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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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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 zh.ng 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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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 zh.ng-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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NONMONOTONE LOCAL MINIMAX METHODS FOR FINDIng MULTIPLE SADDLE POINTS

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Journal of Computational Mathematics 2024年第3期42卷 851-884页

作者： Wei Liu Ziqing Xie Wenfan yi South China Research Center for Applied Mathematics and Interdisciplinary Studies South China Normal UniversityGuangzhou 510631China Key Laboratory of Computing and Stochastic Mathematics(Ministry of Education) Hunan Normal UniversityChangshaHunan 410081China Hunan Provincial Key Laboratory of Intelligent Information Processing and Applied Mathematics School of MathematicsHunan UniversityChangshaHunan 410082China

In this paper,by designing a normalized nonmonotone search strategy with the BarzilaiBorwein-type step-size,a novel local minimax method(LMM),which is a globally convergent iterative method,is proposed and analyzed to find multiple(unstable)saddle points of nonconvex functionals in Hilbert *** to traditional LMMs with monotone search strategies,this approach,which does not require strict decrease of the objective functional value at each iterative step,is observed to converge faster with less ***,based on a normalized iterative scheme coupled with a local peak selection that pulls the iterative point back onto the solution submanifold,by generalizing the zh.ng-Hager(zh)search strategy in the optimization theory to the LMM framework,a kind of normalized zh-type nonmonotone step-size search strategy is introduced,and then a novel nonmonotone LMM is *** feasibility and global convergence results are rigorously carried out under the relaxation of the monotonicity for the functional at the iterative ***,in order to speed up the convergence of the nonmonotone LMM,a globally convergent Barzilai-Borwein-type LMM(GBBLMM)is presented by explicitly constructing the Barzilai-Borwein-type step-size as a trial step-size of the normalized zh-type nonmonotone step-size search strategy in each ***,the GBBLMM algorithm is implemented to find multiple unstable solutions of two classes of semilinear elliptic boundary value problems with variational structures:one is the semilinear elliptic equations with the homogeneous Dirichlet boundary condition and another is the linear elliptic equations with semilinear Neumann boundary *** numerical results indicate that our approach is very effective and speeds up the LMMs significantly.

关键词： Multiple saddle points Local minimax method Barzilai-Borwein gradient method Normalized nonmonotone search strategy Global convergence

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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 zh.ngshan 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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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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Fangji Fuling Decoction Alleviates Sepsis by Blocking MAPK14/FOXO3A Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第3期30卷 230-242页

作者： WAng yi CHEN Ming-qi DAI Lin-feng zh.ng Hai-dong WAng Xing Department of Critical Care Medicine Changzhou Hospital of Traditional of Chinese Medicine Affiliated to Nanjing University of Chinese MedicineChangzhouJiangsu Province213000China Department of Critical Care Medicine Jiangsu Province Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese MedicineNanjing210029China

Objective:To examine the therapeutic effect of Fangji Fuling Decoction(FFD) on sepsis through network pharmacological analysis combined with in vitro and in vivo ***:A sepsis mouse model was constructed through intraperitoneal injection of 20 mg/kg lipopolysaccharide(LPS).RAW264.7 cells were stimulated by 250 ng/m L LPS to establish an in vitro cell *** pharmacology analysis identified the key molecular pathway associated with FFD in *** ectopic expression and depletion experiments,the effect of FFD on multiple organ damage in septic mice,as well as on cell proliferation and apoptosis in relation to the mitogen-activated protein kinase 14/Forkhead Box O 3A(MAPK14/FOXO3A) signaling pathway,was ***:FFD reduced organ damage and inflammation in LPS-induced septic mice and suppressed LPS-induced macrophage apoptosis and inflammation in vitro(Png pathway during *** confirmed by in vitro cell experiments,FFD inhibited the MAPK14 signaling pathway or FOXO3A expression to relieve LPS-induced macrophage apoptosis and inflammation(Png pathway to inhibit LPS-induced macrophage apoptosis in the lung tissue of septic mice(Png the MAPK14/FOXO3A signaling pathway.

关键词： sepsis Fangji Fuling Decoction mitogen-activated protein kinase 14/Forkhead Box O 3A signaling pathway inflammatory response apoptosis lung injury Chinese medicine

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Boson star superradiance

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Science China(Physics,Mechanics & Astronomy) 2024年第6期67卷 69-78页

作者： He-Yu Gao Paul M.Saffin yi-Jie Wang Qi-Xin Xie Shuang-Yong zhou School of Physical Sciences University of Science and Technology of ChinaHefei 230026China School of Physics and Astronomy University of NottinghamUniversity ParkNottingham NG72RDUK Interdisciplinary Center for Theoretical Study University of Science and Technology of ChinaHefei 230026China Peng Huanwu Center for Fundamental Theory Hefei 230026China

Recently,it has been realized that in some systems internal space rotation can induce energy amplification for scattered waves,similar to rotation in real *** particularly,it has been shown that energy extraction is possible for a Q-ball,a stationary non-topological soliton that is coherently rotating in its field *** this paper,we generalize the analysis to the case of boson stars,and show that the same energy extraction mechanism still works for boson stars.

