Government Level(2060302)Collaborative Innovation Project of Dendrobium Industrialization Development in Anhui Province.
文摘Brain energy homeostasis is a vital physiological function in maintaining a balanced internal metabolic environment.The impairment of energy homeostasis is recognized as a key pathophysiological basis for brain metabolic disorders and related neurodegenerative diseases.Dendrobium species(‘Shihu’in Chinese)such as D.officinale,D.huoshanense,D.nobile,D.chrysanthum,D.loddigesii,D.moniliforme,D.gratiosissimum,D.candidum and D.caulis are widely used as traditional Chinese medicines/nutraceuticals to control and treat neurodegenerative disorders.These dietary herbs and their derived compounds possess a variety of biological properties,such as suppression of oxidative stress and neuroinflammation,regulation of energy homeostasis mainly through improving brain mitochondria function,insulin signaling and lipid metabolism.Furthermore,they reduce neurotoxicity,alleviate brain injury and neuropathy,and prevent neurodegenerative conditions including stroke,Alzheimer’s disease,Parkinson’s disease,and Huntington’s disease in humans and/or rodents.Moreover,the nutraceuticals from Dendrobium species promote gut health and aid digestion,which appear to be associated with beneficial effects on brain energy homeostasis.Based on the above-mentioned health benefits associated with Dendrobium species,this work reviews their nutraceutical role in neurodegenerative disorders and further suggests the need to elucidate mechanisms of the underlying molecular actions.
基金supported by the National Natural Science Foundation of China(31872869)the State Key Laboratory of North China Crop Improvement and Regulation(NCCIR2022ZZ-7)+2 种基金the National Key R&DProgram of China(SQ2022YFD1200002)the Science and Technology Planning Project of Hebei Province,China(216Z6401G)the Postgraduate Innovation Funding Project of Hebei Province,China(CXZZSS2021071)。
文摘Transcription factors(TFs)regulate diverse stress defensive-associated physiological processes and plant stress responses.We characterized TaNF-YB11,a gene of the NF-YB TF family in Triticum aestivum,in mediating plant drought tolerance.TaNF-YB11 harbors the conserved domains specified by its NF-YB partners and targets the nucleus after the endoplasmic reticulum(ER)assortment.Yeast two-hybrid assay indicated the interactions of TaNF-YB11 with TaNF-YA2 and TaNF-YC3,two proteins encoded by genes in the NF-YA and NF-YC families,respectively.These results suggested that the heterotrimer established among them further regulated downstream genes at the transcriptional level.The transcripts of TaNF-YB11 were promoted in roots and leaves under a 27-h drought regime.Moreover,its upregulated expression levels under drought were gradually restored following a recovery treatment,suggesting its involvement in plant drought response.TaNF-YB11 conferred improved drought tolerance on plants;the lines overexpressing target gene displayed improved phenotype and biomass compared with wild type(WT)under drought treatments due to enhancement of stomata closing,osmolyte accumulation,and cellular reactive oxygen species(ROS)homeostasis.Knockdown expression of TaP5CS2,a P5CS family gene modulating proline biosynthesis that showed upregulated expression in drought-challenged TaNF-YB11 lines,alleviated proline accumulation of plants treated by drought.Likewise,TaSOD2 and TaCAT3,two genes encoding superoxide dismutase(SOD)and catalase(CAT)that were upregulated underlying TaNF-YB11 regulation,played critical roles in ROS homeostasis via regulating SOD and CAT activities.RNA-seq analysis revealed that numerous genes associated with processes of‘cellular processes',‘environmental information processing',‘genetic information processing',‘metabolism',and‘organismal systems'modified transcription under drought underlying control of TaNF-YB11.These results suggested that the TaNF-YB11-mediated drought response is possibly accomplished through the target gene in modifying gene transcription at the global level,which modulates complicated biological processes related to drought response.TaNF-YB11 is essential in plant drought adaptation and a valuable target for molecular breeding of drought-tolerant cultivars in T.aestivum.
基金supported by the National Natural Science Foundation of China(NSFC)(No.41877310)partly by the National Key Research and Development Program of China(No.2016YFC0503600).
文摘The Beijing“Coal to Electricity”program provides a unique opportunity to explore air quality impacts by replacing residential coal burning with electrical appliances.In this study,the atmospheric ROS(Gas-phase ROS and Particle-phase ROS,abbreviated to G-ROS and P-ROS)were measured by an online instrument in parallel with concurrent PM_(2.5) sample collections analyzed for chemical composition and cellular ROS in a baseline year(Coal Use Year-CUY)and the first year following implementation of the“Coal to Electricity”program(Coal Ban Year-CBY).The results showed PM_(2.5) concentrations had no significant difference between the two sampling periods,but the activities of G-ROS,P-ROS,and cellular ROS in CBY were 8.72 nmol H_(2)O_(2)/m^(3),9.82 nmol H 2 O 2/m 3,and 2045.75μg UD/mg PM higher than in CUY.Six sources were identified by factor-analysis from the chemical components of PM_(2.5).Secondary sources(SECs)were the dominant source of PM_(2.5) in the two periods,with 15.90%higher contribution in CBY than in CUY.Industrial Emission&Coal Combustion sources(Ind.&CCs),mainly from regional transport,also increased significantly in CBY.The contributions of Aged Sea Salt&Residential Burning sources to PM_(2.5) decreased 5.31% from CUY to CBY.The correlation results illustrated that Ind.&CCs had significant positive correlations with atmospheric ROS,and SECs significantly associated with cellular ROS,especially nitrates(r=0.626,p=0.000).Therefore,the implementation of the“Coal to Electricity”program reduced PM_(2.5) contributions from coal and biomass combustion,but had little effect on the improvement of atmospheric and cellular ROS.
基金supported by the National Key Research and Development Program of China(Grant No.2022YFB3804500)the National Natural Science Foundation of China(Grant No.52202352,22335006)+4 种基金the Shanghai Municipal Health Commission(Grant No.20224Y0010)the CAMS Innovation Fund for Medical Sciences(Grant No.2021-I2M-5-012)the Basic Research Program of Shanghai Municipal Government(Grant No.21JC1406000)the Fundamental Research Funds for the Central Universities(Grant No.22120230237,2023-3-YB-11,22120220618)the Basic Research Program of Shanghai Municipal Government(23DX1900200).
文摘The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with iron.The constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial effects.Attractively,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading SACs.Consequently,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/C.In addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)depletion.Both in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound healing.This work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.
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.
