DEAR EDITOR,Bostrychus,a genus in the family Eleotridae of the order Gobiiformes,was first established by Lacepède in 1801(Buffon,1801).Bostrychus currently contains seven recognized species,including two recent ...DEAR EDITOR,Bostrychus,a genus in the family Eleotridae of the order Gobiiformes,was first established by Lacepède in 1801(Buffon,1801).Bostrychus currently contains seven recognized species,including two recent additions(B.microphthalmos and B.scalaris)described in 2005(Hoese&Kottelat,2005)and 2008(Larson,2008),respectively.The natural range of Bostrychus species extends from East Asia to Australia,with the exception of B.africanus,Steindachner,1879,which is distributed in West Africa(Herre,1946).Among the recognized species,B.sinensis,B.zonatus,and B.africanus are relatively widespread,inhabiting diverse areas from estuaries to freshwater streams,while B.scalaris is only found at a single mangrove site in the Selangor State of Malaysia(Larson,2008).The remaining three species exhibit a high degree of habitat specialization and are highly localized(Hoese&Kottelat,2005):B.microphthalmos inhabits a cave stream in the Maros karst of southern Sulawesi,B.aruensis is confined to freshwater environments in the Aru Islands of Indonesia,and B.strigogenys is found only in freshwater areas in southern Papua New Guinea and Irian Jaya.展开更多
Cullin-RING E3 ubiquitin ligases(CRLs),the largest family of multi-subunit E3 ubiquitin ligases in eukaryotic cells,represent core cellular machinery for executing protein degradation and maintaining proteostasis.Here...Cullin-RING E3 ubiquitin ligases(CRLs),the largest family of multi-subunit E3 ubiquitin ligases in eukaryotic cells,represent core cellular machinery for executing protein degradation and maintaining proteostasis.Here,we asked what roles Cullin proteins play in human mesenchymal stem cell(hMSC)homeostasis and senescence.To this end,we conducted a comparative aging phenotype analysis by individually knocking down Cullin members in three senescence models:replicative senescent hMSCs,Hutchinson-Gilford Progeria Syndrome hMSCs,and Werner syndrome hMSCs.Among all family members,we found that CUL2 deficiency rendered hMSCs the most susceptible to senescence.To investigate CUL2-specific underlying mechanisms,we then applied CRISPR/Cas9-mediated gene editing technology to generate CUL2-deficient human embryonic stem cells(hESCs).When we differentiated these into h MSCs,we found that CUL2 deletion markedly accelerates hMSC senescence.Importantly,we identified that CUL2 targets and promotes ubiquitin proteasome-mediated degradation of TSPYL2(a known negative regulator of proliferation)through the substrate receptor protein APPBP2,which in turn downregulates one of the canonical aging marker-P21^(waf1/cip1),and thereby delays senescence.Our work provides important insights into how CRL2^(APPBP2)-mediated TSPYL2 degradation counteracts hMSC senescence,providing a molecular basis for directing intervention strategies against aging and aging-related diseases.展开更多
Epigenetic clocks are accurate predictors of human chronological age based on the analysis of DNA methylation(DNAm)at specific CpG sites.However,a systematic comparison between DNA methylation data and other omics dat...Epigenetic clocks are accurate predictors of human chronological age based on the analysis of DNA methylation(DNAm)at specific CpG sites.However,a systematic comparison between DNA methylation data and other omics datasets has not yet been performed.Moreover,available DNAm age predictors are based on datasets with limited ethnic representation.To address these knowledge gaps,we generated and analyzed DNA methylation datasets from two independent Chinese cohorts,revealing age-related DNAm changes.Additionally,a DNA methylation aging clock(iCAS-DNAmAge)and a group of DNAm-based multi-modal clocks for Chinese individuals were developed,with most of them demonstrating strong predictive capabilities for chronological age.The clocks were further employed to predict factors influencing aging rates.The DNAm aging clock,derived from multi-modal aging features(compositeAge-DNAmAge),exhibited a close association with multi-omics changes,lifestyles,and disease status,underscoring its robust potential for precise biological age assessment.Our findings offer novel insights into the regulatory mechanism of age-related DNAm changes and extend the application of the DNAm clock for measuring biological age and aging pace,providing the basis for evaluating aging intervention strategies.展开更多
