目的探究血清网膜素-1(Omentin-1)、补体/C1q肿瘤坏死因子相关蛋白9(CTRP-9)水平与急性脑梗死(ACI)神经功能康复的相关性。方法选取2022年11月至2024年2月于该院治疗的ACI患者106例作为研究组,其中包括ACI神经功能康复良好患者62例(良好...目的探究血清网膜素-1(Omentin-1)、补体/C1q肿瘤坏死因子相关蛋白9(CTRP-9)水平与急性脑梗死(ACI)神经功能康复的相关性。方法选取2022年11月至2024年2月于该院治疗的ACI患者106例作为研究组,其中包括ACI神经功能康复良好患者62例(良好组)和康复不良患者44例(不良组)。采用酶联免疫吸附试验检测所有研究对象的血清Omentin-1、CTRP-9水平;采用Spearman相关性分析血清Omentin-1、CTRP-9水平与ACI患者入院时的美国国立卫生研究院卒中量表(NIHSS)评分及脑梗死体积的相关性;采用多因素Logistic回归分析ACI患者神经功能康复不良的影响因素;采用受试者工作特征(ROC)曲线分析血清Omentin-1、CTRP-9水平对ACI患者神经功能康复不良的诊断价值。结果良好组血清Omentin-1、CTRP-9水平明显高于不良组(P<0.05),入院时NIHSS评分、脑梗死面积和发病90 d时改良Rankin量表(mRS)评分明显低于不良组(P<0.05);Spearman相关性分析显示,血清Omentin-1、CTRP-9水平与90 d mRS评分呈负相关(r=-0.648,-0.573,均P<0.001);多因素Logistic回归分析结果显示,90 d mRS评分是ACI患者神经功能康复不良的危险因素(P<0.05),血清Omentin-1、CTRP-9水平是ACI患者神经功能康复不良的保护因素(P<0.05);ROC曲线分析结果显示,血清Omentin-1、CTRP-9水平诊断ACI患者神经功能康复不良的曲线下面积(AUC)为0.843、0.828,二者联合诊断的AUC为0.937,明显大于二者单独诊断(Z_(二者联合-Omentin-1)=2.321,P=0.020;Z_(二者联合-CTRP-9)=2.532,P=0.011)。结论ACI神经功能康复不良患者血清Omentin-1、CTRP-9水平明显降低,且Omentin-1、CTRP-9水平与90 d mRS评分呈负相关,与神经功能康复情况密切相关。展开更多
Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in s...Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.展开更多
Drought stress significantly impedes apple growth,development,and yield,leading to substantial economic losses within the global apple industry.Malus prunifolia(Mp),a commonly utilized apple rootstock,has shown promis...Drought stress significantly impedes apple growth,development,and yield,leading to substantial economic losses within the global apple industry.Malus prunifolia(Mp),a commonly utilized apple rootstock,has shown promise in augmenting cultivated apple resistance to abiotic stress.Although Alfin-like(ALs)proteins have demonstrated pivotal roles in dicotyledonous plants'response to abiotic stresses,knowledge about AL genes in apple rootstocks is limited,and their functions remain largely elusive.In this study,we identified and characterized 10 MpAL gene members in the apple rootstock genome,confirming their localization within the nucleus.Our investigation revealed the significant regulation of MpALs'expression under drought and abscisic acid(ABA)stresses in M.prunifolia.In this study,one of the members,MpAL1,was selected for further exploration in Arabidopsis and apple to explore its potential function in response to drought and ABA stresses.The results showed that overexpression-MpAL1 transgenic apple calli grew significantly better than WT and MpAL1-RNAi lines,which regulates the accumulation of H_(2)O_(2)and O_(2).-levels.Additionally,transgenic Arabidopsis plants overexpressing MpAL1 exhibited positively regulating antioxidant enzymes activities under stress treatments.Further study showed that silencing MpAL1 in apple plants showed obvious chlorosis in leaves,and accumulation of reactive oxygen species under drought stress.Moreover,our detailed analysis established that MpAL1 regulates several drought and ABA-responsive genes,exerting an influence on their expression in transgenic apple.Collectively,our findings identify MpAL1 as a positive regulator that increases drought stress in apple,shedding light on its potential significance in bolstering drought resistance in this fruit crop.展开更多
Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genoty...Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genotype data and 681 participants with gene expression data from the Molecular Epidemiology of ARDS(MEARDS),the Molecular Epidemiology of Sepsis in the ICU(MESSI),and the Molecular Diagnosis and Risk Stratification of Sepsis(MARS)cohorts in a three-step study focusing on sepsis-associated ARDS and sepsis-only controls.First,we identified and validated interferon-related genes associated with sepsis-associated ARDS risk using genetically regulated gene expression(GReX).Second,we examined the association of the confirmed gene(interferon regulatory factor 1,IRF1)with ARDS risk and survival and conducted a mediation analysis.Through discovery and validation,we found that the GReX of IRF1 was associated with ARDS risk(odds ratio[OR_(MEARDS)]=0.84,P=0.008;OR_(MESSI)=0.83,P=0.034).Furthermore,individual-level