关键词： superradiance boson star field space rotation

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High glucose reduces Nrf2-dependent cRAGE release and enhances inflammasome-dependent IL-1βproduction in monocytes:the modulatory effects of EGCG

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Food Science and Human Wellness 2024年第3期13卷 1531-1542页

作者： Chi-Hao Wu yin-Hsuan Chang Chin-Lin Hsu Sheng-yi Chen Gow-Chin Yen Graduate Programs of Nutrition Science School of Life ScienceTaiwan Normal UniversityTaipei 106209TaiwanChina Department of Food Science and Biotechnology Chung Hsing UniversityTaichung 40227TaiwanChina School of Nutrition Chung Shan Medical UniversityTaichung 40201TaiwanChina

Soluble receptor for advanced glycation end products(sRAGE)acts as a decoy sequestering of RAGE ligands,thus preventing the activation of the ligand-RAGE axis linking human ***,the molecular mechanisms underlying sRAGE remain *** this study,THP-1 monocytes were cultured in normal glucose(ng,5.5 mmol/L)and high glucose(HG,15 mmol/L)to investigate the effects of diabetesrelevant glucose concentrations on sRAGE and interleukin-1β(IL-1β)*** modulatory effects of epigallocatechin gallate(EGCG)in response to HG challenge were also *** enhanced intracellular reactive oxygen species(ROS)generation and RAGE *** secretion of sRAGE,including esRAGE and cRAGE,was reduced under HG conditions,together with the downregulation of a disintegrin and metallopeptidase 10(ADAM10)and nuclear factor erythroid 2-related factor 2(Nrf2)nuclear ***,the HG effects were counteracted by siRAGE and exacerbated by *** immunoprecipitation results showed that Nrf2 binding to the ADAM10 promoter and HG interfered with this *** data reinforce the notion that RAGE and Nrf2 might be sRAGE-regulating *** HG conditions,the treatment of EGCG reduced ROS generation and RAGE ***-stimulated cRAGE release was likely caused by the upregulation of the Nrf2-ADAM10 *** inhibited HG-mediated NLRP3 inflammasome activation at least partly by stimulating sRAGE,thereby reducing IL-1βrelease.

关键词： Epigallocatechin gallate(EGCG) Inflammasome Nuclear factor erythroid 2-related factor 2(Nrf2) Receptor for advanced glycation end products(RAGE) Soluble RAGE(sRAGE)

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Assessing recent recurrence after hepatectomy for hepatitis Brelated hepatocellular carcinoma by a predictive model based on sarcopenia

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World Journal of Gastroenterology 2024年第12期30卷 1727-1738页

作者： Hong Peng Si-yi Lei Wei Fan Yu Dai yi zh.ng Gen Chen Ting-Ting Xiong Tian-zhao Liu Yue Huang Xiao-Feng Wang Jin-Hui Xu Xin-Hua Luo Department of Infectious Diseases Guizhou Provincial People’s HospitalGuiyang 550002Guizhou ProvinceChina Department of Hepatobiliary Surgery Guizhou Provincial People’s HospitalGuiyang 550002Guizhou ProvinceChina

BACKGROUND Sarcopenia may be associated with hepatocellular carcinoma(HCC)following *** traditional single clinical variables are still insufficient to predict *** still lack effective prediction models for recent recurrence(time to recurrenceng cohort.A nomogram model was developed to predict the RFS of HCC patients,and its predictive performance was *** predictive efficacy of this model was evaluated using the receiver operating characteristic *** Multivariate analysis showed that sarcopenia[Hazard ratio(HR)=1.767,95%CI:1.166-2.678,Png/mL(HR=1.984,95%CI:1.307-3.011,P5 cm(HR=2.222,95%CI:1.285-3.842,Png cohort(sensitivity 81%,specificity 63%)and 0.773(95%CI:0.707-0.838)in the validation ***,a SAMD score≥110 was better to distinguish the high-risk group of postoperative recurrence of *** Sarcopenia is associated with recent recurrence after hepatectomy for hepatitis B-rel

关键词： Alpha-fetoprotein Hepatitis B virus Hepatectomy Hepatocellular carcinoma Nomogram Predictive models Recurrence Recurrence-free survival Risk factors Sarcopenia

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