Mitochondrial dysfunction is a hallmark feature of cellular senescence and organ aging.Here,we asked whether the mitochondrial antiviral signaling protein(MAVS),which is essential for driving antiviral response,also r...Mitochondrial dysfunction is a hallmark feature of cellular senescence and organ aging.Here,we asked whether the mitochondrial antiviral signaling protein(MAVS),which is essential for driving antiviral response,also regulates human stem cell senescence.To answer this question,we used CRISPR/Cas9-mediated gene editing and directed differentiation techniques to generate various MAVS-knockout human stem cell models.We found that human mesenchymal stem cells(hMSCs)were sensitive to MAVS deficiency,as manifested by accelerated senescence phenotypes.We uncovered that the role of MAVS in maintaining mitochondrial structural integrity and functional homeostasis depends on its interaction with the guanosine triphosphatase optic atrophy type 1(OPA1).Depletion of MAVS or OPA1 led to the dysfunction of mitochondria and cellular senescence,whereas replenishment of MAVS or OPA1 in MAVS-knockout hMSCs alleviated mitochondrial defects and premature senescence phenotypes.Taken together,our data underscore an uncanonical role of MAVS in safeguarding mitochondrial homeostasis and antagonizing human stem cell senescence.展开更多
Aging poses a major risk factor for cardiovascular diseases,the leading cause of death in the aged population.However,the cell type-specific changes underlying cardiac aging are far from being clear.Here,we performed ...Aging poses a major risk factor for cardiovascular diseases,the leading cause of death in the aged population.However,the cell type-specific changes underlying cardiac aging are far from being clear.Here,we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age.We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profles.Via transcription regulatory network analysis,we identified FOxP1,a core transcription factor in organ development,as a key downregulated factor in aged cardiomyocytes,concomitant with the dysregulation of FoxP1 target genes associated with heart function and cardiac diseases.Consistently,the deficiency of FOxP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes.Altogether,our findings depict the celiular and molecular landscape of ventricular aging at the single-cell resolution,and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.展开更多
Dear Editor,Cells enter senescence,or irreversible growth arrest,when exposed to stressors such as DNA damage,epigenetic alterations and chronic inflammation(Zhao and Chen,2022).In aging and aging-related diseases,sen...Dear Editor,Cells enter senescence,or irreversible growth arrest,when exposed to stressors such as DNA damage,epigenetic alterations and chronic inflammation(Zhao and Chen,2022).In aging and aging-related diseases,senescent cells are known to accumulate across tissues and organs(Sun et al.,2022;Lopez-Otin et al.,2023).展开更多
Dear Editor,Cardiovascular diseases(CVDs)are the leading cause of death world-wide.Thus,diagnosing and treating CVD remains at the forefront for clinicians while identifying targetable disease mechanisms in preclinica...Dear Editor,Cardiovascular diseases(CVDs)are the leading cause of death world-wide.Thus,diagnosing and treating CVD remains at the forefront for clinicians while identifying targetable disease mechanisms in preclinical models are focus areas for researchers and drug developers(Cai et al.,2022a).The polymorphic protein apolipoprotein E(APOE),central to lipid transport and metabolism,is well-recognized for the role of its isoforms as important predictors for human cardiovascular disorders and neurodegenerative diseases(Tudorache et al.,2017).Plasma APOE is generated primarily from liver hepatocytes,accounting for around 75%of the APOE production from the whole body(Getz and Reardon,2009),and plays important functional roles in monocytes/macrophages,adipocytes,and the central nervous system(Kockx et al.,2018).However,despite the fact that APOE is widely expressed in different mammalian cells,studies on the functional roles of APOE mostly focus on its extracellular secreted form,and the specific effects of APOE,particularly intracellular form in cell types closely related to human cardiovascular diseases are therefore still poorly understood.展开更多
