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Contactin-associated protein-like 2(CNTNAP2)mutations impair the essentialα-secretase cleavages,leading to autism-like phenotypes

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1625-1636页

作者： Qing Zhang mengen xing Zhengkai Bao Lu Xu Yang Bai Wanqi Chen Wenhao Pan Fang Cai Qunxian Wang Shipeng Guo Jing Zhang Zhe Wang Yili Wu Yun Zhang Jia-Da Li Weihong Song Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Zhejiang Key Laboratory of Alzheimer's DiseaseZhejiang Provincial Clinical Research Center for Mental DisordersSchool of Mental Health and Wenzhou Kangning HospitalThe Second Affiliated Hospital and Yuying Children's HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325035China Townsend Family Laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders Ministry of Education Key Laboratory of Child Development and DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Center for Medical Genetics Hunan Key Laboratory of Animal Models for Human DiseasesHunan Key Laboratory of Medical GeneticsHunan International Scientific and Technological Cooperation Base of Animal Models for Human DiseasesSchool of Life SciencesCentral South UniversityChangsha 410078 HunanChina The National Clinical Research Center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijing 100053Chin

Mutations in the Contactin-associated protein-like 2(CNTNAP2)gene are associated with autism spectrum disorder(ASD),and ectodomain shedding of the CNTNAP2 protein plays a role in its ***,key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown,and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain *** this report we showed that CNTNAP2 undergoes sequential cleavages by furin,ADAM10/17-dependent a-secretase and presenilindependent *** identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2 locate at its C-terminal residue I79 and L96,and the main a-cleavage product C79 by ADAM10 is required for the subsequent y-secretase cleavage to generate CNTNAP2 intracellular domain(CICD).ASD-associated CNTNAP2 mutations impair the a-cleavage to generate C79,and the inhibition leads to ASDIlike repetitive and social behavior abnormalties in the Cntnap2l1254T knock-in ***,exogenous expression of 79 improves autism-ike phenotypes in the Cntnap2^(11254T) knock-in and Cntnap2^(-/-)knockout *** data demonstrates that the a-secretase is essential for CNTNAP2 processing and its *** study indicates that inhibition of the cleavage by pathogenic mutations underlies ASD pathogenesis,and upregulation of its C-terminal fragments could have therapeutical potentials for ASD treatment.

关键词： NAP2 cleavage subsequent

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Do Systemic Infections Contribute to the Pathogenesis of Dementia?

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Neuroscience Bulletin 2022年第3期38卷 331-333页

作者： Keenan Sterling mengen xing Weihong Song Townsend Family Laboratories Department of PsychiatryThe University of British ColumbiaVancouverBCV6T 1Z3Canada Institute of Aging Key Laboratory of Alzheimer’s Disease of Zhejiang ProvinceSchool of Mental Health and Kangning HospitalThe Second Affiliated Hospital and Yuying Children’s HospitalWenzhou Medical UniversityWenzhou325035China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Wenzhou325000China

With over 50 million people currently living with dementia and numbers expected to double every twenty years,the world is currently facing a dementia ***,a poor understanding of the etiology of dementia has resulted in the inability to develop any successful disease-modifying *** the past year,several researchers have highlighted the role of systemic infections in increasing the risk of developing *** findings are particularly troubling given the ongoing coronavirus 19(COVID-19)pandemic,adding yet another cause for concern over the long-term impact of COVID-19 on the public’s mental health.

关键词： adding etiology finding

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CNTNAP2 intracellular domain(CICD)generated byγ-secretase cleavage improves autism-related behaviors

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Signal Transduction and Targeted Therapy 2023年第7期8卷 3415-3426页

作者： Jing Zhang Fang Cai Renbin Lu Xiaoliang xing Lu Xu Kunyang Wu Zishan Gong Qing Zhang Yun Zhang mengen xing Weihong Song Jia-Da Li Furong Laboratory Center for Medical GeneticsHunan Key Laboratory of Animal Models for Human DiseasesHunan Key Laboratory of Medical GeneticsHunan International Scientific and Technological Cooperation Base of Animal Models for Human DiseasesSchool of Life SciencesCentral South UniversityChangsha 410078 HunanChina Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)WenzhouZhejiang 325000China Townsend Family Laboratories Department of PsychiatryThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Institute of Aging Key Laboratory of Alzheimer’s Disease of Zhejiang ProvinceSchool of Mental Health and Kangning HospitalThe Second Affiliated Hospital and Yuying Children’s HospitalWenzhou Medical UniversityWenzhouZhejiang 325035China Advanced Innovation Center for Human Brain Protection The National Clinical Research Center for Geriatric DiseaseXuanwu HospitalCapital Medical UniversityBeijing 100053China

As the most prevalent neurodevelopmental disorders in children,autism spectrum disorders(ASD)are characterized by deficits in language development,social interaction,and repetitive behaviors or inflexible *** associated protein like 2(CNTNAP2),encoding a single transmembrane protein(CNTNAP2)with 1331 amino acid residues,is a widely validated ASD-susceptible gene.

