检索结果-南通市图书馆

AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis

在线全文

学校读者我要写书评

暂无评论

Science China Life Sciences 2025年第1期68卷 204-218页

作者： chen Xiong Hong ling Yingdan Huang Hanzhi Dong Bangxiang Xie Qian Hao Xiang Zhou Fudan University Shanghai Cancer Center and Institutes of Biomedical Sciences Fudan University Department of Oncology Shanghai Medical CollegeFudan University Department of Breast Surgery Fudan University Shanghai Cancer CenterFudan University Department of Oncology First Affiliated Hospital of Nanchang University Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical University Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer Key Laboratory of Breast Cancer in Shanghai Fudan University Shanghai Cancer CenterFudan University Shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan University

Tumor suppressor p53-mediated cell cycle arrest and DNA damage repair may exert cytoprotective effects against cancer therapies, including WEE1 inhibition. Considering that p53 activation can also lead to multiple types of cell death, the role of this tumor suppressor in WEE1 inhibitor-based therapies remains disputed. In this study, we reported that nucleolar stress-mediated p53 activation enhanced the WEE1 inhibitor AZD1775-induced ferroptosis to suppress lung cancer growth. Our findings showed that AZD1775 promoted ferroptosis by blocking cystine uptake, an action similar to that of Erastin. Meanwhile, inhibition of WEE1 by the WEE1 inhibitors or si RNAs induced compensatory upregulation of SLC7A11, which conferred resistance to ferroptosis. Mechanistically, AZD1775 prevented the enrichment of H3K9me3, a histone marker of transcriptional repression, on the SLC7A11 promoter by repressing the expression of the histone methyltransferase SETDB1, thereby enhancing NRF2-mediated SLC7A11 transcription. This finding was also validated using the H3K9me3 inhibitor BRD4770. Remarkably, we found that the nucleolar stress-inducing agent Actinomycin D(Act. D) inhibited SLC7A11 expression by activating p53, thus augmenting AZD1775-induced ferroptosis. Moreover, the combination of AZD1775 and Act. D synergistically suppressed wild-type p53-harboring lung cancer cell growth both in vitro and in vivo. Altogether, our study demonstrates that AZD1775 promotes ferroptosis by targeting cystine uptake but also mediates the adaptive activation of SLC7A11 through the WEE1-SETDB1 cascade and NRF2-induced transcription, and inhibition of SLC7A11 by Act. D boosts the anti-tumor efficacy of AZD1775 by enhancing ferroptosis in cancers with wild-type p53.

关键词： p53 NRF2 SLC7A11 WEE1 AZD1775 ferroptosis nucleolar stress

在线全文

同方期刊数据库

学校读者我要写书评

暂无评论

某斜靠式拱桥施工期主梁变形分析及处理

世界桥梁 2021年第4期49卷 112-117页

作者：易云焜陈如凌厦门理工学院福建厦门361000 福州大学福建福州350116

某斜靠式钢拱桥为3跨连续梁拱组合体系,跨径布置为(14.9+82.2+14.9)m,位于软土地基上。施工顺序为先梁后拱,主梁采用钢管支架法施工,主梁安装完成后,发生了中跨主梁下陷、边跨主梁上翘的现象。通过力学和有限元分析,得出中跨主梁下陷的... 详细信息

某斜靠式钢拱桥为3跨连续梁拱组合体系,跨径布置为(14.9+82.2+14.9)m,位于软土地基上。施工顺序为先梁后拱,主梁采用钢管支架法施工,主梁安装完成后,发生了中跨主梁下陷、边跨主梁上翘的现象。通过力学和有限元分析,得出中跨主梁下陷的主要原因是地基沉降,边跨主梁上翘的主要原因是白天高温时段安装。针对变形原因,对中跨主梁采用了临时支墩顶升优先、吊索上拉备用的处理措施,对边跨主梁采用了“配重下压、中跨顶升”的综合措施,并结合处理措施调整了施工工序。经过处理后主梁成桥高程误差满足规范要求,处理措施有效、得当。

关键词：斜靠式拱桥主梁变形原因分析地基沉降温度变化处理措施临时支墩顶升配重

The emerging role of nitric oxide in the synaptic dysfunction of vascular dementia

在线全文

学校读者我要写书评

暂无评论

Neural Regeneration Research 2025年第2期20卷 402-415页

作者： Xiaorong Zhang Zhiying chen Yinyi Xiong Qin Zhou ling-Qiang Zhu Dan Liu Department of Pathology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Jiujiang Clinical Precision Medicine Research Center JiujiangJiangxi ProvinceChina Center for Cognitive Science and Transdisciplinary Studies Jiujiang UniversityJiangxi ProvinceChina Department of Neurology Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Department of Rehabilitation Affiliated Hospital of Jiujiang UniversityJiujiangJiangxi ProvinceChina Department of Pathophysiology School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

With an increase in global aging,the number of people affected by cerebrovascular diseases is also increasing,and the incidence of vascular dementia-closely related to cerebrovascular risk-is increasing at an epidemic ***,few therapeutic options exist that can markedly improve the cognitive impairment and prognosis of vascular dementia *** in Alzheimer’s disease and other neurological disorders,synaptic dysfunction is recognized as the main reason for cognitive *** oxide is one of the ubiquitous gaseous cellular messengers involved in multiple physiological and pathological processes of the central nervous ***,nitric oxide has been implicated in regulating synaptic plasticity and plays an important role in the pathogenesis of vascular *** review introduces in detail the emerging role of nitric oxide in physiological and pathological states of vascular dementia and summarizes the diverse effects of nitric oxide on different aspects of synaptic dysfunction,neuroinflammation,oxidative stress,and blood-brain barrier dysfunction that underlie the progress of vascular ***,we propose that targeting the nitric oxide-sGC-cGMP pathway using certain specific approaches may provide a novel therapeutic strategy for vascular dementia.

