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Toward understanding the role of genomic repeat elements in neurodegenerative diseases

Neural Regeneration Research 2025年第3期20卷 646-659页

作者： Zhengyu An Aidi Jiang Jingqi Chen Institute of Science and Technology for Brain-Inspired Intelligence Fudan UniversityShanghaiChina MOE Frontiers center for Brain Science Fudan UniversityShanghaiChina MOE Key Laboratory of computational Neuroscience and Brain-Inspired Intelligence Fudan UniversityShanghaiChina Zhangjiang Fudan International Innovation center ShanghaiChina

Neurodegenerative diseases cause great medical and economic burdens for both patients and society;however, the complex molecular mechanisms thereof are not yet well understood. With the development of high-coverage sequencing technology, researchers have started to notice that genomic repeat regions, previously neglected in search of disease culprits, are active contributors to multiple neurodegenerative diseases. In this review, we describe the association between repeat element variants and multiple degenerative diseases through genome-wide association studies and targeted sequencing. We discuss the identification of disease-relevant repeat element variants, further powered by the advancement of long-read sequencing technologies and their related tools, and summarize recent findings in the molecular mechanisms of repeat element variants in brain degeneration, such as those causing transcriptional silencing or RNA-mediated gain of toxic function. Furthermore, we describe how in silico predictions using innovative computational models, such as deep learning language models, could enhance and accelerate our understanding of the functional impact of repeat element variants. Finally, we discuss future directions to advance current findings for a better understanding of neurodegenerative diseases and the clinical applications of genomic repeat elements.

关键词： Alzheimer's disease ataxia deep learning long-read sequencing neurodegeneration neurodegenerative diseases Parkinson's disease repeat element structural variant

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Small extrachromosomal circular DNA in amyotrophic lateral sclerosis matter

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Neural Regeneration Research 2025年第5期20卷 1411-1413页

作者： Marcos J.Arauzo-Bravo Daniela Gerovska Matthias Schwab Alexandra Kretz computational Biology and Systems Biomedicine Biodonostia Health Research InstituteSan SebastianSpain Basque Foundation for Science IKERBASQUEBilbaoSpainMax Planck Institute for Molecular BiomedicineComputational Biology and Bioinformatics GroupMünsterNorth Rhine-WestphaliaGermany Department of Cell Biology and Histology Faculty of Medicine and NursingUniversity of Basque Country(UPV/EHU)LeioaSpain Department of Neurology Jena University HospitalJenaThuringiaGermany

Comprehensive studies identify motor neuron spectrum disorders including amyotrophic lateral sclerosis(ALS)as globally rising fatal disorders with the highest prevalence in aging populations,influenced by ethnicity and ancestry(GBD 2016 Motor Neuron Disease Colla borators,2018).While~10% of diagnoses involve a family history(fALS),most cases are considered sporadic(sALS).However,population-based studies suggest that even cases without a common index mutation impart heritability(Ryan et al.,2019),indicating a crucial role of rare and as yet unknown genetic denominators.

关键词： amyotrophic sclerosis

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Single-cell omics: experimental workflow, data analyses and applications

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Science China Life Sciences 2025年第1期68卷 5-102页

作者： Fengying Sun Haoyan Li Dongqing Sun Shaliu Fu Lei Gu Xin Shao Qinqin Wang Xin Dong Bin Duan Feiyang Xing Jun Wu Minmin Xiao Fangqing Zhao Jing-Dong J.Han Qi Liu Xiaohui Fan Chen Li Chenfei Wang Tieliu Shi Department of Clinical Laboratory the Affiliated Wuhu Hospital of East China Normal University (The Second People's Hospital of Wuhu City) Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang University Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Tongji University) Ministry of EducationOrthopaedic DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Frontier Science center for Stem Cells School of Life Sciences and TechnologyTongji University Translational Medical center for Stem Cell Therapy and Institute for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Research Institute of Intelligent Computing Zhejiang Lab Shanghai Research Institute for Intelligent Autonomous Systems center for Single-cell Omics School of Public HealthShanghai Jiao Tong University School of Medicine National Key Laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang University center for Bioinformatics and computational Biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal University Beijing Institutes of Life Science Chinese Academy of Sciences Peking-Tsinghua center for Life Sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology (CQB)Peking University Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's HospitalZhejiang University School of Medicine Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE School of StatisticsEast China Normal University

Cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. Since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome,proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial sc RNA-seq and CRISPR screening. Single-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

关键词： single-cell sequencing genome epigenome proteomics metabolomics multimodal spatial transcriptomics CRISPR screening

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Olfactory receptors in neural regeneration in the central nervous system

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Neural Regeneration Research 2025年第9期20卷 2480-2494页