Dear Editor,Chloroquine(CQ)has long been used as an anti-malarial agent(Wellems and Plowe,2001).Recently,CQ has also been applied to treat viral infection and related diseases(Wellems and Plowe,2001;Huang et al.,2020)...Dear Editor,Chloroquine(CQ)has long been used as an anti-malarial agent(Wellems and Plowe,2001).Recently,CQ has also been applied to treat viral infection and related diseases(Wellems and Plowe,2001;Huang et al.,2020).However,the safety and efficacy of its applications are still under extensive debate(Solomon and Lee,2009).Here,we discovered that low-dose CQ has a geroprotective effect on physiologically aged rats.Low-dose CQ prolonged lifespan,repressed systemic inflammation,and inhibited fibrosis across multiple tissue types in aged rats.Furthermore,we constructed transcriptomic maps for 6 tissues(kidney,small intestine,liver,heart,lung,and aorta)upon CQ treatment,thus revealing the effects of CQ at a systemic level.CQ treatment mitigated age-related molecular changes and repressed genes linked to fibrosis and the inflammatory response.Altogether,our data provide a valuable resource for investigating the impact of CQ on multiple aged tissues,which may facilitate the development of clinical applications that mitigate age-related changes in the elderly.展开更多
OBJECTIVE:To optimize the vinegar-steaming process of Wuweizi(Fructus Schisandrae Chinensis)using the response surface method(RSM)based on the Box-Behnken design.METHODS:A regression model was constructed with the res...OBJECTIVE:To optimize the vinegar-steaming process of Wuweizi(Fructus Schisandrae Chinensis)using the response surface method(RSM)based on the Box-Behnken design.METHODS:A regression model was constructed with the response variables,the content of Deoxyschizandrin,and the three explanatory factors:length of steaming time,the quantity of vinegar and length of moistening time to evaluate the effects on the processing of Wuweizi(Fructus SchisandraeChinensis).RESULTS:There was a linear relationship between the content of Deoxyschizandrin and the three explanatory factors.When the steaming time was5.49 h,with 2.365 g of vinegar added and a moistening time of 4.13 h,the content of Deoxyschizandrin reached the maximum predicted value of0.1076%,and under the conditions the average content of Deoxyschizandrin was 0.1058%.CONCLUSION:The correlation coefficient of thenonlinear mathematical model was relatively high and the model matched the data well,potentially providing a method for the study of the steaming process.展开更多
Li Mn_(2)O_(4)(LMO)is the substance of choice for small and medium-sized energy storage materials in daily life.In this work,Li3InCl6(LIC)is prepared on the surface of LiMn_(2)O_(4)by hydrothermal method using InCl_(3...Li Mn_(2)O_(4)(LMO)is the substance of choice for small and medium-sized energy storage materials in daily life.In this work,Li3InCl6(LIC)is prepared on the surface of LiMn_(2)O_(4)by hydrothermal method using InCl_(3)and LiCl as raw materials.This method stabilizes the LMO crystal structure by uniformly coating the LIC on the LMO surface and effectively maintains the morphology of LMO crystals during the cycling process.SEM and EDS analysis confirm the morphology and homogeneity of the synthesized material LIC on the LMO surface.The prepared material is put into a battery,and the charge-discharge test is carried out at 0.5 C and 1 C.The results show that the LIC surface-modified samples exhibit more than 6%higher cycling performance than the unmodified samples after long cycling.展开更多
基金supported by the National Natural Science Foundation of China(41776143)。
文摘DEAR EDITOR,Bostrychus,a genus in the family Eleotridae of the order Gobiiformes,was first established by Lacepède in 1801(Buffon,1801).Bostrychus currently contains seven recognized species,including two recent additions(B.microphthalmos and B.scalaris)described in 2005(Hoese&Kottelat,2005)and 2008(Larson,2008),respectively.The natural range of Bostrychus species extends from East Asia to Australia,with the exception of B.africanus,Steindachner,1879,which is distributed in West Africa(Herre,1946).Among the recognized species,B.sinensis,B.zonatus,and B.africanus are relatively widespread,inhabiting diverse areas from estuaries to freshwater streams,while B.scalaris is only found at a single mangrove site in the Selangor State of Malaysia(Larson,2008).The remaining three species exhibit a high degree of habitat specialization and are highly localized(Hoese&Kottelat,2005):B.microphthalmos inhabits a cave stream in the Maros karst of southern Sulawesi,B.aruensis is confined to freshwater environments in the Aru Islands of Indonesia,and B.strigogenys is found only in freshwater areas in southern Papua New Guinea and Irian Jaya.
