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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

Stability and Generalization of Hypergraph Collaborative Networks

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Machine Intelligence Research 2024年第1期21卷 184-196页

作者： Michael K.ng Hanrui Wu Andy Yip Institute of Data Science The University of Hong KongHong KongChina Department of Mathematics The University of Hong KongHong KongChina College of Information Science and Technology Jinan UniversityGuangzhou 510006China

Graph neural networks have been shown to be very effective in utilizing pairwise relationships across ***,there have been several successful proposals to generalize graph neural networks to hypergraph neural networks to exploit more com-plex *** particular,the hypergraph collaborative networks yield superior results compared to other hypergraph neural net-works for various semi-supervised learning *** collaborative network can provide high quality vertex embeddings and hyperedge embeddings together by formulating them as a joint optimization problem and by using their consistency in reconstructing the given *** this paper,we aim to establish the algorithmic stability of the core layer of the collaborative network and provide generaliz--ation *** analysis sheds light on the design of hypergraph filters in collaborative networks,for instance,how the data and hypergraph filters should be scaled to achieve uniform stability of the learning *** experimental results on real-world datasets are presented to illustrate the theory.

关键词： Hypergraphs vertices hyperedges collaborative networks graph convolutional neural networks(CNNs) stability generalization guarantees

Perspectives in human brain plasticity sparked by glioma invasion:from intraoperative(re)mappings to neural reconfigurations

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Neural Regeneration Research 2024年第5期19卷 947-948页

作者： Sam ng Hugues Duffau Guillaume Herbet Department of Neurosurgery Gui de Chauliac HospitalMontpellier University Medical CenterMontpellierFrance Institute of Functional Genomics University of MontpellierCNRSINSERMMontpellierFrance Praxiling Laboratory UMR5267CNRSPaul Valéry-Montpellier 3 UniversityMontpellierFrance

Exploring the aptitude of the human brain to compensate functional consequences of a lesion damaging its structural architecture is a key challenge to improve patient care in various neurological diseases,to optimize neuroscientifically-informed strategies of postlesional rehabilitation,and ultimately to develop innovative neuro-regenerative *** term‘plasticity’,initially referring to the intrinsic propensity of neurons to modulate their synaptic transmission in a learning situation,was progressively transposed to brain injury research and clinical ***,in the event of brain damage,adaptive mechanisms of compensation allow a partial reshaping of the structure and activities of the central nervous system,thus permitting to some extent the maintenance of brain functions.

关键词： plasticity figuration consequences

Three-dimensional numerical analysis of plant-soil hydraulic interactions on pore water pressure of vegetated slope under different rainfall patterns

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第9期16卷 3696-3706页

作者： Haowen Guo Charles Wang Wai ng Qi Zhang Department of Civil and Environmental Engineering The Hong Kong University of Science and TechnologyHong KongChina

Understanding the pore water pressure distribution in unsaturated soil is crucial in predicting shallow landslides triggered by rainfall,mainly when dealing with different temporal patterns of rainfall ***,the hydrological response of vegetated slopes,especially three-dimensional(3D)slopes covered with shrubs,under different rainfall patterns remains unclear and requires further *** address this issue,this study adopts a novel 3D numerical model for simulating hydraulic interactions between the root system of the shrub and the surrounding *** series of numerical parametric studies are conducted to investigate the influences of slope inclination,rainfall pattern and rainfall *** rainfall patterns(advanced,bimodal,delayed,and uniform)and two rainfall durations(4-h intense and 168-h mild rainfall)are considered to study the hydrological response of the *** computed results show that 17%higher transpiration-induced suction is found for a steeper slope,which remains even after a short,intense rainfall with a 100-year return *** extreme rainfalls with advanced(PA),bimodal(PB)and uniform(PU)rainfall patterns need to be considered for the short rainfall duration(4 h),while the delayed(PD)and uniform(PU)rainfall patterns are highly recommended for long rainfall durations(168 h).The presence of plants can improve slope stability markedly under extreme rainfall with a short duration(4 h).For the long duration(168 h),the benefit of the plant in preserving pore-water pressure(PWP)and slope stability may not be sufficient.