关键词： endoplasmic reticulum stress endothelial nitric oxide synthase gene therapy nitric oxide NO-sGC-cGMP pathway synaptic dysfunction vascular dementia

关节镜下治疗关节内外粘连型屈膝功能障碍的方法与疗效分析

在线全文

学校读者我要写书评

暂无评论

天津医科大学学报 2007年第1期13卷 96-97,106页

作者：陈汝岭天津市咸水沽医院骨科天津300350

目的:探讨采用关节镜下松解膝关节内、外粘连所致的屈膝功能障碍的治疗方法与疗效。方法:对2003年1月～2005年12月屈膝功能障碍51例患者行粘连松解术,在关节镜下采用钩刀、刨刀、射频切除关节内髌上囊、内外侧间隙、髌下脂肪垫间隙、踝... 详细信息

目的:探讨采用关节镜下松解膝关节内、外粘连所致的屈膝功能障碍的治疗方法与疗效。方法:对2003年1月～2005年12月屈膝功能障碍51例患者行粘连松解术,在关节镜下采用钩刀、刨刀、射频切除关节内髌上囊、内外侧间隙、髌下脂肪垫间隙、踝间窝等和关节外的股骨与股中间肌间隙、肌内外侧间隙的粘连以及配合手法松解和术后康复治疗。51例屈膝功能障碍病例经治疗后随访8～12个月,平均10.2个月。结果:屈膝活动度增强30°～80°,平均70°,膝关节Lysholm功能评分术前(55±8.2)分,术后(86±11.2)分(P<0.01)取得优于非关节镜手术治疗的满意疗效。结论:关节镜下关节内外粘连松解治疗屈膝功能障碍有效、创伤小、恢复快、值得推广。

关键词：屈膝功能障碍关节镜粘连松解

在线全文

学校读者我要写书评

暂无评论

可调油压减振器的稳健设计

浙江大学学报（工学版） 2005年第3期39卷 359-363页

作者：潘双夏杨礼康陈入领冯培恩浙江大学CAD&CG国家重点实验室浙江杭州310027 浙江科技学院机电工程学系浙江杭州310012

为提高可调油压减振器阻尼性能,并降低其制造成本,提出一种基于优化设计的油压减振器稳健设计方法.对于加工精度要求较高的阻尼阀件,该方法依据流体动力特性、阻尼调节原理和动态特性要求分析并选定敏度参数后,以加工成本和产品性能及... 详细信息

为提高可调油压减振器阻尼性能,并降低其制造成本,提出一种基于优化设计的油压减振器稳健设计方法.对于加工精度要求较高的阻尼阀件,该方法依据流体动力特性、阻尼调节原理和动态特性要求分析并选定敏度参数后,以加工成本和产品性能及其稳健性为优化目标,设计参数及其容差为优化变量,建立了可调线性油压减振器的稳健设计模型.研究结果表明,应用该方法合理分配设计参数的容差,可使加工精度要求降低,性能稳健性提高.

关键词：油压减振器稳健设计优化设计制造成本

神阙穴帖敷治疗骨科骨折患者术后便秘的疗效观察

在线全文

学校读者我要写书评

暂无评论

蛇志 2017年第2期29卷 192-193页

作者：张艳陈如玲广西东兴市人民医院广西东兴538100

目的探讨大黄水蜜贴敷"神阙"穴对骨折术后便秘的治疗效果。方法选取我院骨科骨折术后发生便秘的患者100例,随机分成治疗组和对照组各50例。对照组采用传统的治疗方法,即在骨科常规护理措施上指导患者多饮水,多进食水果、蔬菜,必要时给... 详细信息

目的探讨大黄水蜜贴敷"神阙"穴对骨折术后便秘的治疗效果。方法选取我院骨科骨折术后发生便秘的患者100例,随机分成治疗组和对照组各50例。对照组采用传统的治疗方法,即在骨科常规护理措施上指导患者多饮水,多进食水果、蔬菜,必要时给予缓泻药或开塞露纳肛。治疗组在对照组的基础上加用大黄水蜜贴敷"神阙"穴治疗,并对两组患者的便秘情况和相关症状进行比较。结果治疗组的治疗有效率为90%,对照组为60%,两组比较差异有统计学意义(P<0.05);观察组发生便秘的相关症状少于对照组,差异有统计学意义(P<0.05)。结论大黄水蜜贴敷"神阙"穴治疗骨科骨折术后便秘的疗效显著,值得临床推广应用。