基金supported by the National Key Research and Development Program of China(2020YFA0804000,2022YFA1103700,2020YFA0112200,2021YFF1201000,the STI2030-Major Projects-2021ZD0202400,2022YFA1103800)the National Natural Science Foundation of China(82201714,81921006,82125011,92149301,92168201,91949209,92049304,92049116,32121001,82192863,82122024,82071588,32000500,82271600,82001477,82201727)+12 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16000000)CAS Project for Young Scientists in Basic Research(YSBR-076,YSBR-012)the Program of the Beijing Natural Science Foundation(Z190019)the Fellowship of China Postdoctoral Science Foundation(2022M712216)the Project for Technology Development of Beijing-affiliated Medical Research Institutes(11000023T000002036310)the Pilot Project for Public Welfare Development and Reform of Beijing-affiliated Medical Research Institutes(11000022T000000461062)Youth Innovation Promotion Association of CAS(E1CAZW0401,2022083,2023092)Young Elite Scientists Sponsorship Program by CAST(YESS20200012,YESS20210002)the Informatization Plan of Chinese Academy of Sciences(CAS-WX2021SF-0301,CAS-WX2022SDC-XK14,CASWX2021SF-0101)New Cornerstone Science Foundation through the XPLORER PRIZE(2021-1045)Excellent Young Talents Program of Capital Medical University(12300927)Excellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team(BPHR202203105)Beijing Hospitals Authority Youth Programme(QML20230806)。
文摘Cullin-RING E3 ubiquitin ligases(CRLs),the largest family of multi-subunit E3 ubiquitin ligases in eukaryotic cells,represent core cellular machinery for executing protein degradation and maintaining proteostasis.Here,we asked what roles Cullin proteins play in human mesenchymal stem cell(hMSC)homeostasis and senescence.To this end,we conducted a comparative aging phenotype analysis by individually knocking down Cullin members in three senescence models:replicative senescent hMSCs,Hutchinson-Gilford Progeria Syndrome hMSCs,and Werner syndrome hMSCs.Among all family members,we found that CUL2 deficiency rendered hMSCs the most susceptible to senescence.To investigate CUL2-specific underlying mechanisms,we then applied CRISPR/Cas9-mediated gene editing technology to generate CUL2-deficient human embryonic stem cells(hESCs).When we differentiated these into h MSCs,we found that CUL2 deletion markedly accelerates hMSC senescence.Importantly,we identified that CUL2 targets and promotes ubiquitin proteasome-mediated degradation of TSPYL2(a known negative regulator of proliferation)through the substrate receptor protein APPBP2,which in turn downregulates one of the canonical aging marker-P21^(waf1/cip1),and thereby delays senescence.Our work provides important insights into how CRL2^(APPBP2)-mediated TSPYL2 degradation counteracts hMSC senescence,providing a molecular basis for directing intervention strategies against aging and aging-related diseases.
