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Celastrol enhances transcription factor EB (TFEB)-mediated autophagy and mitigates Tau pathology:Implications for Alzheimer's disease therapy

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Acta Pharmaceutica Sinica B 2022年第4期12卷 1707-1722页

作者： Chuanbin yang Chengfu Su Ashok Iyaswamy Senthil Kumar Krishnamoorthi Zhou Zhu sichang yang Benjamin Chunkit Tong Jia Liu Sravan G.Sreenivasmurthy Xinjie Guan Yuxuan Kan Aston Jiaxi Wu Alexis Shiying Huang Jieqiong Tan Kingho Cheung Juxian Song Min Li Mr.&Mrs.Ko Chi-Ming Centre for Parkinson’s Disease Research School of Chinese MedicineHong Kong Baptist UniversityHong Kong SARChina Department of Geriatrics Shenzhen People’s Hospital(the Second Clinical Medical CollegeJinan Universitythe First Affiliated HospitalSouthern University of Science and Technology)Shenzhen 518020China Institute for Research and Continuing Education Hong Kong Baptist UniversityShenzhen 518057China College of Pharmacy Henan University of Chinese MedicineZhengzhou 450000China Center for Medical Genetics and Hunan Key Laboratory of Animal Model for Human Diseases School of Life SciencesCentral South UniversityChangsha 410078China Medical College of Acupuncture-Moxibustion and Rehabilitation Guangzhou University of Chinese MedicineGuangzhou 510632China

Alzheimer's disease(AD),characterized by the accumulation of protein aggregates including phosphorylated Tau aggregates,is the most common neurodegenerative disorder with limited therapeutic agents.Autophagy plays a critical role in the degradation of phosphorylated Tau aggregates,and transcription factor EB(TFEB)is a master regulator of autophagy and lysosomal biogenesis.Thus,small-molecule autophagy enhancers targeting TFEB hold promise for AD therapy.Here,we found that celastrol,an active ingredient isolated from the root extracts of Tripterygium wilfordii(Lei Gong Teng in Chinese)enhanced TFEB-mediated autophagy and lysosomal biogenesis in vitro and in mouse brains.Importantly,celastrol reduced phosphorylated Tau aggregates and attenuated memory dysfunction and cognitive deficits in P301S Tau and 3xTg mice,two commonly used AD animal models.Mechanistical studies suggest that TFEB-mediated autophagy-lysosomal pathway is responsible for phosphorylated Tau degradation in response to celastrol.Overall,our findings indicate that Celastrol is a novel TFEB activator that promotes the degradation of phosphorylated Tau aggregates and improves memory in AD animal models.Therefore,Celastrol shows potential as a novel agent for the treatment and/or prevention of AD and other tauopathies.

关键词： TFEB Autophagy Lysosome biogenesis Alzheimer’s disease(AD) Tau Celastrol mTOR Therapeutic target

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《审计学》课程课堂教学运用“对分课堂”教学模式研究

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九江学院学报（社会科学版） 2024年第2期43卷 72-76页

作者：靳思昌许昌学院商学院河南许昌461000

“对分课堂”是针对当前高校课堂存在的学生缺课率高、上课玩手机、学习主动性差、不认真听课、课堂教学效果差等问题而提出的一种新型课堂教学模式。该模式汲取了讲授式课堂与讨论式课堂的精华,符合学生获取知识的认知规律。文章在阐... 详细信息

“对分课堂”是针对当前高校课堂存在的学生缺课率高、上课玩手机、学习主动性差、不认真听课、课堂教学效果差等问题而提出的一种新型课堂教学模式。该模式汲取了讲授式课堂与讨论式课堂的精华,符合学生获取知识的认知规律。文章在阐述“对分课堂”教学模式的理论基础上,分析了《审计学》课程的学科性质及其与“对分课堂”教学模式的契合点,提出了在《审计学》课程中实施“对分课堂”教学模式的路径,以调动学生的自主性,激发学生课堂参与的积极性,降低教师的教学负担,提升学生的学习效果。

关键词： “对分课堂” 教学模式《审计学》课程

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我国养老机构精神赡养的困境及其优解

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安徽师范大学学报（社会科学版） 2024年第2期52卷 92-99页

