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Dysfunction of synaptic endocytic trafficking in Parkinson's disease

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

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NADPH oxidase 4(NOX4)as a biomarker and therapeutic target in neurodegenerative diseases

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Neural Regeneration Research 2024年第9期19卷 1961-1966页

作者： Napissara Boonpraman Sun shin yi BK21 four Program Department of Medical SciencesSoonchunhyang UniversityAsanSouth Korea Department of Biomedical Laboratory Science Soonchunhyang UniversityAsanSouth Korea iConnectome Co.Ltd.CheonanSouth Korea

Diseases like Alzheimer’s and Parkinson’s diseases are defined by inflammation and the damage neurons undergo due to oxidative stress. A primary reactive oxygen species contributor in the central nervous system, NADPH oxidase 4, is viewed as a potential therapeutic touchstone and indicative marker for these ailments. This in-depth review brings to light distinct features of NADPH oxidase 4, responsible for generating superoxide and hydrogen peroxide, emphasizing its pivotal role in activating glial cells, inciting inflammation, and disturbing neuronal functions. Significantly, malfunctioning astrocytes, forming the majority in the central nervous system, play a part in advancing neurodegenerative diseases, due to their reactive oxygen species and inflammatory factor secretion. Our study reveals that aiming at NADPH oxidase 4 within astrocytes could be a viable treatment pathway to reduce oxidative damage and halt neurodegenerative processes. Adjusting NADPH oxidase 4 activity might influence the neuroinflammatory cytokine levels, including myeloperoxidase and osteopontin, offering better prospects for conditions like Alzheimer’s disease and Parkinson’s disease. This review sheds light on the role of NADPH oxidase 4 in neural degeneration, emphasizing its drug target potential, and paving the path for novel treatment approaches to combat these severe conditions.

关键词： Alzheimer’s disease astrocytes mitochondrial dysfunction myeloperoxidase NADPH oxidase 4 NADPH oxidase 4 inhibitors neurodegenerative diseases osteopontin Parkinson’s disease reactive oxygen species

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Advances of machine learning in materials science: Ideas and techniques

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Frontiers of physics 2024年第1期19卷 155-194页

作者： Sue Sin Chong yi Sheng ng Hui-Qiong Wang Jin-Cheng Zheng Department of New Energy Science and Engineering Xiamen University MalaysiaSepang 43900Malaysia Engineering Research Center of Micro-nano Optoelectronic Materials and Devices Ministry of EducationFujian Key Laboratory of Semiconductor Materials and ApplicationsCI Center for OSEDand Department of PhysicsXiamen UniversityXiamen 361005China

In this big data era, the use of large dataset in conjunction with machine learning (ML) has been increasingly popular in both industry and academia. In recent times, the field of materials science is also undergoing a big data revolution, with large database and repositories appearing everywhere. Traditionally, materials science is a trial-and-error field, in both the computational and experimental departments. With the advent of machine learning-based techniques, there has been a paradigm shift: materials can now be screened quickly using ML models and even generated based on materials with similar properties;ML has also quietly infiltrated many sub-disciplinary under materials science. However, ML remains relatively new to the field and is expanding its wing quickly. There are a plethora of readily-available big data architectures and abundance of ML models and software;The call to integrate all these elements in a comprehensive research procedure is becoming an important direction of material science research. In this review, we attempt to provide an introduction and reference of ML to materials scientists, covering as much as possible the commonly used methods and applications, and discussing the future possibilities.

关键词： machine learning materials science

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Analysis of Critical Incidents during Anesthesia in a Tertiary Hospital

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International Journal of Clinical Medicine 2016年第5期7卷 320-333页

作者： Ling Antonia Zeng shin yi ng Sze ying Thong Department of Anaesthesia Singapore General Hospital Singapore City Singapore

Introduction: Critical incident monitoring is important in quality improvement as it identifies potential risks to patients by analyzing adverse events or near-misses. Methods: This study analyses the reported incidents in a tertiary hospital over a 4-year period. Results: A total of 441 incidents were reported out of 98,502 anesthetics performed during the study period. Of these incidents, 67 resulted in no harm caused, 116 with unanticipated ICU admissions and 20 mortalities. The odds of having a critical incident increased with ASA status: from an odds ratio of 2.08 (95% CI: 1.58 to 2.74) for ASA 2 patients compared to ASA1, to OR of 13.70 (5.91 to 31.74) in ASA 5 compared to ASA 1. Critical incidents also have higher odds occurring out of hours (OR 1.7 (1.45 to 2.23) compared to daytime hours (08:00-17:00). They occurred most commonly in maintenance phase (142, 32.7%), followed by induction (120, 27.6%). The most common types of incidents include airway and respiratory (110, 24.9%) followed by drug related incidents (67, 15.2%). Human error was attributed as a significant contributing factor in 276 incidents (61.5%) followed by patient factors in 112 incidents (25.4%). Mitigating factors such as vigilance by staff involved were significant in 136 incidents (30.3%). Conclusion: Higher ASA status appears to be the most important factor associated with actual or potential patient harm in our study. Also significant, was time of incident, with incidents more likely out of hours. Critical incident reporting is a valuable part of quality assurance. We should continue to invest in incident reporting, incident analysis and improvement plans.

