Photocatalytic decomposition of sugars is a promising way of providing H_(2),CO,and HCOOH as sus-tainable energy vectors.However,the production of C_(1) chemicals requires the cleavage of robust C−C bonds in sugars wi...Photocatalytic decomposition of sugars is a promising way of providing H_(2),CO,and HCOOH as sus-tainable energy vectors.However,the production of C_(1) chemicals requires the cleavage of robust C−C bonds in sugars with concurrent production of H_(2),which remains challenging.Here,the photo-catalytic activity for glucose decomposition to HCOOH,CO(C_(1) chemicals),and H_(2) on Cu/TiO_(2)was enhanced by nitrogen doping.Owing to nitrogen doping,atomically dispersed and stable Cu sites resistant to light irradiation are formed on Cu/TiO_(2).The electronic interaction between Cu and nitrogen ions originates valence band structure and defect levels composed of N 2p orbit,distinct from undoped Cu/TiO_(2).Therefore,the lifetime of charge carriers is prolonged,resulting in the pro-duction of C_(1) chemicals and H_(2) with productivities 1.7 and 2.1 folds that of Cu/TiO_(2).This work pro-vides a strategy to design coordinatively stable Cu ions for photocatalytic biomass conversion.展开更多
Background:Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury(TBI).However,the heterogeneity,multifunctionality,and time-dependent modulatio...Background:Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury(TBI).However,the heterogeneity,multifunctionality,and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood.Methods:Using the combined single-cell transcriptomics,metabolomics,and proteomics analysis from TBI patients and the TBI mouse model,we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests.We also characterized the underlying mechanisms both invitro and invivo through molecular simulations,signaling detections,gene expression regulation assessments[including dual-luciferase reporter and chromatin immunoprecipitation(ChIP)assays],primary cultures or co-cultures of neutrophils and oligodendrocytes,intracellular iron,and lipid hydroperoxide concentration measurements,as well as forkhead box protein O1(FOXO1)conditional knockout mice.Results:We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model.Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI,aggravating acute brain inflammatory damage and promoting late TBI-induced depression.In the acute stage,FOXO1 upregulated cytoplasmic Versican(VCAN)to interact with the apoptosis regulator B-cell lymphoma-2(BCL-2)-associated X protein(BAX),suppressing the mitochondrial translocation of BAX,which mediated the antiapoptotic effect companied with enhancing interleukin-6(IL-6)production of FOXO1high neutrophils.In the chronic stage,the“FOXO1-transferrin receptor(TFRC)”mechanism contributes to FOXO1high neutrophil ferroptosis,disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein,which contributes to the progression of late depression after TBI.Conclusions:FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI,which provides insight into the heterogeneity,reprogramming activity,and versatility of neutrophils in TBI.展开更多
