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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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Mechanistic insight into the synergy between nickel single atoms and nanoparticles on N-doped carbon for electroreduction of CO2

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Journal of Energy Chemistry 2025年第1期100卷 327-336页

作者： Mingdong Sun Wenwen Guan Cailing chen Chao Wu Xiaoling Liu Biao Meng Tao chen Yu Han Jun Wang Shibo Xi Yu Zhou State Key Laboratory of Materials-Oriented Chemical Engineering College of Chemical Engineering Nanjing Tech University Advanced Membranes and Porous Materials Center Physical Sciences and Engineering Division King Abdullah University of Science and Technology Institute of Sustainability for Chemicals Energy and Environment A*STAR (Agency for Science Technology and Research) College of Materials Science and Engineering Sichuan University

The synergy of single atoms （SAs） and nanoparticles （NPs） has demonstrated great potential in promoting the electrocatalytic carbon dioxide reduction reaction （CO2RR）;however,the rationalization of the SAs/NPs proportion remains one challenge for the catalyst ***,a Ni2+-loaded porous poly（ionic liquids）(PIL) precursor synthesized through the free radical self-polymerization of the ionic liquid monomer,1-allyl-3-vinylimidazolium chloride,was pyrolyzed to prepare the Ni,N co-doped carbon materials,in which the proportion of Ni SAs and NPs could be facilely modulated by controlling the annealing *** catalyst Ni-NC-1000 with a moderate proportion of Ni SAs and NPs exhibited high efficiency in the electrocatalytic conversion of CO2into *** Ni K-edge X-ray absorption near-edge structure （XANES） spectra and theoretical calculations were conducted to gain insight into the synergy of Ni SAs and *** charge transfer from Ni NPs to the surrounding carbon layer and then to the Ni SAs resulted in the electron-enriched Ni SAs active *** the electroreduction of CO2,the coexistence of Ni SAs and NPs strengthened the CO2activation and the affinity towards the key intermediate of*COOH,lowering the free energy for the potential-determining*CO2→*COOH step,and therefore promoted the catalysis efficiency.

关键词： Single atom catalyst Synergy effect Carbon catalyst Electrocatalysis

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Ammonia pyrolysis oxidation excited by nanosecond pulsed discharge:Global/fluid models hybrid solution

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Journal of Energy Chemistry 2025年第1期100卷 385-396页

作者： Mingming Zhang Hanyu Wu Qi chen Jiaxin Yang Bonan Liu School of Mechanical Electronic and Control Engineering Beijing Jiaotong University China University of Petroleum

The kinetic characteristics of plasma-assisted oxidative pyrolysis of ammonia are studied by using the global/fluid models hybrid solution ***,the stable products of plasma-assisted oxidative pyrolysis of ammonia are *** results show that the consumption of NH3/O2and the production of N2/H2change linearly with the increase of voltage,which indicates the decoupling of nonequilibrium molecular excitation and oxidative pyrolysis of ammonia at low ***,the detailed reaction kinetics mechanism of ammonia oxidative pyrolysis stimulated by a nanosecond pulse voltage at low pressure and room temperature is *** on the reaction path analysis,the simplified mechanism is *** detailed and simplified mechanism simulation results are compared with experimental data to verify the accuracy of the simplified ***,based on the simplified mechanism,the fluid model of ammonia oxidative pyrolysis stimulated by the nanosecond pulse plasma is established to study the pre-sheath/sheath behavior and the resultant consumption and formation of key *** results show that the generation,development,and propagation of the pre-sheath have a great influence on the formation and consumption of *** consumption of NH3by the cathode pre-sheath is greater than that by the anode pre-sheath,but the opposite is true for OH and O（1S）.However,within the sheath,almost all reactions do not ***,by changing the parameters of nanosecond pulse power supply voltage,it is found that the electron number density,electron current density,and applied peak voltages are not the direct reasons for the structural changes of the sheath and ***,the discharge interval has little effect on the sheath structure and gas mixture *** research results of this paper not only help to understand the kinetic promotion of non-equilibrium excitation in the process of oxidative pyrolysis but also help to explore th

