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Targeting amyloid proteins for clinical diagnosis of neurodegenerative diseases

Fundamental Research 2023年第4期3卷 505-519页

作者： Shenqing Zhang Hui dong Jiang Bian Dan li Cong liu Bio-X institutes Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders(Ministry of Education)Shanghai Jiao Tong UniversityShanghai 200030China School of life Sciences and Biotechnology Shanghai Jiao Tong UniversityShanghai 200030China interdisciplinary Research Center on Biology and Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 201210China University of the Chinese Academy of Sciences Beijing 100049China State Key Laboratory of Bio-Organic and Natural Products Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 200032China Bio-X-Renji Hospital Research Center Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200240China Zhangjiang institute for Advanced Study Shanghai Jiao Tong UniversityShanghai 200240China.

Abnormal aggregation and accumulation of pathological amyloid proteins such as amyloid-β,Tau,and𝛼α-synuclein play key pathological roles and serve as histological hallmarks in different neurodegenerative diseases(NDs)such as Alzheimer’s disease(AD)and Parkinson’s disease(PD).in addition,various post-translational modifications(PTMs)have been identified on pathological amyloid proteins and are subjected to change during disease *** the central role of amyloid proteins in NDs,tremendous efforts have been made to develop amyloid-targeting strategies for clinical diagnosis and molecular classification of *** this review,we summarize two major strategies for targeting amyloid aggregates,with a focus on the trials in AD *** first strategy is a positron emission tomography(PET)scan of protein aggregation in the *** mainly focus on introducing the development of small-molecule PET tracers for specifically recognizing pathological amyloid *** second strategy is the detection of PTM biomarkers on amyloid proteins in cerebrospinal fluid and *** discuss the pathological roles of different PTMs in diseases and how we can use the PTM profile of amyloid proteins for clinical ***,we point out the potential technical challenges of these two strategies,and outline other potential strategies,as well as a combination of multiple strategies,for molecular diagnosis of NDs.

关键词： Amyloid aggregation Neurodegenerative diseases Clinical diagnosis Alzheimer’s disease Positron emission tomography(PET)tracer Tau Biomarker Post-translational modification

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High-fat diet aggravates colitis via mesenteric adipose tissue derived exosome metastasis-associated lung adenocarcinoma transcript 1

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World Journal of gastroenterology 2022年第29期28卷 3838-3853页

作者： dong Chen Miao-Miao Lu Jin-Hai Wang Yue Ren ling-ling Xu Wei-xin Cheng Sai-Sai Wang xiao-lin li xiao-Fei Cheng Jian-guo gao Farhin Shaheed Kalyani xi Jin Department of Colorectal Surgery The First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310003Zhejiang ProvinceChina Department of Medicine Zhejiang University School of MedicineHangzhou 310003Zhejiang ProvinceChina Department of Emergency The First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310003Zhejiang ProvinceChina Department of gastroenterology The First affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310003Zhejiang ProvinceChina

BACKgROUND Obesity is associated with an increased risk of developing Crohn’s disease(CD),higher disease activity,and comparatively worse clinical *** To investigate the role of mesenteric adipose tissue-derived exosomes in the pathogenesis of CD aggravation in obese *** First,we induced colitis in mice initiated on high-fat and normal diets and compared the severity of *** then extracted and identified exosomes from mesenteric adipose tissue and determined the levels of metastasis-associated lung adenocarcinoma transcript 1(MALAT1)in mesenteric adipose tissue-derived exosomes and the ***,we demonstrated an interaction between MALAT1 and the miR-15a-5p/activating transcription factor 6(ATF6)***,we explored the effects of mesenteric adipose tissue-derived exosomes extracted from mice fed a high-fat or normal diet on the severity of 2,4,6-trinitrobe-nzenesulfonic acid(TNBS)-induced colitis and ATF6-related endoplasmic reticulum stress *** High-fat diet was found to aggravate TNBS-induced colitis in *** expression of MALAT1 in mesenteric adipose tissue-derived exosomes of high-fat diet-fed mice *** increased expression of MALAT1 in colon tissue exacerbated TNBS-induced colitis and activated the ATF6 endoplasmic reticulum stress *** effect was partially reversed by the reduced expression of MALAT1 and overexpression of *** Mesenteric adipose tissue-derived exosome-encapsulated long noncoding RNAs MALAT1 targets the colon and aggravates TNBS-induced colitis in obese mice,which may potentially act on the miR-15a-5p/ATF6 axis and activate endoplasmic reticulum stress.