关键词：骨折术后便秘大黄水蜜贴 " 神阙" 穴外敷

Nanoparticles for the treatment of spinal cord injury

在线全文

学校读者我要写书评

暂无评论

Neural Regeneration Research 2025年第6期20卷 1665-1680页

作者： Qiwei Yang Di Lu Jiuping Wu Fuming Liang Huayi Wang Junjie Yang Ganggang Zhang chen Wang Yanlian Yang ling Zhu Xinzhi Sun Department of Orthopedic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan ProvinceChina CAS Key Laboratory of Standardization and Measurement for Nanotechnology CAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyCAS Center for Excellence in NanoscienceNational Center for Nanoscience and TechnologyBeijingChina University of Chinese Academy of Sciences BeijingChina Department of Neurosurgery The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

Spinal cord injuries lead to significant loss of motor, sensory, and autonomic functions, presenting major challenges in neural regeneration. Achieving effective therapeutic concentrations at injury sites has been a slow process, partly due to the difficulty of delivering drugs effectively. Nanoparticles, with their targeted delivery capabilities, biocompatibility, and enhanced bioavailability over conventional drugs, are garnering attention for spinal cord injury treatment. This review explores the current mechanisms and shortcomings of existing treatments, highlighting the benefits and progress of nanoparticle-based approaches. We detail nanoparticle delivery methods for spinal cord injury, including local and intravenous injections, oral delivery, and biomaterial-assisted implantation, alongside strategies such as drug loading and surface modification. The discussion extends to how nanoparticles aid in reducing oxidative stress, dampening inflammation, fostering neural regeneration, and promoting angiogenesis. We summarize the use of various types of nanoparticles for treating spinal cord injuries, including metallic, polymeric, protein-based, inorganic non-metallic, and lipid nanoparticles. We also discuss the challenges faced, such as biosafety, effectiveness in humans, precise dosage control, standardization of production and characterization, immune responses, and targeted delivery in vivo. Additionally, we explore future directions, such as improving biosafety, standardizing manufacturing and characterization processes, and advancing human trials. Nanoparticles have shown considerable progress in targeted delivery and enhancing treatment efficacy for spinal cord injuries, presenting significant potential for clinical use and drug development.

关键词： antioxidants axon regeneration biocompatible materials drug carriers nanoparticles nerve regeneration neuroinflammatory diseases neuroprotection spinal cord injury stem cells

Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

在线全文

学校读者我要写书评

暂无评论

Neural Regeneration Research 2025年第1期20卷 265-276页

作者： Yao Yuan lingqi Yu Xudong Zhuang Dongjing Wen Jin He Jingmei Hong Jiayu Xie Shengan ling Xiaoyue Du Wenfeng chen Xinrui Wang Institute of Life Sciences College of Biological Science and EngineeringFuzhou UniversityFuzhouFujian ProvinceChina NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate(Fujian Maternity and Child Health Hospital) FuzhouFujian ProvinceChina Medical Research Center Fujian Maternity and Child Health HospitalCollege of Clinical Medicine for Obstetrics&Gynecology and PediatricsFujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology and Institute of Neurology of The First Affiliated Hospital Institute of Neuroscienceand Fujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian ProvinceChina

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory *** develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause *** located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)*** addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive *** these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut *** found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in *** heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal *** Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

关键词： ATP1A1 Atpα bang-sensitive paralysis Charcot-Marie-Tooth disease type 2 CRISPR/Cas9 homology-directed repair Na^(+)/K^(+)-ATPase point mutation seizures sodium pump

单螺杆挤出的进料均匀性分析及其结构优化设计

在线全文

学校读者我要写书评

暂无评论

塑料工业 2022年第2期50卷 80-86页

作者：朱玉珩黄瑶邹鲲陈入领彭倚天东华大学机械工程学院上海201600 纺织装备教育部工程研究中心上海201600

螺杆挤出设备因其自身结构简单、设备能耗低等优点,在橡胶塑料、纤维成型等领域被广泛使用。但实际生产中螺杆的进口总会出现进料不均匀、不连续的情况。因此,采用Fluent软件对单螺杆挤出机中聚合物的三维等温流场进行数值模拟,探究了... 详细信息

螺杆挤出设备因其自身结构简单、设备能耗低等优点,在橡胶塑料、纤维成型等领域被广泛使用。但实际生产中螺杆的进口总会出现进料不均匀、不连续的情况。因此,采用Fluent软件对单螺杆挤出机中聚合物的三维等温流场进行数值模拟,探究了均匀进料和不均匀进料对聚合物流场的影响,并针对不均匀进料的不良影响,对螺杆的导程和螺棱间隙进行优化改进。研究结果表明,进料的不均匀性会增大物料反应过程中的死区占比和停留时间,同时出口流量的稳定性也会遭到破坏,而适当增大螺杆导程和螺棱间隙可有效改善以上问题,加强挤出螺杆的轴向输送能力,提升产品的生产质量。

关键词：进料均匀性螺杆导程螺杆间隙输送性能