目的 探究叉头状转录因子O亚家族蛋白1(FOXO1)和髓细胞白血病因子1(MCL1)在多囊卵巢综合征(PCOS)患者中的表达及其与糖脂代谢和胰岛素抵抗的关系研究。方法 选择2022年1月—2023年1月丽水市人民医院收治的确诊为PCOS的146例患者为PCOS组...目的 探究叉头状转录因子O亚家族蛋白1(FOXO1)和髓细胞白血病因子1(MCL1)在多囊卵巢综合征(PCOS)患者中的表达及其与糖脂代谢和胰岛素抵抗的关系研究。方法 选择2022年1月—2023年1月丽水市人民医院收治的确诊为PCOS的146例患者为PCOS组,另分为肥胖组44例、非肥胖组102例,胰岛素抵抗组95例、非胰岛素抵抗组51例,选择同期在丽水市人民医院体检健康的146例女性为对照组;采用酶联免疫吸附测定(ELISA)法检测血清中FOXO1和MCL1的表达水平。采用酶偶联比色法检测空腹血糖(FPG)、餐后2 h血糖(2 h PBG)水平。采用电化学发光法检测空腹胰岛素(FINS),计算胰岛素抵抗指数(HOMA-IR)。Pearson法分析PCOS患者血清中FOXO1、MCL1水平与糖脂代谢指标以及胰岛素抵抗指标的相关性。结果 与对照组相比,PCOS组的睾酮(T)、黄体生成素(LH)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、2 h PBG、FINS、HOMA-IR水平显著升高(均P<0.05)。与对照组FOXO1、MLC1水平[(7.02±0.89)ng/ml、(9.12±1.02)ng/ml]比较,PCOS组患者血清中FOXO1水平[(5.85±0.72)ng/ml]显著降低,MCL1水平[(10.68±1.36)ng/ml]显著升高,差异均有统计学意义(t=12.349、11.088,均P<0.05)。与非肥胖组FOXO1、MCL1水平[(6.42±0.73)ng/ml、(9.68±1.38)ng/ml]比较,肥胖组患者血清中FOXO1水平[(4.52±0.71)ng/ml]显著降低,MCL1水平[(12.99±1.32)ng/ml]显著升高,差异均有统计学意义(t=14.548、13.471,均P<0.05)。与非胰岛素抵抗组FOXO1、MCL1水平[(6.58±0.73)ng/ml、(9.85±1.35)ng/ml]比较,胰岛素抵抗组患者血清中FOXO1水平[(5.46±0.71)ng/ml]显著降低,MCL1水平[(11.12±1.37)ng/ml]显著升高,差异均有统计学意义(t=8.998、5.367,均P<0.05)。相关性分析显示,PCOS患者血清中FOXO1水平与TC、LDL-C、2 h PBG、FINS、HOMA-IR水平呈负相关关系,MCL1与TC、LDL-C、2 h PBG、FINS、HOMA-IR水平呈正相关关系(均P<0.05)。结论 PCOS患者血清中FOXO1呈低表达,MCL1呈高表达,二者与糖脂代谢和胰岛素抵抗具有相关性。展开更多
目的观察去泛素化酶Abraxas兄弟蛋白(ABRO1)对李斯特菌(LM)感染的小鼠单核巨噬细胞J774A.1白细胞介素(IL)-1β释放的影响,并探讨相关机制。方法培养J774A.1细胞,分别感染有李斯特菌溶血素O(LLO)的野生型LM菌株(野生型组)、敲除LLO的hly...目的观察去泛素化酶Abraxas兄弟蛋白(ABRO1)对李斯特菌(LM)感染的小鼠单核巨噬细胞J774A.1白细胞介素(IL)-1β释放的影响,并探讨相关机制。方法培养J774A.1细胞,分别感染有李斯特菌溶血素O(LLO)的野生型LM菌株(野生型组)、敲除LLO的hly基因缺失(Δhly)LM菌株(基因缺失组)及Δhly株回补hly基因的LM菌株(回补株组),采用Western blotting法检测ABRO1蛋白,ELISA法检测细胞培养液上清中的IL-1β。将J774A.1细胞分为NI组(未感染LM菌株)、WT组(感染WT LM菌株)与Δhly组(感染Δhly LM菌株),各组分别转染NC si RNA、ABRO1 si RNA,采用ELISA法检测细胞培养液上清中的IL-1β,采用Western blotting法检测炎症小体相关分子Caspase-1、p20(Caspase-1活化形式)、IL-1β、p17。结果随着感染时间延长,野生型组、回补株组ABRO1表达、IL-1β水平逐渐增高,在感染120 min达到最高、均高于基因缺失组(P均<0.05);基因缺失组不同时点ABRO1表达、IL-1β水平无明显变化。WT组转染ABRO1 si RNA的细胞培养液上清中IL-1β水平及p20、p17表达低于转染NC si RNA的细胞(P均<0.05);WT组转染NC si RNA的细胞培养液上清中IL-1β水平及p20、p17表达高于NI组(P均<0.05);Δhly组转染NC si RNA的细胞培养液上清中IL-1β水平及p20、p17表达低于WT组(P均<0.05)。结论李斯特菌感染的J774A.1细胞中ABRO1表达增高,下调ABRO1表达后,J774A.1细胞中IL-1β释放减少;LLO可能通过激活炎症小体从而促进LM感染诱导的IL-1β释放。展开更多
