Numerical simulation of hemodynamics under the combined effects of both the host blood vessel and the microvascular network, which is based on a 2-D tumor inside and outside vascular network generated from a discrete ...Numerical simulation of hemodynamics under the combined effects of both the host blood vessel and the microvascular network, which is based on a 2-D tumor inside and outside vascular network generated from a discrete mathematical model of tumor-induced angiogenesis, is performed systemically. And a ＂microvascular network-- transport across microvascular network--flow in interstitium＂ model is developed to study the flow in solid tumor. Simulations are carried out to examine the effects of the variations of the inlet Reynolds number in the host blood vessel, the hydraulic conductivity of the microvascular wall, and interstitial hydraulic conductivity coefficient on the fluid flow in tumor microcirculation. The results are consistent with data obtained in terms of physiology. These results may provide some theoretical references and the bases for further clinical experimental research.展开更多
Background:Sweat glands(SGs)have low regenerative potential after severe burns or trauma and their regeneration or functional recovery still faces many obstacles.In practice,restoring SG function requires not only the...Background:Sweat glands(SGs)have low regenerative potential after severe burns or trauma and their regeneration or functional recovery still faces many obstacles.In practice,restoring SG function requires not only the structural integrity of the gland itself,but also its neighboring tissues,especially blood vessels.Collagen triple helix repeat containing-1(CTHRC1)was first identified in vascular repair,and increasing reports showed a close correlation between cutaneous appendage specification,patterning and regeneration.The purpose of the present study was to clarify the role of CTHRC1 in SGs and their adjacent microvessels and find therapeutic strategies to restore SG function.Methods:The SGs and their adjacent microvascular network of Cthrc^(1−/−)mice were first inves-tigated using sweat test,laser Doppler imaging,tissue clearing technique and transcriptome analysis.The effects of CTHRC1 on dermal microvascular endothelial cells(DMECs)were further explored with cell proliferation,DiI-labeled acetylated low-density lipoprotein uptake,tube for-mation and intercellular junction establishment assays.The effects of CTHRC1 on SG function restoration were finally confirmed by replenishing the protein into the paws of Cthrc(1−/−)mice.Results:CTHRC1 is a key regulator of SG function in mice.At the tissue level,Cthrc1 deletion resulted in the disorder and reduction of the microvascular network around SGs.At the molecular level,the knockout of Cthrc1 reduced the expression of vascular development genes and functional proteins in the dermal tissues.Furthermore,CTHRC1 administration considerably enhanced SG function by inducing adjacent vascular network reconstruction.Conclusions:CTHRC1 promotes the development,morphogenesis and function execution of SGs and their neighboring vasculature.Our study provides a novel target for the restoration or regeneration of SG function in vivo.展开更多