关键词： Critical Incidents Anaesthesia Patient Safety Human Error Complications

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Understanding the correlation between energy-state mismatching and open-circuit voltage loss in bulk heterojunction solar cells

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Carbon Energy 2024年第5期6卷 164-174页

作者： Hyun-Seock Yang Danbi Kim Chang-Mok Oh Vellaiappillai Tamilavan Pesi MHangoma Hojun yi Bo RLee Insoo shin In-Wook Hwang Sung Heum Park Pukyong National University BusanRepublic of Korea Clarendon Laboratory University of OxfordOxfordUK Institute of Energy Transport and Fusion Research Pukyong National UniversityBusanRepublic of Korea Advanced Photonics Research Institute Gwangju Institute of Science and TechnologyGwangjuRepublic of Korea Department of Chemical and Biomolecular Engineering Tandon School of EngineeringNew York UniversityBrooklynNew YorkUSA

Photoinduced intermolecular charge transfer(PICT)determines the voltage loss in bulk heterojunction(BHJ)organic photovoltaics(OPVs),and this voltage loss can be minimized by inducing efficient PICT,which requires energy-state matching between the donor and acceptor at the BHJ ***,both geometrically and energetically accessible delocalized state matching at the hot energy level is crucial for achieving efficient *** this study,an effective method for quantifying the hot state matching of OPVs was *** degree of energy-state matching between the electron donor and acceptor at BHJ interfaces was quantified using a mismatching factor(MF)calculated from the modified optical density of the ***,the correlation between the open-circuit voltage(Voc)of the OPV device and energy-state matching at the BHJ interface was investigated using the calculated *** OPVs with small absolute MF values exhibited high Voc *** result clearly indicates that the energy-state matching between the donor and acceptor is crucial for achieving a high Voc in *** the MF indicates the degree of energy-state matching,which is a critical factor for suppressing energy loss,it can be used to estimate the Voc loss in OPVs.

关键词： bulk heterojunction open circuit voltage organic photovoltaics photoinduced charge transfer voltage loss

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Prevalence and risk factors of depression among patients with perianal fistulizing Crohn’s disease

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World Journal of Psychiatry 2024年第5期14卷 715-725页

作者： Jing Li Wing-yi ng Li-Chao Qiao Fen Yuan Xing Lan Li-Bei Zhu Bo-Lin Yang Zhong-Qiu Wang Department of Radiology Jiangsu Province Hospital of Chinese Medicine Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029Jiangsu ProvinceChina Department of Acupuncture and Rehabilitation Jiangsu Province Hospital of Chinese Medicine Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029Jiangsu ProvinceChina Department of Colorectal Surgery Jiangsu Province Hospital of Chinese Medicine Affiliated Hospital of Nanjing University of Chinese MedicineNanjing 210029Jiangsu ProvinceChina

BACKGROUND Psychological distress,especially depression,associated with perianal fistulizing Crohn’s disease(PFCD)is widespread and ***,there is a surprising paucity of studies to date that have sought to identify the prevalence and risk factors of depression associated with *** To estimate the prevalence of depressive symptoms and investigate the depression-related risk factors in patients with *** The study was conducted in the form of survey and clinical data collection via questionnaire and specialized medical *** symptoms,life quality,and fatigue severity of patients with PFCD were assessed by Patient Health Questionnaire-9,Inflammatory Bowel Disease Patient Quality of Life Questionnaire(IBDQ),and Inflammatory Bowel Disease(IBD)Fatigue Patient Self-assessment *** basic demographic information,overall disease features,perianal clinical information,and laboratory inflammation indicators were also *** regression analysis was ultimately used to ascertain the risk factors of depression associated with *** A total of 123 patients with PFCD were involved,and 56.91%were suffering from *** to multivariate logistic regression analysis,Perianal Disease Activity Index(PDAI)score[odds ratio(OR)=0.69,95%confidence interval(CI):0.50 to 0.95],IBDQ score(OR=0.93,95%CI:0.88 to 0.97),modified Van Assche index(OR=1.24,95%CI:1.01 to 1.53),and IBD Fatigue score(OR=1.72,95%CI:1.23 to 2.42)were independent risk factors of depression-related prevalence among patients with PFCD(Png perianal modified Van Assche index(βvalue=0.166,95%CI:0.02 to 0.31)and decreasing IBDQ score(βvalue=-0.116,95%CI:-0.14 to-0.09)were independently associated with the severity of depression(P<0.05).CONCLUSION Depressive symptoms in PFCD patients have significantly high *** score,modified Van Assche index,quality of life,and fatigue severity