基金supported by the National Key Research and Development Program of China(2021YFF1201000,2022YFA1103700)the Quzhou Technology Projects(2022K46)+13 种基金the National Natural Science Foundation of China(Grant Nos.32121001,81921006,82125011,92149301,82361148131,82192863)the National Key Research and Development Program of China(2020YFA0804000,2020YFA0112200,the STI2030-Major Projects-2021ZD0202400,2021YFA1101000)the National Natural Science Foundation of China(Grant Nos.92168201,92049304,92049116,82122024,82071588,32000510,8236114813082271600,82322025,82330044,32341001)CAS Project for Young Scientists in Basic Research(YSBR-076,YSBR-012)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB38010400)the Science and Technology Service Network Initiative of Chinese Academy of Sciences(KFJSTS-QYZD-2021-08-001)the Beijing Natural Science Foundation(Z230011,5242024)the Informatization Plan of Chinese Academy of Sciences(CAS-WX2021SF-0301,CAS-WX2022SDC-XK14,CAS-WX2021SF-0101)New Cormerstone Science Foundation through the XPLORER PRIZE(2021-1045)YouthInnovation Promotion Association of CAS(E1CAZW0401,2022083)Excellent Young Talents Program of Capital Medical University(12300927)the Project for Technology Development of Beijing-affliated Medical ResearchInstitutes(11000023T000002036310)ExcellentYoung Talents Training Program for the Construction of Beijing Municipal University Teacher Team(BPHR202203105)Young Elite Scientists Sponsorship Program by CAST(2021QNRC001)Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(JYY202X-X).
文摘Epigenetic clocks are accurate predictors of human chronological age based on the analysis of DNA methylation(DNAm)at specific CpG sites.However,a systematic comparison between DNA methylation data and other omics datasets has not yet been performed.Moreover,available DNAm age predictors are based on datasets with limited ethnic representation.To address these knowledge gaps,we generated and analyzed DNA methylation datasets from two independent Chinese cohorts,revealing age-related DNAm changes.Additionally,a DNA methylation aging clock(iCAS-DNAmAge)and a group of DNAm-based multi-modal clocks for Chinese individuals were developed,with most of them demonstrating strong predictive capabilities for chronological age.The clocks were further employed to predict factors influencing aging rates.The DNAm aging clock,derived from multi-modal aging features(compositeAge-DNAmAge),exhibited a close association with multi-omics changes,lifestyles,and disease status,underscoring its robust potential for precise biological age assessment.Our findings offer novel insights into the regulatory mechanism of age-related DNAm changes and extend the application of the DNAm clock for measuring biological age and aging pace,providing the basis for evaluating aging intervention strategies.
基金supported by the National Key Research and Development Program of China(2022YFA1103700,2020YFA0804000,2020YFA0112200,2021YFF1201005,and the STI2030-Major Projects-2021ZD0202400)the National Natural Science Foundation of China(81921006,82125011,92149301,92168201,91949209,92049304,92049116,32121001,82192863,82122024,and 82071588)+9 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16000000)CAS Project for Young Scientists in Basic Research(YSBR-076,YSBR-012)the Program of the Beijing Natural Science Foundation(Z190019)Youth Innovation Promotion Association of CAS(E1CAZW0401)the Pilot Project for Public Welfare Development and Reform of Beijing-affiliated Medical Research Institutes(11000022T000000461062)the Informatization Plan of Chinese Academy of Sciences(CAS-WX2021SF-0101,CAS-WX2021SF-0301,and CAS-WX2022SDC-XK14)Young Elite Scientists Sponsorship Program by CAST(YESS20200012)the New Cornerstone Science Foundation through the XPLORER PRIZE(2021-1045)the Excellent Young Talents Program of Capital Medical University(12300927)the Excellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team(BPHR202203105).