There is a pressing need for effective therapeutics for coronavirus disease 2019(COVID-19),the respiratory disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The process of drug develop...There is a pressing need for effective therapeutics for coronavirus disease 2019(COVID-19),the respiratory disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The process of drug development is a costly and meticulously paced process,where progress is often hindered by the failure of initially promising leads.To aid this chal-lenge,in vitro human microphysiological systems need to be refined and adapted for mechanistic studies and drug screening,thereby saving valuable time and resources during a pandemic crisis.The SARS-CoV-2 virus attacks the lung,an organ where the unique three-dimensional(3D)structure of its functional units is critical for proper respiratory function.The in vitro lung models essentially recapitulate the distinct tissue structure and the dynamic mechanical and biological interactions between different cell types.Current model systems include Transwell,organoid and organ-on-a-chip or microphysiological systems(MPSs).We review models that have direct relevance toward modeling the pathology of COVID-19,including the processes of inflammation,edema,coagulation,as well as lung immune function.We also consider the practical issues that may influence the design and fabrication of MPS.The role of lung MPS is addressed in the context of multi-organ models,and it is discussed how high-throughput screening and artificial intelligence can be integrated with lung MPS to accelerate drug development for COVID-19 and other infectious diseases.展开更多
目的运用图论的方法探讨2型糖尿病伴微血管并发症(T2DM with microvascular complications,T2DM-C)患者的大脑功能拓扑属性改变。方法纳入37例T2DM-C患者及人口学资料相匹配的41例健康被试(HC),采集所有被试的静息态功能磁共振数据及神...目的运用图论的方法探讨2型糖尿病伴微血管并发症(T2DM with microvascular complications,T2DM-C)患者的大脑功能拓扑属性改变。方法纳入37例T2DM-C患者及人口学资料相匹配的41例健康被试(HC),采集所有被试的静息态功能磁共振数据及神经心理学量表测试结果。通过图论网络分析,探讨T2DM-C患者大脑功能网络的聚类系数(C_(p))、特征路径长度(L_(p))、标准化聚类系数(γ)、标准化特征路径长度(λ)、小世界属性(σ)、全局效率(E_(g))、局部效率(E_(loc))等全局拓扑指标的改变,以及脑网络中每个节点拓扑属性改变,包括度中心性(DC)、介数中心(BC)和节点效率(NE),并且对存在组间差异的拓扑指标与患者的神经心理学评分进行偏相关分析。结果T2DM-C组的标准化聚类系数、小世界属性以及局部效率均显著高于HC组(P<0.05)。此外,T2DM-C患者的视觉网络、小脑和感觉运动皮层的节点拓扑属性存在异常。T2DM-C患者的E_(loc)与糖化血红蛋白水平呈正相关(r=0.515,P=0.001),右侧中央旁小叶的节点效率值(NE)与血清肌酐值呈负相关(r=-0.517,P=0.001)。结论T2DM-C患者全局网络拓扑属性和节点拓扑属性均表现出广泛的变化,视觉网络和小脑皮层可能是T2DM-C患者易受损的中枢区域。展开更多
基金Project supported by the National Natural Science Foundation of China (Grant No:10372026)
文摘Numerical simulation of hemodynamics under the combined effects of both the host blood vessel and the microvascular network, which is based on a 2-D tumor inside and outside vascular network generated from a discrete mathematical model of tumor-induced angiogenesis, is performed systemically. And a ＂microvascular network-- transport across microvascular network--flow in interstitium＂ model is developed to study the flow in solid tumor. Simulations are carried out to examine the effects of the variations of the inlet Reynolds number in the host blood vessel, the hydraulic conductivity of the microvascular wall, and interstitial hydraulic conductivity coefficient on the fluid flow in tumor microcirculation. The results are consistent with data obtained in terms of physiology. These results may provide some theoretical references and the bases for further clinical experimental research.
基金supported by grants from the National Natural Science Foundation of China(81830064,81721092,32000969,82002056)Key Support Program for Growth Factor Research(SZYZ-TR-03)+3 种基金Chinese PLA General Hospital for Military Medical Innovation Research Project(CX-19026)the CAMS Innovation Fund for Medical Sciences(CIFMS,2019-I2M-5-059)the Military Medical Research and Development Projects(AWS17J005)Beijing Natural Science Foundation(7204306).
