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A new tau dephosphorylation-targeting chimera for the treatment of tauopathies

中国药理学报（英文版） 2024年第11期45卷 2267-2276页

作者： Jing-fen Su Yue Xiao Lin-yu Wei Hui-yang Lei Fei Sun Wei-xia Wang Shi-hong Li Xiao-chuan Wang Jie Zheng Jian-zhi Wang Department of Pathophysiology School of Basic MedicineKey Laboratory of Education Ministry of China/Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Department of Pathophysiology School of Basic MedicineKey Laboratory of Education Ministry of China/Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China School of Artificial Intelligence and Automation Huazhong University of Science and TechnologyWuhan 430030China Department of Pathophysiology School of Basic MedicineKey Laboratory of Education Ministry of China/Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Sino-UK Joint Laboratory of Brain Function and Injury of Henan Province Department of Physiology and PathophysiologySchool of Basic Medical SciencesXinxiang Medical UniversityXinxiang 453003China Department of Anesthesiology the First Affiliated Hospital of Gannan Medical UniversityGanzhou 341000China Neuroscience Research Institute and Department of Neurobiology School of Basic Medical SciencesPeking University Key Laboratory for Neuroscience Ministry of Education/National Health CommissionPeking UniversityBeijing 100083China Beijing Life Science Academy Beijing 102209China Department of Pathophysiology School of Basic MedicineKey Laboratory of Education Ministry of China/Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China Co-innovation Center of Neuroregeneration Nantong UniversityNantong 226000China

Abnormal accumulation of hyperphosphorylated tau protein plays a pivotal role in a collection of neurodegenerative diseases named tauopathies,including Alzheimer's disease(AD).We have recently conceptualized the design of hetero-bifunctional chimeras for selectively promoting the proximity between tau and phosphatase,thus specifically facilitating tau dephosphorylation and ***,we sought to optimize the construction of tau dephosphorylating-targeting chimera(DEPTAC)and obtained a new chimera D14,which had high efficiency in reducing tau phosphorylation both in cell and tauopathy mouse models,while showing limited ***,D14 ameliorated neurodegeneration in primary cultured hippocampal neurons treated with toxic tau-K1 8 fragments,and improved cognitive functions of tauopathy *** results suggested D14 as a cost-effective drug candidate for the treatment of tauopathies.

关键词： Tau dephosphorylation targeting chimera(DEPTAC) tauopathy Alzheimer's disease drug development

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Metal coordination-driven assembly of stimulator of interferon genes-activating nanoparticles for tumor chemo-immunotherapy

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BMEMat(BioMedical Engineering Materials) 2024年第2期2卷 118-133页

作者： Guiqiang Zhang Ning Wang Yuan Ma Shumei Zhai To Ngai Shilei Ni Xinyi Jiang Jianwei Jiao Jiwei Cui Key Laboratory of Colloid and Interface Chemistry of the Ministry of Education School of Chemistry and Chemical EngineeringShandong UniversityJinanChina Medical Science and Technology Innovation Center Shandong First Medical University&Shandong Academy of Medical SciencesJinanChina Department of Neurosurgery Qilu Hospital and Institute of Brain and Brain-Inspired ScienceCheeloo College of MedicineShandong UniversityJinanChina Department of Chemistry The Chinese University of Hong KongHong KongChina Department of Pharmaceutics School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinanChina

Activating the stimulator of interferon genes(STING)signaling pathway is critical for enhancing antitumor immunity and remodeling the immunosuppressive tumor microenvironment(TME).Herein,we report the preparation of STING-activating nanoparticles via metal coordination-driven assembly of a synthetic STING agonist(i.e.,SR717)and a chemotherapeutic drug(i.e.,curcumin).After intravenous administration,the assembled nanoparticles could efficiently accumulate in tumors to improve the bioavailability of SR717 and trigger potent STING pathway activation for effective immune ***,the released curcumin evokes immunogenic cell death in tumors and regulates amino acid metabolism by inhibiting the activation of indoleamine 2,3-dioxygenase 1,leading to the reversal of the immunosuppressive *** antitumor immunity induced by nanoparticles significantly inhibits the growth of primary,recurrent,and metastatic *** assembled nanoparticles are promising for the co-delivery of STING agonists and drugs in improved tumor chemo-immunotherapy.

