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Dysfunction of synaptic endocytic trafficking in Parkinson's disease

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Neural Regeneration Research 2024年第12期19卷 2649-2660页

作者： Xin yi Ng Mian Cao Programme in Neuroscience and Behavioural Disorders Duke-NUS Medical SchoolSingaporeSingapore Department of Physiology National University of SingaporeSingaporeSingapore

Parkinson's disease is characterized by the selective degeneration of dopamine neurons in the nigrostriatal pathway and dopamine deficiency in the *** precise reasons behind the specific degeneration of these dopamine neurons remain largely *** investigations have identified over 20 causative PARK genes and 90 genomic risk loci associated with both familial and sporadic Parkinson's ***,several of these genes are linked to the synaptic vesicle recycling process,particularly the clathrinmediated endocytosis *** suggests that impaired synaptic vesicle recycling might represent an early feature of Parkinson's disease,followed by axonal degeneration and the eventual loss of dopamine cell bodies in the midbrain via a"dying back"***,several new animal and cellular models with Parkinson's disease-linked mutations affecting the endocytic pathway have been created and extensively *** models faithfully recapitulate certain Parkinson's disease-like features at the animal,circuit,and cellular levels,and exhibit defects in synaptic membrane trafficking,further supporting the findings from human genetics and clinical *** this review,we will first summarize the cellular and molecular findings from the models of two Parkinson's disease-linked clathrin uncoating proteins:auxilin(DNAJC6/PARK19)and synaptojanin 1(SYNJ1/PARK20).The mouse models carrying these two PARK gene mutations phenocopy each other with specific dopamine terminal pathology and display a potent synergistic ***,we will delve into the involvement of several clathrin-mediated endocytosis-related proteins(GAK,endophilin A1,SAC2/INPP5 F,synaptotagmin-11),identified as Parkinson's disease risk factors through genome-wide association studies,in Parkinson's disease *** will also explore the direct or indirect roles of some common Parkinson's disease-linked proteins(alpha-synuclein(PARK1/4),Parkin(PARK2),and LRRK2(PARK

关键词： autophagy auxilin/PARK19 clathrin-mediated endocytosis dopamine neurons neurodegeneration nigrostriatal pathway Parkinson's disease synaptic vesicle recycling synaptojanin1/PARK20

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

DDX21 is a new player in co-transcriptional RNA modification and functions

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Science China Life Sciences 2024年第10期67卷 2291-2293页

作者： Chengqi yi State Key Laboratory of Protein and Plant Gene Research School of Life SciencesPeking University Peking-Tsinghua Center for Life Sciences Peking University Department of Chemical Biology and Synthetic and Functional Biomolecules Center College of Chemistry and Molecular EngineeringPeking University Beijing Advanced Center of RNA Biology (BEACON) Peking University

Ever since the first discovery of chemical modifications of RNA in 1951,researchers have been captivated by the diverse types of modifications,their associated enzymes and proteins（writers,erasers,or readers）,and their downstream functional implications（Song and yi,2017）.Among the over 170 distinct types of RNA modifications identified thus far,N6-methyladenosine（m6A） stands out as the most prevalent internal modification on mammalian messenger RNA（mRNA）(Song and yi,2017).

关键词： N-6-METHYLADENOSINE

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Cordyceps as potential therapeutic agents for atherosclerosis

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Journal of Integrative Medicine 2024年第2期22卷 102-114页

作者： yi Zhang Si-jing Liu School of Marxism Chengdu University of Traditional Chinese MedicineChengdu 61137Sichuan ProvinceChina College of Medical Technology Chengdu University of Traditional Chinese MedicineChengdu 611137Sichuan ProvinceChina Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases with Integrated Chinese and Western Medicine Chengdu University of Traditional Chinese MedicineChengdu 611137Sichuan ProvinceChina

Atherosclerosis is a leading cause of mortality and morbidity *** the challenges in managing atherosclerosis,researchers continue to investigate new treatments and complementary *** is a traditional Chinese medicine that has recently gained attention as a potential therapeutic agent for *** studies have demonstrated the effectiveness of cordyceps in treating atherosclerosis through various pharmacological actions,including anti-inflammatory and antioxidant activities,lowering cholesterol,inhibiting platelet aggregation,and modulating apoptosis or autophagy in vascular endothelial ***,the current misuse of the terms cordyceps and Ophiocordyceps sinensis has caused confusion among researchers,and complicated the current academic research on *** review focuses on the chemical composition,pharmacological actions,and underlying mechanisms contributing to the anti-atherosclerotic effects of cordyceps and the mycelium of Ophiocordyceps *** review provides a resource for the research on the development of new drugs for atherosclerosis from cordyceps.