关键词： Crohn’s disease Fistula Depression Inflammatory bowel diseases Risk factors

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Manipulating Nanowires in Interconnecting Layer for Efficient Tandem Organic Photovoltaics

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Chinese Journal of Chemistry 2024年第4期42卷 377-383页

作者： Yanjie Tang Jiaming Fu Hao Li Du Hyeon Ryu Won Suk shin Jianqi Zhang yi Yang yiming Yang Deyuan Li Zhong Zheng Shaoqing Zhang Jianhui Hou School of Chemistry and Biology Engineering University of Science and Technology Beijing(USTB)Beijing100083 China State Key Laboratory of Polymer Physics and Chemistry Beijing National Laboratory for Molecular SciencesInstitute of ChemistryChinese Academy of Sciences(ICCAS)Beijing100190 China Energy Materials Research Center Korea Research Institute of Chemical Technology(KRICT)Advanced Materials&Chemical EngineeringUniversity of Science&Technology(UST)Korea The National Center for Nanoscience and Technology(NCNST) Beijing100190 China University of Chinese Academy of Sciences Beijing(UCAS) Beijing100049 China China Railway Resources Group Survey and Design Co.Ltd. LangfangHebei065000 China

Owing to the function of manipulating light absorption distribution,tandem organic solar cells containing multiple sub-cells exhibit high power conversion ***,there is a substantial challenge in precisely controlling the inter-subcells carrier migration which determines the balance of charge transport across the entire *** conductivity of"nanowires"-like conducting channel in interconnecting layer between sub-cells should be improved which calls for fine engineering on the morphology of polyelectrolyte in interconnecting ***,we develop a simple method to effectively manipulating the domains of conductive components in commercially available polyelectrolyte PEDOT:*** use of poor solvent could effectively modify the configuration of polystyrene sulfonic acid and thus the space for conductive *** on our strategy,the insulated shells wrapping conductive domains are thinned and the efficiencies of tandem organic solar cells are *** believe our method might provide guidance for the manufacture of tandem organic solar cells.

关键词： Tandem organic solar cells Power conversion efficiency interconnecting layer Tunneling junction Interfacial layers Conformationanalysis π-πstacking Donor-acceptorsystems

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Application of artifcial intelligence in cataract management:current and future directions

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Eye and Vision 2024年第1期10卷 21-30页

作者： Laura Gutierrez Jane Sujuan Lim Li Lian Foo Wei Yan ng Michelle yip Gilbert Yong San Lim Melissa Hsing yi Wong Allan Fong Mohamad Rosman Jodhbir Singth Mehta Haotian Lin Darren Shu Jeng Ting Daniel Shu Wei Ting Singapore Eye Research Institute SingaporeSingapore Singapore National Eye Center 11 Third Hospital AvenueSingapore 168751Singapore Academic Ophthalmology School of MedicineUniversity of NottinghamNottinghamUK Zhongshan Ophthalmic Center Sun Yet Sen UniversityGuangzhouChina

The rise of artifcial intelligence(AI)has brought breakthroughs in many areas of *** ophthalmology,AI has delivered robust results in the screening and detection of diabetic retinopathy,age-related macular degeneration,glaucoma,and retinopathy of *** management is another feld that can beneft from greater AI *** is the leading cause of reversible visual impairment with a rising global clinical *** diagnosis,monitoring,and surgical management are necessary to address this *** addition,patients in large developing countries often sufer from limited access to tertiary care,a problem further exacerbated by the ongoing COVID-19 *** on the other hand,can help transform cataract management by improving automation,efcacy and overcoming geographical ***,AI can be applied as a telediagnostic platform to screen and diagnose patients with cataract using slit-lamp and fundus *** utilizes a deep-learning,convolutional neural network(CNN)to detect and classify referable cataracts ***,some of the latest intraocular lens formulas have used AI to enhance prediction accuracy,achieving superior postoperative refractive results compared to traditional ***,AI can be used to augment cataract surgical skill training by identifying diferent phases of cataract surgery on video and to optimize operating theater workfows by accurately predicting the duration of surgical ***,some AI CNN models are able to efectively predict the progression of posterior capsule opacifcation and eventual need for YAG laser *** advances in AI could transform cataract management and enable delivery of efcient ophthalmic *** key challenges include ethical management of data,ensuring data security and privacy,demonstrating clinically acceptable performance,improving the generalizability of AI models across heterogeneous populations,and improving the trust of e

关键词： Artifcial intelligence Telemedicine Cataract Cataract screening Cataract surgery IOL calculations Biometry Machine learning

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SARS-CoV-2 aberrantly elevates mitochondrial bioenergetics to induce robust virus propagation

