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The relationship between amyloid-beta and brain capillary endothelial cells in Alzheimer's disease

Neural Regeneration Research 2022年第11期17卷 2355-2363页

作者： Yan-Li zhang Juan Wang zhi-na zhang Qiang Su Jun-Hong Guo Department of Neurology First Hospital of Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Department of Neurology Sixth Hospital of Shanxi Medical University(General Hospital of Tisco)TaiyuanShanxi ProvinceChina School of Public Health Shanxi Medical UniversityTaiyuanShanxi ProvinceChina

Neurovascular dysfunction,as an integral part of Alzheimer's disease,may have an important influence on the onset and progression of chronic neurodegenerative processes.The bloodbrain barrier(BBB)pathway is one of the main pathways that mediates the clearance of amyloidbeta(Aβ)in the brain parenchyma.A large number of studies have shown that receptors and ATPbinding cassette transporte rs expressed on endothelial cells play an important role in Aβtransport across the BBB,but the specific mechanism is not clear.In this review,we summarize the possible mechanisms of Aβproduction and clearance,and in particular the relationship between Aβand brain capillary endothelial cells.Aβis produced by abnormal cleavage of the amyloid precursor protein via amyloidogenic processing under pathological conditions.Dys regulation of Aβclearance is considered to be the main reason for the massive accumulation of Aβin the brain parenchyma.Several pathways mediating Aβclearance from the brain into the periphery have been identified,including the BBB pathway,the blood-cerebros pinal fluid barrier and arachnoid granule pathway,and the lymphoidrelated pathway.Brain ca pilla ry endothelial cells are the key components of Aβclearance mediated by BBB.Receptors(such as LRP1,RAGE,and FcRn)and ATP-binding cassette transporters(such as P-gp,ABCA1,and ABCC1)expressed on endothelial cells play a critical role in Aβtranscytosis across the BBB.The toxic effects of Aβcan induce dysregulation of receptor and transpo rter expression on endothelial cells.Excessive Aβexerts potent detrimental cerebrovascular effects by promoting oxidative stress,inducing chronic inflammation,and impairing endothelial structure and functions.All of these are main causes for the reduction in Aβclearance across the BBB and the accumulation of Aβin the brain parenchyma.Therefo re,studies on the intera ctions between Aβand brain capillary endothelial cells,including their receptors and transporters,studies on inhibition of the toxic effects of Aβon endothelial cells,and stud

关键词： Alzheimer's disease amyloid beta Aβclearance blood-brain barrier cerebral amyloid angiopathy dementia endothelial cells oxidative stress review therapeutics transcytosis

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Application of GNSS-PPP on Dynamic Deformation Monitoring of Offshore Platforms

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China Ocean Engineering 2024年第2期38卷 352-361页

作者： YU Li-na XIONG Kuan GAO Xi-feng LI zhi FAN Li-long zhang Kai Institute of Ocean Energy and Intelligent Construction Tianjin University of TechnologyTianjin 300384China China Railway Construction Bridge Engineering Bureau Group Co.LTD Tianjin 300300China School of Civil Engineering Tianjin UniversityTianjin 300072China Department of Land Surveying and Geo-Informatics The Hong Kong Polytechnic UniversityHong KongChina State Key Laboratory of Precision Blasting Jianghan UniversityWuhan 430056China

The real-time dynamic deformation monitoring of offshore platforms under environmental excitation is crucial to their safe operation.Although Global navigation Satellite System-Precise Point Positioning(GNSS-PPP)has been considered for this purpose,its monitoring accuracy is relatively low.Moreover,the influence of background noise on the dynamic monitoring accuracy of GNSS-PPP remains unclear.Hence,it is imperative to further validate the feasibility of GNSS-PPP for deformation monitoring of offshore platforms.To address these concerns,vibration table tests with different amplitudes and frequencies are conducted.The results demonstrate that GNSS-PPP can effectively monitor horizontal vibration displacement as low as±30 mm,which is consistent with GNSS-RTK.Furthermore,the spectral characteristic of background noise in GNSS-PPP is similar to that of GNSS-RTK(Real Time Kinematic).Building on this observation,an improved Complete Ensemble Empirical Mode Decomposition with Adaptive Noise(CEEMDAN)has been proposed to de-noise the data and enhance the dynamic monitoring accuracy of GNSS-PPP.Field monitoring application research is also undertaken,successfully extracting and analyzing the dynamic deformation of an offshore platform structure under environmental excitation using GNSS-PPP monitoring in conjunction with improved CEEMDAN de-noising.By comparing the de-noised dynamic deformation trajectories of the offshore platform during different periods,it is observed that the platform exhibits reversible alternating vibration responses under environmental excitation,with more pronounced displacement deformation in the direction of load action.The research results confirm the feasibility and potential of GNSS-PPP for dynamic deformation monitoring of offshore platforms.