关键词： amino acid metabolism immunotherapy nanoparticles self-assembly STING

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Social isolation, loneliness and subsequent risk of major adverse cardiovascular events among individuals with type 2 diabetes mellitus

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General Psychiatry 2023年第6期36卷 481-490页

作者： Yannis Yan Liang Yilin Chen Hongliang Feng Huachen Xue Yu Nie Qi-Yong H Ai Jiacheng Ma Lulu Yang Jihui Zhang Sizhi Ai Center for Sleep and Circadian Medicine The Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China Guangzhou Medical UniversityGuangzhouGuangdongChina institute of Psycho-neuroscience The Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina Guangdong Cardiovascular Institute Guangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdongChina State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Department of Neurology and National Center for Neurological DisordersHuashan HospitalFudan UniversityShanghaiChina Department of Health Technology and Informatics The Hong Kong Polytechnic UniversityKowloonHong Kong Department of Cardiology Heart CenterThe First Affiliated Hospital of Xinxiang Medical UniversityWeihuiHenanChina

Background Individuals with type 2 diabetes mellitus(T2DM)are more vulnerable to social disconnection compared with the general population;however,there are few relevant studies investigating this *** To investigate whether social isolation or loneliness may be associated with subsequent risk of developing major adverse cardiovascular events,whether these associations vary according to fatal and non-fatal outcomes and how behavioural,psychological and physiological factors mediate these *** This longitudinal analysis included data from 19360 individuals with T2DM at baseline(2006-2010)from the UK *** isolation and loneliness were measured using self-report *** study outcomes included the first events of myocardial infarction(MI)or stroke(n=2273)and all-cause(n=2820)or cardiovascular disease-related mortality through linked hospital data ordeath *** Over a median follow-up of 12.4 years(interquartile range(IQR):11.6-13.3 years),participants who were more socially isolated(most social isolation vs least social isolation)experienced increased risks for all-cause(hazard ratio(HR):1.33,95%confidence interval(Cl):1.19 to 1.47)and cardiovascular disease(HR:1.36,95%Cl:1.17 to 1.59)mortality but not first Ml or ***(yes vs no)was associated with a greater risk for a composite of incident MI or stroke(HR:1.37,95%Cl:1.19 to 1.57)but not *** isolation was associated with fatal Ml and stroke,whereas loneliness was associated with non-fatal Ml and *** significant associations of social isolation and loneliness with outcomes were mainly mediated by behavioural factors(mediating proportion:17.8%-28.2%and 17.6%-17.8%,respectively).Conclusions Among individuals with T2DM,social isolation and loneliness are associated with a greater risk of developing major adverse cardiovascular events,with differences in both risks stratified according to fatal and non-fatal events and underlying mediat

关键词： cardiovascular mortality mellitus

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Evolving Constrained Reinforcement Learning Policy

arXiv

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arXiv 2023年

作者： Hu, Chengpeng Pei, Jiyuan Liu, Jialin Yao, Xin Southern University of Science and Technology Shenzhen China Guangdong Key Laboratory of Brain-inspired Intelligent Computation Department of Computer Science and Engineering Southern University of Science and Technology Shenzhen China

Evolutionary algorithms have been used to evolve a population of actors to generate diverse experiences for training reinforcement learning agents, which helps to tackle the temporal credit assignment problem and improves the exploration efficiency. However, when adapting this approach to address constrained problems, balancing the trade-off between the reward and constraint violation is hard. In this paper, we propose a novel evolutionary constrained reinforcement learning (ECRL) algorithm, which adaptively balances the reward and constraint violation with stochastic ranking, and at the same time, restricts the policy’s behaviour by maintaining a set of Lagrange relaxation coefficients with a constraint buffer. Extensive experiments on robotic control benchmarks show that our ECRL achieves outstanding performance compared to state-of-the-art algorithms. Ablation analysis shows the benefits of introducing stochastic ranking and constraint buffer. Copyright © 2023, The Authors. All rights reserved.

关键词： Reinforcement learning

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Impairments of working memory for object-location associations in depression

Impairments of working memory for object-location associatio...

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2014 International Conference on Applied Mechanics and Mechanical Automation, AMMA 2014

作者： Liu, Peng-Fei Li, Mi Lu, Sheng-Fu Wang, Jing Zhou, Yu Su, Xing-Yu Zhong, Ning The International WIC Institute Beijing University of Technology Beijing 100124 China The School of Computer and Communication Engineering Liaoning ShiHua University Liaoning113001 China Department of Life Science and Informatics Maebashi Institute of Technology Maebashi 371-0816 Japan Beijing Key Laboratory of MRI and Brain Informatics Beijing 100153 China

ISBN: (纸本)9783038351511

In this paper, we investigated the working memory for object-location associations of 11 depressions when they induced by different emotional pictures (positive, neutral and negative), and compared with a control group of 14 normal subjects. The results showed that there was no significant difference in the correct rate of associative memory between depression and control group (P > 0.05), however, there was significant difference in the memory retrieval time (P < 0.05), which suggest that the memory retrieval needs more time resources. These results indicate that depression has a normal memory encoding network, but an abnormal memory retrieval network for object-location associations. © (2014) Trans Tech Publications, Switzerland.

