In recent years,rising life expectancy has led to a significant increase in the prevalence of neurodegenerative disorders,including Alzheimer’s disease(AD),Parkinson’s disease,and age-related cognitive decline.Addit...In recent years,rising life expectancy has led to a significant increase in the prevalence of neurodegenerative disorders,including Alzheimer’s disease(AD),Parkinson’s disease,and age-related cognitive decline.Additionally,other neurological conditions such as glioblastoma,the most common and aggressive brain tumor in adults have been more frequently reported in aging populations.The brain itself is highly vulnerable to age-related changes,particularly disruptions in homeostatic regulation,which further contribute to its functional decline and heightened susceptibility to disease.This has led to a surge of interest in understanding the cellular and molecular mechanisms driving these changes.展开更多
Neurodegenerative disorders,including Alzheimer’s disease(AD),Parkinson’s disease(PD),and amyotrophic lateral sclerosis,impose a considerable social and economic burden on society and have dramatic consequences for ...Neurodegenerative disorders,including Alzheimer’s disease(AD),Parkinson’s disease(PD),and amyotrophic lateral sclerosis,impose a considerable social and economic burden on society and have dramatic consequences for individuals and their families.The majority of existing interventions have been found to be capable of only a slight modification of disease progression or to moderately delay significant functional decline in motor,cognitive,or mental domains.展开更多
Musculoskeletal disorders,including osteoarthritis,rheumatoid arthritis,osteoporosis,bone fracture,intervertebral disc degeneration,tendinopathy,and myopathy,are prevalent conditions that profoundly impact quality of ...Musculoskeletal disorders,including osteoarthritis,rheumatoid arthritis,osteoporosis,bone fracture,intervertebral disc degeneration,tendinopathy,and myopathy,are prevalent conditions that profoundly impact quality of life and place substantial economic burdens on healthcare systems.Traditional bulk transcriptomics,genomics,proteomics,and metabolomics have played a pivotal role in uncovering disease-associated alterations at the population level.However,these approaches are inherently limited in their ability to resolve cellular heterogeneity or to capture the spatial organization of cells within tissues,thus hindering a comprehensive understanding of the complex cellular and molecular mechanisms underlying these diseases.To address these limitations,advanced single-cell and spatial omics techniques have emerged in recent years,offering unparalleled resolution for investigating cellular diversity,tissue microenvironments,and biomolecular interactions within musculoskeletal tissues.These cutting-edge techniques enable the detailed mapping of the molecular landscapes in diseased tissues,providing transformative insights into pathophysiological processes at both the single-cell and spatial levels.This review presents a comprehensive overview of the latest omics technologies as applied to musculoskeletal research,with a particular focus on their potential to revolutionize our understanding of disease mechanisms.Additionally,we explore the power of multi-omics integration in identifying novel therapeutic targets and highlight key challenges that must be overcome to successfully translate these advancements into clinical applications.展开更多
Fear memory is crucial for survival and adaptation in complex and dynamically changing environments that enables individuals to avoid or escape from potentially dangerous situations.However,excessive fear memories can...Fear memory is crucial for survival and adaptation in complex and dynamically changing environments that enables individuals to avoid or escape from potentially dangerous situations.However,excessive fear memories can significantly contribute to emotional disabilities and mental disorders,including panic disorder,phobias,social anxiety disorder,and post-traumatic stress disorder(PTSD).展开更多
Estrogen fluctuations have been implicated in various mood disorders,including perimenopausal and postpartum depression(PPD),likely through complex neural networks.γ-aminobutyric acid-ergic(GABAergic)neurons in the m...Estrogen fluctuations have been implicated in various mood disorders,including perimenopausal and postpartum depression(PPD),likely through complex neural networks.