作者： Rafael Franco Claudia Garrigós Toni Capó Joan Serrano-Marín Rafael Rivas-Santisteban Jaume Lillo Molecular Neurobiology Laboratory Department of Biochemistry and Molecular BiomedicineFacultat de BiologiaUniversitat de BarcelonaBarcelonaSpain CiberNed Network center for Biomedical Research in Neurodegenerative Diseases Spanish National Health Institute Carlos ⅢMadridSpain School of Chemistry Universitat de BarcelonaBarcelonaSpain Department of Biochemistry and Physiology School of Pharmacy and Food SciencesUniversitat de BarcelonaBarcelonaSpain Laboratory of computational Medicine Biostatistics UnitFaculty of MedicineAutonomous University of BarcelonaCampus BellaterraBarcelonaSpain

Olfactory receptors are crucial for detecting odors and play a vital role in our sense of smell,influencing behaviors from food choices to emotional *** receptors also contribute to our perception of flavor and have potential applications in medical diagnostics and environmental *** ability of the olfactory system to regenerate its sensory neurons provides a unique model to study neural regeneration,a phenomenon largely absent in the central nervous *** gained from how olfactory neurons continuously replace themselves and reestablish functional connections can provide strategies to promote similar regenerative processes in the central nervous system,where damage often results in permanent *** the molecular and cellular mechanisms underpinning olfactory neuron regeneration could pave the way for developing therapeutic approaches to treat spinal co rd injuries and neurodegenerative diseases like Alzheimer's *** ctory receptors are found in almost any cell of eve ry orga n/tissue of the mammalian *** ectopic expression provides insights into the chemical structures that can activate olfactory *** addition to odors,olfactory receptors in ectopic expression may respond to endogenous compounds and molecules produced by mucosal colonizing *** analysis of the function of olfactory receptors in ectopic expression provides valuable information on the signaling pathway engaged upon receptor activation and the receptor's role in proliferation and cell differentiation *** review explo res the ectopic expression of olfa ctory receptors and the role they may play in neural regeneration within the central nervous system,with particular attention to compounds that can activate these receptors to initiate regenerative *** suggests that olfactory receptors could serve as potential therapeutic targets for enhancing neural repair and recovery following central nervous syste

关键词： adenosine receptors adrenergic receptors ectopic expression G proteincoupled receptors glia neurons

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Regulation of graphdiyne-based nanozymes with enhanced oxidaselike activity by cobalt and nitrogen codoping

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Nano Research 2025年第1期18卷 21-29页

作者： Jiali Liu Xiaoli Wang Yongfu Lian Xue Wang Xiuxiu Wang Xingfa Gao Baoyun Sun Xihong Guo CAS Key Laboratory for Biomedical Effects of Nanomaterial&Nanosafety Institute of High Energy PhysicsChinese Academy of ScienceBeijing 100049China Key Laboratory of Functional Inorganic Material Chemistry Ministry of EducationSchool of Chemistry and Materials ScienceHeilongjiang UniversityHarbin 150080China Laboratory of Theoretical and computational Nanoscience National Center for Nanoscience and TechnologyBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China

The development of nanozymes with excellent intrinsic oxidase-like activity and specificity has received increasing ***(GDY)could be a promising choice for designing nanozymes with enhanced oxidase(OXD)-like activity due to its unique structure and ***,Co-N-GDY with high OXD activity but no peroxidase(POD)activity was synthesized by codoping of cobalt(Co)and nitrogen(N)into GDY and compared with other GDY-based nanozymes(including GDY,Co-GDY,and N-GDY).Upon analyzing the doping effect of Co and N on the OXD-like and POD-like activities,we found that the combination of Co and N in GDY played a significant role in enhancing the OXD-like activity,and even reversed the POD-like activity of N-GDY to OXD-like activity of *** electrochemical experiment and the theoretical calculations provided an explanation for the mechanism and showed that the activity was closely linked to the reduction ability of O_(2) or H_(2)O_(2) on the nanozyme substrates,which was determined by the ratedetermining step of the catalytic reaction.

关键词： nanozymes oxidase-like activity graphdiyne heteroatom doping regulation

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An overview of simulation-based hydrodynamic design of ship hull forms

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Journal of Hydrodynamics 2016年第6期28卷 947-960页

作者： Chi YANG Fuxin HUANG center for computational Fluid Dynamics George Mason University

This review paper presents an overview of simulation-based hydrodynamic design optimization of ship hull forms. A computational tool that is aimed to accomplishing early-stage simulation-based design in terms of hydrodynamic performance is discussed in detail. The main components of this computational tool consist of a hydrodynamic module, a hull surface modeling module, and an optimization module. The hydrodynamic module includes both design-oriented simple CFD tools and high-fidelity CFD tools. These integrated CFD tools are used for evaluating hydrodynamic performances at different design stages. The hull sur- face modeling module includes various techniques for ship hull surface representation and modification. This module is used to automatically produce hull forms or modify existing hull forms in terms of hydrodynamic performance and design constraints. The optimization module includes various optimization algorithms and surrogate models, which are used to determine optimal designs in terms of given hydrodynamic performance. As an illustration of the computational tool, a Series 60 hull is optimized for reduced drag using three different modification strategies to outline the specific procedure for conducting simulation-based hydrodynamic design of ship hull forms using the present tool. Numerical results show that the present tool is well suited for the hull form design optimization at early design stage because it can produce effective optimal designs within a short period of time.

