Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the devel...Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the development of more effective and safer targeted therapies.Utilizing a zebrafish(Danio rerio)larval model of osteoporosis,we explored the influence of the metabolite spermine on bone homeostasis.Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption.Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity.Notably,spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae.At the molecular level,Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine,with P53 potentially acting downstream of Rac1.These findings were confirmed using mouse(Mus musculus)models,in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions,suggesting strong potential as a bonestrengthening agent.This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development,highlighting pivotal molecular mediators.Given their efficacy and safety,human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.展开更多
Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain unclear.It is well-recognized that age is the most important independent predictor of poor outcomes af...Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain unclear.It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke.Mounting evidence suggests that axonal regeneration and angiogenesis,the major forms of brain plasticity responsible for post-stroke recovery,diminished with advanced age.Previous studies suggest that Ras-related C3 botulinum toxin substrate(Rac)1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model.Here,we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged(male,18 to 22 months old C57BL/6J)brain after ischemic stroke.We found that as mice aged,Rac1 expression declined in the brain.Delayed overexpression of Rac1,using lentivirus encoding Rac1 injected day 1 after ischemic stroke,promoted cognitive(assessed using novel object recognition test)and sensorimotor(assessed using adhesive removal tests)recovery on days 14–28.This was accompanied by the increase of neurite and proliferative endothelial cells in the periinfarct zone assessed by immunostaining.In a reverse approach,pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial cells.Furthermore,Rac1 inhibition reduced the activation of p21-activated kinase 1,the protein level of brain-derived neurotrophic factor,and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after stroke.Our work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.展开更多
Following the publication,concerns have been raised about a number of figures in this article.The western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in man...Following the publication,concerns have been raised about a number of figures in this article.The western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.The authors were contacted and invited to comment on the concerns raised and to provide the original,unmodified figures,but did not respond.The Editors-in-Chief therefore no longer have confidence in the integrity of the data in this article and decided to retract this article.展开更多
【目的】R A C/R O P s是一类植物特有的小G蛋白,作为分子开关参与众多的植物信号转导途径。OsRAC3通过与细胞分裂素信号组分互作,调控水稻Oryza sativa L.冠根发育,但是否影响水稻地上部分的性状尚不清楚。本研究主要分析OsRAC3对水稻...【目的】R A C/R O P s是一类植物特有的小G蛋白,作为分子开关参与众多的植物信号转导途径。OsRAC3通过与细胞分裂素信号组分互作,调控水稻Oryza sativa L.冠根发育,但是否影响水稻地上部分的性状尚不清楚。本研究主要分析OsRAC3对水稻穗发育以及产量性状的影响。【方法】对水稻OsRAC3promoter::GUS转基因植株的花序组织进行GUS染色,分析OsRAC3的表达模式。分析转基因材料持续激活型突变体(CA-osrac3)和显性失活型突变体(DN-osrac3)2种试验材料的每穗粒数、粒长、粒宽、千粒质量等主要农艺性状。【结果】OsRAC3在花序分生组织、雄蕊和雌蕊中强烈表达;CA-osrac3株系的穗粒数减少,籽粒更加饱满,粒长、粒宽、千粒质量均显著高于野生型;DN-osrac3株系的穗分枝数少且育性差,籽粒粒长、粒宽、千粒质量则显著低于野生型。【结论】OsRAC3影响水稻穗的发育过程,持续激活型突变体CA-osrac3促进水稻籽粒的发育;OsRAC3在水稻高产育种和遗传改良中具有重要的应用价值。展开更多
文摘针对传统随机共振系统(Stochastic resonance,SR)的参数选择和未考虑历史信息影响随机共振效果的问题,提出一种基于改进布谷鸟算法(Ranking-based Adaptive Cuckoo Search,RACS)的自适应改进势模型随机共振方法。首先,对大参数信号进行移频尺度变换处理,使其满足SR的绝热近似理论要求;其次,提出一种时延分数阶偏置非线性过阻尼随机共振系统(Time-delayed Overdamped Stochastic Resonance System with Fractional Deflection Nonlinearity,TFODF-SR),并研究势模型参数对随机共振效果的影响;进而利用以信噪比作为评价函数的RACS算法自适应确定随机共振系统的结构参数;最后经过时、频域分析提取出滚动轴承故障特征。通过仿真与实测实验分析对所提出方法相比于传统SR系统及没有引入时延反馈项的ODF系统(Overdamped System with Fractional Deflection Nonlinearity,ODF)在滚动轴承故障提取上的有效性和优越性进行验证。
基金supported by the National Natural Science Foundation of China (81921002,81900970,82130027)Innovative Research Team of High-Level Local Universities in Shanghai (SHSMUZLCX20212400)+1 种基金Young Physician Innovation Team Project (QC202003)of Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of MedicineShanghai“Rising Stars of Medical Talent”Youth Development Program is also acknowledged。
文摘Osteoporosis(OP)is a prevalent metabolic bone disease.While drug therapy is essential to prevent bone loss in osteoporotic patients,current treatments are limited by side effects and high costs,necessitating the development of more effective and safer targeted therapies.Utilizing a zebrafish(Danio rerio)larval model of osteoporosis,we explored the influence of the metabolite spermine on bone homeostasis.Results showed that spermine exhibited dual activity in osteoporotic zebrafish larvae by increasing bone formation and decreasing bone resorption.Spermine not only demonstrated excellent biosafety but also mitigated prednisolone-induced embryonic neurotoxicity and cardiotoxicity.Notably,spermine showcased protective attributes in the nervous systems of both zebrafish embryos and larvae.At the molecular level,Rac1 was identified as playing a pivotal role in mediating the antiosteoporotic effects of spermine,with P53 potentially acting downstream of Rac1.These findings were confirmed using mouse(Mus musculus)models,in which spermine not only ameliorated osteoporosis but also promoted bone formation and mineralization under healthy conditions,suggesting strong potential as a bonestrengthening agent.This study underscores the beneficial role of spermine in osteoporotic bone homeostasis and skeletal system development,highlighting pivotal molecular mediators.Given their efficacy and safety,human endogenous metabolites like spermine are promising candidates for new anti-osteoporotic drug development and daily bone-fortifying agents.