关键词： Root-soil interactions Rainfall patterns Slope stability Three-dimensional(3D)

Defined hydrogels for spinal cord organoids:challenges and potential applications

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Neural Regeneration Research 2024年第11期19卷 2329-2330页

作者： Wai Hon Chooi Yuewen Wu Shi-Yan ng Institute of Molecular and Cell Biology(IMCB) Agency for ScienceTechnology and Research(A*STAR)SingaporeSingapore Department of Physiology Yong Loo Lin School of MedicineNational University of Singapore(NUS)SingaporeSingapore

Organoids of the central nervous system,primarily derived from pluripotent stem cells or neural stem cells,are three-dimensional tissue cultures with self-organizing *** exposed to the right combinations of signals,they differentiate into a 3D tissue consisting of complex cytoarchitecture and native cell types,including various neuron subtypes and glial *** features closely mimic native tissues,making them invaluable for developmental studies and disease *** recent years,spinal cord organoids(SCOs)have been developed to investigate spinal cord development,injuries,and various neurological *** an integral part of the central nervous system,SCOs play a vital role and serve as a site for studying both neurodevelopment and neurodegenerative diseases.

关键词： properties injuries primarily

A novel non-invasive model to predict high-risk varices in cirrhotic patients

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Hepatobiliary Surgery and Nutrition 2024年第3期13卷 530-532页

作者： Kelvin K.C.ng Department of Surgery The Chinese University of Hong Kong Medical CentreHong KongChina

Acute variceal bleeding is one of the most common and potentially life-threatening complications in patients with liver *** is conventionally diagnosed by oesophagogastroduodenoscopy,which is invasive to patients and carries hospital *** would be more cost-effective if non-invasive tests could screen out high-risk patients who developed acute variceal bleeding requiring endoscopic *** can potentially reduce the need for invasive procedures for cirrhotic *** recent years,there have been advancements in non-invasive methods for assessing the risk of variceal *** include transient elastography(FibroScan)of the liver and spleen,platelet count,imaging modalities[ultrasound or magnetic resonance imaging(MRI)],and non-invasive liver function tests[Child-Pugh score or the Model for End-Stage Liver Disease(MELD)score].The 2015 Baveno VI consensus is developed by an international panel of experts to improve the diagnosis and management of portal hypertension and its complications,specifically focusing on variceal bleeding in patients with cirrhosis(1).The consensus emphasizes using noninvasive methods to screen out high-risk varices(HRV)requiring therapeutic *** key features of the Baveno VI criteria include a liver stiffness measurement(LSM)150,000/*** can confidently rule out *** has been proven to avoid unnecessary endoscopy up to 40%with a specificity of up to 46%(2).In recent years,spleen stiffness measurement(SSM)has been a useful tool to assess portal hypertension and to predict ***,the revised Baveno VII consensus in 2022 recommends SSM≤40 kPa would avoid more unnecessary endoscopy in patients who fall outside Baveno VI criteria,with a missed HRV rate of<5%(3).

关键词： Non-invasive model high-risk varices cirrhosis

Mg/MgO interfaces as efficient hydrogen evolution cathodes causing accelerated corrosion of additive manufactured Mg alloys:A DFT analysis

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Journal of Magnesium and Alloys 2024年第1期12卷 110-119页

作者： Man-Fai ng Kai Xiang Kuah Teck Leong Tan Daniel John Blackwood Department of Materials Science&Engineering National University of Singapore9 Engineering Drive 1Singapore 117575Republic of Singapore Institute of High Performance Computing(IHPC) Agency for ScienceTechnology and Research(A∗STAR)1 Fusionopolis Way#16-16 ConnexisSingapore 138632Republic of Singapore