关键词： Nanosecond pulsed discharge Ammonia Oxidative pyrolysis Fluid model Global model

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New mode of universal access and Global Memory Net

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2005年第11期6卷 1206-1215页

作者： chen ching-chih Graduate School of Library and Information Science Simmons College Boston MA 02115 USA

In this digital era, we have witness the exciting convergence of content, technology, and global collaboration in the development of digital libraries. The mode of universal access for information seeking and knowledge acquisition differs greatly fi＇om the traditional ways. From the information resources point of views, the old model of“owning” a collection has given way to “sharing,” and the new emphases have shifted fi＇om possessing large “physical libraries” to “virtual libraries” digitally distributed all over the world. “Universal access” has taken on a very different meaning when one has the ability to share invaluable resources through the use of cutting edge technologies. The author has experienced much of these transformations through her own R＆D activities-from the creation of interactive videodisc and multimedia CD on the First Emperor of China＇s terracotta warriors and horses in the 1980s and 1990s to leading a current international digital library project, Global Memory Net （GMNet）, supported by the US National Science Foundation. In presenting her vision for linking world digital resources together for universal access, she will share with the audience the latest development of Global Memory Net.

关键词： Global Memory Net (GMNet) Collaboration Digital library Digital image library system development Management system Cultural Historical Heritage collections NSF Intemational digital library PITAC Global Collaboration

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Tranylcypromine upregulates Sestrin 2 expression to ameliorate NLRP3-related noise-induced hearing loss

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Neural Regeneration Research 2025年第5期20卷 1483-1494页

作者： Xihang chen Zhifeng chen Menghua Li Weiwei Guo Shuolong Yuan Liangwei Xu Chang Lin Xi Shi Wei chen Shiming Yang Senior Department of Otolaryngology Head and Neck Surgery Chinese PLA General HospitalChinese PLA Medical SchoolBeijingChina State Key Laboratory of Hearing and Balance Science BeijingChina National Clinical Research Center for Otolaryngologic Diseases BeijingChina Key Laboratory of Hearing Science Ministry of EducationBeijingChina Beijing Key Laboratory of Hearing Impairment Prevention and Treatment BeijingChina Department of Otorhinolaryngology Head and Neck Surgery The First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Otolaryngology Head and Neck Surgery The 940th Hospital of Joint Logistics Support Force of Chinese PLALanzhouGansu ProvinceChina Key Laboratory of Tropical Biological Resources of Ministry of Education School of Pharmaceutical SciencesHainan UniversityHaikouHainan ProvinceChina Academician Workstation of Hainan University School of Pharmaceutical SciencesYazhou BaySanyaHainan ProvinceChina

Noise-induced hearing loss is the primary non-genetic factor contributing to auditory ***,there are currently no effective pharmacological interventions for patients with noise-induced hearing ***,we present evidence suggesting that the lysine-specific demethylase 1 inhibitor–tranylcypromine is an otoprotective agent that could be used to treat noise-induced hearing loss,and elucidate its underlying regulatory *** established a mouse model of permanent threshold shift hearing loss by exposing the mice to white broadband noise at a sound pressure level of 120 d B for 4 *** found that tranylcypromine treatment led to the upregulation of Sestrin2(SESN2)and activation of the autophagy markers light chain 3B and lysosome-associated membrane glycoprotein 1 in the cochleae of mice treated with *** noise exposure group treated with tranylcypromine showed significantly lower average auditory brainstem response hearing thresholds at click,4,8,and 16 k Hz frequencies compared with the noise exposure group treated with *** findings indicate that tranylcypromine treatment resulted in increased SESN2,light chain 3B,and lysosome-associated membrane glycoprotein 1 expression after noise exposure,leading to a reduction in levels of 4-hydroxynonenal and cleaved caspase-3,thereby reducing noise-induced hair cell ***,immunoblot analysis demonstrated that treatment with tranylcypromine upregulated SESN2 expression via the autophagy *** treatment also reduced the production of NOD-like receptor family pyrin domaincontaining 3(NLRP3)*** conclusion,our results showed that tranylcypromine treatment ameliorated cochlear inflammation by promoting the expression of SESN2,which induced autophagy,thereby restricting NLRP3-related inflammasome signaling,alleviating cochlear hair cell loss,and protecting hearing *** findings suggest that inhibiting lysine-specific demethylase 1 is a