关键词： GNSS-PPP offshore platform dynamic deformation monitoring improved CEEMDAN de-noising

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Gene therapy for monogenic disorders: challenges, strategies, and perspectives

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Journal of Genetics and Genomics 2024年第2期51卷 133-143页

作者： Yi zhang zhi-Ying Wu Department of Medical Genetics and Center for Rare Diseases Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Department of Neurology Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Key Laboratory of Medical Neurobiology of Zhejiang Province HangzhouZhejiang 310009China

Monogenic disorders refer to a group of human diseases caused by mutations in single genes. While disease-modifying therapies have offered some relief from symptoms and delayed progression for some monogenic diseases, most of these diseases still lack effective treatments. In recent decades, gene therapy has emerged as a promising therapeutic strategy for genetic disorders. Researchers have developed various gene manipulation tools and gene delivery systems to treat monogenic diseases. Despite this progress, concerns about inefficient delivery, persistent expression, immunogenicity, toxicity, capacity limitation, genomic integration, and limited tissue specificity still need to be addressed. This review gives an overview of commonly used gene therapy and delivery tools, along with the challenges they face and potential strategies to counter them.

关键词： Gene therapy Monogenic diseases Geneediting Genedelivery Challenges

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Public transport inclusion and active aging: A systematic review on elderly mobility

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Journal of Traffic and Transportation Engineering(English Edition) 2024年第2期11卷 312-347页

作者： na zhang Qi Yang School of Humanities Chang'an UniversityXi'an 710064China School of Transportation Engineering Chang'an UniversityXi'an 710064China School of Economics and Management Chang'an UniversityXi'an 710064China

Global aging has brought attention to addressing the elderly mobility dilemma,and a commitment to address inclusive transport in aging.Transport inclusion for older adults aims at establishing an age-friendly transport system.As a direct policy goal and promoting active aging as an indirect social goal,to help older populations gain access to transport and social opportunities.Based on the analysis of scientific knowledge mapping over the past 30 years,this study visualizes the hotspots and trends in elderly mobility research.Through a qualitative analysis of 138 papers,this paper reviews the theoretical foundations for transport inclusion and three themes of elderly mobility research,proposes a framework for public transport(PT)inclusion research as well as future research directions.The study suggests that transport inclusion can help enhance elderly health,social participation,and subjective well-being.It can improve their travel opportunities for active aging in four ways:opportunity accessibility,physical accessibility,age-friendly informationalization,and cost affordability.Future research should pay attention to examining the mechanism of perceived transport inclusion on active aging,expanding the multilevel research space of the capability approach(CA),and exploring the subjectiveobjective integrated research model for PT inclusion.This research contributes to the overall knowledge of the theoretical and empirical researches on PT inclusion for the elderly and promotes the integrated application of interdisciplinary knowledge in the field.