关键词： Location

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Progress in research on ultrasound radiomics for predicting the prognosis of breast cancer

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Cancer Innovation 2023年第4期2卷 283-289页

作者： Xuantong Gong Xuefeng Liu Xiaozheng Xie Yong Wang Department of Ultrasound National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBijingChina State Key Laboratory of Virtual Reality Technology and Systems School of Computer Science and EngineeringBejjing Advanced Innovation Center for Big Data and Brain Computing(BDBC)Beihang UniversityBeijingChina School of Computer and Communication Engi neering.University of Science and Technology Beijing BeijingChina

Breast cancer is the most common malignant tumor and the leading cause of cancer-related deaths in women *** means of predicting the prognosis of breast cancer are very helpful in guiding treatment and improving patients'*** extracted by radiomics reflect the genetic and molecular characteristics of a tumor and are related to its biological behavior and the patient's ***,radiomics provides a new approach to noninvasive assessment of breast cancer *** is one of the commonest clinical means of examining breast *** recent years,some results of research into ultrasound radiomics for diagnosing breast cancer,predicting lymph node status,treatment response,recurrence and survival times,and other aspects,have been *** this article,we review the current research status and technical challenges of ultrasound radiomics for predicting breast cancer *** aim to provide a reference for radiomics researchers,promote the development of ultrasound radiomics,and advance its clinical application.

关键词： breast cancer deeplearning prognosisprediction radiomics ultrasound

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Reducing idleness in financial cloud services via multi-objective evolutionary reinforcement learning based load balancer

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science China(Information sciences) 2024年第2期67卷 20-40页

作者： Peng YANG Laoming ZHANG Haifeng LIU Guiying LI Department of Statistics and Data Science Southern University of Science and Technology Guangdong Provincial Key Laboratory of Brain-Inspired Intelligent Computation Department of Computer Science and EngineeringSouthern University of Science and Technology Academy for Advanced Interdisciplinary Studies Southern University of Science and Technology Guangdong OPPO Mobile Telecommunications Corp. Ltd Research Institute of Trustworthy Autonomous Systems Southern University of Science and Technology

In recent years, various companies have started to shift their data services from traditional data centers to the cloud. One of the major motivations is to save on operational costs with the aid of cloud elasticity. This paper discusses an emerging need from financial services to reduce the incidence of idle servers retaining very few user connections, without disconnecting them from the server side. This paper considers this need as a bi-objective online load balancing problem. A neural network based scalable policy is designed to route user requests to varied numbers of servers for the required elasticity. An evolutionary multi-objective training framework is proposed to optimize the weights of the policy. Not only is the new objective of idleness reduced by over 130% more than traditional industrial solutions, but the original load balancing objective itself is also slightly improved. Extensive simulations with both synthetic and real-world data help reveal the detailed applicability of the proposed method to the emergent problem of reducing idleness in financial services.

关键词： evolutionary reinforcement learning evolutionary multi-objective optimization load balance cloud computing

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A Blind Driving System Leveraging Multimodal Feedback

A Blind Driving System Leveraging Multimodal Feedback

引用

Smart World Congress (SWC), IEEE

作者： Ruizhe Zhang Sha Zhao Wei Yang Shijian Li Gang Pan the College of Computer Science and Technology Zhejiang University Hangzhou China the State Key Laboratory of Brain-machine Intelligence Zhejiang University Hangzhou China

