El Nino-Southern Oscillation(ENSO),the leading mode of global interannual variability,usually intensifies the Hadley Circulation(HC),and meanwhile constrains its meridional extension,leading to an equatorward movement...El Nino-Southern Oscillation(ENSO),the leading mode of global interannual variability,usually intensifies the Hadley Circulation(HC),and meanwhile constrains its meridional extension,leading to an equatorward movement of the jet system.Previous studies have investigated the response of HC to ENSO events using different reanalysis datasets and evaluated their capability in capturing the main features of ENSO-associated HC anomalies.However,these studies mainly focused on the global HC,represented by a zonal-mean mass stream function(MSF).Comparatively fewer studies have evaluated HC responses from a regional perspective,partly due to the prerequisite of the Stokes MSF,which prevents us from integrating a regional HC.In this study,we adopt a recently developed technique to construct the three-dimensional structure of HC and evaluate the capability of eight state-of-the-art reanalyses in reproducing the regional HC response to ENSO events.Results show that all eight reanalyses reproduce the spatial structure of HC responses well,with an intensified HC around the central-eastern Pacific but weakened circulations around the Indo-Pacific warm pool and tropical Atlantic.The spatial correlation coefficient of the three-dimensional HC anomalies among the different datasets is always larger than 0.93.However,these datasets may not capture the amplitudes of the HC responses well.This uncertainty is especially large for ENSO-associated equatorially asymmetric HC anomalies,with the maximum amplitude in Climate Forecast System Reanalysis(CFSR)being about 2.7 times the minimum value in the Twentieth Century Reanalysis(20CR).One should be careful when using reanalysis data to evaluate the intensity of ENSO-associated HC anomalies.展开更多
Global cerebral ischemia/hypoxia may occur due to various causes such as cardiac arrest,shock,and asphyxiation.Even though the patient’s life may be saved after cardiopulmonary resuscitation,cerebral ischemia– reper...Global cerebral ischemia/hypoxia may occur due to various causes such as cardiac arrest,shock,and asphyxiation.Even though the patient’s life may be saved after cardiopulmonary resuscitation,cerebral ischemia– reperfusion injury is likely to occur and often results in neurological dysfunction.Apart from motor and speech impediments,patients with such injury may also suffer from impaired higher-level cognitive functions such as learning and memory,placing a heavy burden on families and society.Brain areas associated with the limbic system include the hippocampus,corpus striatum,and amygdala,which are linked with cognitive function.Those brain regions are easily damaged by hypoxia,and since they are connected with the dopaminergic pathway,global cerebral ischemia–reperfusion can damage the dopaminergic pathway as well and affect the projection of dopaminergic neurons in the limbic system.This review article examines the feasibility of using dopamine,a neurotransmitter heavily involved in cognitive function,in experimental research and clinical treatment of global cerebral ischemia–reperfusion injury.Specifically,we examine the effects of dopamine on post-injury cognition and neuronal plasticity,with the ultimate goal of identifying a new tool for clinical treatment.展开更多
Ulcerative colitis(UC)is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis.Previous studies have indicated that celastrol(CSR)has strong anti-inflammat...Ulcerative colitis(UC)is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis.Previous studies have indicated that celastrol(CSR)has strong anti-inflammatory and immune-inhibitory effects.Here,we investigated the effects of CSR on colonic inflammation and mucosal immunity in an experimental colitis model,and addressed the mechanism by which CSR exerts the protective effects.We characterized the therapeutic effects and the potential mechanism of CSR on treating UC using histological staining,intestinal permeability assay,cytokine assay,flow cytometry,fecal microbiota transplantation(FMT),16S rRNA sequencing,untargeted metabolomics,and cell differentiation.CSR administration significantly ameliorated the dextran sodium sulfate(DSS)-induced colitis in mice,which was evidenced by the recovered body weight and colon length as well as the decreased disease activity index(DAI)score and intestinal permeability.Meanwhile,CSR down-regulated the production of pro-inflammatory cytokines and up-regulated the amount of anti-inflammatory mediators at both mRNA and protein levels,and improved the balances of Treg/Th1 and Treg/Th17 to maintain the colonic immune homeostasis.Notably,all the therapeutic effects were exerted in a gut microbiota-dependent manner.Furthermore,CSR treatment increased the gut microbiota diversity and changed the compositions of the gut microbiota and metabolites,which is probably associated with the gut microbiota-mediated protective effects.In conclusion,this study provides the strong evidence that CSR may be a promising therapeutic drug for UC.展开更多
Enhancers are often mutated and dysregulated in various diseases such as cancer.By integrating the function annotation of the mammalian genome(FANTOM)enhancers expression profiles and RNA-seq data from The Cancer Geno...Enhancers are often mutated and dysregulated in various diseases such as cancer.By integrating the function annotation of the mammalian genome(FANTOM)enhancers expression profiles and RNA-seq data from The Cancer Genome Atlas(TCGA)of 13 cancers and their corresponding para-cancerous tissues,we systematically identified a total of 4702 significantly differentially expressed(DE)enhancers.Furthermore,a total of 1036 DE genes regulated by DE enhancerswere identified.Itwas found that in these 13 cancers,most(61.13%)enhancers were ubiquitously expressed,whereas DE enhancers were more likely to be tissue-specific expressed,and the DE genes regulated by DE enhancers were significantly enriched in cancer-related pathways.Finally,it was manifested that 74 single nucleotide polymorphisms(SNPs)were located in 37 DE enhancers,and these SNPs affected the gain and loss of functional transcription factor binding sites of 758 transcription factors,which were shown to be highly correlated with tumorigenesis and development.展开更多
基金supported by the National Key Research and Development Program of China(Grant No.2018YFA0605703)the National Natural Science Foundation of China(Grant Nos.42176243,41976193 and 41676190)supported by National Natural Science Foundation of China(Grant No.41975079)。
文摘El Nino-Southern Oscillation(ENSO),the leading mode of global interannual variability,usually intensifies the Hadley Circulation(HC),and meanwhile constrains its meridional extension,leading to an equatorward movement of the jet system.Previous studies have investigated the response of HC to ENSO events using different reanalysis datasets and evaluated their capability in capturing the main features of ENSO-associated HC anomalies.However,these studies mainly focused on the global HC,represented by a zonal-mean mass stream function(MSF).Comparatively fewer studies have evaluated HC responses from a regional perspective,partly due to the prerequisite of the Stokes MSF,which prevents us from integrating a regional HC.In this study,we adopt a recently developed technique to construct the three-dimensional structure of HC and evaluate the capability of eight state-of-the-art reanalyses in reproducing the regional HC response to ENSO events.Results show that all eight reanalyses reproduce the spatial structure of HC responses well,with an intensified HC around the central-eastern Pacific but weakened circulations around the Indo-Pacific warm pool and tropical Atlantic.The spatial correlation coefficient of the three-dimensional HC anomalies among the different datasets is always larger than 0.93.However,these datasets may not capture the amplitudes of the HC responses well.This uncertainty is especially large for ENSO-associated equatorially asymmetric HC anomalies,with the maximum amplitude in Climate Forecast System Reanalysis(CFSR)being about 2.7 times the minimum value in the Twentieth Century Reanalysis(20CR).One should be careful when using reanalysis data to evaluate the intensity of ENSO-associated HC anomalies.
