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Sorl1 knockout inhibits expression of brain-derived neurotrophic factor:involvement in the development of late-onset Alzheimer's disease

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Neural Regeneration Research 2024年第7期19卷 1602-1607页

作者： Mingri Zhao xun chen Jiangfeng Liu Yanjin Feng chen Wang Ting Xu Wanxi Liu Xionghao Liu Mujun Liu Deren Hou Department of Neurology The Third Xiangya Hospital of Central South UniversityChangshaHunan ProvinceChina Center for Medical Genetics&Hunan Key Laboratory of Medical Genetics School of Life SciencesCentral South UniversityChangshaHunan ProvinceChina Department of Cell Biology School of Life SciencesCentral South UniversityChangshaHunan ProvinceChina

Sortilin-related receptor 1(SORL1)is a critical gene associated with late-onset Alzheimer’s disease.SORL1 contributes to the development and progression of this neurodegenerative condition by affecting the transport and metabolism of intracellularβ-amyloid precursor protein.To better understand the underlying mechanisms of SORL1 in the pathogenesis of late-onset Alzheimer s disease,in this study,we established a mouse model of SorI1 gene knockout using cluste red regularly inters paced short palindro mic repeats-associated protein 9 technology.We found that Sorl1-knocko ut mice displayed deficits in learning and memory.Furthermore,the expression of brain-derived neurotrophic factor was significantly downregulated in the hippocampus and co rtex,and amyloidβ-protein deposits were observed in the brains of 5orl1-knockout mice.In vitro,hippocampal neuronal cell synapses from homozygous Sorl1-knockout mice were impaired.The expression of synaptic proteins,including Drebrin and NR2B,was significantly reduced,and also their colocalization.Additionally,by knocking out the Sorl1 gene in N2a cells,we found that expression of the N-methyl-D-aspartate receptor,NR2B,and cyclic adenosine monophosphate-response element binding protein was also inhibited.These findings suggest that SORL1 participates in the pathogenesis of late-onset Alzheimer s disease by regulating the N-methyl-D-aspartate receptor NR2B/cyclic adenosine monophosphate-response element binding protein signaling axis.

关键词： brain-derived neurotrophic factor late-onset Alzheimer’s disease N-methyl-D-aspartate receptor sortilin-related receptor 1 synapse

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Highly Stable sp^(2) Carbon-Conjugated Porous Organic Cages

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CCS Chemistry 2024年第1期6卷 149-156页

作者： Fenglei Qiu xun chen Wenjing Wang Kongzhao Su Daqiang Yuan State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhouFujian 350002 College of Chemistry Fuzhou UniversityFuzhouFujian 350116 University of the Chinese Academy of Sciences Beijing 100049

The high-yield synthesis of ultrastable porous organic cages(POCs)by facile methods is highly desirable but challenging.Inspired by highly stable sp^(2) carbon-conjugated(C=C)covalent organic frameworks,we used rational design and synthesized the first family of sp^(2) carbon-linked POCs(sp^(2)c-POCs)with triangular prism shapes by a one-step Knoevenagel reaction that is a high yield[2+3]condensation reaction.The stability of sp^(2)c-POC was demonstrated under strenuous conditions involving for example concentrated HCl or saturated NaOH solution.sp^(2)c-POC was used as a robust adsorbent for efficient separation of CO_(2)/CH_(4) or CO_(2)/N_(2) mixtures.In view of their facile synthesis and unique properties,we expect widespread use of these sp^(2) C=C linkages in the development of POC materials.

关键词： porous organic cages Knoevenagel condensation sp^(2)C=C linkage exceptional chemical stability gas adsorption and separation properties

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Cluster analysis reveals a homogeneous subgroup of PCOS women with metabolic disturbance associated with adverse reproductive outcomes

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Chinese Medical Journal 2024年第5期137卷 604-612页

作者： Hanxiao chen Rujun Zeng xun Zeng Lang Qin The Reproductive Medical Center Department of Obstetrics and GynecologyWest China Second University HospitalSichuan UniversityChengduSichuan 610041China Key Laboratory of Birth Defects and Related of Women and Children of Ministry of Education West China Second University HospitalSichuan UniversityChengduSichuan 610041China