γ-aminobutyric acid-ergic(GABAergic)neurons in the medial preoptic area(MPOA)that express estrogen receptor 1(ESR1)are essential for the development and expression of depressive-like behaviors in ovarian hormone withdrawal(HW)mice.However,the precise circuit mechanisms through which MPOA GABAergic neurons influence behavior remain incompletely understood.Here,we identified robust projections from MPOA GABAergic neurons to the paraventricular nucleus of the hypothalamus(PVN).In HW mice,chemogenetic activation of MPOA GABAergic neurons targeting PVN attenuated depressive-like behaviors.Conversely,in nonhormone withdrawal(NHW)control mice(which received continuous estrogen),suppression of MPOA GABAergic projections to PVN exacerbated depressive-like behaviors.Further analyses using quantitative polymerase chain reaction and immunostaining identified arginine vasopressin(^(AVP))as a key neuropeptide in this pathway in the HW mouse model.Chemogenetic inhibition of PVN^(AVP)neurons significantly alleviated depressive-like behaviors in HW mice,while their activation in NHW mice worsened depressive-like behaviors.These behaviors were dependent on^(AVP)expression in PVN^(AVP)neurons.Moreover,in HW mice,chemogenetic inhibition of PVN^(AVP)neurons receiving MPOA input mitigated depressive-like behaviors.Conversely,in NHW mice,activation of these neurons exacerbated depressive-like behaviors.Electrophysiological recordings demonstrated that MPOA GABAergic neurons directly inhibit PVN^(AVP)neurons.Thus,our findings suggest that PVN^(AVP)neurons serve as downstream effectors of MPOA GABAergic neurons via monosynaptic inhibitory signaling to regulate depressive-like behaviors.Targeting this circuit may offer a novel therapeutic strategy for PPD.展开更多
Cardiac disorders, including myocardial infarction, heart failure, and arrhythmias, are marked causes of morbidity and mortality worldwide. Early diagnosis and effective management of these conditions are crucial for ...Cardiac disorders, including myocardial infarction, heart failure, and arrhythmias, are marked causes of morbidity and mortality worldwide. Early diagnosis and effective management of these conditions are crucial for improving patient outcomes. Biomarkers, which are measurable biological indicators, have emerged as essential tools in the diagnosis, prognosis, and risk stratification of cardiac diseases. Among the well-established biomarkers, cardiac troponins (cardiac troponin I and cardiac troponin T) exhibit high sensitivity and specificity in the detection of myocardial infarction, and recent advances have improved early diagnosis and risk evaluation. B-type natriuretic peptide and its precursor N-terminal pro-B-type natriuretic peptide play critical roles in the diagnosis and management of heart failure;elevated levels of these factors indicate poor prognosis and can guide therapeutic decision-making. Additionally, C-reactive protein levels have been widely used in cardiovascular risk assessment and show high sensitivity. Emerging biomarkers, such as galectin-3, suppression of tumorigenicity 2, and microRNAs, show promise in enhancing the prediction of heart failure, assessment of myocardial stress, and detection of cardiac conditions in early stages. This review provides a comprehensive evaluation of these biomarkers, highlighting their clinical applications and limitations, as well as the integration of these biomarkers with imaging techniques. This review also explores the potential for future research aimed at developing personalized treatment strategies based on biomarker profiles. Biomarkers are becoming increasingly vital in optimizing cardiac care and improving patient outcomes through more targeted and individualized approaches.展开更多
Metabolic homeostasis is regulated by a network of organs and tissues,primarily involving adipose tissue,muscle,liver,and the hypothalamus,which act as central metabolic regulators.Cellular dysregulation within these ...Metabolic homeostasis is regulated by a network of organs and tissues,primarily involving adipose tissue,muscle,liver,and the hypothalamus,which act as central metabolic regulators.Cellular dysregulation within these tissues substantially associates with metabolic disorders,including obesity,type 2 diabetes,and non-alcoholic fatty liver disease(NAFLD)[1].Understanding the molecular mechanisms governing metabolic control requires dedicated analysis of physiological and pathological cellular heterogeneity within these tissues.However,investigations at the single cell level to decipher the complexities of cellular mechanisms remain challenging due to the fragile nature of certain cell types and technical noise within these metabolically active tissues,resulting in limited studies compared to well-characterized atlases in immune cell populations[2].展开更多
基金supported by the Swedish ResearchCouncil and the Swedish Brain Foundation,theCancer Research Funds of Radiumhemmet,theStrategic Research Area in Cancer(StratCan),the Strategic Research Area in Neuroscience(StratNeuro),the Swedish Cancer Society,theSwedish Childhood Cancer Foundation,theKarolinska Institutet Foundation,the InnoHKinitiative of the Innovation and TechnologyCommission of the Hong Kong SpecialAdministrative Region Government(to BJ).Openaccess funding is provided by the KarolinskaInstitute.