基金This study was supported by the National Natural Science Foundation of China(grant number:81100982)Central Public-Interest Scientific Institution Basal Research Fund(grant number:2018CZ-5).
文摘Global cerebral ischemia/hypoxia may occur due to various causes such as cardiac arrest,shock,and asphyxiation.Even though the patient’s life may be saved after cardiopulmonary resuscitation,cerebral ischemia– reperfusion injury is likely to occur and often results in neurological dysfunction.Apart from motor and speech impediments,patients with such injury may also suffer from impaired higher-level cognitive functions such as learning and memory,placing a heavy burden on families and society.Brain areas associated with the limbic system include the hippocampus,corpus striatum,and amygdala,which are linked with cognitive function.Those brain regions are easily damaged by hypoxia,and since they are connected with the dopaminergic pathway,global cerebral ischemia–reperfusion can damage the dopaminergic pathway as well and affect the projection of dopaminergic neurons in the limbic system.This review article examines the feasibility of using dopamine,a neurotransmitter heavily involved in cognitive function,in experimental research and clinical treatment of global cerebral ischemia–reperfusion injury.Specifically,we examine the effects of dopamine on post-injury cognition and neuronal plasticity,with the ultimate goal of identifying a new tool for clinical treatment.
基金funded by the grants from the National Key R&D Program of China(Grant No.2019YFC1316204)the National Natural Science Foundation of China(Grant Nos.81974249,31770983,82070136,and 82104488)the Hubei Provincial Natural Science Foundation of China(Grant No.2020BHB016).
文摘Ulcerative colitis(UC)is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis.Previous studies have indicated that celastrol(CSR)has strong anti-inflammatory and immune-inhibitory effects.Here,we investigated the effects of CSR on colonic inflammation and mucosal immunity in an experimental colitis model,and addressed the mechanism by which CSR exerts the protective effects.We characterized the therapeutic effects and the potential mechanism of CSR on treating UC using histological staining,intestinal permeability assay,cytokine assay,flow cytometry,fecal microbiota transplantation(FMT),16S rRNA sequencing,untargeted metabolomics,and cell differentiation.CSR administration significantly ameliorated the dextran sodium sulfate(DSS)-induced colitis in mice,which was evidenced by the recovered body weight and colon length as well as the decreased disease activity index(DAI)score and intestinal permeability.Meanwhile,CSR down-regulated the production of pro-inflammatory cytokines and up-regulated the amount of anti-inflammatory mediators at both mRNA and protein levels,and improved the balances of Treg/Th1 and Treg/Th17 to maintain the colonic immune homeostasis.Notably,all the therapeutic effects were exerted in a gut microbiota-dependent manner.Furthermore,CSR treatment increased the gut microbiota diversity and changed the compositions of the gut microbiota and metabolites,which is probably associated with the gut microbiota-mediated protective effects.In conclusion,this study provides the strong evidence that CSR may be a promising therapeutic drug for UC.
基金This work was supported by Basic Research Cultivation Support Programof Fundamental Research Funds for the Central Universities(Grant No.2682021ZTPY016)the National Science and Technology Major Project of Infectious Diseases(Grant No.R111320H01004).
文摘Enhancers are often mutated and dysregulated in various diseases such as cancer.By integrating the function annotation of the mammalian genome(FANTOM)enhancers expression profiles and RNA-seq data from The Cancer Genome Atlas(TCGA)of 13 cancers and their corresponding para-cancerous tissues,we systematically identified a total of 4702 significantly differentially expressed(DE)enhancers.Furthermore,a total of 1036 DE genes regulated by DE enhancerswere identified.Itwas found that in these 13 cancers,most(61.13%)enhancers were ubiquitously expressed,whereas DE enhancers were more likely to be tissue-specific expressed,and the DE genes regulated by DE enhancers were significantly enriched in cancer-related pathways.Finally,it was manifested that 74 single nucleotide polymorphisms(SNPs)were located in 37 DE enhancers,and these SNPs affected the gain and loss of functional transcription factor binding sites of 758 transcription factors,which were shown to be highly correlated with tumorigenesis and development.