The corrosion rates of additive-manufactured Mg alloys are higher than their as-cast counterparts,possibly due to increased kinetics for the hydrogen evolution reaction on secondary phases,which may include oxide *** Kelvin Probe Force Microscopy demonstrated that MgO inclusions could act as cathodes for Mg corrosion,but their low conductivity likely precludes ***,the density of state calculations through density functional theory using hybrid HSE06 functional revealed overlapping electronic states at the Mg/MgO interface,which facilitates electron transfers and participates in redox *** determination of the hydrogen absorption energy at the Mg/MgO interface reveals it to be an excellent catalytic site,with HER being found to be a factor of 23x more efficient at the interface than on metallic *** results not only support the plausibility of the Mg/MgO interface being an effective cathode to the adjacent anodic Mg matrix during corrosion but also contribute to the understanding of the enhanced cathodic activities observed during the anodic dissolution of magnesium.

关键词： Magnesium Magnesium oxide Interface Hydrogen evolution DFT

Developmental impacts and toxicological hallmarks of silver nanoparticles across diverse biological models

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Environmental Science and Ecotechnology 2024年第3期19卷 60-79页

作者： Yán Wāng Yapeng Han De-Xiang Xu Department of Toxicology School of Public Health&Key Laboratory of Environmental Toxicology of Anhui Higher Education InstitutesAnhui Medical UniversityHefei230032China

Silver nanoparticles(AgNPs),revered for their antimicrobial prowess,have become ubiquitous in a range of products,from biomedical equipment to food ***,amidst their rising popularity,concerns loom over their possible detrimental effects on fetal development and subsequent adult *** review delves into the developmental toxicity of AgNPs across diverse models,from aquatic species like zebrafish and catfish to mammalian rodents and in vitro embryonic stem *** focus encompasses the fate of AgNPs in different contexts,elucidating associated hazardous results such as embryotoxicity and adverse pregnancy ***,we scrutinize the enduring adverse impacts on offspring,spanning impaired neurobehavior function,reproductive disorders,cardiopulmonary lesions,and *** hallmarks of developmental harm are identified,encompassing redox imbalances,inflammatory cascades,DNA damage,and mitochondrial ***,we explore potential explanations,linking immunoregulatory dysfunction and disrupted epigenetic modifications to AgNPsinduced developmental *** substantial progress,our understanding of the developmental risks posed by AgNPs remains incomplete,underscoring the urgency of further research in this critical area.

关键词： Silver nanoparticles(AgNPs) Developmental toxicity Maternal exposure Fetal development Redox imbalance Mitochondrial dysfunction

Modelling the water diversion of a sustainable cover system under humid climates

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第7期16卷 2429-2440页

作者： Haowen Guo Charles Wang Wai ng Qi Zhang Chuanxiang Qu Liwen Hu Shenzhen Research Institute of Hong Kong University of Science and Technology Shenzhen518057China Department of Civil and Environmental Engineering The Hong Kong University of Science and TechnologyHong Kong SAR999077China CCCC Fourth Harbor Engineering Institute Co. LtdGuangzhou510230China

Extreme rainfall significantly threatens the safety of the landfill cover system,especially under humid *** study aims to provide design recommendations for a sustainable landfill cover system consisting of a low-permeability soil layer underlying a two-layer capillary barrier for humid ***,the numerical back-analysis was conducted for verification against a series of flume model ***,a parametric study was performed to investigate the effects of inclination angle,particle size and layer thickness on the lateral diversion length(DL)of the three-layer cover system under the 100-year return period rainfall of humid *** results show that the water lateral DL of the cover system can be greatly enhanced by increasing the inclination angle from 3°to 18°.Moreover,the bottom layer of the cover system with a coarser d10 was more susceptible to the impact of the heavy rainfall,while this can be alleviated by increasing the thickness of the bottom layer.A dimensionless number,defined as the ratio of thickness and d_(10) of the bottom layer,is proposed for designing lateral diversion of the three-layer cover system under humid *** preserve the maximum DL,it is suggested that the proposed dimensionless number should be larger than 95 and 110 for the design of rainfall events with 50-year and 100-year return periods for humid climates,respectively.

关键词： Unsaturated soil Recycling Construction waste Three-layer landfill cover Water infiltration