Background:Polycystic ovarian syndrome(PCOS)is a heterogeneous and complex reproductive endocrinological disease that could lead to infertility.There were many attempts to classify PCOS but it remains unclear whether there is a specific subgroup of PCOS that is associated with the best or worst reproductive outcomes of assisted reproductive techniques(ART).Methods:Infertile PCOS patients who underwent their first cycle of in vitro fertilization(IVF)in West China Second University Hospital,Sichuan University from January 2019 to December 2021 were included.Basic clinical and laboratory information of each individual were extracted.Unsupervised cluster analysis was performed.Controlled ovarian stimulation parameters and reproductive outcomes were collected and compared between the different clusters of PCOS.Results:Our analysis clustered women with PCOS into"reproductive","metabolic",and"balanced"clusters based on nine traits.Reproductive group was characterized by high levels of testosterone(T),sex hormone-binding globulin(SHBG),follicular stimulation hormone(FSH),luteinizing hormone(LH),and anti-Müllerian hormone(AMH).Metabolic group was characterized by high levels of body mass index(BMI),fasting insulin,and fasting glucose.Balanced group was characterized by low levels of the aforementioned reproductive and metabolic parameters,except for SHBG.Compared with PCOS patients in reproductive and balanced clusters,those in metabolic cluster had lower rates of good quality day 3 embryo and blastocyst formation.Moreover,PCOS patients in the reproductive cluster had greater fresh embryo transfer(ET)cancelation rate and clinical pregnancy rate after fresh ET than metabolic cluster(odds ratio[OR]=3.37,95%confidence interval[CI]:1.77-6.44,and OR=6.19,95%CI:1.58-24.24,respectively).And compared with PCOS of metabolic cluster,PCOS of balanced cluster also had higher chance for fresh ET cancelation(OR=2.83,95%CI:1.26-6.35).Conclusion:Our study suggested that PCOS patients in metabolic cluster may be associated with adverse re

关键词： Polycystic ovarian syndrome Assisted reproductive techniques Clustering analysis Metabolic disturbance Clinical pregnancy

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G protein-coupled receptors(GPCRs):advances in structures,mechanisms,and drug discovery

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1938-1980页

作者： Mingyang Zhang Ting chen xun Lu Xiaobing Lan Ziqiang chen Shaoyong Lu Key Laboratory of Protection Development and Utilization of Medicinal Resources in Liupanshan AreaMinistry of EducationPeptide&Protein Drug Research CenterSchool of PharmacyNingxia Medical UniversityYinchuan 750004China Medicinal Chemistry and Bioinformatics Center Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of Cardiology Changzheng HospitalAffiliated to Naval Medical UniversityShanghai 200003China Department of Orthopedics Changhai HospitalAffiliated to Naval Medical UniversityShanghai 200433China

G protein-coupled receptors(GPCRs),the largest family of human membrane proteins and an important class of drug targets,play a role in maintaining numerous physiological processes.Agonist or antagonist,orthosteric effects or allosteric effects,and biased signaling or balanced signaling,characterize the complexity of GPCR dynamic features.In this study,we first review the structural advancements,activation mechanisms,and functional diversity of GPCRs.We then focus on GPCR drug discovery by revealing the detailed drug-target interactions and the underlying mechanisms of orthosteric drugs approved by the US Food and Drug Administration in the past five years.Particularly,an up-to-date analysis is performed on available GPCR structures complexed with synthetic small-molecule allosteric modulators to elucidate key receptor-ligand interactions and allosteric mechanisms.Finally,we highlight how the widespread GPCR-druggable allosteric sites can guide structure-or mechanism-based drug design and propose prospects of designing bitopic ligands for the future therapeutic potential of targeting this receptor family.

关键词： steric designing mechanisms

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Distributed Economic MPC for Synergetic Regulation of the Voltage of an Island DC Micro-Grid

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IEEE/CAA Journal of Automatica Sinica 2024年第3期11卷 734-745页

作者： Yi Zheng Yanye Wang xun Meng Shaoyuan Li Hao chen IEEE the Department of Automation Shanghai Jiao Tong UniversityShanghai 200240 the Key Laboratory of System Control and Information Processing Ministry of Education of ChinaShanghai 200240China Haixi Institutes Chinese Academy of SciencesJinjiang 362216China

In this paper,distributed model predictive control(DMPC) for island DC micro-grids(MG) with wind/photovoltaic(PV)/battery power is proposed,which coordinates all distributed generations(DG) to stabilize the bus voltage together with the insurance of having computational efficiency under a real-time requirement.Based on the feedback of the bus voltage,the deviation of the current is dispatched to each DG according to cost over the prediction horizon.Moreover,to avoid the excessive fluctuation of the battery power,both the discharge-charge switching times and costs are considered in the model predictive control(MPC) optimization problems.A Lyapunov constraint with a time-varying steady-state is designed in each local MPC to guarantee the stabilization of the entire system.The voltage stabilization of the MG is achieved by this strategy with the cooperation of DGs.The numeric results of applying the proposed method to a MG of the Shanghai Power Supply Company shows the effectiveness of the distributed economic MPC.