关键词： Atherosclerosis Cordyceps Ophiocordyceps sinensis

Relationship between seismic structures and the diverse rupture processes of the 2023 Türkiye earthquake doublet

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Science China Earth Sciences 2024年第9期67卷 2810-2823页

作者： Zhi WANG yi FU Shunping PEI CAS Key Laboratory of Ocean and Marginal Sea Geology South China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou 510301China Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou) Guangzhou 511458China Key Laboratory of Tibetan Plateau Earth System Environment and Resources(TPESER)Institute of Tibetan Plateau ResearchChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China

Recent geodetic and seismological observations of two major earthquakes in southeastern Türkiye in February 2023 have revealed complex rupture initiation,propagation,and segmentation along the East Anatolian Fault Zone(EAFZ)and surrounding ***,the role of upper crust structures along the EAFZ in determining the diverse rupture processes of this earthquake doublet remains *** further investigate this,we employed double-difference location and seismic tomography techniques to determine high-resolution seismic velocities(V_(P),V_(S))and Poisson’s ratio(σ)structures using a multiparameter joint tomographic *** dataset includes 100,833 high-quality source-receiver travel-time pairs of P-and *** find that the unique rupture processes of this earthquake doublet were primarily influenced by contrasting crustal seismic structures and localized geological *** M_(w)7.8 mainshock was initiated within a transitional edge zone characterized by a rigid part(asperity)of the seismogenic zone with sharp contrast variations in rock strength ranging from low to high along the *** comparison,the M_(w)7.6 rupture originated in a ductile belt featuring fluid saturation with low-VP,low-VS,and high-σvalues that extended parallel to the Cardak *** pronounced contrast structures observed along the former rupture can be attributed to the oblique collision system between the weakened section of the east Anatolian plateau and the brittle Arabian platform,while the latter rupture was initiated within the ductile structure associated with fluid intrusion caused by the northward subduction of the Cyprus slab and subsequent ***,the occurrence of the first earthquake(E1)serves to alleviate shear stress on the second earthquake(E2)fault,potentially impeding the initiation of an E2 *** the contrary,this event also significantly reduces the normal stress acting on the E2 fault due to a double left-lateral strike-slip system

关键词： 2023 Turkiye earthquake doublet Joint seismic tomography Tomographic transition edge Seismic rupture process Strong fault coupling

Multiscale observation in wide-spatial radar surveillance based on coherent FDA design

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Science China(Information Sciences) 2024年第2期67卷 232-252页

作者： Lei YU Feng HE yi SU College of Electronics Science National University of Defense Technology

Wide-spatial radar surveillance missions are challenging tasks, requiring an increased power budget and agility in transmission aimed at extracting information from multiple targets in different environments. These requirements necessitate high transmitting degrees of freedom(DOF) to achieve the objective of multiscale observation for specific tasks in specialized regions of interest. Herein, we exploit the multiscale observation ability in wide-spatial radar surveillance based on frequency diverse array(FDA)radar. The proposed method facilitates spatial anisotropic control of multiple radar resources, including the transmitting waveforms, beampattern, and bandwidth. By utilizing a coherent FDA radar, we offer principles for the selection of baseband waveforms, in addition to the quantitative design of the beampattern gain and optimal bandwidth from the perspective of detection. The feasibility of the proposed method is validated through numerical experiments, thus indicating the potential in wide-spatial radar surveillance. Moreover,this work can be regarded as a preliminary attempt to gauge the efficacy of the computational array, a novel academic concept.

关键词： multi-scale observation wide-spatial surveillance frequency diverse array (FDA) beampattern synthesis frequency diversity gain computational array

When debugging encounters artificial intelligence: state of the art and open challenges

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Science China(Information Sciences) 2024年第4期67卷 42-84页

作者： yi SONG Xiaoyuan XIE Baowen XU School of Computer Science Wuhan University State Key Laboratory of Novel Software Technology Nanjing University