关键词： Transportation engineering Elderly mobility Transport-related social exclusion Transport inclusion Active aging

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Epidemiology and prognostic nomogram for locally advanced gastric signet ring cell carcinoma:A population-based study

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2610-2630页

作者： Ze-Hao Yu Lei-Ming zhang zhi-Qi Dai Meng-na zhang Si-Ming Zheng Health Science Center The First Affiliated Hospital of Ningbo UniversityNingbo 315000Zhejiang ProvinceChina Health Science Center Ningbo UniversityNingbo 315211Zhejiang ProvinceChina College of Medicine The First Affiliated Hospital of Zhejiang UniversityHangzhou 310058Zhejiang ProvinceChina

BACKGROUND Gastric signet ring cell carcinoma(GSRC)represents a specific subtype of gastric cancer renowned for its contentious epidemiological features,treatment principles,and prognostic factors.AIM To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC(LAGSRC)after surgery.METHODS The annual rates of GSRC incidence and mortality,covering the years 1975 to 2019,were extracted from the Surveillance,Epidemiology,and End Results(SEER)database to explore the temporal trends in both disease incidence and mortality rates using Joinpoint software.The clinical data of 3793 postoperative LAGSRC patients were collected from the SEER database for the analysis of survival rates.The Cox regression model was used to explore the independent prognostic factors for overall survival(OS).The risk factors extracted were used to establish a prognostic nomogram.RESULTS The overall incidence of GSRC increased dramatically between 1975 and 1998,followed by a significant downward trend in incidence after 1998.In recent years,there has been a similarly optimistic trend in GSRC mortality rates.The trend in GSRC showed discrepancies based on age and sex.Receiver operating characteristic curves,calibration curves,and decision curve analysis for 1-year,3-year,and 5-year OS demonstrated the high discriminative ability and clinical utility of this nomogram.The area under the curve indicated that the performance of the new model outperformed that of the pathological staging system.CONCLUSION The model we established can aid clinicians in the early prognostication of LAGSRC patients,resulting in improved clinical outcomes by modifying management strategies and patient health care.

关键词： Signet ring cell carcinoma Locally advanced gastric cancer Adjuvant chemotherapy Nomogram Epidemiology Overall survival

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Deciphering and integrating invariants for neural operator learning with various physical mechanisms

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national Science Review 2024年第4期11卷 111-122页

作者： Rui zhang Qi Meng zhi-Ming Ma Academy of Mathematics and Systems Science Chinese Academy of Sciences(CAS) Microsoft Research

Neural operators have been explored as surrogate models for simulating physical systems to overcome the limitations of traditional partial differential equation(PDE) solvers. However, most existing operator learning methods assume that the data originate from a single physical mechanism, limiting their applicability and performance in more realistic scenarios. To this end, we propose the physical invariant attention neural operator(PIANO) to decipher and integrate the physical invariants for operator learning from the PDE series with various physical mechanisms. PIANO employs self-supervised learning to extract physical knowledge and attention mechanisms to integrate them into dynamic convolutional layers.Compared to existing techniques, PIANO can reduce the relative error by 13.6%–82.2% on PDE forecasting tasks across varying coefficients, forces or boundary conditions. Additionally, varied downstream tasks reveal that the PI embeddings deciphered by PIANO align well with the underlying invariants in the PDE systems, verifying the physical significance of PIANO.

关键词： neural operator PDE solver contrastive learning physical invariants

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Asynchronous gain-scheduled control of deepwater drilling riser system with hybrid event-triggered sampling and unreliable communication

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Frontiers of Information Technology & Electronic Engineering 2024年第2期25卷 272-285页

作者： na PANG Dawei zhang Shuqian ZHU School of Mathematics Shandong UniversityJinan250100China

This paper investigates the recoil control of the deepwater drilling riser system with nonlinear tension force and energy-bounded friction force under the circumstances of limited network resources and unreliable communication.Different from the existing linearization modeling method,a triangle-based polytope modeling method is applied to the nonlinear riser system.Based on the polytope model,to improve resource utilization and accommodate random data loss and communication delay,an asynchronous gain-scheduled control strategy under a hybrid event-triggered scheme is proposed.An asynchronous linear parameter-varying system that blends input delay and impulsive update equation is presented to model the nonlinear networked recoil control system,where the asynchronous deviation bounds of scheduling parameters are calculated.Resorting to the Lyapunov-Krasovskii functional method,some solvable conditions of disturbance attenuation analysis and recoil control design are derived such that the resulting networked system is exponentially mean-square stable with prescribed H∞performance.The obtained numerical results verified that the proposed nonlinear networked control method can achieve a better recoil response of the riser system with less transmission data compared with the linear control method.