ISBN: (数字)9798331520861

ISBN: (纸本)9798331520878

Driving poses a significant challenge for blind and visually impaired (BVI) individuals, due to the loss of vision. Fortunately, the metaverse presents a promising platform where BVI individuals can experience independent driving just like sighted individuals. In order to assist such individuals in driving in the metaverse, we have devised a blind driving system that leverages multimodal feedback. We utilized stereo headphones and vibration motors to convey necessary information, including current and predicted vehicle states (i.e., speed, position, and direction) during driving, through sound, voice, and vibration feedback. Meanwhile, in order to improve the user-friendliness, we reduced the user’s information burden by data combination and compression. With the help of the multimodal feedback, BVI drivers could intuitively perceive the position and direction of the vehicle, thereby improving their driving experience. To evaluate the effectiveness of the system, we designed virtual scenarios to simulate a real driving environment, and we further devised two tasks: lane-keeping and lane-changing. We conducted user studies where sighted individuals wearing blindfolds were involved in the two tasks. The results suggest that our system demonstrates a beneficial effect in assisting BVI individuals in driving. Users could keep the vehicle in the center area of the lane for over ninety percent of driving time, and completed a lane-changing task with a high success rate. This study provides a potential solution for blind driving for BVI people by employing multimodal feedback.

关键词： Vibrations Headphones Metaverse Tactile sensors Motors Vehicles

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High-frequency terahertz waves disrupt Alzheimer’s β-amyloid fibril formation

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eLight 2023年第1期3卷 85-93页

作者： Wenyu Peng Zhi Zhu Jing Lou Kun Chen Yuanming Wu Chao Chang Department of Biochemistry and Molecular Biology Shaanxi Provincial Key Laboratory of Clinic GeneticsSchool of Basic MedicineAir Force Medical UniversityXi’an 710032China Innovation Laboratory of Terahertz Biophysics National Innovation Institute of Defense TechnologyBeijing 100071China Key Laboratory of Optical Technology and Instrument for Medicine Ministry of EducationCollege of Optical-Electrical and Computer EngineeringUniversity of Shanghai for Science and TechnologyShanghai 200093China Department of Anatomy Histology and Embryology and K.K.Leung Brain Research CentreSchool of Basic MedicineAir Force Medical UniversityXi’an 710032China School of Physics Peking UniversityBeijing 100871China

The accumulation and deposition of amyloid can cause a variety of neurodegenerative diseases,including Alzheimer’s and Parkinson’s *** degradation or clearance of this accumulation is currently the most widely accepted therapeutic strategy for intervention in these *** study on amyloid-β(Aβ)oligomers in vitro revealed that high-frequency terahertz(THz)waves at a specific frequency of 34.88 THz could serve as a physical,efficient,non-thermal denaturation technique to delay the fibrotic process by 80%,as monitored by a thioflavine T(ThT)binding assay and Fourier transform infrared(FTIR)***,THz waves of this frequency have been shown to have no side effects on normal cells,as confirmed by cell viability and mitochondrial membrane potential ***,molecular dynamic(MD)simulations revealed that the THz waves could resonate with Aβ fibrils,disrupting the dense conformation by breaking the β-sheet structure and promoting the formation of abundant coil and bend *** study uses the amyloid of Aβ as an example,and the results will further guide interventions for the accumulation of other amyloids,which may provide new ideas for the remission of related diseases.

关键词： amyloid Alzheimer Aβ

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A Transformer-based deep neural network model for SSVEP classification

arXiv

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arXiv 2022年

作者： Chen, Jianbo Zhang, Yangsong Pan, Yudong Xu, Peng Guan, Cuntai Laboratory for Brain Science and Medical Artificial Intelligence School of Computer Science and Technology Southwest University of Science and Technology Mianyang China MOE Key Laboratory for NeuroInformation Clinical Hospital of Chengdu Brain Science Institute Center for Information in BioMedicine School of Life Science and Technology University of Electronic Science and Technology of China Chengdu China School of Computer Science and Engineering Nanyang Technological University Singapore

Steady-state visual evoked potential (SSVEP) is one of the most commonly used control signal in the brain-computer interface (BCI) systems. However, the conventional spatial filtering methods for SSVEP classification highly depend on the subject-specific calibration data. The need for the methods that can alleviate the demand for the calibration data become urgent. In recent years, developing the methods that can work in inter-subject classification scenario has become a promising new direction. As the popular deep learning model nowadays, Transformer has excellent performance and has been used in EEG signal classification tasks. Therefore, in this study, we propose a deep learning model for SSVEP classification based on Transformer structure in inter-subject classification scenario, termed as SSVEPformer, which is the first application of the transformer to the classification of SSVEP. Inspired by previous studies, the model adopts the frequency spectrum of SSVEP data as input, and explores the spectral and spatial domain information for classification. Furthermore, to fully utilize the harmonic information, an extended SSVEPformer based on the filter bank technology (FB-SSVEPformer) is proposed to further improve the classification performance. Experiments were conducted using two open datasets © 2022, CC BY.

关键词： Classification (of information)

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