文摘Mitochondrial dysfunction is a hallmark feature of cellular senescence and organ aging.Here,we asked whether the mitochondrial antiviral signaling protein(MAVS),which is essential for driving antiviral response,also regulates human stem cell senescence.To answer this question,we used CRISPR/Cas9-mediated gene editing and directed differentiation techniques to generate various MAVS-knockout human stem cell models.We found that human mesenchymal stem cells(hMSCs)were sensitive to MAVS deficiency,as manifested by accelerated senescence phenotypes.We uncovered that the role of MAVS in maintaining mitochondrial structural integrity and functional homeostasis depends on its interaction with the guanosine triphosphatase optic atrophy type 1(OPA1).Depletion of MAVS or OPA1 led to the dysfunction of mitochondria and cellular senescence,whereas replenishment of MAVS or OPA1 in MAVS-knockout hMSCs alleviated mitochondrial defects and premature senescence phenotypes.Taken together,our data underscore an uncanonical role of MAVS in safeguarding mitochondrial homeostasis and antagonizing human stem cell senescence.
基金supported by the National Key Research and Development Program of China(2018YFC2000100)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16000000)+6 种基金the National Natural Science Foundation of China(81921006,92149301,92168201,82125011,91949209,92049304,92049116,32121001,82192863,82122024,82071588,81901432,32000510,81861168034,32000500,81901433,81870228,81922027)the National Key Research and Development Program of China(2020YFA0804000,2020YFA0113400,2018YFA0107203,2020YFA0112200,2021YFF1201005,2021ZD0202401)the Program of the Beijing Natural Science Foundation(Z190019,JQ20031)K.C.Wong Education Foundation(GJTD-2019-06,GJTD-2019-08),Young Elite Scientists Sponsorship Program by CAST(YESS20200012,YESS20210002)The Pilot Project for Public Welfare Development and Reform of Beijing-affliated Medical Research Institutes(11000022T000000461062)CAS Project for Young Scientists in Basic Research(YSBR-012),Youth Innovation Promotion Association of CAS(E1CAZW0401,2022083)the Informatization Plan of Chinese Academy of Sciences(CAS-WX2021SF-0301,CASWX2022SDC-XK14),the Tencent Foundation(2021-1045).
文摘Aging poses a major risk factor for cardiovascular diseases,the leading cause of death in the aged population.However,the cell type-specific changes underlying cardiac aging are far from being clear.Here,we performed single-nucleus RNA-sequencing analysis of left ventricles from young and aged cynomolgus monkeys to define cell composition changes and transcriptomic alterations across different cell types associated with age.We found that aged cardiomyocytes underwent a dramatic loss in cell numbers and profound fluctuations in transcriptional profles.Via transcription regulatory network analysis,we identified FOxP1,a core transcription factor in organ development,as a key downregulated factor in aged cardiomyocytes,concomitant with the dysregulation of FoxP1 target genes associated with heart function and cardiac diseases.Consistently,the deficiency of FOxP1 led to hypertrophic and senescent phenotypes in human embryonic stem cell-derived cardiomyocytes.Altogether,our findings depict the celiular and molecular landscape of ventricular aging at the single-cell resolution,and identify drivers for primate cardiac aging and potential targets for intervention against cardiac aging and associated diseases.
基金supported by the National Key Research and Development Program of China (2020YFA0804000)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16000000)+9 种基金the National Natural Science Foundation of China (81921006,82125011,92149301,92168201,91949209,92049304,92049116,32121001,82271600,82192863,32000500,82122024,82071588,32000510)the National Key Research and Development Program of China (2018YFC2000100,2018YFA0107203,2020YFA0112200,2021YFF1201005,the STI2030-Major Projects-2021ZD0202400,2022YFA1103700)CAS Project for Young Scientists in Basic Research (YSBR-076,YSBR-012)the Program of the Beijing Natural Science Foundation (Z190019)K.C.Wong Education Foundation (GJTD-2019-06,GJTD-2019-08)The Pilot Project for Public Welfare Development and Reform of Beijingaffiliated Medical Research Institutes (11000022T000000461062)Youth Innovation Promotion Association of CAS (E1CAzW0401,2022083)Young Elite Scientists Sponsorship Program by CAST (YESS20200012,YESS20210002)the Informatization Plan of Chinese Academy of Sciences (CAS-WX2021SF-0301,CASWX2022SDC-XK14,CAS-WX2021SF-0101)the Tencent Foundation (2021-1045).