作者：蒲晓红何思长四川大学公共管理学院成都610065

扎实推进共同富裕必须关注精神富裕,重视精神赡养是养老机构高质量发展的必然要求。基于社会生态系统理论,从微观、中观和宏观三个维度系统分析养老机构精神赡养面临的困境可知,其主要表现为老年人精神自养能力薄弱、家庭成员支持弱化... 详细信息

扎实推进共同富裕必须关注精神富裕,重视精神赡养是养老机构高质量发展的必然要求。基于社会生态系统理论,从微观、中观和宏观三个维度系统分析养老机构精神赡养面临的困境可知,其主要表现为老年人精神自养能力薄弱、家庭成员支持弱化、养老机构功能发挥不力、社会组织缺乏协同性及政府保障力度不足等。为此,需要老年人自我增能、家庭成员强化支持、养老机构服务提质、社会组织系统集成和政府引导赋权,多方主体协同聚力,共同提高养老机构精神赡养水平。

关键词：养老机构精神赡养共同富裕

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静电纺丝在制备高性能锂离子电池负极材料中的应用

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化学进展 2024年第5期36卷 757-770页

作者：马思畅李东阳徐睿北京科技大学材料科学与工程学院北京100083

大规模储能设备的快速发展对锂离子电池的能量密度提出了更高要求,负极材料作为锂离子电池的重要组成部分,对电池的性能提升起着关键作用。但目前商用电池负极以导电性能良好的石墨类材料为主,其普遍存在能量密度低、倍率性能差等缺点... 详细信息

大规模储能设备的快速发展对锂离子电池的能量密度提出了更高要求,负极材料作为锂离子电池的重要组成部分,对电池的性能提升起着关键作用。但目前商用电池负极以导电性能良好的石墨类材料为主,其普遍存在能量密度低、倍率性能差等缺点。而新一代硅碳负极尽管可以提升负极比容量,却仍存在多种问题,包括体积膨胀、倍率性能差、循环寿命短等。因此,开发新型负极材料以实现具有更高能量密度、更长循环寿命和更优异倍率特性的锂离子电池十分重要。高电压静电纺丝作为一种制备柔性纳米纤维的常用方法,用其制备柔性负极材料有望提高电池的能量密度并解决其他相关问题,具有极大的发展前景。因此,本文综述了静电纺丝在制备关键锂离子电池负极材料的设计策略和研究进展,包括碳基、钛基、硅基、锡基以及其他金属化合物,并对未来电纺负极材料的发展方向进行了展望。

关键词：锂离子电池静电纺丝负极材料碳基钛基硅基锡基金属化合物

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分布式光纤传感技术及其应用研究

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内蒙古科技与经济 2024年第7期 117-121页

作者：周萍蒋思尝国家知识产权局专利局专利审查协作广东中心广东广州510000 南方科技大学电子与电气工程系广东深圳518055

分布式光纤传感技术作为一种新兴的传感技术,利用光纤作为传感介质,通过对光纤中传输光的光学特性的解调可在长距离的光纤沿线对探测特征量进行连续的分布式解调。文章主要研究了基于受激拉曼散射原理的分布式光纤温度传感仪和基于光学... 详细信息

分布式光纤传感技术作为一种新兴的传感技术,利用光纤作为传感介质,通过对光纤中传输光的光学特性的解调可在长距离的光纤沿线对探测特征量进行连续的分布式解调。文章主要研究了基于受激拉曼散射原理的分布式光纤温度传感仪和基于光学相位相干解调的分布式光纤振动传感仪的基本原理及不同实现技术的优缺点,对其在各领域的应用作了探讨。

关键词：分布式光纤传感拉曼散射 Mach-Zehnder干涉光时域反射

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An Improved Binary Search Anti-Collision Protocol for RFID Tag Identification

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Computers, Materials & Continua 2020年第11期65卷 1855-1868页

作者： Guozhong Dong Weizhe Zhang sichang Xuan Feng Qin Haowen Tan The Cyberspace Security Research Center Peng Cheng LaboratoryShenzhen518000China School of Computer Science and Technology Harbin Institute of TechnologyHarbin150001China Information Security Research Center Harbin Engineering UniversityHarbin150001China Wuhan Maritime Communication Research Institute Wuhan430205China Department of Computer Engineering Chosun UniversityGwangju61452Korea

