Arrhythmias are very common in the healthy populations as well as patients with cardiovascular diseases.Among them,atrial fibrillation(AF)and malignant ventricular arrhythmias are usually associated with some clinical...Arrhythmias are very common in the healthy populations as well as patients with cardiovascular diseases.Among them,atrial fibrillation(AF)and malignant ventricular arrhythmias are usually associated with some clinical events.Early diagnosis of arrhythmias,particularly AF and ventricular arrhythmias,is very important for the treatment and prognosis of patients.Holter is a gold standard commonly recommended for noninvasive detection of paroxysmal arrhythmia.However,it has some shortcomings such as fixed detection timings,delayed report and inability of remote real-time detection.To deal with such problems,we designed and applied a new wearable 72-hour triple-lead H3-electrocardiogram(ECG)device with a remote cloud-based ECG platform and an expertsupporting system.In this study,31 patients were recruited and 24-hour synchronous ECG data by H3-ECG and Holter were recorded.In the H3-ECG group,ECG signals were transmitted using remote real-time modes,and confirmed reports were made by doctors in the remote expert-supporting system,while the traditional modes and detection systems were used in the Holter group.The results showed no significant differences between the two groups in 24-hour total heart rate(HR),averaged HR,maximum HR,minimum HR,premature atrial complexes(PACs)and premature ventricular complexes(PVCs)(P>0.05).The sensitivity and specificity of capture and remote automatic cardiac events detection of PACs,PVCs,and AF by H3-ECG were 93%and 99%,98%and 99%,94%and 98%,respectively.Therefore,the long-term limb triple-lead H3-ECG device can be utilized for domiciliary ECG self-monitoring and remote management of patients with common arrhythmia under medical supervision.展开更多
Aging increases the risk ofliver diseases and systemic susceptibility to aging-related diseases.However,cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely ...Aging increases the risk ofliver diseases and systemic susceptibility to aging-related diseases.However,cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely characterized.Here,we constructed the first single-nucleus transcriptomic landscape of primate liver aging,in which we resolved cell type-specific gene expression fluctuation in hepatocytes across three liver zonations and detected aberrant cell-cell interactions between hepatocytes and niche cells.Upon in-depth dissection of this rich dataset,we identifed impaired lipid metabolism and upregulation of chronic inflammation-related genes prominently associated with declined liver functions during aging.In particular,hyperactivated sterol regulatory element-binding protein(SREBP)signaling was a hallmark of the aged liver,and consequently,forced activation of SREBP2 in human primary hepatocytes recapitulated in vivo aging phenotypes,manifesting as impaired detoxification and accelerated cellular senescence.This study expands our knowledge of primate liver aging and informs the development of diagnostics and therapeutic interventions for liver aging and associated diseases.展开更多
Hair loss affects millions of people at some time in their life,and safe and efficient treatments for hair loss are a significant unmet medical need.We report that topical delivery of quercetin(Que)stimulates resting ...Hair loss affects millions of people at some time in their life,and safe and efficient treatments for hair loss are a significant unmet medical need.We report that topical delivery of quercetin(Que)stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice.We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1αin endothelial cells.Skin administration of a HIF-1αagonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que.Together,these findings provide a molecular understanding for the efficacy of Que in hair regrowth,which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine,and suggest a route of pharmacological intervention that may promote hair regrowth.展开更多
Vertically aligned carbon nanotubes arrays(VACNTs)are a promising candidate for the thermal interface material(TIM)of next-generation electronic devices due to their attractive thermal and mechanical properties.Howeve...Vertically aligned carbon nanotubes arrays(VACNTs)are a promising candidate for the thermal interface material(TIM)of next-generation electronic devices due to their attractive thermal and mechanical properties.However,the environment required for synthesizing VACNTs is harsh and severely incompatible with standard device packaging processes.VACNTs’extremely low in-plane thermal conductivity also limits its performance for cooling hot spots.Here,using a transfer-and-encapsulate strategy,a two-step soldering method is developed to cap both ends of the VACNTs with copper microfoils,forming a standalone Cu-VACNTs-Cu sandwich TIM and avoiding the need to directly grow VACNTs on chip die.This new TIM is fully compatible with standard packaging,with excellent flexibility and high thermal conductivities in both in-plane and through-plane directions.The mechanical compliance behavior and mechanism,which are critical for TIM applications,are investigated in depth using in situ nanoindentation.The thermal performance is further verified in an actual light emitting diode(LED)cooling experiment,demonstrating low thermal resistance,good reliability,and achieving a 17℃ temperature reduction compared with state-of-the-art commercial TIMs.This study provides a viable solution to VACNTs’longstanding problem in device integration and free-end contact resistance,bringing it much closer to application and solving the critical thermal bottleneck in next-generation electronics.展开更多
基金This research was funded by the Key Research and Development Plan of Jiangsu Province under grant BE2017735.Q.S.conceived the study and wrote the manuscript.Q.S.,C.C.,H.G.X.W.collected,analyzed,and interpreted the data.H.G.and X.W.contributed substantially to the development of ECG signal conversion Matlab software and remote automatic detection algorithm.J.L.,M.C.and C.L.revised the manuscript,evaluated and supervised the study.
