TEA domain transcription factor 1(TEAD1)induces cardiac fibroblasts cells remodeling through BRD4/Wnt4 pathway

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.

Design of nanofibre interlayer supported forward osmosis composite membranes and its evaluation in fouling study with cleaning

Nanofibre-supported forward osmosis(FO)membranes have gained popularity owing to their low structural parameters and high water flux.However,the nanofibrous membranes are less stable in long-term use,and their fouling behaviours with foulants in both feed solution(FS)and draw solution(DS)is less studied.This study developed a nanofibrous thin-film composite(TFC)FO membrane by designing a tiered dual-layer nanofibrous substrate to enhance membrane stability during long-term usage and cleaning.Various characterisation methods were used to study the effect of the electrospun nanofibre interlayer and drying time,which is the interval after removing the M-phenylenediamine(MPD)solution and before reacting with trimesoyl chloride(TMC)solution,on the intrinsic separation FO performance.The separation performance of the dual-layer nanofibrous FO membranes was examined using model foulants(sodium alginate and bovine serum albumin)in both the FS and DS.The dual-layer nanofibrous substrate was superior to the single-layer nanofibrous substrate and showed a flux of 30.2 L/m^(2)/h(LMH)when using 1.5 mol/L NaCl against deionised(DI)water in the active layer facing draw solution(AL-DS)mode.In the fouling test,the water flux was effectively improved without sacrificing the water/solute selectivity under the condition that foulants existed in both the FS and DS.In addition,the dual-layer nanofibrous TFC FO membrane was more robust during the fouling test and cleaning.