Disruption of the intestinal epithelial barrier and incomplete repair are critical for the development of colitis.V-domain immunoglobulin domain suppressor of T-cell activation(VISTA),encoded by Vsir,functions as an i...Disruption of the intestinal epithelial barrier and incomplete repair are critical for the development of colitis.V-domain immunoglobulin domain suppressor of T-cell activation(VISTA),encoded by Vsir,functions as an immune checkpoint.In the present work,we report that VISTA is predominantly upregulated in macrophages from patients with inflammatory bowel disease(IBD)and in mice with dextran sulfate sodium(DSS)-induced colitis.VISTA deficiency or blockade ameliorates DSS-induced colitis severity.Epithelial damage is notably less severe in Vsir−/−Rag1−/−mice than in Vsir+/+Rag1−/−mice.Intriguingly,macrophage depletion eliminates disease severity differences between Vsir−/−and wild-type(WT)mice.Vsir ablation does not alter cytokine profiles or macrophage differentiation but alleviates macrophage-mediated epithelial injury,as Vsir−/−macrophage transfer induces milder damage than WT macrophage transfer does.Interestingly,Vsir−/−mice exhibit accelerated mucosal regeneration during acute colitis.Mechanistically,macrophage-derived VISTA interacts with leucine-rich repeats and immunoglobulin-like domain 1(LRIG1)in intestinal stem cells and suppresses peroxisome proliferator-activated receptor alpha(PPARα),leading to impeded growth of intestinal organoids and increased epithelial damage in mice with DSS-induced colitis.These findings reveal a pathogenic function of macrophage-derived VISTA in epithelial damage during colitis.Targeting the VISTA/LRIG1 axis could promote epithelial repair and serve as a promising therapeutic strategy for patients with IBD.展开更多
为提高WindowsVista平台上Internet Explorer7程序的安全性能,提出了基于IE保护模式架构的安全性增强方案设计方法。对Windows Vista系统访问控制机制和Internet Explorer 7程序进行了认知与分解,指出IE保护模式架构在执行用户界面特权...为提高WindowsVista平台上Internet Explorer7程序的安全性能,提出了基于IE保护模式架构的安全性增强方案设计方法。对Windows Vista系统访问控制机制和Internet Explorer 7程序进行了认知与分解,指出IE保护模式架构在执行用户界面特权隔离策略时所存在的安全隐患,并分析该隐患所导致的攻击者可绕过IE保护模式限制非法访问用户资源等安全威胁。最后根据该弱点成因设计并实现了一套IE保护模式安全性增强组件,实验结果表明了该设计的可行性和有效性。展开更多
Ground Water Vistas软件是目前国际上盛行的三维地下水水流和溶质运移模拟的图形使用界面.本文介绍了Ground Water Vistas在三种模式下的功能,分析评述了它的优缺点.并以美国Edwards含水层Barton泉稳定流模型为实例,展示了Ground Water...Ground Water Vistas软件是目前国际上盛行的三维地下水水流和溶质运移模拟的图形使用界面.本文介绍了Ground Water Vistas在三种模式下的功能,分析评述了它的优缺点.并以美国Edwards含水层Barton泉稳定流模型为实例,展示了Ground Water Vistas强大的前处理、后处理功能及其优良的三维可视化效果.Edwards含水层喀斯特发育程度极高,其模型研究对我国喀斯特地区地下水资源的评价与管理具有借鉴意义和指导作用.展开更多
基金supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project(2023ZD0507600)the National Natural Science Foundation of China(82471764,92474103,82071819)to HZthe National Natural Science Foundation of China(82100577)to YZ.
文摘Disruption of the intestinal epithelial barrier and incomplete repair are critical for the development of colitis.V-domain immunoglobulin domain suppressor of T-cell activation(VISTA),encoded by Vsir,functions as an immune checkpoint.In the present work,we report that VISTA is predominantly upregulated in macrophages from patients with inflammatory bowel disease(IBD)and in mice with dextran sulfate sodium(DSS)-induced colitis.VISTA deficiency or blockade ameliorates DSS-induced colitis severity.Epithelial damage is notably less severe in Vsir−/−Rag1−/−mice than in Vsir+/+Rag1−/−mice.Intriguingly,macrophage depletion eliminates disease severity differences between Vsir−/−and wild-type(WT)mice.Vsir ablation does not alter cytokine profiles or macrophage differentiation but alleviates macrophage-mediated epithelial injury,as Vsir−/−macrophage transfer induces milder damage than WT macrophage transfer does.Interestingly,Vsir−/−mice exhibit accelerated mucosal regeneration during acute colitis.Mechanistically,macrophage-derived VISTA interacts with leucine-rich repeats and immunoglobulin-like domain 1(LRIG1)in intestinal stem cells and suppresses peroxisome proliferator-activated receptor alpha(PPARα),leading to impeded growth of intestinal organoids and increased epithelial damage in mice with DSS-induced colitis.These findings reveal a pathogenic function of macrophage-derived VISTA in epithelial damage during colitis.Targeting the VISTA/LRIG1 axis could promote epithelial repair and serve as a promising therapeutic strategy for patients with IBD.
文摘为提高WindowsVista平台上Internet Explorer7程序的安全性能,提出了基于IE保护模式架构的安全性增强方案设计方法。对Windows Vista系统访问控制机制和Internet Explorer 7程序进行了认知与分解,指出IE保护模式架构在执行用户界面特权隔离策略时所存在的安全隐患,并分析该隐患所导致的攻击者可绕过IE保护模式限制非法访问用户资源等安全威胁。最后根据该弱点成因设计并实现了一套IE保护模式安全性增强组件,实验结果表明了该设计的可行性和有效性。
文摘Ground Water Vistas软件是目前国际上盛行的三维地下水水流和溶质运移模拟的图形使用界面.本文介绍了Ground Water Vistas在三种模式下的功能,分析评述了它的优缺点.并以美国Edwards含水层Barton泉稳定流模型为实例,展示了Ground Water Vistas强大的前处理、后处理功能及其优良的三维可视化效果.Edwards含水层喀斯特发育程度极高,其模型研究对我国喀斯特地区地下水资源的评价与管理具有借鉴意义和指导作用.