文摘Arrhythmias are very common in the healthy populations as well as patients with cardiovascular diseases.Among them,atrial fibrillation(AF)and malignant ventricular arrhythmias are usually associated with some clinical events.Early diagnosis of arrhythmias,particularly AF and ventricular arrhythmias,is very important for the treatment and prognosis of patients.Holter is a gold standard commonly recommended for noninvasive detection of paroxysmal arrhythmia.However,it has some shortcomings such as fixed detection timings,delayed report and inability of remote real-time detection.To deal with such problems,we designed and applied a new wearable 72-hour triple-lead H3-electrocardiogram(ECG)device with a remote cloud-based ECG platform and an expertsupporting system.In this study,31 patients were recruited and 24-hour synchronous ECG data by H3-ECG and Holter were recorded.In the H3-ECG group,ECG signals were transmitted using remote real-time modes,and confirmed reports were made by doctors in the remote expert-supporting system,while the traditional modes and detection systems were used in the Holter group.The results showed no significant differences between the two groups in 24-hour total heart rate(HR),averaged HR,maximum HR,minimum HR,premature atrial complexes(PACs)and premature ventricular complexes(PVCs)(P>0.05).The sensitivity and specificity of capture and remote automatic cardiac events detection of PACs,PVCs,and AF by H3-ECG were 93%and 99%,98%and 99%,94%and 98%,respectively.Therefore,the long-term limb triple-lead H3-ECG device can be utilized for domiciliary ECG self-monitoring and remote management of patients with common arrhythmia under medical supervision.
基金supported by the National Key Research and Development Program of China (Grant Nos.2022YFA1103700,2020YFA0804000,2020YFA0112200,2021YFF1201000,2022YFA1103800,2021YFA1101401,the STI2030-Major Projects-2021ZD0202400)the National Natural Science Foundation of China (Grant Nos.92049116,81921006,82125011,92149301,92168201,91949209,92049304,32121001,82192863,82122024,82071588,32000500,82271600)+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)the Pilot Project for Public Welfare Development and Reform of Beijing-affiliated Medical Research Institutes (No.11000022T000000461062)Youth Innovation Promotion Association of CAS (E1CAZW0401,2023092,2022083)Young Elite Scientists Sponsorship Program by CAST (YESS20200012,YESS20210002)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)Excellent Young Talents Program of Capital Medical University (No.12300927)Excellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team (BPHR202203105).
文摘Aging increases the risk ofliver diseases and systemic susceptibility to aging-related diseases.However,cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely characterized.Here,we constructed the first single-nucleus transcriptomic landscape of primate liver aging,in which we resolved cell type-specific gene expression fluctuation in hepatocytes across three liver zonations and detected aberrant cell-cell interactions between hepatocytes and niche cells.Upon in-depth dissection of this rich dataset,we identifed impaired lipid metabolism and upregulation of chronic inflammation-related genes prominently associated with declined liver functions during aging.In particular,hyperactivated sterol regulatory element-binding protein(SREBP)signaling was a hallmark of the aged liver,and consequently,forced activation of SREBP2 in human primary hepatocytes recapitulated in vivo aging phenotypes,manifesting as impaired detoxification and accelerated cellular senescence.This study expands our knowledge of primate liver aging and informs the development of diagnostics and therapeutic interventions for liver aging and associated diseases.