文摘In recent years,rising life expectancy has led to a significant increase in the prevalence of neurodegenerative disorders,including Alzheimer’s disease(AD),Parkinson’s disease,and age-related cognitive decline.Additionally,other neurological conditions such as glioblastoma,the most common and aggressive brain tumor in adults have been more frequently reported in aging populations.The brain itself is highly vulnerable to age-related changes,particularly disruptions in homeostatic regulation,which further contribute to its functional decline and heightened susceptibility to disease.This has led to a surge of interest in understanding the cellular and molecular mechanisms driving these changes.
文摘Neurodegenerative disorders,including Alzheimer’s disease(AD),Parkinson’s disease(PD),and amyotrophic lateral sclerosis,impose a considerable social and economic burden on society and have dramatic consequences for individuals and their families.The majority of existing interventions have been found to be capable of only a slight modification of disease progression or to moderately delay significant functional decline in motor,cognitive,or mental domains.
基金supported by two DoD grants(HT94252310534 to R.J.T.and HT94252310519 to C.M.K.)the following NIH/NIAMS grants:R01 grants(AR078035 and AR076900 to C.L.+10 种基金AG069401 and AG067698 to L.Q.AI186118,HD112474,and HD107034 to R.J.T.AR076325 and AR071967 to C.M.K.AR080902 and AR072999 to F.G.AR074441 and AR077678 to S.Y.T.AR082667 and AR077527 to A.E.L.AR083900,AR075860 and AR077616 to J.S.),R21 grants(AR077226 to J.S.AR083217 to A.E.L.AR081517 to S.Y.T.)a T32 grant(HD007434 to D.R.K.)P30 center grants(AR074992 and AR073752).
文摘Musculoskeletal disorders,including osteoarthritis,rheumatoid arthritis,osteoporosis,bone fracture,intervertebral disc degeneration,tendinopathy,and myopathy,are prevalent conditions that profoundly impact quality of life and place substantial economic burdens on healthcare systems.Traditional bulk transcriptomics,genomics,proteomics,and metabolomics have played a pivotal role in uncovering disease-associated alterations at the population level.However,these approaches are inherently limited in their ability to resolve cellular heterogeneity or to capture the spatial organization of cells within tissues,thus hindering a comprehensive understanding of the complex cellular and molecular mechanisms underlying these diseases.To address these limitations,advanced single-cell and spatial omics techniques have emerged in recent years,offering unparalleled resolution for investigating cellular diversity,tissue microenvironments,and biomolecular interactions within musculoskeletal tissues.These cutting-edge techniques enable the detailed mapping of the molecular landscapes in diseased tissues,providing transformative insights into pathophysiological processes at both the single-cell and spatial levels.This review presents a comprehensive overview of the latest omics technologies as applied to musculoskeletal research,with a particular focus on their potential to revolutionize our understanding of disease mechanisms.Additionally,we explore the power of multi-omics integration in identifying novel therapeutic targets and highlight key challenges that must be overcome to successfully translate these advancements into clinical applications.
文摘Fear memory is crucial for survival and adaptation in complex and dynamically changing environments that enables individuals to avoid or escape from potentially dangerous situations.However,excessive fear memories can significantly contribute to emotional disabilities and mental disorders,including panic disorder,phobias,social anxiety disorder,and post-traumatic stress disorder(PTSD).
基金supported by grants from National Natural Science Foundation of China(grant nos.32471073,32171011,and 32100816 to J.J.or G.Z.)STI2030 Major Projects(grant no.2021ZD0202805 to J.-N.Z.)the State Key Laboratory of Pharmaceutical Biotechnology(grant no.LNSN-202402 to J.-N.Z.).