关键词： 4-hydroxynonenal apoptosis autophagy cleaved caspase-3 inflammation NOD-like receptor family pyrin domain-containing 3(NLRP3) noise-induced hearing loss oxidative stress Sestrin2 tranylcypromine

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Interannual variability of boreal summer intraseasonal oscillation over the northwestern Pacific influenced by the Pacific Meridional Mode

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Atmospheric and Oceanic Science Letters 2025年第1期18卷 6-11页

作者： Haoyu Zhou Pang-Chi Hsu Lin chen Yitian Qian Key Laboratory of Meteorological Disaster Ministry of Education/Joint International Research Laboratory of Climate and Environmental Change/Collaborative Innovation Center on Forecast and Evaluation of Meteorological DisastersNanjing University of Information Science and TechnologyNanjingChina

During the boreal summer,intraseasonal oscillations exhibit significant interannual variations in intensity over two key regions:the central-western equatorial Pacific(5°S-5°N,150°E-150°W)and the subtropical Northwestern Pacific(10°-20°N,130°E-175°W).The former is well-documented and considered to be influenced by the ENSO,while the latter has received comparatively less attention and is likely influenced by the Pacific Meridional Mode(PMM),as suggested by partial correlation analysis *** elucidate the physical processes responsible for the enhanced(weakened)intraseasonal convection over the subtropical northwestern Pacific during warm(cold)PMM years,the authors employed a moisture budget *** findings reveal that during warm PMM years,there is an increase in summer-mean moisture over the subtropical northwestern *** increase interacts with intensified vertical motion perturbations in the region,leading to greater vertical moisture advection in the lower troposphere and consequently resulting in convective *** a process is pivotal in amplifying intraseasonal convection *** observational findings were further verified by model experiments forced by PMM-like sea surface temperature patterns.

关键词： Boreal summer intraseasonal oscillation Interannual variability Pacific Meridional Mode Moisture budget analysis

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Targeting cholesterol trafficking to mitigate axonal degeneration in hereditary spastic paraplegia

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Neural Regeneration Research 2025年第5期20卷 1397-1398页

作者： Zhenyu chen Xue-Jun Li Department of Biomedical Sciences University of Illinois College of Medicine RockfordRockfordILUSA Department of Bioengineering University of Illinois at ChicagoChicagoILUSA

Axonal degeneration underlies many debilitating diseases including hereditary spastic paraplegia(HSP),a genetically and clinically diverse group of disorders characterized by spasticity and weakness of the lower *** is one significant cause of chronic neurodisability due to the lack of effective treatments and a wide range of onset ages from early childhood to 70 years.

关键词： degeneration diseases hereditary

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Autophagy-targeting modulation to promote peripheral nerve regeneration

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Neural Regeneration Research 2025年第7期20卷 1864-1882页

作者： Yan chen Hongxia Deng Nannan Zhang Department of Obstetrics and Gynecology West China Second HospitalSichuan UniversityChengduSichuan ProvinceChina Key Laboratory of Birth Defects and Women and Children’s Diseases Ministry of EducationSichuan UniversityChengduSichuan ProvinceChina Laboratory of Reproductive Endocrinology and Reproductive Regulation Sichuan UniversityChengduSichuan ProvinceChina National Center for Birth Defect Monitoring West China Second University HospitalSichuan UniversityChengduSichuan ProvinceChina

Nerve regeneration following traumatic peripheral nerve injuries and neuropathies is a complex process modulated by diverse factors and intricate molecular *** studies have focused on factors that stimulate axonal outgrowth and myelin ***,recent studies have highlighted the pivotal role of autophagy in peripheral nerve regeneration,particularly in the context of traumatic ***,autophagy-targeting modulation has emerged as a promising therapeutic approach to enhancing peripheral nerve *** current understanding suggests that activating autophagy facilitates the rapid clearance of damaged axons and myelin sheaths,thereby enhancing neuronal survival and mitigating injury-induced oxidative stress and *** actions collectively contribute to creating a favorable microenvironment for structural and functional nerve regeneration.A range of autophagyinducing drugs and interventions have demonstrated beneficial effects in alleviating peripheral neuropathy and promoting nerve regeneration in preclinical models of traumatic peripheral nerve *** review delves into the regulation of autophagy in cell types involved in peripheral nerve regeneration,summarizing the potential drugs and interventions that can be harnessed to promote this *** hope that our review will offer novel insights and perspectives on the exploitation of autophagy pathways in the treatment of peripheral nerve injuries and neuropathies.

