Cardiac fibroblasts(CFs)are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure(HF).TEAD1 has been shown to be essential for heart development and homeostas...Cardiac fibroblasts(CFs)are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure(HF).TEAD1 has been shown to be essential for heart development and homeostasis.However,fibroblast endogenous TEAD1 in cardiac remodeling remains incompletely understood.Transcriptomic analyses revealed consistently upregulated cardiac TEAD1 expression in mice 4 weeks after transverse aortic constriction(TAC)and Ang-l infusion.Further investigation revealed that CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure overload.Conditional TEAD1 knockout was achieved by crossing TEAD1-floxed mice with CFs-and myofibroblasts-specific Cre mice.Echocardiographic and histological analyses demonstrated that CFs-and myofibroblasts-specific TEAD1 deficiency and treatment with TEAD1 inhibitor,VT103,ameliorated TAC-induced cardiac remodeling.Mechanistically,RNA-seq and ChiP-seq analysis identified Wnt4 as a novel TEAD1 target.TEAD1 has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway,and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1 overexpression.Furthermore,coimmunoprecipitation combined with mass spectrometry,chromatin immunoprecipitation,and luciferase assays demonstrated interaction between TEAD1 and BET protein BRD4,leading to the binding and activation of the Wnt4 promoter.In conclusion,TEAD1 is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signallingpathway.展开更多
Truncated L1 regularization proposed by Fan in[5],is an approximation to the L0 regularization in high-dimensional sparse models.In this work,we prove the non-asymptotic error bound for the global optimal solution to ...Truncated L1 regularization proposed by Fan in[5],is an approximation to the L0 regularization in high-dimensional sparse models.In this work,we prove the non-asymptotic error bound for the global optimal solution to the truncated L1 regularized linear regression problem and study the support recovery property.Moreover,a primal dual active set algorithm(PDAS)for variable estimation and selection is proposed.Coupled with continuation by a warm-start strategy leads to a primal dual active set with continuation algorithm(PDASC).Data-driven parameter selection rules such as cross validation,BIC or voting method can be applied to select a proper regularization parameter.The application of the proposed method is demonstrated by applying it to simulation data and a breast cancer gene expression data set(bcTCGA).展开更多
A hydrogel can be coated on various substrates to enable multiple functions.Potential applications include biomedical devices,anti-fouling surfaces and microfluidics.In practical use,hydrogel coatings are often submer...A hydrogel can be coated on various substrates to enable multiple functions.Potential applications include biomedical devices,anti-fouling surfaces and microfluidics.In practical use,hydrogel coatings are often submerged in fluids.The swell of hydrogel coating deteriorates the interfacial bonding with the substrate.This paper presents a stress analysis of a hydrogel coating on a cylindrical metal substrate.We adopt the thermodynamic theory coupling large deformation and water migration and formulate two boundary value problems for the coating-substrate system with and without an interfacial crack.The inhomogeneous stress fields in the hydrogel coating are obtained.The influences of modulus,thickness of the hydrogel coating on the maximum radial stress at the interface are analyzed.These results may guide the design of hydrogel coating to avoid interfacial failure.展开更多
基金supported by the China National Funds for Young Scientists(grant number 82000309 to Shuai Song,82200290 to Yongchao Zhao)the Shanghai Sailing Program(grant number 20YF1429600 to Shuai Song),Basic Science Center Project(grant number T2288101 to Junbo Ge)+2 种基金the National Natural Science Foundation(grant number 82130010 to Aijun Sun)the Shanghai Clinical Research Center for Interventional Medicine(grant number 19MC1910300 to Junbo Ge)Fuqing Scholar of Fudan University,Shanghai Medical School(grant number FQXZ202204B to Zihang Huang).
文摘Cardiac fibroblasts(CFs)are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure(HF).TEAD1 has been shown to be essential for heart development and homeostasis.However,fibroblast endogenous TEAD1 in cardiac remodeling remains incompletely understood.Transcriptomic analyses revealed consistently upregulated cardiac TEAD1 expression in mice 4 weeks after transverse aortic constriction(TAC)and Ang-l infusion.Further investigation revealed that CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure overload.Conditional TEAD1 knockout was achieved by crossing TEAD1-floxed mice with CFs-and myofibroblasts-specific Cre mice.Echocardiographic and histological analyses demonstrated that CFs-and myofibroblasts-specific TEAD1 deficiency and treatment with TEAD1 inhibitor,VT103,ameliorated TAC-induced cardiac remodeling.Mechanistically,RNA-seq and ChiP-seq analysis identified Wnt4 as a novel TEAD1 target.TEAD1 has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway,and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1 overexpression.Furthermore,coimmunoprecipitation combined with mass spectrometry,chromatin immunoprecipitation,and luciferase assays demonstrated interaction between TEAD1 and BET protein BRD4,leading to the binding and activation of the Wnt4 promoter.In conclusion,TEAD1 is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signallingpathway.
文摘Truncated L1 regularization proposed by Fan in[5],is an approximation to the L0 regularization in high-dimensional sparse models.In this work,we prove the non-asymptotic error bound for the global optimal solution to the truncated L1 regularized linear regression problem and study the support recovery property.Moreover,a primal dual active set algorithm(PDAS)for variable estimation and selection is proposed.Coupled with continuation by a warm-start strategy leads to a primal dual active set with continuation algorithm(PDASC).Data-driven parameter selection rules such as cross validation,BIC or voting method can be applied to select a proper regularization parameter.The application of the proposed method is demonstrated by applying it to simulation data and a breast cancer gene expression data set(bcTCGA).
基金the support of the National Natural Foundation of China(Grants 11922210 and 11772249)the support of the National Natural Foundation of China(Grant 12002255).
文摘A hydrogel can be coated on various substrates to enable multiple functions.Potential applications include biomedical devices,anti-fouling surfaces and microfluidics.In practical use,hydrogel coatings are often submerged in fluids.The swell of hydrogel coating deteriorates the interfacial bonding with the substrate.This paper presents a stress analysis of a hydrogel coating on a cylindrical metal substrate.We adopt the thermodynamic theory coupling large deformation and water migration and formulate two boundary value problems for the coating-substrate system with and without an interfacial crack.The inhomogeneous stress fields in the hydrogel coating are obtained.The influences of modulus,thickness of the hydrogel coating on the maximum radial stress at the interface are analyzed.These results may guide the design of hydrogel coating to avoid interfacial failure.