关键词： Riser system Recoil control Asynchronous gain-scheduled control Data loss Event-triggered scheme

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Partial Linear Model Averaging Prediction for Longitudinal Data

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Journal of Systems Science & Complexity 2024年第2期37卷 863-885页

作者： LI na FEI Yu zhang Xinyu Faculty of Science Kunming University of Science and TechnologyKunming 650500China School of Statistics and Mathematics Yunnan University of Finance and EconomicsKunming 650221China Academy of Mathematics and Systems Science Chinese Academy of SciencesBeijing 100190China

Prediction plays an important role in data analysis.Model averaging method generally provides better prediction than using any of its components.Even though model averaging has been extensively investigated under independent errors,few authors have considered model averaging for semiparametric models with correlated errors.In this paper,the authors offer an optimal model averaging method to improve the prediction in partially linear model for longitudinal data.The model averaging weights are obtained by minimizing criterion,which is an unbiased estimator of the expected in-sample squared error loss plus a constant.Asymptotic properties,including asymptotic optimality and consistency of averaging weights,are established under two scenarios:(i)All candidate models are misspecified;(ii)Correct models are available in the candidate set.Simulation studies and an empirical example show that the promise of the proposed procedure over other competitive methods.

关键词： Asymptotic optimality longitudinal data model averaging estimator partially linear model prediction

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P-symmetric Subharmonic Solutions for Nonlinear Hamiltonian Systems

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Acta Mathematica Sinica,English Series 2024年第6期40卷 1388-1408页

作者： Duan zhi zhang zhi Hao ZHAO School of Mathematical Sciences Nankai UniversityTianjin 300071P.R.China

In this paper,we prove that for each positive k≡1 mod m there exists a P-symmetric kmτ-periodic solution xk for asymptotically linear mτ-periodic Hamiltonian systems,which are nonautonomous and endowed with a P-symmetry.If the P-symmetric Hamiltonian function is semi-positive,one can prove,under a new iteration inequality of the Maslov-type P-index,that xk_(1) and xk_(2) are geometrically distinct for k_(1)/k_(2)≥(2n+1)m+1;and xk_(1),xk_(2) are geometrically distinct for k_(1)/k_(2)≥m+1 provided xk_(1) is non-degenerate.

关键词： P-symmetric subharmonic Hamiltonian systems Maslov-type index theory iteration inequality asymptotically linear

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Enhanced memristor performance via coupling effect of oxygen vacancy and ferroelectric polarization

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Journal of Materials Science & Technology 2024年第4期171卷 139-146页

作者： zhi Yun Yue zhi Dong zhang Zhan Jie Wang Shenyang national Laboratory for Materials Science Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China School of Materials Science and Engineering University of Science and Technology of ChinaShenyang 110016China School of Materials Science and Engineering Shenyang University of TechnologyShenyang 110870China

As a new type of nonvolatile memory,the resistive memristor has broad application prospects in in-formation storage and neural computing based on its excellent resistive switching(RS)performance.At present,it is still a great challenge to improve both ferroelectric polarization and leakage current to achieve a high RS on/offratio of ferroelectric memristors.Herein,epitaxial Pb(Zr_(0.40)Ti_(0.60))O_(3)(PZT)thin films with low content Ca doping were deposited on the Nb:SrTiO_(3)substrate to prepare PCZT/NSTO het-erostructures and their RS behaviors were studied.The research findings show that compared with pure PZT film,the ferroelectric polarization of 1-mol%-Ca-doped PZT film is slightly improved,while the leak-age current is increased by three orders of magnitude.Therefore,the RS on/offratio reaches 2.5×10^(5),about three orders of magnitude higher than pure PZT films.The theoretical analysis reveals that the RS behavior of PCZT/NSTO heterostructures is controlled by the PCZT/NSTO interfacial barrier and the space charge-limited current mechanism.Our results demonstrate that the ferroelectricity and electricity of ferroelectric thin films can be improved simultaneously by doping low-content Ca ions to increase the RS performance,which provides a good reference for the development of high-performance ferroelectric memristor devices.

关键词： Ferroelectric memristor Ca-doped PZT Ferroelectric polarization Oxygen vacancies Resistive switching

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