The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs ...The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with iron.The constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial effects.Attractively,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading SACs.Consequently,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/C.In addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)depletion.Both in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound healing.This work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.展开更多
Osteoporosis is a reduction in skeletal mass due to the decrease of osteogenic ability and the activation of the osteoclastic function.Inhibiting bone resorption and accelerating the new bone formation is a promising ...Osteoporosis is a reduction in skeletal mass due to the decrease of osteogenic ability and the activation of the osteoclastic function.Inhibiting bone resorption and accelerating the new bone formation is a promising strategy to repair the bone defect of osteoporosis.In this study,we first systematically investigated the roles of Chinese medicine Asperosaponin Ⅵ(ASP Ⅵ)on osteogenic mineralization of BMSCs and osteoclastogenesis of BMMs,and then explored the synergistic effect of ASP Ⅵ and BS(BMP-2 immobilized in 2-N,6-O-sulfated chitosan)on bone formation.The result showed that ASP Ⅵ with the concentration lower than 10^(-4) M contributed to the expression of osteogenic gene and inhibited osteoclastic genes RANKL of BMSCs.Simultaneously,ASP Ⅵ significantly reduced the differentiation of mononuclear osteoclasts in the process of osteoclast formation induced by M-CSF and RANKL.Furthermore,by stimulating the SMADs,TGF-β1,VEGFA,and OPG/RANKL signaling pathways,ASBS(ASP Ⅵ and BS)substantially enhanced osteogenesis,greatly promoted angiogenesis,and suppressed osteoclastogenesis.The findings provide a new perspective on osteoporosis care and prevention.展开更多
基金supported by the National Key Research and Development Program of China(Grant No.2022YFB3804500)the National Natural Science Foundation of China(Grant No.52202352,22335006)+4 种基金the Shanghai Municipal Health Commission(Grant No.20224Y0010)the CAMS Innovation Fund for Medical Sciences(Grant No.2021-I2M-5-012)the Basic Research Program of Shanghai Municipal Government(Grant No.21JC1406000)the Fundamental Research Funds for the Central Universities(Grant No.22120230237,2023-3-YB-11,22120220618)the Basic Research Program of Shanghai Municipal Government(23DX1900200).
文摘The current single-atom catalysts(SACs)for medicine still suffer from the limited active site density.Here,we develop a synthetic method capable of increasing both the metal loading and mass-specific activity of SACs by exchanging zinc with iron.The constructed iron SACs(h^(3)-FNC)with a high metal loading of 6.27 wt%and an optimized adjacent Fe distance of~4 A exhibit excellent oxidase-like catalytic performance without significant activity decay after being stored for six months and promising antibacterial effects.Attractively,a“density effect”has been found at a high-enough metal doping amount,at which individual active sites become close enough to interact with each other and alter the electronic structure,resulting in significantly boosted intrinsic activity of single-atomic iron sites in h^(3)-FNCs by 2.3 times compared to low-and medium-loading SACs.Consequently,the overall catalytic activity of h^(3)-FNC is highly improved,with mass activity and metal mass-specific activity that are,respectively,66 and 315 times higher than those of commercial Pt/C.In addition,h^(3)-FNCs demonstrate efficiently enhanced capability in catalyzing oxygen reduction into superoxide anion(O_(2)·^(−))and glutathione(GSH)depletion.Both in vitro and in vivo assays demonstrate the superior antibacterial efficacy of h^(3)-FNCs in promoting wound healing.This work presents an intriguing activity-enhancement effect in catalysts and exhibits impressive therapeutic efficacy in combating bacterial infections.
基金funded by National Key Research and Development Program of China(No.2016YFC1102900)National Natural Science Foundation of China(No.51772100 and No.32171342)+2 种基金Shanghai Science and Technology Agriculture Project(No.202002080002F01474)Shanghai Pujiang Program(16PJD015)Joint Fund for equipment pre-research of the ministry of education(6141A02022618).
文摘Osteoporosis is a reduction in skeletal mass due to the decrease of osteogenic ability and the activation of the osteoclastic function.Inhibiting bone resorption and accelerating the new bone formation is a promising strategy to repair the bone defect of osteoporosis.In this study,we first systematically investigated the roles of Chinese medicine Asperosaponin Ⅵ(ASP Ⅵ)on osteogenic mineralization of BMSCs and osteoclastogenesis of BMMs,and then explored the synergistic effect of ASP Ⅵ and BS(BMP-2 immobilized in 2-N,6-O-sulfated chitosan)on bone formation.The result showed that ASP Ⅵ with the concentration lower than 10^(-4) M contributed to the expression of osteogenic gene and inhibited osteoclastic genes RANKL of BMSCs.Simultaneously,ASP Ⅵ significantly reduced the differentiation of mononuclear osteoclasts in the process of osteoclast formation induced by M-CSF and RANKL.Furthermore,by stimulating the SMADs,TGF-β1,VEGFA,and OPG/RANKL signaling pathways,ASBS(ASP Ⅵ and BS)substantially enhanced osteogenesis,greatly promoted angiogenesis,and suppressed osteoclastogenesis.The findings provide a new perspective on osteoporosis care and prevention.