关键词： Metastasis-associated lung adenocarcinoma transcript Crohn’s disease miR-15a-5p Mesenteric adipose tissue Obesity Colitis inflammatory bowel disease

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Paired quasi-periodic pulsations of hard X-ray emission in a solar flare

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Science China(Physics,Mechanics & Astronomy) 2023年第5期66卷 195-206页

作者： Hai-Sheng Zhao dong li Shao-lin xi.ng Yan-Qiu Zhang Yang Su Wei Chen Yi Zhao xiao-Bo li Jia-Cong liu Wen-xi Peng Rui Qiao xin-Qiao li xi.ng-Yang Wen li-Ming Song Shi-Jie Zheng xin-Ying Song xiao-Yun Zhao Yue Huang Shuang-Nan Zhang Shuo xiao Ce Cai Zheng-Hua An Can Chen gang Chen Wei Chen Yan-Qi Du Min gao Ke gong dong-Ya guo zhi-Wei guo Jian-Jian He Bin li Chao li Chao-Yang li gang li Jian-Hui li Lu li Qing-xin li Yan-guo li Jing liang xiao-Hua liang Jin-Yuan liao xiao-Jing liu Ya-Qing liu Qi Luo xi.ng Ma Bin Meng ge Ou dong-li Shi Jing-Yan Shi gong-xing Sun xi-Lei Sun You-li Tuo Chen-Wei Wang Hui Wang Jin Wang Jin-Zhou Wang Ping Wang Wen-Shuai Wang Hong Wu Sheng-Lun xie Yan-Bing Xu Yu-Peng Xu Wang-Chen Xue Sheng Yang Min Yao Jian-Ying Ye Qi-Bin Yi Chao-Yue Zhang Da-li Zhang Fan Zhang Fei Zhang Hong-Mei Zhang Kai Zhang Peng Zhang xiao-Lu Zhang Zhen Zhang guo-Ying Zhao Shi-Yi Zhao Chao Zheng xing Zhou Yue Zhu Key Laboratory for Particle Astrophysics Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China Purple Mountain Observatory Chinese Academy of SciencesNanjing 210023China University of Chinese Academy of Sciences Beijing 100049China Department of Astronomy Beijing Normal UniversityBeijing 100875China School of Computing and Artificial intelligence Southwest Jiaotong UniversityChengdu 611756China Physics and Space Science College China West Normal UniversityNanchong 637002China Key Laboratory of Stellar and interstellar Physics and Department of Physics Xiangtan UniversityXiangtan 411105China institute of Astrophysics Central China Normal UniversityWuhan 430079China School of Physics Changchun University of Science and TechnologyChangchun 130022China College of Physics and Engineering Qufu Normal UniversityQufu 273165China College of Physics Sciences&Technology Hebei UniversityBaoding 071002China

We investigate high time resolution data obtained by the gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor(gECAM)during the flare event on 2022 April 21 at 01:52 *** subpeaks with durations of 4-6 s have been detected in the hard X-ray precursor phase,and the key feature is that they appear in pairs and seem like double-peak *** subpeaks are rarely observed in hard X-ray band and confirmed by the microwave obtained by Nobeyama Radio Polarimeters(NoRP)and Radio Solar Telescope Network(RSTN).While an exponential function can describe the continuum component of the time profile from the precursor to part of the impulsive *** periods of quasi-periodic pulsations(QPPs)are detected to be about 7.3 and 12.8 s for the precursor and impulsive phase,respectively,with at least 95%confidence *** paired QPPs are assumed to be double-peak QPPs and then the scenario of current loop coalescence model is found to be in good agreement with our *** precursor phase can be interpreted as the oscillating coalescence of two islands,while the impulsive phase can be interpreted as more islands to coalesce one by one to form larger islands.

关键词： solar flare QPPs loop coalescence circular-ribbon flare

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强流脉冲电子束表面合金化的涂层厚度优化模拟

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材料热处理学报 2015年第11期36卷 244-249页

作者：秦颖李光芝董闯大连理工大学三束材料改性重点实验室辽宁大连116024 大连理工大学高科技研究院辽宁大连116024

通过建立三维温度场模型,利用数值模拟方法,模拟316L钢表面进行Ti和Al合金化的温度场分布,分析Ti、Al涂层厚度以及电子束能量密度对合金化的影响。结果表明,在能量密度为6 J/cm2电子束的一次脉冲处理下,316L钢表面合金化Ti的优化涂层厚... 详细信息

通过建立三维温度场模型,利用数值模拟方法,模拟316L钢表面进行Ti和Al合金化的温度场分布,分析Ti、Al涂层厚度以及电子束能量密度对合金化的影响。结果表明,在能量密度为6 J/cm2电子束的一次脉冲处理下,316L钢表面合金化Ti的优化涂层厚度为1.1μm,表面合金化Al的优化涂层厚度为2μm。

