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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

Geochemistry and mineral chemistry of the armoor granitoids,eastern dharwar craton: implications for the redox conditions and tectono-magmatic environment

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Acta Geochimica 2024年第1期43卷 110-133页

作者： A.Ajay Kumar ch.Ashok Department of Geology Osmania UniversityHyderabad 500007India CSIR-National Geophysical Research Institute UppalHyderabad 500007India

The mineralogical and geochemical characteristics of the K-rich granites from the Armoor granitic rocks in the northeastern portion of the Eastern Dharwar Craton(EDC) are *** order to understand its physicochemical conditions,the petrogenesis of the granitoid was explained from biotite chemistry and geochemical *** of mineral chemistry expose that compositionally,K-feldspar and plagioclase in Armoor granite rocks range from An0,Ab_(3-5.9),Or_(94-96.9) and An_(5-29,-Ab71.9-94.9),Or_(0-1.5),*** mineral chemistry of biotite crystals exhibits composition that varies from primary to re-equilibrated primary *** biotites from the Armoor granites generally exhibit an I-type trend,with calc-alkaline parental magma in a subduction *** chemistry of granites displays magnetite(oxidized)series nature,which has oxygen fugacity(fO_(2))=-15.1 to-16.7(log_(10) bar),under high oxidizing *** and pressure estimates for the crystallization of Armoor granites based on biotite composition are T=612-716 ℃ and 1.0-0.4 kbar,***,these rocks are metaluminous to slightly peraluminous and magnesian,with calc-alkaline potassiumrich *** the chondrite normalized REE diagram,the granites have positive europium anomalies;rich Sr/Y,(Dy/Yb)_(N) ratios and reduced Mg#,Rb/Sr,Rb,Sr indicate that the melting of earlier rocks,crystal accumulation and residual garnet source formed at high *** examined granites show that they are produced from the melting of crustal ***,the extensive analyses of the described Armoor granite suggest that they were produced by crust sources and developed under oxidizing conditions in subduction setting.

关键词： Armoor granites Oxygen fugacity Crystal accumulation Remelting Subduction

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

Bile acids,gut microbiota,and therapeutic insights in hepatocellular carcinoma

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Cancer Biology & Medicine 2024年第2期21卷 144-162页

作者： Yang Song Harry ch Lau Xiang Zhang jun Yu Institute of Digestive Disease and Department of Medicine and Therapeutics State Key Laboratory of Digestive DiseaseLi Ka Shing Institute of Health SciencesCUHK Shenzhen Research InstituteThe Chinese University of Hong KongHong KongChina Department of Gastroenterology Zhongshan Hospital Xiamen UniversityXiamen 361004China

Hepatocellular carcinoma(HCC)is a prevalent and aggressive liver *** interplay between bile acids(BAs)and the gut microbiota has emerged as a critical factor in HCC development and *** normal conditions,BA metabolism is tightly regulated through a bidirectional interplay between gut microorganisms and *** gut microbiota plays a critical role in BA metabolism,and BAs are endogenous signaling molecules that help maintain liver and intestinal *** note,dysbiotic changes in the gut microbiota during pathogenesis and cancer development can disrupt BA homeostasis,thereby leading to liver inflammation and fibrosis,and ultimately contributing to HCC ***,understanding the intricate interplay between BAs and the gut microbiota is crucial for elucidating the mechanisms underlying *** this review,we comprehensively explore the roles and functions of BA metabolism,with a focus on the interactions between BAs and gut microorganisms in ***,therapeutic strategies targeting BA metabolism and the gut microbiota are discussed,including the use of BA agonists/antagonists,probiotic/prebiotic and dietary interventions,fecal microbiota transplantation,and engineered *** summary,understanding the complex BA-microbiota crosstalk can provide valuable insights into HCC development and facilitate the development of innovative therapeutic approaches for liver malignancy.

关键词： Bile acid gut microbiota hepatocellular carcinoma therapeutics microbiota modulation

Cavity-agnostic acoustofluidic manipulations enabled by guided flexural waves on a membrane acoustic waveguide actuator

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Microsystems & Nanoengineering 2024年第2期10卷 153-171页

作者： Philippe Vachon Srinivas Merugu jaibir Sharma Amit Lal Eldwin j.ng Yul Koh joshua E.-Y.Lee chengkuo Lee Department of Electrical and Computer Engineering National University of SingaporeSingaporeSingapore Institute of Microelectronics Agency for ScienceTechnology and Research(A*STAR)SingaporeSingapore SonicMEMS Laboratory School of Electrical and Computer EngineeringCornell UniversityIthacaNYUSA School of Electrical and Data Engineering University of Technology SydneyUltimoNSWAustralia

This article presents an in-depth exploration of the acoustofluidic capabilities of guided flexural waves(GfWs)generated by a membrane acoustic waveguide actuator(MAWA).By harnessing the potential of GfWs,cavity-agnostic advanced particle manipulation functions are achieved,unlocking new avenues for microfluidic systems and lab-on-a-chip *** localized acoustofluidic effects of GfWs arising from the evanescent nature of the acoustic fields they induce inside a liquid medium are numerically investigated to highlight their unique and promising *** traditional acoustofluidic technologies,the GfWs propagating on the MAWA’s membrane waveguide allow for cavity-agnostic particle manipulation,irrespective of the resonant properties of the fluidic ***,the acoustofluidic functions enabled by the device depend on the flexural mode populating the active region of the membrane *** demonstrations using two types of particles include in-sessile-droplet particle transport,mixing,and spatial separation based on particle diameter,along with streaming-induced counter-flow virtual channel generation in microfluidic PDMS *** experiments emphasize the versatility and potential applications of the MAWA as a microfluidic platform targeted at lab-on-a-chip development and showcase the MAWA’s compatibility with existing microfluidic systems.

关键词： waveguide fluid cavity

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