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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(DNAj.6/PARK19)and synaptoj.nin 1(SYNj./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 synaptoj.nin1/PARK20

Process,Material,and Regulatory Considerations for 3D Printed Medical Devices and Tissue Constructs

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Engineering 2024年第5期36卷 146-166页

作者： Wei Long ng j.a An chee Kai chua Singapore Centre for 3D Printing(SC3DP) School of Mechanical and Aerospace EngineeringNanyang Technological UniversitySingapore 639798Singapore Centre for Healthcare Education Entrepreneurship and Research@SUTD(CHEERS)Singapore University of Technology and DesignSingapore 487372Singapore

Three-dimensional(3D)printing is a highly automated platform that facilitates material deposition in a layer-by-layer approach to fabricate pre-defined 3D complex structures on *** is a highly promising technique for the fabrication of personalized medical devices or even patient-specific tissue *** type of 3D printing technique has its unique advantages and limitations,and the selection of a suitable 3D printing technique is highly dependent on its intended *** this review paper,we present and highlight some of the critical processes(printing parameters,build orientation,build location,and support structures),material(batch-to-batch consistency,recycling,protein adsorption,biocompatibility,and degradation properties),and regulatory considerations(sterility and mechanical properties)for 3D printing of personalized medical *** goal of this review paper is to provide the readers with a good understanding of the various key considerations(process,material,and regulatory)in 3D printing,which are critical for the fabrication of improved patient-specific 3D printed medical devices and tissue constructs.

关键词： 3D printing Bioprinting Biofabrication Medical devices Tissue constructs

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.Aj.y 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 j.int 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 inj.ry 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

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,inj.ries,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 inj.ries 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 j.n 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 ch.nges 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 j.ibir Sharma Amit Lal Eldwin j.ng Yul Koh j.shua E.-Y.Lee ch.ngkuo 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

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

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j.urnal 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 j.hn 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 adj.cent 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