基金supported by the National Key Research and Development Program of China(No.2020YFA0804000)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA16000000)+12 种基金the National Natural Science Foundation of China(Nos.82001477,81921006,82125011,92149301,92168201,91949209,92049304,92049116,32121001,32171447,82192863,82122024,82071588,32000500,81861168034,82271600 and 82201727)the National Key Research and Development Program of China(Nos.2018YFC2000100,2018YFA0107203,2020YFA0112200,2021YFF1201005,2021ZD0202401,2022YFA1103700 and 2021YFA1101401)CAS Project for Young Scientists in Basic Research(Nos.YSBR-076 and YSBR-012)the Program of the Beijing Natural Science Foundation(No.Z190019)K.C.Wong Education Foundation(Nos.GJTD-2019-06 and GJTD-2019-08)the Tencent Foundation(No.2021-1045)The Pilot Project for Public Welfare Development and Reform of Beijing-affiliated Medical Research Institutes(No.11000022T000000461062)Youth Innovation Promotion Association of CAS(Nos.E1CAZW0401 and 2022083)Young Elite Scientists Sponsorship Program by CAST(Nos.YESS20200012 and YESS20210002)the Informatization Plan of Chinese Academy of Sciences(Nos.CAS-WX2021SF-0301,CASWX2022SDC-XK14,and CAS-WX2021SF-0101)Beijing Hospitals Authority Youth Programme(No.QML20200802)the Open Research Program of State Key Laboratory of Membrane Biology(No.2021KF02)Grant from Key Laboratory of Stem Cells and Tissue Engineering(Sun Yat-Sen University),Ministry of Education(No.2021-A-001).
文摘Hair loss affects millions of people at some time in their life,and safe and efficient treatments for hair loss are a significant unmet medical need.We report that topical delivery of quercetin(Que)stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice.We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1αin endothelial cells.Skin administration of a HIF-1αagonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que.Together,these findings provide a molecular understanding for the efficacy of Que in hair regrowth,which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine,and suggest a route of pharmacological intervention that may promote hair regrowth.
基金supported by the National Natural Science Foundation of China(No.52076041)the Natural Science Foundation of Jiangsu Province(No.BK20200371)the Nanjing Carbon Peak and Carbon Neutrality Science and Technology Innovation Project(No.202211009)。
文摘Vertically aligned carbon nanotubes arrays(VACNTs)are a promising candidate for the thermal interface material(TIM)of next-generation electronic devices due to their attractive thermal and mechanical properties.However,the environment required for synthesizing VACNTs is harsh and severely incompatible with standard device packaging processes.VACNTs’extremely low in-plane thermal conductivity also limits its performance for cooling hot spots.Here,using a transfer-and-encapsulate strategy,a two-step soldering method is developed to cap both ends of the VACNTs with copper microfoils,forming a standalone Cu-VACNTs-Cu sandwich TIM and avoiding the need to directly grow VACNTs on chip die.This new TIM is fully compatible with standard packaging,with excellent flexibility and high thermal conductivities in both in-plane and through-plane directions.The mechanical compliance behavior and mechanism,which are critical for TIM applications,are investigated in depth using in situ nanoindentation.The thermal performance is further verified in an actual light emitting diode(LED)cooling experiment,demonstrating low thermal resistance,good reliability,and achieving a 17℃ temperature reduction compared with state-of-the-art commercial TIMs.This study provides a viable solution to VACNTs’longstanding problem in device integration and free-end contact resistance,bringing it much closer to application and solving the critical thermal bottleneck in next-generation electronics.
基金This work was supported by the National Natural Science Foundation of China (31471208, 31671195, and 31271370), the Natural Science Foundation of Hubei Province (2016CFA012), the Fundamental Research Funds for the Central Universities, Integrated Innovative Team for Major Human Diseases of Tongji Medical College, and the Front Youth Program, Huazhong University of Science and Technology.