文摘Photocatalytic decomposition of sugars is a promising way of providing H_(2),CO,and HCOOH as sus-tainable energy vectors.However,the production of C_(1) chemicals requires the cleavage of robust C−C bonds in sugars with concurrent production of H_(2),which remains challenging.Here,the photo-catalytic activity for glucose decomposition to HCOOH,CO(C_(1) chemicals),and H_(2) on Cu/TiO_(2)was enhanced by nitrogen doping.Owing to nitrogen doping,atomically dispersed and stable Cu sites resistant to light irradiation are formed on Cu/TiO_(2).The electronic interaction between Cu and nitrogen ions originates valence band structure and defect levels composed of N 2p orbit,distinct from undoped Cu/TiO_(2).Therefore,the lifetime of charge carriers is prolonged,resulting in the pro-duction of C_(1) chemicals and H_(2) with productivities 1.7 and 2.1 folds that of Cu/TiO_(2).This work pro-vides a strategy to design coordinatively stable Cu ions for photocatalytic biomass conversion.
基金This work was supported by the National Natural Science Foundation of China(82071779 and 81901626)the Science Fund for Creative Research Groups of Chongqing Municipal Education Commission of China,the grants from the Talent Foundation of Army Medical University(to Shuang-Shuang Dai)+1 种基金the Scientific Research Grant(ALJ22J003)the Chongqing Natural Science Foundation of China(CSTB2022NSCQ-MSX0177).
文摘Background:Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury(TBI).However,the heterogeneity,multifunctionality,and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly understood.Methods:Using the combined single-cell transcriptomics,metabolomics,and proteomics analysis from TBI patients and the TBI mouse model,we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral tests.We also characterized the underlying mechanisms both invitro and invivo through molecular simulations,signaling detections,gene expression regulation assessments[including dual-luciferase reporter and chromatin immunoprecipitation(ChIP)assays],primary cultures or co-cultures of neutrophils and oligodendrocytes,intracellular iron,and lipid hydroperoxide concentration measurements,as well as forkhead box protein O1(FOXO1)conditional knockout mice.Results:We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse model.Infiltration of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI,aggravating acute brain inflammatory damage and promoting late TBI-induced depression.In the acute stage,FOXO1 upregulated cytoplasmic Versican(VCAN)to interact with the apoptosis regulator B-cell lymphoma-2(BCL-2)-associated X protein(BAX),suppressing the mitochondrial translocation of BAX,which mediated the antiapoptotic effect companied with enhancing interleukin-6(IL-6)production of FOXO1high neutrophils.In the chronic stage,the“FOXO1-transferrin receptor(TFRC)”mechanism contributes to FOXO1high neutrophil ferroptosis,disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein,which contributes to the progression of late depression after TBI.Conclusions:FOXO1high neutrophils represent a novel neutrophil phenotype that emerges in response to acute and chronic TBI,which provides insight into the heterogeneity,reprogramming activity,and versatility of neutrophils in TBI.