measured IRF1 expression was associated with reduced ARDS risk(OR=0.58,P=8.67×10^(-4)),and improved overall survival in ARDS patients(hazard ratio[HR_(28-day)]=0.49,P=0.009)and sepsis patients(HR_(28-day)=0.76,P=0.008).Mediation analysis revealed that IRF1 may enhance immune function by regulating the major histocompatibility complex,including HLA-F,which mediated more than 70%of protective effects of IRF1 on ARDS.The findings were validated by in vitro biological experiments including time-series infection dynamics,overexpression,knockout,and chromatin immunoprecipitation sequencing.Early prophylactic interventions to activate IRF1 in sepsis patients,thereby regulating HLA-F,may reduce the risk of ARDS and mortality,especially in severely ill patients.展开更多
文摘目的探究血清网膜素-1(Omentin-1)、补体/C1q肿瘤坏死因子相关蛋白9(CTRP-9)水平与急性脑梗死(ACI)神经功能康复的相关性。方法选取2022年11月至2024年2月于该院治疗的ACI患者106例作为研究组,其中包括ACI神经功能康复良好患者62例(良好组)和康复不良患者44例(不良组)。采用酶联免疫吸附试验检测所有研究对象的血清Omentin-1、CTRP-9水平;采用Spearman相关性分析血清Omentin-1、CTRP-9水平与ACI患者入院时的美国国立卫生研究院卒中量表(NIHSS)评分及脑梗死体积的相关性;采用多因素Logistic回归分析ACI患者神经功能康复不良的影响因素;采用受试者工作特征(ROC)曲线分析血清Omentin-1、CTRP-9水平对ACI患者神经功能康复不良的诊断价值。结果良好组血清Omentin-1、CTRP-9水平明显高于不良组(P<0.05),入院时NIHSS评分、脑梗死面积和发病90 d时改良Rankin量表(mRS)评分明显低于不良组(P<0.05);Spearman相关性分析显示,血清Omentin-1、CTRP-9水平与90 d mRS评分呈负相关(r=-0.648,-0.573,均P<0.001);多因素Logistic回归分析结果显示,90 d mRS评分是ACI患者神经功能康复不良的危险因素(P<0.05),血清Omentin-1、CTRP-9水平是ACI患者神经功能康复不良的保护因素(P<0.05);ROC曲线分析结果显示,血清Omentin-1、CTRP-9水平诊断ACI患者神经功能康复不良的曲线下面积(AUC)为0.843、0.828,二者联合诊断的AUC为0.937,明显大于二者单独诊断(Z_(二者联合-Omentin-1)=2.321,P=0.020;Z_(二者联合-CTRP-9)=2.532,P=0.011)。结论ACI神经功能康复不良患者血清Omentin-1、CTRP-9水平明显降低,且Omentin-1、CTRP-9水平与90 d mRS评分呈负相关,与神经功能康复情况密切相关。
基金supported by the National Natural Science Foundation of China,Nos.82072165 and 82272256(both to XM)the Key Project of Xiangyang Central Hospital,No.2023YZ03(to RM)。
文摘Spinal cord injury represents a severe form of central nervous system trauma for which effective treatments remain limited.Microglia is the resident immune cells of the central nervous system,play a critical role in spinal cord injury.Previous studies have shown that microglia can promote neuronal survival by phagocytosing dead cells and debris and by releasing neuroprotective and anti-inflammatory factors.However,excessive activation of microglia can lead to persistent inflammation and contribute to the formation of glial scars,which hinder axonal regeneration.Despite this,the precise role and mechanisms of microglia during the acute phase of spinal cord injury remain controversial and poorly understood.To elucidate the role of microglia in spinal cord injury,we employed the colony-stimulating factor 1 receptor inhibitor PLX5622 to deplete microglia.We observed that sustained depletion of microglia resulted in an expansion of the lesion area,downregulation of brain-derived neurotrophic factor,and impaired functional recovery after spinal cord injury.Next,we generated a transgenic mouse line with conditional overexpression of brain-derived neurotrophic factor specifically in microglia.We found that brain-derived neurotrophic factor overexpression in microglia increased angiogenesis and blood flow following spinal cord injury and facilitated the recovery of hindlimb motor function.Additionally,brain-derived neurotrophic factor overexpression in microglia reduced inflammation and neuronal apoptosis during the acute phase of spinal cord injury.Furthermore,through using specific transgenic mouse lines,TMEM119,and the colony-stimulating factor 1 receptor inhibitor PLX73086,we demonstrated that the neuroprotective effects were predominantly due to brain-derived neurotrophic factor overexpression in microglia rather than macrophages.In conclusion,our findings suggest the critical role of microglia in the formation of protective glial scars.Depleting microglia is detrimental to recovery of spinal cord injury,whereas targeting brain-derived neurotrophic factor overexpression in microglia represents a promising and novel therapeutic strategy to enhance motor function recovery in patients with spinal cord injury.