文摘Dear Editor,Cells enter senescence,or irreversible growth arrest,when exposed to stressors such as DNA damage,epigenetic alterations and chronic inflammation(Zhao and Chen,2022).In aging and aging-related diseases,senescent cells are known to accumulate across tissues and organs(Sun et al.,2022;Lopez-Otin et al.,2023).
基金supported by the National Key Research and Development Program of China(nos.2020YFA0804000,2022YFA1103700,2020YFA0112200,2021YFF1201005,2022YFA1103800,the STI2030-Major Projects-2021ZD0202400)the National Natural Science Foundation of China(nos.81921006,82125011,92149301,92168201,91949209,92049304,92049116,32121001,82192863,82122024,82071588,32000500,82271600,32100937)+7 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(no.XDA16000000)the Program of the Beijing Natural Science Foundation(no.Z190019)CAS Project for Young Scientists in Basic Research(nos.YSBR-076,YSBR-012)The Pilot Project for Public Welfare Development and Reform of Beijing-affliated Medical Research Institutes(no.11000022T000000461062)Youth Innovation Promotion Association of CAS(nos.E1CAZW0401,2022083)Young Elite Scientists Sponsorship Program by CAST(nos.YESS20200012,YESS20210002)the Informatization Plan of Chinese Academy of Sciences(nos.CAS-WX2021SF-0301,CAS-WX2022SDC-XK14,CASWx2021SF-0101)the Tencent Foundation(no.2021-1045).
文摘Dear Editor,Cardiovascular diseases(CVDs)are the leading cause of death world-wide.Thus,diagnosing and treating CVD remains at the forefront for clinicians while identifying targetable disease mechanisms in preclinical models are focus areas for researchers and drug developers(Cai et al.,2022a).The polymorphic protein apolipoprotein E(APOE),central to lipid transport and metabolism,is well-recognized for the role of its isoforms as important predictors for human cardiovascular disorders and neurodegenerative diseases(Tudorache et al.,2017).Plasma APOE is generated primarily from liver hepatocytes,accounting for around 75%of the APOE production from the whole body(Getz and Reardon,2009),and plays important functional roles in monocytes/macrophages,adipocytes,and the central nervous system(Kockx et al.,2018).However,despite the fact that APOE is widely expressed in different mammalian cells,studies on the functional roles of APOE mostly focus on its extracellular secreted form,and the specific effects of APOE,particularly intracellular form in cell types closely related to human cardiovascular diseases are therefore still poorly understood.
基金the National Key Research and Development Program of China(2018YFC2000100)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16000000)+12 种基金the Program of Beijing Municipal Science and Technology Commission(Z191100001519005)the National Natural Science Foundation of China(Grant Nos.81921006,8162500991749202,81861168034,91949209,92049304,81822018,81870228,81922027,82071588,92049116,31801010,81901433,82125011,82122024,92149301,92168201)the National Key Research and Development Program of China(2020YFA0804000,2020YFA0112200,2017YFA0103304,2017YFA0102802,2018YFA0107203,2020YFA0113400)the Program of the Beijing Natural Science Foundation(Z190019,JQ20031)the Key Research Program of the Chinese Academy of Sciences(KFZDSW-221)K.C.Wong Education Foundation(GJTD-2019-06,GJTD-2019-08)Beijing Hospitals Authority Youth Programme(QML20200802)Youth Innovation Promotion Association of CAS(E1CAZW0401,2021078)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2020-JKCS-011)the State Key Laboratory of Stem Cell and Reproductive Biology,the State Key Laboratory of Membrane Biology,the 14th Five-year Network Security and Informatization Plan of Chinese Academy of Sciences(WX145XQ07-18)the Informatization Plan of Chinese Academy of Sciences(CAS-WX2021SF-0301)the Milky Way Research Foundation(MWRF),Young Elite Scientists Sponsorship Program by CAST(NO.YESS20200012)CAS Project for Young Scientists in Basic Research(YSBR-012)and the Tencent Foundation.
