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| 1 | Metformin activates chaperone-mediated autophagy and improves disease pathologies in an Alzheimer disease mouse model显示文摘Chaperone-mediated autophagy(CMA)is a lysosome-dependent selective degradation pathway implicated in the pathogenesis of cancer and neurodegenerative diseases.However,the mechanisms that regulate CMA are not fully understood.Here,using unbiased drug screening approaches,we discover Metformin,a drug that is commonly the first medication prescribed for type 2 diabetes,can induce CMA.We delineate the mechanism of CMA induction by Metformin to be via activation of TAK1-IKKα/β signaling that leads to phosphorylation of Ser85 of the key mediator of CMA,Hsc70,and its activation.Notably,we find that amyloid-beta precursor protein(APP)is a CMA substrate and that it binds to Hsc70 in an IKKα/β-dependent manner.The inhibition of CMA-mediated degradation of APP enhances its cytotoxicity.Importantly,we find that in the APP/PS1 mouse model of Alzheimer's disease(AD),activation of CMA by Hsc70 overexpression or Metformin potently reduces the accumulated brain Aβplaque levels and reverses the molecular and behavioral AD phenotypes.Our study elucidates a novel mechanism of CMA regulation via Metformin-TAK1-IKKα/β-Hsc70 signaling and suggests Metformin as a new activator of CMA for diseases,such as AD,where such therapeutic intervention could be beneficial. | Xiaoyan Xu Yaqin Sun Xufeng Cen Bing Shan Qingwei Zhao Tingxue Xie Zhe Wang Tingjun Hou Yu Xue Mengmeng Zhang Di Peng Qiming Sun Cong Yi Ayaz Najafov Hongguang Xia | 2021 | Protein & Cell2021，12，10： | 5 |
| 2 | 危重型新型冠状病毒肺炎患者床边内镜诊疗后内镜再处理流程改良分析显示文摘目的:在疫情期间,需要通过保证内镜处理质量,避免过程环节操作中的接触污染,防止气溶胶的散发,从而保护从业人员,杜绝院内感染。创新点:内镜诊疗对改善重症患者预后及降低患者死亡率有重要作用。该研究依据实际临床工作特质,对内镜再处理过程中的部分方法及化学清洗消毒剂的选择进行了改良与替换。方法:从12例重症患者行23次内镜诊治后的内镜处理操作中提取经验,结合相关指南规范,提出了新型冠状病毒肺炎患者床边内镜诊疗后内镜再处理改良流程。结论:内镜诊疗在重症及危重症患者治疗中不可或缺。临床工作中床旁预处理操作及专线转运流程对于预防院内感染具有重要意义。替换后的化学清洗消毒剂(0.23%过氧乙酸)对新冠病毒可达到高水平消毒。改良后的床边内镜诊疗后内镜再处理操作流程顺畅,感染控制严谨,值得临床进一步推广。 | Qing GU Hua-fen WANG Ying FANG Ye LU Zhe SHEN Yan WANG Xin WU Li CEN Yi-shu CHEN | 2020 | Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)2020，21，5： | 3 |
| 3 | Straightforward Guess and Determine Analysis Based on Genetic Algorithm显示文摘With the development of artificial intelligence,the genetic algorithm has been widely used in many fields.In cryptography,the authors find it is natural to code an individual and design its fitness in a genetic algorithm for a straightforward guess and determine analysis(SGDA,in short).Based on this observation,the authors propose an SGDA based on genetic algorithm.Comparing it with the other three SGDAs based on exhaustive search,MILP method and CPP method respectively,the authors illustrate its effectiveness by three stream ciphers:Small scale SNOW 2.0,medium scale Enocoro-128v2 and large scale Trivium.The results show our method is significantly superior to them,especially for Trivium,the method can find a solution of 165 variables in less than one hour,while the other three methods are not applicable due to its enormous search space of size 2^(619.37).As far as we know,it is a best solution in an SGDA for Trivium so far. | CAO Chunping CEN Zhe FENG Xiutao WANG Zhangyi ZHU Yamin | 2022 | Journal of Systems Science & Complexity2022，35，5： | 0 |
| 4 | Correction to:Metformin activates chaperone-mediated autophagy and improves disease pathologies in an Alzheimer disease mouse model显示文摘CORRECTION TO:PROTEIN CELL http://gffzzd3cc09b8251d45dfonqnx5nfqx060699k.ffgz.tsg.suse.edu.cn/10.1007/S13238-021-00858-3 In legend of figure 1,this sentence“(C)293THK cells were treated as in a”should be corrected as“(C)293THK cells were treated as in(A)”.In legend of figure 2,“E-64D(10μmol/L)”in description of panel(B)should be removed.In section“Metformin activates chaperone-mediated autophagy”of RESULTS,E-64D in sentence“Metformininduced degradation of HK2 and PKM2 was blocked by lysosomal inhibitors(E-64D,Bafilomycin A1 and Leupeptin+NH4Cl)”should be removed. | Xiaoyan Xu Yaqin Sun Xufeng Cen Bing Shan Qingwei Zhao Tingxue Xie Zhe Wang Tingjun Hou Yu Xue Mengmeng Zhang Di Peng Qiming Sun Cong Yi Ayaz Najafov Hongguang Xia | 2022 | Protein & Cell2022，13，3： | 0 |
| 5 | Structured Multi-Head Attention Stock Index Prediction Method Based Adaptive Public Opinion Sentiment Vector显示文摘The present study examines the impact of short-term public opinion sentiment on the secondary market,with a focus on the potential for such sentiment to cause dramatic stock price fluctuations and increase investment risk.The quantification of investment sentiment indicators and the persistent analysis of their impact has been a complex and significant area of research.In this paper,a structured multi-head attention stock index prediction method based adaptive public opinion sentiment vector is proposed.The proposedmethod utilizes an innovative approach to transform numerous investor comments on social platforms over time into public opinion sentiment vectors expressing complex sentiments.It then analyzes the continuous impact of these vectors on the market through the use of aggregating techniques and public opinion data via a structured multi-head attention mechanism.The experimental results demonstrate that the public opinion sentiment vector can provide more comprehensive feedback on market sentiment than traditional sentiment polarity analysis.Furthermore,the multi-head attention mechanism is shown to improve prediction accuracy through attention convergence on each type of input information separately.Themean absolute percentage error(MAPE)of the proposedmethod is 0.463%,a reduction of 0.294% compared to the benchmark attention algorithm.Additionally,the market backtesting results indicate that the return was 24.560%,an improvement of 8.202% compared to the benchmark algorithm.These results suggest that themarket trading strategy based on thismethod has the potential to improve trading profits. | Cheng Zhao Zhe Peng Xuefeng Lan Yuefeng Cen Zuxin Wang | 2024 | Computers, Materials & Continua2024，78，1： | 0 |
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