关键词：强流脉冲电子束表面合金化温度场模拟

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insights into human eNOS, nNOS and iNOS structures and medicinal indications from statistical analyses of their interactions with bound compounds

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Biophysics Reports 2023年第3期9卷 159-175页

作者： Jianshu dong Dié li Lei Kang Chenbing Luo Jiangyun Wang School of Pharmaceutical Sciences Zhengzhou University 2. Institute of Drug Discovery and Development Zhengzhou University 3. Key Laboratory of Advanced Drug Preparation Technologies Ministry of Education of China Zhengzhou University 4. Collaborative Innovation Center of New Drug Research and Safety Evaluation Henan Province Zhengzhou University 5. Key Laboratory of Henan Province for Drug Quality control and Evaluation Zhengzhou University Laboratory of RNA Biology Institute of Biophysics Chinese Academy of Sciences

83 Structures of human nNOS, 55 structures of human eNOS, 13 structures of iNOS, and about 126 reported NOS-bound compounds are summarized and analyzed. Structural and statistical analysis show that, at least one copy of each analyzed compound binds to the active site(the substrate arginine binding site) of human NOS. And binding features of the three isoforms show differences, but the binding preference of compounds is not in the way helpful for inhibitor design targeting nNOS and iNOS, or for activator design targeting eNOS. This research shows that there is a strong structural and functional similarity between oxygenase domains of human NOS isoforms, especially the architecture, residue composition, size, shape, and distribution profile of hydrophobicity, polarity and charge of the active site. The selectivity and efficacy of inhibitors over the rest of isoforms rely a lot on chance and randomness. Further increase of selectivity via rational improvement is uncertain, unpredictable and unreliable, therefore, to achieve high selectivity through targeting this site is complicated and requires combinative investigation. After analysis on the current two targeting sites in NOS, the highly conserved arginine binding pocket and H4B binding pocket, new potential drug-targeting sites are proposed based on structure and sequence profiling. This comprehensive analysis on the structure and interaction profiles of human NOS and bound compounds provides fresh insights for drug discovery and pharmacological research, and the new discovery here is practically applied to guide protein-structure based drug discovery.

关键词： Nitric oxide synthase Endothelial NOS Neuronal NOS Drug design Molecular pharmacology inducible NOS

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Temperature-insensitive sensor for glucose brix measurement based on compact spindle-shaped structure with two-mode fiber

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Optoelectronics Letters 2022年第12期18卷 737-742页

作者： dong Miaoyun TOng Zhengrong ZHAng Weihua li Peng WU Meng TiAN Xue Engineering Research Center of Optoelectronic Devices and Communication Technology Ministry of EducationTianjin Key Laboratory of Film Electronic and Communication DevicesSchool of Integrated Circuit Science and EngineeringTianjin University of TechnologyTianjin300384China

A temperature-insensitive sensor for glucose brix measurement based on compact spindle-shaped structure with two-mode fiber(TMF) is proposed. Due to the bending of optical fiber caused by flame baking, some of the light energy transmitted in the core leaks into the cladding area as an evanescent wave, which excites the higher-order cladding mode of the sensor. The experimental results show that when the length of TMF is 3 cm and the bending diameter is 4 mm, the maximum glucose brix sensitivity of the sensor is 0.368 nm/% from 0 to 21%. The sensor is insensitive to temperature from 10 °C to 50 °C, which can avoid the problem of temperature cross-sensitivity. A compact spindle-shaped sensor is a potential effective sensor with a simple structure, easy fabrication and low cost. The sensor can be used to detect glucose content in areas such as crops quality assessment and the research of pharmacy and bioengineering.

关键词： shaped fiber mode

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基于强化学习的多机器人合作行为获取

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上海交通大学学报 2005年第8期39卷 1331-1335页

作者：李冬梅陈卫东席裕庚上海交通大学自动化系上海200030

研究了基于强化学习的多机器人学习社会合作行为的问题.通过定义的分配布尔矩阵,对参与任务者进行奖励回报,并综合基础行为,生成状态到行为的新的映射,形成高级的群体合作行为,使得团队作为一个整体受益.讨论了学习社会行为的可行性和... 详细信息

研究了基于强化学习的多机器人学习社会合作行为的问题.通过定义的分配布尔矩阵,对参与任务者进行奖励回报,并综合基础行为,生成状态到行为的新的映射,形成高级的群体合作行为,使得团队作为一个整体受益.讨论了学习社会行为的可行性和必要性,并采用强化学习方法,给出了多机器人传接合作搬运的详细算法实现.

