Background Follicular atresia,a complex degenerative process regulated by multiple molecular mechanisms,significantly affects female reproductive performance in animals.While granulosa cell(GC)apoptosis has been well ...Background Follicular atresia,a complex degenerative process regulated by multiple molecular mechanisms,significantly affects female reproductive performance in animals.While granulosa cell(GC)apoptosis has been well established as a primary mechanism underlying follicular atresia,the potential involvement of ferroptosis,which is an irondependent form of regulated cell death,remains largely unexplored in chickens.Results Using a tamoxifen(TMX)-induced avian model of follicular atresia,we demonstrated that ferroptosis plays a critical role in follicular degeneration.Inhibition of ferroptosis through pharmacological agents significantly restored follicular function,underscoring its potential as a therapeutic target.Notably,we observed a significant upregulation of ubiquitin-specific peptidase 9,X-linked(USP9X)in GCs during atresia.Through comprehensive in vitro and in vivo investigations,we confirmed that USP9X facilitates follicular atresia by promoting ferroptosis in GCs.Mechanistically,USP9X induces ferroptosis by stabilizing Beclin1 through deubiquitination,thereby activating autophagy-dependent ferroptosis.This pathway was effectively suppressed by autophagy inhibitors,emphasizing the essential role of autophagy in USP9X-mediated ferroptosis.Conclusions Our findings provide the evidence that the USP9X-Beclin1 axis regulates autophagy-dependent ferroptosis during avian follicular atresia.These insights reveal novel molecular targets and potential genetic markers for improving reproductive efficiency in chicken breeding programs.展开更多
目的:探讨胰腺癌组织与癌旁非肿瘤组织中生存素(Survivin)、泛素特异性蛋白酶9X(ubiquitin-specific protease 9X,USP9X)的表达情况及其与生存期的关系,研究Survivin与USP9X表达之间的关系.方法:应用SP法免疫组织化学染色技术检测55例...目的:探讨胰腺癌组织与癌旁非肿瘤组织中生存素(Survivin)、泛素特异性蛋白酶9X(ubiquitin-specific protease 9X,USP9X)的表达情况及其与生存期的关系,研究Survivin与USP9X表达之间的关系.方法:应用SP法免疫组织化学染色技术检测55例手术切除的原发性胰腺癌组织与癌旁非肿瘤胰腺组织中Survivin、USP9X的表达情况,结合临床资料进行相关预后分析,并用相关性检验分析Survivin与USP9X表达之间的关系.结果:胰腺癌组织中Survivin、USP9X的高表达阳性率分别为65.5%(36/55)、58.2%(32/55),癌旁非肿瘤组织中均为低表达.Survivin、U S P9X的表达与患者的性别、年龄、肿瘤部位及肿瘤大小无关(P>0.05),而与肿瘤分化程度、有无淋巴结转移及TNM分期显著相关(P<0.05).USP9X与Survivin在胰腺癌组织中的表达呈正相关性(r=0.624,P<0.05).生存分析显示,Survivin、USP9X高表达组患者的预后明显差于低表达组(P<0.05).Cox比例风险分析显示,肿瘤分化程度、有无淋巴结转移、Survivin及USP9X表达均是影响预后的独立危险因素(P<0.05).结论:在胰腺癌的发生、发展中,Survivin与U S P9X可能存在一定的相互协同作用,USP9X可能是抑制Survivin降解的去泛素化酶之一.Survivin、USP9X高表达的胰腺癌组织可能恶性程度更高,预后更差.展开更多
Infertility is a major health issue,affecting approximately 15%of couples of child-bearing age.Although nearly half of idiopathic infertility cases are assumed to have a genetic basis,the underlying causes remain larg...Infertility is a major health issue,affecting approximately 15%of couples of child-bearing age.Although nearly half of idiopathic infertility cases are assumed to have a genetic basis,the underlying causes remain largely unknown in most infertile men.展开更多
基金funded by The National Key Research and Development Program of China,grant number 2022YFF1000202Sichuan Science and Technology Program,grant number 2023NSFSC1940,2021YFYZ0007 and 2024YFNH0025+1 种基金National Natural Science Foundation of China Grants,grant number 32402745China Agriculture Research System of MOF and MARA,grant number CARS-40。
文摘Background Follicular atresia,a complex degenerative process regulated by multiple molecular mechanisms,significantly affects female reproductive performance in animals.While granulosa cell(GC)apoptosis has been well established as a primary mechanism underlying follicular atresia,the potential involvement of ferroptosis,which is an irondependent form of regulated cell death,remains largely unexplored in chickens.Results Using a tamoxifen(TMX)-induced avian model of follicular atresia,we demonstrated that ferroptosis plays a critical role in follicular degeneration.Inhibition of ferroptosis through pharmacological agents significantly restored follicular function,underscoring its potential as a therapeutic target.Notably,we observed a significant upregulation of ubiquitin-specific peptidase 9,X-linked(USP9X)in GCs during atresia.Through comprehensive in vitro and in vivo investigations,we confirmed that USP9X facilitates follicular atresia by promoting ferroptosis in GCs.Mechanistically,USP9X induces ferroptosis by stabilizing Beclin1 through deubiquitination,thereby activating autophagy-dependent ferroptosis.This pathway was effectively suppressed by autophagy inhibitors,emphasizing the essential role of autophagy in USP9X-mediated ferroptosis.Conclusions Our findings provide the evidence that the USP9X-Beclin1 axis regulates autophagy-dependent ferroptosis during avian follicular atresia.These insights reveal novel molecular targets and potential genetic markers for improving reproductive efficiency in chicken breeding programs.
文摘目的:探讨胰腺癌组织与癌旁非肿瘤组织中生存素(Survivin)、泛素特异性蛋白酶9X(ubiquitin-specific protease 9X,USP9X)的表达情况及其与生存期的关系,研究Survivin与USP9X表达之间的关系.方法:应用SP法免疫组织化学染色技术检测55例手术切除的原发性胰腺癌组织与癌旁非肿瘤胰腺组织中Survivin、USP9X的表达情况,结合临床资料进行相关预后分析,并用相关性检验分析Survivin与USP9X表达之间的关系.结果:胰腺癌组织中Survivin、USP9X的高表达阳性率分别为65.5%(36/55)、58.2%(32/55),癌旁非肿瘤组织中均为低表达.Survivin、U S P9X的表达与患者的性别、年龄、肿瘤部位及肿瘤大小无关(P>0.05),而与肿瘤分化程度、有无淋巴结转移及TNM分期显著相关(P<0.05).USP9X与Survivin在胰腺癌组织中的表达呈正相关性(r=0.624,P<0.05).生存分析显示,Survivin、USP9X高表达组患者的预后明显差于低表达组(P<0.05).Cox比例风险分析显示,肿瘤分化程度、有无淋巴结转移、Survivin及USP9X表达均是影响预后的独立危险因素(P<0.05).结论:在胰腺癌的发生、发展中,Survivin与U S P9X可能存在一定的相互协同作用,USP9X可能是抑制Survivin降解的去泛素化酶之一.Survivin、USP9X高表达的胰腺癌组织可能恶性程度更高,预后更差.
基金supported by the Fundamental Research Funds for the Central Universities(WK2070080005)。
文摘Infertility is a major health issue,affecting approximately 15%of couples of child-bearing age.Although nearly half of idiopathic infertility cases are assumed to have a genetic basis,the underlying causes remain largely unknown in most infertile men.