Radio frequency identification(RFID)has been widespread used in massive items tagged domains.However,tag collision increases both time and energy consumption of RFID network.Tag collision can seriously affect the success of tag identification.An efficient anti-collision protocol is very crucially in RFID system.In this paper,an improved binary search anti-collision protocol namely BRTP is proposed to cope with the tag collision concern,which introduces a Bi-response mechanism.In Bi-response mechanism,two groups of tags allowed to reply to the reader in the same slot.According to Bi-response mechanism,the BRTP strengthens the tag identification of RFID network by reducing the total number of queries and exchanged messages between the reader and tags.Both theoretical analysis and numerical results verify the effectiveness of the proposed BRTP in various performance metrics including the number of total slots,system efficiency,communication complexity and total identification time.The BRTP is suitable to be applied in passive RFID systems.

关键词： RFID anti-collision binary search Bi-response mechanism

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Sewage sludge ditch for recovering heavy metals can improve crop yield and soil environmental quality

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Frontiers of Environmental Science & Engineering 2021年第2期15卷 65-75页

作者： Xianke Lin Xiaohong Chen sichang Li yangmei Chen Zebin Wei Qitang Wu Key Laboratory of Soil Environment and Waste Reuse in Agriculture of Guangdong Higher Education Institutes College of Natural Resources and EnvironmentSouth China Agricultural UniversityGuangzhou 510642China Key Laboratory of the Pearl River Estuarine Dynamics and Associated Process Regulation Ministry of Water ResourcesPearl River Hydraulic Research InstitutePearl River Water Resource CommissionGuangzhou 510611China

The treatment and disposal of municipal sewage sludge(MSS)is an urgent problem to be resolved in many countries.Safely using the nutrients within MSS to increase crop yield and enhance the fertility of poor soil could contribute to achieving sustainable development.An indirect use of MSS in ditches alongside Pennisetum hybridum plants was studied in field plots for 30 months and the contents of heavy metals and macronutrients were monitored in soil,sludge and plant samples.We found that the yield of P.hybridum was significantly increased by 2.39 to 2.80 times and the treated plants had higher N content compared with no sludge.In addition,the organic matter(OM)and N contents in the planted soil increased significantly compared with the initial soil.The OM content in the planted soil of the MSS treatment was 2.9 to 5.2 times higher than that with no sludge,and N increased by 2.0 to 3.8 times.However,MSS had no significant effect on the N,P and K contents in the soil at the bottom of the MSS ditch,and the content of heavy metals(Cd,Pb,Cu and Zn)were also within the safe range.Moreover,the moisture content and phytotoxicity of MSS after this indirect use were reduced and the heavy metal contents changed little,which is favorable to the further disposal of recovered MSS.Therefore,this indirect use of MSS is beneficial to agricultural production,soil quality and environmental sustainability.

关键词： Municipal sewage sludge Indirect use Heavy metals Macronutrients Pennisetum hybridum

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Photochemical properties of a new kind of anti-cancer drug: N-glycoside compound

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Science China Chemistry 2008年第9期51卷 872-877页

作者： ZHAO Ping WANG Mei ZHANG ShuPing SHAO sichang SUN XiaoYu YAO SiDe WANG ShiLong School of Life Science and Technology Tongji UniversityShanghai 200092China Department of Chemistry Tongji UniversityShanghai 200092China School of Chemistry and Chemical Engineering Fuyang Normal CollegeFuyang 236000China

Due to the nontoxicity and efficient anti-cancer activity, more and more attention has been paid to N-glycoside compounds. Laser photolysis of N-(α-D-glucopyranoside) salicyloyl hydrazine (NGSH) has been performed for the first time. The research results show that NGSH has high photosensitivity and is vulnerable to be photo-ionized via a monophotonic process with a quantum yield of 0.02, generating NGSH+· and hydrated electrons. Under the aerobic condition of cells, the hydrated electrons are very easy to combine with oxygen to generate 1O2 and O2-, both of which are powerful oxidants that can kill the cancer cells. In addition, NGSH+· can be changed into neutral radicals by deprotonation with a pKa value of 4.02 and its decay constant was determined to be 2.55×109dm3·mol-1·s-1. NGSH also can be oxidized by SO4-. with a rate constant of 1.76×109 dm3·mol-1.s-1, which further confirms the results of photoionization. All of these results suggest that this new N-glycoside compound might be useful for cancer treatment.