关键词： Distributed model predictive control(DMPC) Lyapunovbased model predictive control micro-grid(MG) voltage control

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A Structural Measurement of the Valuation Effect of China's External Assets:Method and Application

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China & World Economy 2024年第2期32卷 97-124页

作者： Guowei Cai Xiaowei chen xun Wang Lingnan College Sun Yat-sen UniversityChina China Center for Economic Research National School of DevelopmentPeking UniversityChina

Existing research on the measurement of the valuation effect mainly follows the residual method proposed by Lane and Milesi-Ferretti(2001).This cannot be used to perform structural decomposition.We propose an aggregation approach rather than the residual method to measure structurally the investment flow and valuation effect of China's external assets.The results indicate that the valuation effect of China's external assets has been highly volatile and it was negative during the pandemic period.The structural decomposition shows that portfolio investment and direct investment made the main contributions to the valuation effect.The impact of exchange rates on the valuation effect has generally been higher than that of asset price in terms of direct investment and total external assets but the opposite has been true for portfolio investment.China's outward investments are currently more inclined to Asian countries and a few European countries but inflows to China still mainly come from developed countries.

关键词： external asset investment direction structural measurement valuation effect

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Detection of Oscillations in Process Control Loops From Visual Image Space Using Deep Convolutional Networks

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IEEE/CAA Journal of Automatica Sinica 2024年第4期11卷 982-995页

作者： Tao Wang Qiming chen xun Lang Lei Xie Peng Li Hongye Su the Department of Electronic Engineering the School of InformationYunnan UniversityKunming 650091China DAMO Academy Alibaba GroupHangzhou 311100China the State Key Laboratory of Industrial Control Technology Institute of Cyber-Systems and ControlZhejiang UniversityHangzhou 310027China

Oscillation detection has been a hot research topic in industries due to the high incidence of oscillation loops and their negative impact on plant profitability.Although numerous automatic detection techniques have been proposed,most of them can only address part of the practical difficulties.An oscillation is heuristically defined as a visually apparent periodic variation.However,manual visual inspection is labor-intensive and prone to missed detection.Convolutional neural networks(CNNs),inspired by animal visual systems,have been raised with powerful feature extraction capabilities.In this work,an exploration of the typical CNN models for visual oscillation detection is performed.Specifically,we tested MobileNet-V1,ShuffleNet-V2,Efficient Net-B0,and GhostNet models,and found that such a visual framework is well-suited for oscillation detection.The feasibility and validity of this framework are verified utilizing extensive numerical and industrial cases.Compared with state-of-theart oscillation detectors,the suggested framework is more straightforward and more robust to noise and mean-nonstationarity.In addition,this framework generalizes well and is capable of handling features that are not present in the training data,such as multiple oscillations and outliers.

关键词： Convolutional neural networks(CNNs) deep learning image processing oscillation detection process industries

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Noise-Tolerant ZNN-Based Data-Driven Iterative Learning Control for Discrete Nonaffine Nonlinear MIMO Repetitive Systems

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IEEE/CAA Journal of Automatica Sinica 2024年第2期11卷 344-361页

作者： Yunfeng Hu Chong Zhang Bo Wang Jing Zhao xun Gong Jinwu Gao Hong chen State Key Laboratory of Automotive Simulation and Control Jilin UniversityJilin UniversityChangchun 130025China College of Communication Engineering Jilin UniversityJilin UniversityChangchun 130025China Department of Electromechanical Engineering University of MacaoMacao 999078China School of Artificial Intelligence Jilin UniversityChangchun 130012China IEEE College of Electronics and Information Engineering Tongji UniversityShanghai 200092China

Aiming at the tracking problem of a class of discrete nonaffine nonlinear multi-input multi-output(MIMO) repetitive systems subjected to separable and nonseparable disturbances, a novel data-driven iterative learning control(ILC) scheme based on the zeroing neural networks(ZNNs) is proposed. First, the equivalent dynamic linearization data model is obtained by means of dynamic linearization technology, which exists theoretically in the iteration domain. Then, the iterative extended state observer(IESO) is developed to estimate the disturbance and the coupling between systems, and the decoupled dynamic linearization model is obtained for the purpose of controller synthesis. To solve the zero-seeking tracking problem with inherent tolerance of noise,an ILC based on noise-tolerant modified ZNN is proposed. The strict assumptions imposed on the initialization conditions of each iteration in the existing ILC methods can be absolutely removed with our method. In addition, theoretical analysis indicates that the modified ZNN can converge to the exact solution of the zero-seeking tracking problem. Finally, a generalized example and an application-oriented example are presented to verify the effectiveness and superiority of the proposed process.