基金supported by the National Natural Science Foundation of China(Grant Nos.32102311 and 32102338)the China Postdoctoral Science Foundation(Grant No.2021M690129).
文摘Drought stress significantly impedes apple growth,development,and yield,leading to substantial economic losses within the global apple industry.Malus prunifolia(Mp),a commonly utilized apple rootstock,has shown promise in augmenting cultivated apple resistance to abiotic stress.Although Alfin-like(ALs)proteins have demonstrated pivotal roles in dicotyledonous plants'response to abiotic stresses,knowledge about AL genes in apple rootstocks is limited,and their functions remain largely elusive.In this study,we identified and characterized 10 MpAL gene members in the apple rootstock genome,confirming their localization within the nucleus.Our investigation revealed the significant regulation of MpALs'expression under drought and abscisic acid(ABA)stresses in M.prunifolia.In this study,one of the members,MpAL1,was selected for further exploration in Arabidopsis and apple to explore its potential function in response to drought and ABA stresses.The results showed that overexpression-MpAL1 transgenic apple calli grew significantly better than WT and MpAL1-RNAi lines,which regulates the accumulation of H_(2)O_(2)and O_(2).-levels.Additionally,transgenic Arabidopsis plants overexpressing MpAL1 exhibited positively regulating antioxidant enzymes activities under stress treatments.Further study showed that silencing MpAL1 in apple plants showed obvious chlorosis in leaves,and accumulation of reactive oxygen species under drought stress.Moreover,our detailed analysis established that MpAL1 regulates several drought and ABA-responsive genes,exerting an influence on their expression in transgenic apple.Collectively,our findings identify MpAL1 as a positive regulator that increases drought stress in apple,shedding light on its potential significance in bolstering drought resistance in this fruit crop.
基金supported by the National Natural Science Foundation of China(Grant No.82220108002 to F.C.and Grant No.82273737 to R.Z.)the U.S.National Institutes of Health(Grant Nos.CA209414,HL060710,and ES000002 to D.C.C.,Grant Nos.CA209414 and CA249096 to Y.L.)+1 种基金the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)supported by the Qing Lan Project of the Higher Education Institutions of Jiangsu Province and the Outstanding Young Level Academic Leadership Training Program of Nanjing Medical University.
文摘Interferon-related genes are involved in antiviral responses,inflammation,and immunity,which are closely related to sepsis-associated acute respiratory distress syndrome(ARDS).We analyzed 1972 participants with genotype data and 681 participants with gene expression data from the Molecular Epidemiology of ARDS(MEARDS),the Molecular Epidemiology of Sepsis in the ICU(MESSI),and the Molecular Diagnosis and Risk Stratification of Sepsis(MARS)cohorts in a three-step study focusing on sepsis-associated ARDS and sepsis-only controls.First,we identified and validated interferon-related genes associated with sepsis-associated ARDS risk using genetically regulated gene expression(GReX).Second,we examined the association of the confirmed gene(interferon regulatory factor 1,IRF1)with ARDS risk and survival and conducted a mediation analysis.Through discovery and validation,we found that the GReX of IRF1 was associated with ARDS risk(odds ratio[OR_(MEARDS)]=0.84,P=0.008;OR_(MESSI)=0.83,P=0.034).Furthermore,individual-level measured IRF1 expression was associated with reduced ARDS risk(OR=0.58,P=8.67×10^(-4)),and improved overall survival in ARDS patients(hazard ratio[HR_(28-day)]=0.49,P=0.009)and sepsis patients(HR_(28-day)=0.76,P=0.008).Mediation analysis revealed that IRF1 may enhance immune function by regulating the major histocompatibility complex,including HLA-F,which mediated more than 70%of protective effects of IRF1 on ARDS.The findings were validated by in vitro biological experiments including time-series infection dynamics,overexpression,knockout,and chromatin immunoprecipitation sequencing.Early prophylactic interventions to activate IRF1 in sepsis patients,thereby regulating HLA-F,may reduce the risk of ARDS and mortality,especially in severely ill patients.