关键词： N-glycoside compound laser photolysis photoionization quantum yield anti-cancer mechanism

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Detection of EBV and HHV6 in the Brain Tissue of Patients with Rasmussen's Encephalitis

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Virologica Sinica 2018年第5期33卷 402-409页

作者： Dong Liu Xin Wang Yisong Wang Peigang Wang Dongying Fan sichang Chen Yuguang Guan Tianfu Li Jing An Guoming Luan department of neurosurgery sanbo brain hospitalcapital medical universityBeijing 100093China department of microbiology school of basic medical sciencecapital medical universityBeijing 100069China department of neurosurgery xuanwu hospital of capital medical universityBeijing 100053China beijing key laboratory of epilepsy center of epilepsy beijing institute for brain disordersBeijing 100093China

Rasmussen's encephalitis (RE) is a rare pediatric neurological disorder, and the exact etiology is not clear. Viral infection may be involved in the pathogenesis of RE, but conflicting results have reported. In this study, we evaluated the expression of both Epstein-Barr virus (EBV) and human herpes virus (HHV) 6 antigens in brain sections from 30 patients with RE and16 control individuals by immunohistochemistry. In the RE group, EBV and HHV6 antigens were detected in 56.7% (17/30) and 50% (15/30) of individuals, respectively. In contrast, no detectable EBV and HHV6 antigen expression was found in brain tissues of the control group. The co-expression of EBV and HHV6 was detected in 20.0% (6/30) of individuals. In particular, a 4-year-old boy had a typical clinical course, including a medical history of viral encephalitis,intractable epilepsy, and hemispheric atrophy. The co-expression of EBV and HHV6 was detected in neurons and astrocytes in the brain tissue, accompanied by a high frequency of CD8?T cells. Our results suggest that EBV and HHV6 infection and the activation of CD8?T cells are involved in the pathogenesis of RE.

关键词： Rasmussen’s encephalitis (RE) Epstein-Barr virus (EBV) Human herpes virus 6 (HHV6) Seizures CD8^+T cells

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Expression of human cytomegalovirus components in the brain tissues of patients with Rasmussen＇s encephalitis

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Virologica Sinica 2017年第2期32卷 115-121页

作者： Yao Zhang Yisong Wang sichang Chen Shuai Chen Yuguang Guan Changqing Liu Tianfu Li Guoming Luan Jing An Department of Neurosurgery Sanbo Brain Hospital Capital Medical University Beijing100093 China Department of Microbiology School of Basic Medical Science Capital Medical University Beijing 100069 China Beijing Key Laboratory of Epilepsy Beijing100093China Center of Epilepsy Beijing Institute for Brain Disorders Beijing100093 China

Rasmussen's encephalitis(RE) is a rare and severe progressive epileptic syndrome with unknown etiology. Infection by viruses, including human cytomegalovirus(HCMV), has been speculated to be a potential trigger for RE. However, no viral antigens have been detected in the brains of patients with RE; thus, a possible clinical linkage between viral infections and RE has not been firmly established. In this study, we evaluated the expression of HCMV pp65 antigen in brain sections from 26 patients with RE and 20 non-RE patients by immunohistochemistry and in situ hybridization, and assessed the associations between HCMV infection and clinical parameters.Elevated expression of HCMV pp65 protein and DNA was observed in 88.5%(23/26) and 69.2%(18/26) of RE cases, respectively. In the non-RE group, HCMV pp65 antigen was detected only in two cases(10%), both of which were negative for DNA staining. Additionally, the intensity of HCMV pp65 staining was correlated with a shorter duration of the prodromal stage, younger age of seizure onset, and more severe unilateral cortical atrophy. Elevated expression of HCMV pp65 was observed in RE brain tissue and was correlated with the clinical features of RE disease. In summary, our results suggested that HCMV infection may be involved in the occurrence and progression of RE disease. Thus, further studies are needed to determine whether early treatment with anti-HCMV antibodies could modulate the course of RE.

关键词： Rasmussen’s encephalitis human cytomegalovirus(HCMV) pp65 epilepsy

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