关键词：强化学习多机器人传接合作社会行为

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Detecting Larmor Precession of a Single Spin with a Spin-Polarized Tunneling Current

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Chinese Physics Letters 2013年第1期30卷 187-190页

作者： gUO xiao-dong dong li gUO Yang SHAN xin-Yan ZHAO Ji-Min LU xing-Hua Beijing National Laboratory for Condensed Matter Physics and institute of Physics Chinese Academy of SciencesBeijing 100190

Detection and manipulation of a single spin is essential for spin-based quantum information and *** propose an experimental method to detect the Larmor precession of a single spin with a spin-polarized tunneling *** calculation demonstrates that the modulation of the tunneling current is significantly increased as compared with the non-spin-polarized *** signal-to-noise ratio in the current power spectrum will be dramatically improved by this *** longitudinal relaxation time can be measured by temporal control of spin orientation with pulses of magnetic field or radio frequency electromagnetic wave,while the transverse relaxation time can be derived by analyzing the resonant peak profile with a spectrum *** ability in characterizing spin relaxation is of particular interest in providing insights into the coherence/decoherence of a single spin.

关键词： method. relaxation tunneling

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Accelerated evolution of constraint elements for hematophagic adaptation in mosquitoes

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Zoological Research 2015年第6期36卷 320-327页

作者： Ming-Shan WAng Adeniyi C. ADEOLA Yan li Ya-Ping ZHAng dong-dong WU State Key Laboratory of genetic Resources and Evolution Kunming Institute of Zoology Chinese Academy of Sciences Kunming 650223 China University of Chinese Academy of Sciences Beijing 100049 China Laboratory for Conservation and Utilization of Bio-resources Yunnan University Kunming 650091 China

Comparative genomics is a powerful approach that comprehensively interprets the genome. Herein, we performed whole genome comparative analysis of 16 Diptera genomes, including four mosquitoes and 12 Drosophilae. We found more than 540 000 constraint elements （CEs） in the Diptera genome, with the majority found in the intergenic, coding and intronic regions. Accelerated elements （AEs） identified in mosquitoes were mostly in the proteincoding regions （〉93%）, which differs from vertebrates in genomic distribution. Some genes functionally enriched in blood digestion, body temperature regulation and insecticide resistance showed rapid evolution not only in the lineage of the recent common ancestor of mosquitoes （RCAM）, but also in some mosquito lineages. This may be associated with lineage-specific traits and/or adaptations in comparison with other insects. Our findings revealed that although universally fast evolution acted on biological systems in RCAM, such as hematophagy, same adaptations also appear to have occurred through distinct degrees of evolution in different mosquito species, enabling them to be successful blood feeders in different environments.

关键词： Mosquitoes Constraint elements Accelerated elements Hematophagy

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低成本PVA纤维对超高韧性水泥基复合材料力学性能的影响

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工程力学 2019年第11期36卷 121-129,182页

作者：阚黎黎章志张利刘卫东上海理工大学环境与建筑学院

超高韧性纤维增强水泥基复合材料(ECC)因其出色的高韧性及多缝开裂特性备受关注,然而一直以来因配比中进口PVA纤维的使用导致高昂的价格限制了其在工程中的大规模应用。为了进一步降低成本及实现原材料的本土化,研究低成本国产PVA纤维对... 详细信息

超高韧性纤维增强水泥基复合材料(ECC)因其出色的高韧性及多缝开裂特性备受关注,然而一直以来因配比中进口PVA纤维的使用导致高昂的价格限制了其在工程中的大规模应用。为了进一步降低成本及实现原材料的本土化,研究低成本国产PVA纤维对ECC力学性能的影响十分必要。通过单轴拉伸、压缩、三点抗弯及单裂缝拉伸等宏观、细观试验研究两种国产低成本PVA-ECC的力学性能,并借助纤维分散性试验及SEM,探讨纤维的分散等微观特征。结果表明,低成本国产纤维在基体中具有良好的分散性,尽管其纤维桥接余能、最大桥接应力及PSH指数低于进口纤维,但均能满足能量与强度准则,即便相对较差的纤维A试件的3 d、7 d及28 d的极限拉伸应变也可达到2.52%、3.34%及3.08%,可实现良好的应力硬化行为及饱和多缝开裂特性,满足ECC的使用要求。

关键词：低成本 PVA纤维超高韧性纤维增强水泥基复合材料单轴拉伸三点抗弯单裂缝拉伸

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