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2702-2715页

作者： Hye Jin shin Wooseong Lee Keun Bon Ku Gun Young Yoon Hyun-Woo Moon Chonsaeng Kim Mi-Hwa Kim Yoon-Sun yi Sangmi Jun Bum-Tae Kim Jong-Won Oh Aleem Siddiqui Seong-Jun Kim Department of Convergent Research of Emerging Virus Infection Korea Research Institute of Chemical TechnologyDaejeon 34114Republic of Korea Gyeongnam Biohealth Research Center Gyeongnam Branch InstituteKorea Institute of ToxicologyJinju 52834Republic of Korea Center for Research Equipment Korea Basic Science InstituteCheongjuChungcheongbuk-do 28119Republic of Korea Department of Biotechnology Yonsei UniversitySeoul 03722Republic of Korea Division of Infectious Diseases School of MedicineUniversity of CaliforniaSan DiegoLa JollaCA 92093USA Present address:Department of Microbiology Chungnam National University School of MedicineDaejeon 35015Republic of Korea

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a‘highly transmissible respiratory pathogen,leading to severe multiorgan ***,knowledge regarding SARS-CoV-2-induced cellular alterations is *** this study,we report that SARSCoV-2 aberrantly elevates mitochondrial bioenergetics and activates the EGFR-mediated cell survival signal cascade during the early stage of viral ***-CoV-2 causes an increase in mitochondrial transmembrane potential via the SARS-CoV-2 RNAnucleocapsid cluster,thereby abnormally promoting mitochondrial elongation and the OXPHOS process,followed by enhancing ATP ***,SARS-CoV-2 activates the EGFR signal cascade and subsequently induces mitochondrial EGFR trafficking,contributing to abnormal OXPHOS process and viral *** EGFR inhibitors remarkably reduce SARS-CoV-2 propagation,among which vandetanib exhibits the highest antiviral *** of SARS-CoV-2-infected cells with vandetanib decreases SARS-CoV-2-induced EGFR trafficking to the mitochondria and restores SARS-CoV-2-induced aberrant elevation in OXPHOS process and ATP generation,thereby resulting in the reduction of SARS-CoV-2 ***,oral administration of vandetanib to SARS-CoV-2-infected hACE2 transgenic mice reduces SARS-CoV-2 propagation in lung tissue and mitigates SARS-CoV-2-induced lung *** also exhibits potent antiviral activity against various SARS-CoV-2 variants of concern,including alpha,beta,delta and omicron,in in vitro cell culture *** together,our findings provide novel insight into SARS-CoV-2-induced alterations in mitochondrial dynamics and EGFR trafficking during the early stage of viral infection and their roles in robust SARS-CoV-2 propagation,suggesting that EGFR is an attractive host target for combating COVID-19.

关键词： alterations aberrant thereby

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Quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: A comparison between Omicron BA.2 and non-VOC-D614G

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Virologica Sinica 2024年第2期39卷 218-227页

作者： Zigui Chen Rita Way yin ng Grace Lui Lowell Ling Agnes S.Y.Leung Chit Chow Siaw Shi Boon Wendy C.S.Ho Maggie Haitian Wang Renee Wan yi Chan Albert Martin Li David Shu Cheong Hui Paul Kay Sheung Chan Department of Microbiology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Anaesthesia and Intensive Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Paediatrics Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Anatomical and Cellular Pathology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Jockey Club School of Public Health and Primary Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Stanley Ho Centre for Emerging Infectious Diseases Faculty of MedicineThe Chinese University of Hong KongHong KongChina

The SARS-CoV-2 Omicron variants are notorious for their transmissibility,but little is known about their subgenomic RNA(sgRNA)*** study applied RNA-seq to delineate the quantitative and qualitative profiles of canonical sgRNA of 118 respiratory samples collected from patients infected with Omicron BA.2 and compared with 338 patients infected with non-variant of concern(non-VOC)-D614G.A unique characteristic profile depicted by the relative abundance of 9 canonical sgRNAs was reproduced by both BA.2 and non-VOCD614G regardless of host gender,age and presence of ***,such profile was lost in samples with low viral load,suggesting a potential application of sgRNA pattern to indicate viral activity of individual patient at a specific time point.A characteristic qualitative profile of canonical sgRNAs was also reproduced by both BA.2 and *** presence of a full set of canonical sgRNAs carried a coherent correlation with crude viral load(AUC¼0.91,95%CI 0.88–0.94),and sgRNA ORF7b was identified to be the best surrogate marker allowing feasible routine application in characterizing the infection status of individual *** potentials in using sgRNA as a target for vaccine and antiviral development are worth pursuing.

关键词： Coronavirus SARS-CoV-2 Omicron BA.2 Non-VOC-D614G RNA-seq Subgenomic RNA(sgRNA)

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