文摘Dear Editor,Chloroquine(CQ)has long been used as an anti-malarial agent(Wellems and Plowe,2001).Recently,CQ has also been applied to treat viral infection and related diseases(Wellems and Plowe,2001;Huang et al.,2020).However,the safety and efficacy of its applications are still under extensive debate(Solomon and Lee,2009).Here,we discovered that low-dose CQ has a geroprotective effect on physiologically aged rats.Low-dose CQ prolonged lifespan,repressed systemic inflammation,and inhibited fibrosis across multiple tissue types in aged rats.Furthermore,we constructed transcriptomic maps for 6 tissues(kidney,small intestine,liver,heart,lung,and aorta)upon CQ treatment,thus revealing the effects of CQ at a systemic level.CQ treatment mitigated age-related molecular changes and repressed genes linked to fibrosis and the inflammatory response.Altogether,our data provide a valuable resource for investigating the impact of CQ on multiple aged tissues,which may facilitate the development of clinical applications that mitigate age-related changes in the elderly.
基金Supported by Scientific Research Foundation of Health Department of Shaanxi Province(2012D14),China
文摘OBJECTIVE:To optimize the vinegar-steaming process of Wuweizi(Fructus Schisandrae Chinensis)using the response surface method(RSM)based on the Box-Behnken design.METHODS:A regression model was constructed with the response variables,the content of Deoxyschizandrin,and the three explanatory factors:length of steaming time,the quantity of vinegar and length of moistening time to evaluate the effects on the processing of Wuweizi(Fructus SchisandraeChinensis).RESULTS:There was a linear relationship between the content of Deoxyschizandrin and the three explanatory factors.When the steaming time was5.49 h,with 2.365 g of vinegar added and a moistening time of 4.13 h,the content of Deoxyschizandrin reached the maximum predicted value of0.1076%,and under the conditions the average content of Deoxyschizandrin was 0.1058%.CONCLUSION:The correlation coefficient of thenonlinear mathematical model was relatively high and the model matched the data well,potentially providing a method for the study of the steaming process.
基金supported by Guangxi Higher Education Key Laboratory of Advanced MaterialsCenter of Ecological Collaborative Innovation for Aluminum Industry in Guangxi+4 种基金CITIC Dameng Mining Industries Limited-Guangxi University Joint Research Institute of Manganese Resources Utilization and Advanced Materials TechnologyGuangxi University-CITIC Dameng Mining Industries Limited Joint Base of Postgraduate CultivationNational Natural Science Foundation of China(No.11364003)Guangxi Innovation Driven Development Project(Nos.AA17204100,AA18118052)the Natural Science Foundation of Guangxi Province(No.2018GXNSFAA138186)。
文摘Li Mn_(2)O_(4)(LMO)is the substance of choice for small and medium-sized energy storage materials in daily life.In this work,Li3InCl6(LIC)is prepared on the surface of LiMn_(2)O_(4)by hydrothermal method using InCl_(3)and LiCl as raw materials.This method stabilizes the LMO crystal structure by uniformly coating the LIC on the LMO surface and effectively maintains the morphology of LMO crystals during the cycling process.SEM and EDS analysis confirm the morphology and homogeneity of the synthesized material LIC on the LMO surface.The prepared material is put into a battery,and the charge-discharge test is carried out at 0.5 C and 1 C.The results show that the LIC surface-modified samples exhibit more than 6%higher cycling performance than the unmodified samples after long cycling.