基金supported by NIH grants RF1 AG069466(to JL and LDM),R01 NS099628(to JL),and AG069466(to JL and LDM)the American Heart Association award 20POST35180172(to FB)。
文摘Brain functional impairment after stroke is common;however,the molecular mechanisms of post-stroke recovery remain unclear.It is well-recognized that age is the most important independent predictor of poor outcomes after stroke as older patients show poorer functional outcomes following stroke.Mounting evidence suggests that axonal regeneration and angiogenesis,the major forms of brain plasticity responsible for post-stroke recovery,diminished with advanced age.Previous studies suggest that Ras-related C3 botulinum toxin substrate(Rac)1 enhances stroke recovery as activation of Rac1 improved behavior recovery in a young mice stroke model.Here,we investigated the role of Rac1 signaling in long-term functional recovery and brain plasticity in an aged(male,18 to 22 months old C57BL/6J)brain after ischemic stroke.We found that as mice aged,Rac1 expression declined in the brain.Delayed overexpression of Rac1,using lentivirus encoding Rac1 injected day 1 after ischemic stroke,promoted cognitive(assessed using novel object recognition test)and sensorimotor(assessed using adhesive removal tests)recovery on days 14–28.This was accompanied by the increase of neurite and proliferative endothelial cells in the periinfarct zone assessed by immunostaining.In a reverse approach,pharmacological inhibition of Rac1 by intraperitoneal injection of Rac1 inhibitor NSC23766 for 14 successive days after ischemic stroke worsened the outcome with the reduction of neurite and proliferative endothelial cells.Furthermore,Rac1 inhibition reduced the activation of p21-activated kinase 1,the protein level of brain-derived neurotrophic factor,and increased the protein level of glial fibrillary acidic protein in the ischemic brain on day 28 after stroke.Our work provided insight into the mechanisms behind the diminished plasticity after cerebral ischemia in aged brains and identified Rac1 as a potential therapeutic target for improving functional recovery in the older adults after stroke.
文摘Following the publication,concerns have been raised about a number of figures in this article.The western blots in this article were presented with atypical,unusually shaped and possibly anomalous protein bands in many cases.The authors were contacted and invited to comment on the concerns raised and to provide the original,unmodified figures,but did not respond.The Editors-in-Chief therefore no longer have confidence in the integrity of the data in this article and decided to retract this article.
文摘【目的】R A C/R O P s是一类植物特有的小G蛋白,作为分子开关参与众多的植物信号转导途径。OsRAC3通过与细胞分裂素信号组分互作,调控水稻Oryza sativa L.冠根发育,但是否影响水稻地上部分的性状尚不清楚。本研究主要分析OsRAC3对水稻穗发育以及产量性状的影响。【方法】对水稻OsRAC3promoter::GUS转基因植株的花序组织进行GUS染色,分析OsRAC3的表达模式。分析转基因材料持续激活型突变体(CA-osrac3)和显性失活型突变体(DN-osrac3)2种试验材料的每穗粒数、粒长、粒宽、千粒质量等主要农艺性状。【结果】OsRAC3在花序分生组织、雄蕊和雌蕊中强烈表达;CA-osrac3株系的穗粒数减少,籽粒更加饱满,粒长、粒宽、千粒质量均显著高于野生型;DN-osrac3株系的穗分枝数少且育性差,籽粒粒长、粒宽、千粒质量则显著低于野生型。【结论】OsRAC3影响水稻穗的发育过程,持续激活型突变体CA-osrac3促进水稻籽粒的发育;OsRAC3在水稻高产育种和遗传改良中具有重要的应用价值。