文摘Estrogen fluctuations have been implicated in various mood disorders,including perimenopausal and postpartum depression(PPD),likely through complex neural networks.γ-aminobutyric acid-ergic(GABAergic)neurons in the medial preoptic area(MPOA)that express estrogen receptor 1(ESR1)are essential for the development and expression of depressive-like behaviors in ovarian hormone withdrawal(HW)mice.However,the precise circuit mechanisms through which MPOA GABAergic neurons influence behavior remain incompletely understood.Here,we identified robust projections from MPOA GABAergic neurons to the paraventricular nucleus of the hypothalamus(PVN).In HW mice,chemogenetic activation of MPOA GABAergic neurons targeting PVN attenuated depressive-like behaviors.Conversely,in nonhormone withdrawal(NHW)control mice(which received continuous estrogen),suppression of MPOA GABAergic projections to PVN exacerbated depressive-like behaviors.Further analyses using quantitative polymerase chain reaction and immunostaining identified arginine vasopressin(^(AVP))as a key neuropeptide in this pathway in the HW mouse model.Chemogenetic inhibition of PVN^(AVP)neurons significantly alleviated depressive-like behaviors in HW mice,while their activation in NHW mice worsened depressive-like behaviors.These behaviors were dependent on^(AVP)expression in PVN^(AVP)neurons.Moreover,in HW mice,chemogenetic inhibition of PVN^(AVP)neurons receiving MPOA input mitigated depressive-like behaviors.Conversely,in NHW mice,activation of these neurons exacerbated depressive-like behaviors.Electrophysiological recordings demonstrated that MPOA GABAergic neurons directly inhibit PVN^(AVP)neurons.Thus,our findings suggest that PVN^(AVP)neurons serve as downstream effectors of MPOA GABAergic neurons via monosynaptic inhibitory signaling to regulate depressive-like behaviors.Targeting this circuit may offer a novel therapeutic strategy for PPD.
文摘Cardiac disorders, including myocardial infarction, heart failure, and arrhythmias, are marked causes of morbidity and mortality worldwide. Early diagnosis and effective management of these conditions are crucial for improving patient outcomes. Biomarkers, which are measurable biological indicators, have emerged as essential tools in the diagnosis, prognosis, and risk stratification of cardiac diseases. Among the well-established biomarkers, cardiac troponins (cardiac troponin I and cardiac troponin T) exhibit high sensitivity and specificity in the detection of myocardial infarction, and recent advances have improved early diagnosis and risk evaluation. B-type natriuretic peptide and its precursor N-terminal pro-B-type natriuretic peptide play critical roles in the diagnosis and management of heart failure;elevated levels of these factors indicate poor prognosis and can guide therapeutic decision-making. Additionally, C-reactive protein levels have been widely used in cardiovascular risk assessment and show high sensitivity. Emerging biomarkers, such as galectin-3, suppression of tumorigenicity 2, and microRNAs, show promise in enhancing the prediction of heart failure, assessment of myocardial stress, and detection of cardiac conditions in early stages. This review provides a comprehensive evaluation of these biomarkers, highlighting their clinical applications and limitations, as well as the integration of these biomarkers with imaging techniques. This review also explores the potential for future research aimed at developing personalized treatment strategies based on biomarker profiles. Biomarkers are becoming increasingly vital in optimizing cardiac care and improving patient outcomes through more targeted and individualized approaches.
基金funded by the National Key Research and Development Program of China (2024YFA1802800 and 2024YFA1802803)the National Natural Science Foundation of China (32371195)a new PI Start up grant of Fudan University (JIH2303132Y) to G.W
文摘Metabolic homeostasis is regulated by a network of organs and tissues,primarily involving adipose tissue,muscle,liver,and the hypothalamus,which act as central metabolic regulators.Cellular dysregulation within these tissues substantially associates with metabolic disorders,including obesity,type 2 diabetes,and non-alcoholic fatty liver disease(NAFLD)[1].Understanding the molecular mechanisms governing metabolic control requires dedicated analysis of physiological and pathological cellular heterogeneity within these tissues.However,investigations at the single cell level to decipher the complexities of cellular mechanisms remain challenging due to the fragile nature of certain cell types and technical noise within these metabolically active tissues,resulting in limited studies compared to well-characterized atlases in immune cell populations[2].