关键词： behaviors cleavage residues

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Genotypes of Toxoplasma gondii isolated from pigs in Liaoning province, northeastern China

Genotypes of Toxoplasma gondii isolated from pigs in Liaonin...

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中国动物学会寄生虫学专业委员会第十届全国寄生虫学青年工作者学术研讨会

作者： Dawei Wang mengen xing Na Yang Laboratory of Zoonosis of Liaoning Province College of Animal Science & Veterinary Medicine Shenyang Agricultural University

Background: Genetic information for Toxoplasma gondii isolates from pigs in eastern, south, and southwestern regions of China has been reported previously. However, there are no data from pigs in the northeastern area of the country. To better understand the epidemiology of T. gondii, we determined the seroprevalence and genotypes of T. gondii from pigs slaughtered for human consumption in Liaoning province, northeastern China. Methods and results: Out of 2063 pigs examined, 233(11.26 %) were seropositive for T. gondii by the modified agglutination test(MAT), and viable parasites were isolated by bioassay in mice from 23(9.87 %) of the 233 seropositive pigs. Fifteen out of 23 isolates were genotyped using 10 PCR-restriction fragment length polymorphism(RFLP) genetic markers including SAG1, SAG2, SAG3, BTUB, GRA6, c22-8, c29-2, L358, PK1 and Apico. One isolate was identified as Toxo DB genotype #3(type II-variant), and one was genotype #1 or #3. The other 13 isolates were Toxo DB #9(type Chinese 1). Conclusions: To our knowledge, this is the first report of T. gondii isolation and genotyping from pigs in northeastern China. This study indicates that pigs are a potential source for transmission of T. gondii to humans, therefore poses a potential public health concern. The genotyping results revealed the presence of genotype Chinese 1 in northeastern China, enriching the scope of T. gondii genotypes distribution in eastern Asia.

关键词： Toxoplasma gondii Genotype Pig China

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Needs and challenges of optical atmospheric monitoring on the background of carbon neutrality in China

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Frontiers of Environmental Science & Engineering 2024年第6期18卷 49-62页

作者： Wenqing Liu Chengzhi xing Anhui Institute of Optics and Fine Mechanics Hefei Institutes of Physical ScienceChinese Academy of SciencesHefei 23001China

The achievement of the targets of coordinated control of PM2.5 and O3 and the carbon peaking and carbon neutrality depend on the development of pollution and greenhouse gas monitoring *** monitoring technology,based on its technical characteristics of high scalability,high sensitivity and wide-targets detection,has obvious advantages in pollution/greenhouse gases monitoring and has become an important direction in the development of environmental monitoring *** present,a system of environmental optical monitoring technology with differential optical absorption spectroscopy(DOAS),cavity ring-down spectroscopy(CRDS),light detection and ranging(LIDAR),laser heterodyne spectroscopy(LHS),tunable diode laser absorption spectroscopy(TDLAS),fourier transform infrared spectroscopy(FTIR)and fluorescence assay by gas expansion(FAGE)as the main body has been ***,with the promotion of“reduction of pollution and carbon emissions”strategy,there have been significant changes in the sources of pollution/greenhouse gases,emission components and emission concentrations,which have put forward new and higher requirements for the development of monitoring *** the future,we should pay more attention to the development of new optical monitoring techniques and the construction of stereoscopic monitoring system,the interdisciplinarity(among mathematics,physics,chemistry and biology,etc.),and the monitoring of greenhouse gases and research on atmospheric chemistry.

关键词： Pollution Greenhouse gas Optical atmospheric monitoring Needs and challenges

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Distributed Fault-Tolerant Control of Uncertain Multi-Agent Systems with Connectivity Maintenance

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Journal of Systems Science & Complexity 2024年第1期37卷 40-62页

作者： xing Xueyan HU Guoqiang Continental-NTU Corporate Lab Nanyang Technological UniversitySingapore 639798Singapore Continental-NTU Corporate Lab and the School of Electrical and Electronic Engineering Nanyang Technological UniversitySingapore 639798Singapore

In this paper,a distributed cooperative control protocol is presented to deal with actuator failures of multi-agent systems in the presence of connectivity *** the developed strategy,each agent can track the reference trajectory of the leader in the presence of actuator failures,disturbances and *** connectivity of the multi-agent system can always be ensured during the control *** achieve the aforementioned control objectives,a potential function is introduced to the distributed adaptive fault-tolerant control algorithm to preserve the initial connected network among the *** uncertainty of the multi-agent system,which is allowed to be described by discontinuous functions,is approximated and compensated using the fuzzy logic *** asymptotic stability of the closed-loop system is demonstrated through the use of Cellina’s approximate selection theorem of nonsmooth *** to the developed adaptive laws,the upper bound of the disturbance is allowed to be uncertain,which facilitates the implementation of the control ***,simulation results are provided to verify the effectiveness of the proposed control scheme.