关键词： Adaptive control control system synthesis data-driven iterative learning control neurocontroller nonlinear discrete time systems

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Real-time identification of multiple nanoclusters with a protein nanopore in single-cluster level

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Nano Research 2024年第1期17卷 262-269页

作者： Ling Zhang Peilei He Huang chen Qingda Liu Libo Li xun Wang Jinghong Li Department of Chemistry Center for BioAnalytical ChemistryKey Laboratory of Bioorganic Phosphorus Chemistry&Chemical BiologyTsinghua UniversityBeijing 100084China School of Chemistry and Chemical Engineering Guangdong Prov Key Lab Green Chem Prod TechnolSouth China University of TechnologyGuangzhou 510640China New Cornerstone Science Laboratory Shenzhen 518054China Beijing Institute of Life Science and Technology Beijing 102206China Center for BioAnalytical Chemistry Hefei National Laboratory of Physical Science at MicroscaleUniversity of Science and Technology of ChinaHefei 230026China

It is important and challenging to analyze nanocluster structure with atomic precision.Herein,α-hemolysin nanopore was used to identify nanoclusters at the single molecule level by providing two-dimensional(2D)dwell time–current blockage spectra and translocation event frequency which sensitively depended on their structures.Nanoclusters such as Anderson,Keggin,Dawson,and a few lacunary Dawson polyoxometalates with very similar structures,even with only a two-atom difference,could be discriminated.This nanopore device could simultaneously measure multiple nanoclusters in a mixture qualitatively and quantitatively.Furthermore,molecular dynamics(MD)simulations provided microscopic understandings of the nanocluster translocation dynamics and yielded 2D dwell time–current blockage spectra in close agreement with experiments.The nanopore platform provides a novel powerful tool for nanocluster characterization.

关键词： nanopore single-molecule nanocluster polyoxometalates real-time detection

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Challenging anticoagulation therapy for multiple primary malignant tumors combined with thrombosis:A case report and review of literature

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World Journal of Clinical Cases 2024年第9期12卷 1704-1711页

作者： Jia-Xin chen Ling-Ling Xu Jing-Ping cheng xun-Hua Xu Department of Gerontology China Resources and Wisco General HospitalWuhan University of Science and TechnologyWuhan 430080Hubei ProvinceChina Medical College Wuhan University of Science and TechnologyWuhan 430065Hubei ProvinceChina Department of Gerontology China Resources and Wisco General HospitalWuhan 430080Hubei ProvinceChina Department of Radiology China Resources and Wisco General HospitalWuhan 430080Hubei ProvinceChina

BACKGROUND Venous thromboembolism significantly contributes to patient deterioration and mortality.Management of its etiology and anticoagulation treatment is intricate,necessitating a comprehensive consideration of various factors,including the bleeding risk,dosage,specific anticoagulant medications,and duration of therapy.Herein,a case of lower extremity thrombosis with multiple primary malignant tumors and high risk of bleeding was reviewed to summarize the shortcomings of treatment and prudent anticoagulation experience.CASE SUMMARY An 83-year-old female patient was admitted to the hospital due to a 2-wk history of left lower extremity edema that had worsened over 2 d.Considering her medical history and relevant post-admission investigations,it was determined that the development of left lower extremity venous thrombosis and pulmonary embolism in this case could be attributed to a combination of factors,including multiple primary malignant tumors,iliac venous compression syndrome,previous novel coronavirus infection,and inadequate treatment for prior thrombotic events.However,the selection of appropriate anticoagulant medications,determination of optimal drug dosages,and establishment of an appropriate duration of anticoagulation therapy were important because of concurrent thrombocytopenia,decreased quantitative fibrinogen levels,and renal insufficiency.CONCLUSION Anticoagulant prophylaxis should be promptly initiated in cases of high-risk thrombosis.Individualized anticoagulation therapy is required for complex thrombosis.

关键词： Venous thromboembolism Cancer-associated thrombosis Anticoagulation therapy iliac vein compression syndrome COVID-19 Thrombocytopenia Case report

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