Although various anti-osteoporosis drugs are available,the limitations of these therapies,including drug resistance and collateral responses,require the development of novel anti-osteoporosis agents.Rhizoma Drynariae ...Although various anti-osteoporosis drugs are available,the limitations of these therapies,including drug resistance and collateral responses,require the development of novel anti-osteoporosis agents.Rhizoma Drynariae displays a promising anti-osteoporosis effect,while the effective component and mechanism remain unclear.Here,we revealed the therapeutic potential of Rhizoma Drynariae-derived nanovesicles(RDNVs)for postmenopausal osteoporosis and demonstrated that RDNVs potentiated osteogenic differentiation of human bone marrow mesenchymal stem cells(hBMSCs)by targeting estrogen receptor-alpha(ERα).RDNVs,a natural product isolated from fresh Rhizoma Drynariae root juice by differential ultracentrifugation,exhibited potent bone tissue-targeting activity and anti-osteoporosis efficacy in an ovariectomized mouse model.RDNVs,effectively internalized by hBMSCs,enhanced proliferation and ERαexpression levels of hBMSC,and promoted osteogenic differentiation and bone formation.Mechanistically,via the ERαsignaling pathway,RDNVs facilitated mRNA and protein expression of bone morphogenetic protein 2 and runt-related transcription factor 2 in hBMSCs,which are involved in regulating osteogenic differentiation.Further analysis revealed that naringin,existing in RDNVs,was the active component targeting ERαin the osteogenic effect.Taken together,our study identified that naringin in RDNVs displays exciting bone tissue-targeting activity to reverse osteoporosis by promoting hBMSCs proliferation and osteogenic differentiation through estrogen-like effects.展开更多
This work investigated the evolution of multiphase microstructure and impact fracture behavior of medium carbon high silicon high strength steel subjected to the austempering treatment at 240,360,and400℃.The results ...This work investigated the evolution of multiphase microstructure and impact fracture behavior of medium carbon high silicon high strength steel subjected to the austempering treatment at 240,360,and400℃.The results show that martensite,bainite,and retained austenite(RA)are the main microstructural phases.The austempering treatments at 360 and 400℃ caused the formation of carbon-poor ferrite in the matrix,and the transformation of ultrafine bainite into coarse lath bainite and granular bainite,respectively.Thick filmy RA was distributed between bainite laths.The polygonal martensiteaustenite islands and blocky RA formed along the grain boundaries.The average carbon concentration in the matrix decreased with the temperature increase,while the impact toughness initially increased and then dropped with temperature.The quasi-cleavage brittle fracture dominated the impact fracture mechanism of the sample austempered at 240℃ by forming tearing surfaces and tearing steps.The microcracks disappeared in the RA on the prior austenite grain boundaries.On the other side,the fracture surface of the sample austempered at 360℃ exhibited ductile fracture with deep dimples and brittle fracture with cleavage river patterns.The polygonal martensite-austenite islands or blocky RA constrained the microcracks.After austempered at 400℃,the brittle fracture was dominant,showing river patterns,and the microcracks propagated through the granular bainite without any resistance.展开更多
基金This work was supported by the National Natural Science Foundation of China(Nos.82174119,81973633 and 82274220)Science and Technology Projects in Liwan District,Guangzhou(Nos.20230710 and 202201009,China)+2 种基金Young Talent Support Project of Guangzhou Association for Science and Technology(No.QT2023036,China)Special focus areas for General Universities in Guangdong Province(No.2022ZDZX2016,China)Guangdong Provincial Administration of Traditional Chinese Medicine Project(No.20233025,China).
文摘Although various anti-osteoporosis drugs are available,the limitations of these therapies,including drug resistance and collateral responses,require the development of novel anti-osteoporosis agents.Rhizoma Drynariae displays a promising anti-osteoporosis effect,while the effective component and mechanism remain unclear.Here,we revealed the therapeutic potential of Rhizoma Drynariae-derived nanovesicles(RDNVs)for postmenopausal osteoporosis and demonstrated that RDNVs potentiated osteogenic differentiation of human bone marrow mesenchymal stem cells(hBMSCs)by targeting estrogen receptor-alpha(ERα).RDNVs,a natural product isolated from fresh Rhizoma Drynariae root juice by differential ultracentrifugation,exhibited potent bone tissue-targeting activity and anti-osteoporosis efficacy in an ovariectomized mouse model.RDNVs,effectively internalized by hBMSCs,enhanced proliferation and ERαexpression levels of hBMSC,and promoted osteogenic differentiation and bone formation.Mechanistically,via the ERαsignaling pathway,RDNVs facilitated mRNA and protein expression of bone morphogenetic protein 2 and runt-related transcription factor 2 in hBMSCs,which are involved in regulating osteogenic differentiation.Further analysis revealed that naringin,existing in RDNVs,was the active component targeting ERαin the osteogenic effect.Taken together,our study identified that naringin in RDNVs displays exciting bone tissue-targeting activity to reverse osteoporosis by promoting hBMSCs proliferation and osteogenic differentiation through estrogen-like effects.
基金financially supported by the National Key Research and Development Program of China(No.2016YFB0300105)the Fundamental Research Funds for the Central Universities(No.N180725021)the Fundamental Research Funds for the Central Universities(No.N2024005-4)。
文摘This work investigated the evolution of multiphase microstructure and impact fracture behavior of medium carbon high silicon high strength steel subjected to the austempering treatment at 240,360,and400℃.The results show that martensite,bainite,and retained austenite(RA)are the main microstructural phases.The austempering treatments at 360 and 400℃ caused the formation of carbon-poor ferrite in the matrix,and the transformation of ultrafine bainite into coarse lath bainite and granular bainite,respectively.Thick filmy RA was distributed between bainite laths.The polygonal martensiteaustenite islands and blocky RA formed along the grain boundaries.The average carbon concentration in the matrix decreased with the temperature increase,while the impact toughness initially increased and then dropped with temperature.The quasi-cleavage brittle fracture dominated the impact fracture mechanism of the sample austempered at 240℃ by forming tearing surfaces and tearing steps.The microcracks disappeared in the RA on the prior austenite grain boundaries.On the other side,the fracture surface of the sample austempered at 360℃ exhibited ductile fracture with deep dimples and brittle fracture with cleavage river patterns.The polygonal martensite-austenite islands or blocky RA constrained the microcracks.After austempered at 400℃,the brittle fracture was dominant,showing river patterns,and the microcracks propagated through the granular bainite without any resistance.