关键词： simulation based design ship hull form optimization radial basis function NURBS hydrodynamics

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A Survey of the L1 Scheme in the Discretisation of Time-Fractional Problems

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Numerical Mathematics(Theory,Methods and Applications) 2022年第4期15卷 1173-1192页

作者： Martin Stynes Applied and computational Mathematics Division Beijing Computational Science Research CenterBeijing 100193China

A survey is given of convergence results that have been proved when the L1 scheme is used to approximate the Caputo time derivative D_(t)^(α)(where 0<α<1)in initial-boundary value problems governed by D_(t)^(α)u−△u=f and similar equations,while taking into account the weak singularity that is present in typical solutions of such *** aspects of these analyses are outlined,such as global and local convergence bounds and the techniques used to derive them,fast implementation of the L1 scheme,semilinear problems,multi-term time derivatives,α-robustness,a posteriori error analysis,and two modified L1 schemes that achieve better *** fifty references are provided in the bibliography,more than half of which are from the period 2019-2022.

关键词： L1 scheme fractional derivative survey

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Sub-diffusive scaling with power-law trapping times

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Chinese Physics B 2014年第7期23卷 64-72页

作者：罗亮汤雷翰 Beijing computational Science Research center Department of Physics and Institute of computational and Theoretical Studies Hong Kong Baptist University

Thermally driven diffusive motion of a particle underlies many physical and biological processes. In the presence of traps and obstacles, the spread of the particle is substantially impeded, leading to subdiffusive scaling at long times. The statistical mechanical treatment of diffusion in a disordered environment is often quite involved. In this short review, we present a simple and unified view of the many quantitative results on anomalous diffusion in the literature, including the scaling of the diffusion front and the mean first-passage time. Varioust analytic calculations and physical arguments are examined to highlight the role of dimensionality, energy landscape, and rare events in affecting the particle trajectory statistics. The general understanding that emerges will aid the interpretation of relevant experimental and simulation results.

关键词： anomalous diffusion subdiffusive scaling random walk in a disordered medium glass transition

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Three-mode optomechanical system for angular velocity detection

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Chinese Physics B 2018年第8期27卷 254-260页

作者： Kai Li Sankar Davuluri Yong Li Beijing computational Science Research center Beijing 100193China

We propose a scheme for measuring the angular velocity of absolute rotation using a three-mode optomechanical system in which one mode of the two-dimensional （2D） mechanical resonator is coupled to an optical cavity. When the total system rotates, the Coriolis force acting on the 2D mechanical resonator due to the absolute rotation will affect the mechanical motion and thus change the phase of the output field from the cavity. The angular velocity of the absolute rotation can be estimated by monitoring the spectrum of the output field from the cavity via homodyne measurement. The minimum measurable angular velocity, which is determined by the noise spectrum, is calculated. The working range of the gyroscope for measuring angular velocity is discussed.

关键词： optomechanics gyroscope

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Calibration of a γ-Re_θ transition model and its validation in low-speed flows with high-order numerical method

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Chinese Journal of Aeronautics 2015年第3期28卷 704-711页

作者： Wang Yuntao Zhang Yulun Li Song Meng Dehong computational Aerodynamics Institute China Aerodynamics Research and Development Center

Abstract Based on the Reynolds-averaged Navier--Stokes （RANS） equations and structured grid technology, the calibration and validation of Y-Reo transition model is preformed with fifth-order weighted compact nonlinear scheme （WCNS）, and the purpose of the present work is to improve the numerical accuracy for aerodynamic characteristics simulation of low-speed flow with transition model on the basis of high-order numerical method study. Firstly, the empirical correlation functions involved in the Y-Reo transition model are modified and calibrated with experimental data of turbulent flat plates. Then, the grid convergence is studied on NLR-7301 two-element airfoil with the modified empirical correlation. At last, the modified empirical correlation is validated with NLR-7301 two-element airfoil and high-lift trapezoidal wing from transition location, velocity pro- file in boundary layer, surface pressure coefficient and aerodynamic characteristics. The numerical results illustrate that the numerical accuracy of transition length and skin friction behind transition location are improved with modified empirical correlation function, and obviously increases the numerical accuracy of aerodynamic characteristics prediction for typical transport configurations in low-speed range.

关键词： Aerodynamic characteristicsFinite difference scheme High-order method Laminar to turbulenttransition RANS

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