文摘目的 探究叉头状转录因子O亚家族蛋白1(FOXO1)和髓细胞白血病因子1(MCL1)在多囊卵巢综合征(PCOS)患者中的表达及其与糖脂代谢和胰岛素抵抗的关系研究。方法 选择2022年1月—2023年1月丽水市人民医院收治的确诊为PCOS的146例患者为PCOS组,另分为肥胖组44例、非肥胖组102例,胰岛素抵抗组95例、非胰岛素抵抗组51例,选择同期在丽水市人民医院体检健康的146例女性为对照组;采用酶联免疫吸附测定(ELISA)法检测血清中FOXO1和MCL1的表达水平。采用酶偶联比色法检测空腹血糖(FPG)、餐后2 h血糖(2 h PBG)水平。采用电化学发光法检测空腹胰岛素(FINS),计算胰岛素抵抗指数(HOMA-IR)。Pearson法分析PCOS患者血清中FOXO1、MCL1水平与糖脂代谢指标以及胰岛素抵抗指标的相关性。结果 与对照组相比,PCOS组的睾酮(T)、黄体生成素(LH)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、2 h PBG、FINS、HOMA-IR水平显著升高(均P<0.05)。与对照组FOXO1、MLC1水平[(7.02±0.89)ng/ml、(9.12±1.02)ng/ml]比较,PCOS组患者血清中FOXO1水平[(5.85±0.72)ng/ml]显著降低,MCL1水平[(10.68±1.36)ng/ml]显著升高,差异均有统计学意义(t=12.349、11.088,均P<0.05)。与非肥胖组FOXO1、MCL1水平[(6.42±0.73)ng/ml、(9.68±1.38)ng/ml]比较,肥胖组患者血清中FOXO1水平[(4.52±0.71)ng/ml]显著降低,MCL1水平[(12.99±1.32)ng/ml]显著升高,差异均有统计学意义(t=14.548、13.471,均P<0.05)。与非胰岛素抵抗组FOXO1、MCL1水平[(6.58±0.73)ng/ml、(9.85±1.35)ng/ml]比较,胰岛素抵抗组患者血清中FOXO1水平[(5.46±0.71)ng/ml]显著降低,MCL1水平[(11.12±1.37)ng/ml]显著升高,差异均有统计学意义(t=8.998、5.367,均P<0.05)。相关性分析显示,PCOS患者血清中FOXO1水平与TC、LDL-C、2 h PBG、FINS、HOMA-IR水平呈负相关关系,MCL1与TC、LDL-C、2 h PBG、FINS、HOMA-IR水平呈正相关关系(均P<0.05)。结论 PCOS患者血清中FOXO1呈低表达,MCL1呈高表达,二者与糖脂代谢和胰岛素抵抗具有相关性。
文摘目的观察去泛素化酶Abraxas兄弟蛋白(ABRO1)对李斯特菌(LM)感染的小鼠单核巨噬细胞J774A.1白细胞介素(IL)-1β释放的影响,并探讨相关机制。方法培养J774A.1细胞,分别感染有李斯特菌溶血素O(LLO)的野生型LM菌株(野生型组)、敲除LLO的hly基因缺失(Δhly)LM菌株(基因缺失组)及Δhly株回补hly基因的LM菌株(回补株组),采用Western blotting法检测ABRO1蛋白,ELISA法检测细胞培养液上清中的IL-1β。将J774A.1细胞分为NI组(未感染LM菌株)、WT组(感染WT LM菌株)与Δhly组(感染Δhly LM菌株),各组分别转染NC si RNA、ABRO1 si RNA,采用ELISA法检测细胞培养液上清中的IL-1β,采用Western blotting法检测炎症小体相关分子Caspase-1、p20(Caspase-1活化形式)、IL-1β、p17。结果随着感染时间延长,野生型组、回补株组ABRO1表达、IL-1β水平逐渐增高,在感染120 min达到最高、均高于基因缺失组(P均<0.05);基因缺失组不同时点ABRO1表达、IL-1β水平无明显变化。WT组转染ABRO1 si RNA的细胞培养液上清中IL-1β水平及p20、p17表达低于转染NC si RNA的细胞(P均<0.05);WT组转染NC si RNA的细胞培养液上清中IL-1β水平及p20、p17表达高于NI组(P均<0.05);Δhly组转染NC si RNA的细胞培养液上清中IL-1β水平及p20、p17表达低于WT组(P均<0.05)。结论李斯特菌感染的J774A.1细胞中ABRO1表达增高,下调ABRO1表达后,J774A.1细胞中IL-1β释放减少;LLO可能通过激活炎症小体从而促进LM感染诱导的IL-1β释放。
