Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy pre...Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes.This study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone loss.Methods:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis.Micro-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also investigated.The underlying mechanism was verified using qRT-PCR,Western blot(WB),immunofluorescence(IF),etc.Results:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs.Both BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting osteogenesis.Conclusion:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.展开更多
A combinatorial approach was applied to investigating the influence of Fe content on the microstructures and properties of Ti6Al4V alloy.A diffusion couple was manufactured with Ti6Al4V and Ti6Al4V20Fe alloys and anne...A combinatorial approach was applied to investigating the influence of Fe content on the microstructures and properties of Ti6Al4V alloy.A diffusion couple was manufactured with Ti6Al4V and Ti6Al4V20Fe alloys and annealed at 1000°C for 600 h to obtain a wide range of compositions.By combining electron probe micro-analysis(EPMA),scanning electron microscopy(SEM)and nanoindentation,the relationships between composition and microstructure as well as hardness were determined.It is found that after aging the Ti6Al4V5Fe sample contains reasonable(about 55%)volume fraction of fineαphase and shows the peak hardness among the Ti6Al4VxFe alloys.Therefore,it is a promising candidate for the development of titanium alloys.HAADF-STEM and XRD reveal that after quenching from the singleβphase field,the metastableα''lamellae form in the Ti6Al4V5Fe alloy,and on subsequent isothermal aging,theα''lamellae become coarse and act as precursors/preferential nucleation sites for the stableαphase.展开更多
基金Beijing Natural Science Foundation,Grant/Award Number:L222145 and L222030Emerging Engineering Interdisciplinary Project and the Fundamental Research Funds for the Central Universities,Grant/Award Number:PKU2022XGK008Peking University Medicine Fund of Fostering Young Scholars’Scientific&Technological Innovation,Grant/Award Number:BMU2022PY010。
文摘Background:Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength.However,current anti-resorptive drugs carry a risk of various complications.The deep learning-based efficacy prediction system(DLEPS)is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes.This study aimed to explore the protective effect and potential mechanisms of cinobufotalin(CB),a traditional Chinese medicine(TCM),on bone loss.Methods:DLEPS was employed for screening anti-osteoporotic agents according to gene profile changes in primary osteoporosis.Micro-CT,histological and morphological analysis were applied for the bone protective detection of CB,and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells(hBMMSCs)were also investigated.The underlying mechanism was verified using qRT-PCR,Western blot(WB),immunofluorescence(IF),etc.Results:A safe concentration(0.25mg/kg in vivo,0.05μM in vitro)of CB could effectively preserve bone mass in estrogen deficiency-induced bone loss and promote osteogenic differentiation/function of hBMMSCs.Both BMPs/SMAD and Wnt/β-catenin signaling pathways participated in CB-induced osteogenic differentiation,further regulating the expression of osteogenesis-associated factors,and ultimately promoting osteogenesis.Conclusion:Our study demonstrated that CB could significantly reverse estrogen deficiency-induced bone loss,further promoting osteogenic differentiation/function of hBMMSCs,with BMPs/SMAD and Wnt/β-catenin signaling pathways involved.
基金Project(2014CB644000)supported by the National Basic Research Program of ChinaProject(2016YFB0701301)supported by the National Key Technology R&D Program of China+1 种基金Projects(51371200,51671218)supported by the National Natural Science Foundation of ChinaProject supported by State Key Laboratory of Powder Metallurgy,Central South University,China
文摘A combinatorial approach was applied to investigating the influence of Fe content on the microstructures and properties of Ti6Al4V alloy.A diffusion couple was manufactured with Ti6Al4V and Ti6Al4V20Fe alloys and annealed at 1000°C for 600 h to obtain a wide range of compositions.By combining electron probe micro-analysis(EPMA),scanning electron microscopy(SEM)and nanoindentation,the relationships between composition and microstructure as well as hardness were determined.It is found that after aging the Ti6Al4V5Fe sample contains reasonable(about 55%)volume fraction of fineαphase and shows the peak hardness among the Ti6Al4VxFe alloys.Therefore,it is a promising candidate for the development of titanium alloys.HAADF-STEM and XRD reveal that after quenching from the singleβphase field,the metastableα''lamellae form in the Ti6Al4V5Fe alloy,and on subsequent isothermal aging,theα''lamellae become coarse and act as precursors/preferential nucleation sites for the stableαphase.