关键词： Actuator failure connectivity maintenance coordination control uncertainties

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Reinforcement Learning-Based Dynamic Order Recommendation for On-Demand Food Delivery

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Tsinghua Science and Technology 2024年第2期29卷 356-367页

作者： xing Wang Ling Wang Chenxin Dong Hao Ren Ke xing Department of Automation Tsinghua UniversityBeijing 100080China School of Mechanical and Automotive Engineering Qingdao Hengxing University of Science and TechnologyQingdao 266100China Meituan Beijing 100015China

On-demand food delivery(OFD)is gaining more and more popularity in modern *** a kernel order assignment manner in OFD scenario,order recommendation directly influences the delivery efficiency of the platform and the delivery experience of *** paper addresses the dynamism of the order recommendation problem and proposes a reinforcement learning solution *** actor-critic network based on long short term memory(LSTM)unit is designed to deal with the order-grabbing conflict between different ***,three rider sequencing rules are accordingly proposed to match different time steps of the LSTM unit with different *** test the performance of the proposed method,extensive experiments are conducted based on real data from Meituan delivery *** results demonstrate that the proposed reinforcement learning based order recommendation method can significantly increase the number of grabbed orders and reduce the number of order-grabbing conflicts,resulting in better delivery efficiency and experience for the platform and riders.

关键词： on-demand food delivery order recommendation reinforcement learning actor-critic network long short term memory

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Dynamic plugging regulating strategy of pipeline robot based on reinforcement learning

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Petroleum Science 2024年第1期21卷 597-608页

作者： xing-Yuan Miao Hong Zhao College of Mechanical and Transportation Engineering China University of PetroleumBeijing102249China

Pipeline isolation plugging robot (PIPR) is an important tool in pipeline maintenance operation. During the plugging process, the violent vibration will occur by the flow field, which can cause serious damage to the pipeline and PIPR. In this paper, we propose a dynamic regulating strategy to reduce the plugging-induced vibration by regulating the spoiler angle and plugging velocity. Firstly, the dynamic plugging simulation and experiment are performed to study the flow field changes during dynamic plugging. And the pressure difference is proposed to evaluate the degree of flow field vibration. Secondly, the mathematical models of pressure difference with plugging states and spoiler angles are established based on the extreme learning machine (ELM) optimized by improved sparrow search algorithm (ISSA). Finally, a modified Q-learning algorithm based on simulated annealing is applied to determine the optimal strategy for the spoiler angle and plugging velocity in real time. The results show that the proposed method can reduce the plugging-induced vibration by 19.9% and 32.7% on average, compared with single-regulating methods. This study can effectively ensure the stability of the plugging process.

关键词： Pipeline isolation plugging robot Plugging-induced vibration Dynamic regulating strategy Extreme learning machine Improved sparrow search algorithm Modified Q-learning algorithm

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Research on the influences of motion characteristics of jetting projectile charge under water

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Defence Technology（防务技术） 2024年第3期33卷 411-425页

作者： xing Chen Yong-gang Lu Institute of Systems Engineering China Academy of Engineering PhysicsMianyang 621900SichuanChina

Shaped charge warhead is important for enhancing the damage performance of underwater *** paper used finite element analysis software and based on JPC water penetration experiments to examine the influence of liner parameters(wall thickness,material),charge aspect ratio,and stand-off distance on the movement characteristics of JPC in *** findings reveal that the head diameter of the JPC increases and experiences significant erosion after entering the water,the effective length of the JPC in water undergoes two distinct phases:a growth phase and a decrease phase,with the velocity of the JPC decaying *** the liner thickness,stand-off distance and the charge aspect ratio can improve the erosion resistance and the velocity retention capacity of the *** optimal ranges for liner thickness and stand-off distance are 0.0363D_(k) to 0.0545D_(k)(D_(k) is the charge diameter),the stand-off distance should be within 1.0D_(k).After the charge aspect ratio higher than 1.25,the charge structure exerts minimal influence the movement characteristics of the JPC in *** density plays a crucial role in the velocity decay pattern of the JPC during *** with higher densities exhibit superior velocity retention capabilities in water,with the velocity decay pattern converging if the densities are ***,copper,tantalum and tungsten liners are deemed appropriate for underwater shaped charge ***,the results will provide an important reference for the design of underwater shaped charge warhead.

关键词： JPC Movement characteristics Underwater penetration Numerical simulation

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Adverse Effects of Opioid Analgesics in Osteoarthritis Treatment:A Global Meta-Analysis,2000-2022

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China CDC weekly 2024年第25期6卷 589-596,I0001-I0012页

作者： Heng Jiang xing xing He Zhu Tuo Dong School of Public Health Harbin Medical UniversityHarbin CityHeilongjiang ProvinceChina School of Public Health Peking UniversityBeijingChina

Osteoarthritis(OA)treatment commonly depends on nonsteroidal anti-inflammatory drugs and opioid ***,the clinical use of opioids is controversial due to their adverse effects and addiction *** study,drawing on 24 randomized controlled trials(RCTs)with a total of 9,586 patients,thoroughly explored the various side effects associated with opioid use in OA *** results provide additional insight into the non-addictive risks of opioids and may assist clinicians in their judicious use,potentially fostering the advancement of safer treatment *** reducing the risks of misuse and addiction,public health and safety can be enhanced.

关键词： potential thoroughly insight

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