文摘Background:Sweat glands(SGs)have low regenerative potential after severe burns or trauma and their regeneration or functional recovery still faces many obstacles.In practice,restoring SG function requires not only the structural integrity of the gland itself,but also its neighboring tissues,especially blood vessels.Collagen triple helix repeat containing-1(CTHRC1)was first identified in vascular repair,and increasing reports showed a close correlation between cutaneous appendage specification,patterning and regeneration.The purpose of the present study was to clarify the role of CTHRC1 in SGs and their adjacent microvessels and find therapeutic strategies to restore SG function.Methods:The SGs and their adjacent microvascular network of Cthrc^(1−/−)mice were first inves-tigated using sweat test,laser Doppler imaging,tissue clearing technique and transcriptome analysis.The effects of CTHRC1 on dermal microvascular endothelial cells(DMECs)were further explored with cell proliferation,DiI-labeled acetylated low-density lipoprotein uptake,tube for-mation and intercellular junction establishment assays.The effects of CTHRC1 on SG function restoration were finally confirmed by replenishing the protein into the paws of Cthrc(1−/−)mice.Results:CTHRC1 is a key regulator of SG function in mice.At the tissue level,Cthrc1 deletion resulted in the disorder and reduction of the microvascular network around SGs.At the molecular level,the knockout of Cthrc1 reduced the expression of vascular development genes and functional proteins in the dermal tissues.Furthermore,CTHRC1 administration considerably enhanced SG function by inducing adjacent vascular network reconstruction.Conclusions:CTHRC1 promotes the development,morphogenesis and function execution of SGs and their neighboring vasculature.Our study provides a novel target for the restoration or regeneration of SG function in vivo.
基金funding from National Institutes of Health(No.1UG3TR003148-01)the American Heart Association(No.442611-NU-80922)+1 种基金California Institute for Regenerative Medicine(No.DISC2COVID19-11838)COVID-19 research funding from David Geffen School of Medicine at UCLA.
文摘There is a pressing need for effective therapeutics for coronavirus disease 2019(COVID-19),the respiratory disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus.The process of drug development is a costly and meticulously paced process,where progress is often hindered by the failure of initially promising leads.To aid this chal-lenge,in vitro human microphysiological systems need to be refined and adapted for mechanistic studies and drug screening,thereby saving valuable time and resources during a pandemic crisis.The SARS-CoV-2 virus attacks the lung,an organ where the unique three-dimensional(3D)structure of its functional units is critical for proper respiratory function.The in vitro lung models essentially recapitulate the distinct tissue structure and the dynamic mechanical and biological interactions between different cell types.Current model systems include Transwell,organoid and organ-on-a-chip or microphysiological systems(MPSs).We review models that have direct relevance toward modeling the pathology of COVID-19,including the processes of inflammation,edema,coagulation,as well as lung immune function.We also consider the practical issues that may influence the design and fabrication of MPS.The role of lung MPS is addressed in the context of multi-organ models,and it is discussed how high-throughput screening and artificial intelligence can be integrated with lung MPS to accelerate drug development for COVID-19 and other infectious diseases.
文摘目的运用图论的方法探讨2型糖尿病伴微血管并发症(T2DM with microvascular complications,T2DM-C)患者的大脑功能拓扑属性改变。方法纳入37例T2DM-C患者及人口学资料相匹配的41例健康被试(HC),采集所有被试的静息态功能磁共振数据及神经心理学量表测试结果。通过图论网络分析,探讨T2DM-C患者大脑功能网络的聚类系数(C_(p))、特征路径长度(L_(p))、标准化聚类系数(γ)、标准化特征路径长度(λ)、小世界属性(σ)、全局效率(E_(g))、局部效率(E_(loc))等全局拓扑指标的改变,以及脑网络中每个节点拓扑属性改变,包括度中心性(DC)、介数中心(BC)和节点效率(NE),并且对存在组间差异的拓扑指标与患者的神经心理学评分进行偏相关分析。结果T2DM-C组的标准化聚类系数、小世界属性以及局部效率均显著高于HC组(P<0.05)。此外,T2DM-C患者的视觉网络、小脑和感觉运动皮层的节点拓扑属性存在异常。T2DM-C患者的E_(loc)与糖化血红蛋白水平呈正相关(r=0.515,P=0.001),右侧中央旁小叶的节点效率值(NE)与血清肌酐值呈负相关(r=-0.517,P=0.001)。结论T2DM-C患者全局网络拓扑属性和节点拓扑属性均表现出广泛的变化,视觉网络和小脑皮层可能是T2DM-C患者易受损的中枢区域。