Both software debugging and artificial intelligence techniques are hot topics in the current field of software engineering. Debugging techniques, which comprise fault localization and program repair, are an important part of the software development lifecycle for ensuring the quality of software systems. As the scale and complexity of software systems grow, developers intend to improve the effectiveness and efficiency of software debugging via artificial intelligence(artificial intelligence for software debugging, AI4SD). On the other hand, many artificial intelligence models are being integrated into safety-critical areas such as autonomous driving, image recognition, and audio processing, where software debugging is highly necessary and urgent(software debugging for artificial intelligence, SD4AI). An AI-enhanced debugging technique could assist in debugging AI systems more effectively, and a more robust and reliable AI approach could further guarantee and support debugging techniques. Therefore, it is important to take AI4SD and SD4AI into consideration comprehensively. In this paper, we want to show readers the path, the trend, and the potential that these two directions interact with each other. We select and review a total of 165 papers in AI4SD and SD4AI for answering three research questions, and further analyze opportunities and challenges as well as suggest future directions of this cross-cutting area.

关键词： software debugging fault localization program repair artificial intelligence machine learning

Evaluation of water management on arsenic methylation and volatilization in arsenic-contaminated soils strengthened by bioaugmentation and biostimulation

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Journal of Environmental Sciences 2024年第3期137卷 515-526页

作者： Peng Chen yi Liu Guo-Xin Sun State Key Laboratory of Urban and Regional Ecology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China Key Laboratory of Aquatic Botany and Watershed Ecology Wuhan Botanical GardenChinese Academy of SciencesWuhan 430074China University of Chinese Academy of Sciences Beijing 100049China

Arsenic(As) fate in paddy fields has been one of the most significant current issues due to the strong As accumulation potential of rice plants under fooded conditions. However,no attempt was done to explore As methylation and volatilization under non-fooded conditions. Herein, we investigated the effects of water management on As methylation and volatilization in three arsenic-contaminated soils enhanced by biostimulation with strawderived organic matter and bioaugmentation with genetic engineered Pseudomonas putida KT2440(GE P. putida). Under fooded conditions, the application of biochar(BC), rice straw(RS)and their combination(BC+RS) increased total As in porewater. However, these effects were greatly attenuated under non-fooded conditions. Compared with RS amendment alone, the combination of GE P. putida and RS further promoted the As methylation and volatilization,and the promotion percentage under non-fooded conditions were significantly higher than that under fooded conditions. The combined GE P. putida and RS showed the highest efficiency in As methylation(88 μg/L) and volatilization(415.4 μg/(kg·year)) in the non-fooded soil with moderate As contamination. Finally, stepwise multiple linear regression analysis presented that methylated As, DOC and p H in porewater were the most important factors contributing to As volatilization. Overall, our findings suggest that combination of bioaugmentation with GE P. putida and biostimulation with RS/BC+RS is a potential strategy for bioremediation of arsenic-contaminated soils by enhancing As methylation and volatilization under non-fooded conditions.

关键词： Arsenic methylation Arsenic volatilization Water management Straw incorporation Bioaugmentation

Rapidly growing primordial black holes as seeds of the massive high-redshift JWST Galaxies

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Science China(Physics,Mechanics & Astronomy) 2024年第10期Mechanics & Astronomy) .卷 143-150页

作者： Guan-Wen Yuan Lei Lei Yuan-Zhu Wang Bo Wang yi-ying Wang Chao Chen Zhao-Qiang Shen yi-Fu Cai yi-Zhong Fan Key Laboratory of Dark Matter and Space Astronomy Purple Mountain ObservatoryChinese Academy of Sciences School of Astronomy and Space Science University of Science and Technology of China Institute of High Energy Physics Chinese Academy of Sciences Deep Space Exploration Laboratory/Department of Astronomy School of Physical SciencesUniversity of Science and Technology of China Jockey Club Institute for Advanced Study The Hong Kong University of Science and Technology

A group of massive galaxies at redshifts of z■7 have been recently detected by the James Webb Space Telescope（JWST）, which were unexpected to form at such an early time within the standard Big Bang cosmology. In this work, we propose that this puzzle can be explained by the presence of some primordial black holes（PBHs） with a mass of ～1000M⊙. These PBHs act as seeds for early galaxy formation with masses of ～10～8-1010M⊙at high redshift, hence accounting for the JWST observations. We use a hierarchical Bayesian inference framework to constrain the PBH mass distribution models, and find that the Lognormal model with the Mc～750M⊙is preferred over other hypotheses. These rapidly growing BHs are expected to have strong radiation and may appear as high-redshift compact objects, similar to those recently discovered by JWST. Although we focused on PBHs in this work, the bound on the initial mass of the seed black holes remains robust even if they were formed through astrophysical channels.

关键词： primordial black hole dark matter halo black hole accretion primordial galaxies

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