关键词： autophagy autophagy related genes Charcot–Marie–Tooth diseases diabetic peripheral neuropathy metformin myelination peripheral nerve injury Schwann cells sciatic nerve Wallerian degeneration

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Glucocorticoid receptor signaling in the brain and its involvement in cognitive function

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Neural Regeneration Research 2025年第9期20卷 2520-2537页

作者： Chonglin Su Taiqi Huang Meiyu Zhang Yanyu Zhang Yan Zeng Xingxing chen Brain Science and Advanced Technology Institute Hubei Province Key Laboratory of Occupational Hazard Identification and ControlSchool of MedicineWuhan University of Science and TechnologyWuhanHubei ProvinceChina

The hypothalamic-pituitary-adrenal axis regulates the secretion of glucoco rticoids in response to environmental *** the brain,a nuclear receptor transcription fa ctor,the glucocorticoid recepto r,is an important component of the hypothalamicpituitary-a d renal axis's negative feedback loop and plays a key role in regulating cognitive equilibrium and *** glucoco rticoid receptor influences cognitive processes,including glutamate neurotransmission,calcium signaling,and the activation of brain-derived neurotrophic factor-mediated pathways,through a combination of genomic and non-genomic *** interactions within the central nervous system can alter the expression and activity of the glucocorticoid receptor,there by affecting the hypothalamic-pituitary-a d renal axis and stress-related cognitive *** appropriate level of glucocorticoid receptor expression can improve cognitive function,while excessive glucocorticoid receptors or long-term exposure to glucoco rticoids may lead to cognitive *** with cognitive impairment-associated diseases,such as Alzheimer's disease,aging,depression,Parkinson's disease,Huntington's disease,stroke,and addiction,often present with dysregulation of the hypothalamic-pituitary-adrenal axis and glucocorticoid receptor *** review provides a comprehensive overview of the functions of the glucoco rticoid receptor in the hypothalamic-pituitary-a d renal axis and cognitive *** emphasizes that appropriate glucocorticoid receptor signaling fa cilitates learning and memory,while its dysregulation can lead to cognitive *** provides clues about how glucocorticoid receptor signaling can be targeted to ove rcome cognitive disability-related disorders.

关键词： brain-derived neurotrophic factor calcium signaling glucocorticoid receptor glucocorticoid glutamate transmission hypothalamic-pituitary-adrenal axis long-term potentiation neurocognitive disorders neuroplasticity stress

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From demand response to transactive energy: state of the art

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Journal of Modern Power Systems and Clean Energy 2017年第1期5卷 10-19页

作者： Sijie chen chen-ching LIU Washington State University Pullman WA 99163 USA Shanghai Jiao Tong University Shanghai 200240 China

This paper reviews the state of the art of research and industry practice on demand response and the new methodology of transactive energy. Demand response programs incentivize consumers to align their demand with power supply conditions, enhancing power system reliability and economic operation. The design of demand response programs, performance of pilot projects and programs, consumer behaviors, and barriers are *** energy is a variant and a generalized form of demand response in that it manages both the supply and demand sides. It is intended for a changing environment with an increasing number of distributed resources and intelligent devices. It utilizes the flexibility of various generation/load resources to maintain a dynamic balance of supply and demand. These distributed resources are controlled by their owners. However, the design of transaction mechanisms should align the individual behaviors with the interests of the entire system. Transactive energy features real-time, autonomous, and decentralized decision *** transition from demand response to transactive energy is also discussed.

关键词： Demand response Incentive-based program Price-based program Direct load control Transactive energy

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