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ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating BCL2–BECN1 interaction

Acta Pharmaceutica Sinica B 2024年第5期14卷 2026-2038页

作者： Shiqiang Xu Qilian Ma Junwen Shen Ningning Li Shan Sun Nana Wang Yang Chen Chunsheng Dong kin yip tam Jochen H.M.Prehn Hongfeng Wang Zheng Ying Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences Soochow UniversitySuzhou 215123China MOE Key Laboratory of Geriatric Diseases and Immunology College of Pharmaceutical SciencesSuzhou Medical College of Soochow UniversitySuzhou 215123China Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development Soochow UniversitySuzhou 215123China Dept.of Physiology&Medical Physics and FUTURE-NEURO Research Centre Royal College of Surgeons in IrelandDublin D02 YN77Ireland Faculty of Health Sciences University of MacaoTaipaMacao 999078China Insititutes of Biology and Medical Science Soochow UniversitySuzhou 215123China

Growing evidences indicate that dysfunction of autophagy contributes to the disease pathogenesis of amyotrophic lateral sclerosis(ALS)and frontotemporal dementia(FTD),two neurodegenerative *** GGGGCC·GGCCCC repeat RNA expansion in chromosome 9 open reading frame 72(C9orf72)is the most genetic cause of both ALS and *** to the previous studies,GGGGCC·GGCCCC repeat undergoes the unconventional repeat-associated non-ATG translation,which produces dipeptide repeat(DPR)*** there is a growing understanding that C9orf72 DPRs have a strong ability to harm neurons and induce C9orf72-linked ALS/FTD,whether these DPRs can affect autophagy remains *** the present study,we find that poly-GR and poly-PR,two arginine-containing DPRs which display the most cytotoxic properties according to the previous studies,strongly inhibit starvation-induced ***,our data indicate that arginine-rich DPRs enhance the interaction between BCL2 and BECN1/Beclin 1 by inhibiting BCL2 phosphorylation,therefore they can impair autophagic clearance of neurodegenerative disease-associated protein aggregates under starvation condition in ***,our study not only highlights the role of C9orf72 DPR in autophagy dysfunction,but also provides novel insight that pharmacological intervention of autophagy using SW063058,a small molecule compound that can disrupt the interaction between BECN1 and BCL2,may reduce C9orf72 DPR-induced neurotoxicity.

关键词： Amyotrophic lateral sclerosis Frontotemporal dementia C9orf72 Autophagy BCL2 BECN1/Beclin 1 Dipeptide repeat Neurodegeneration

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Pathological mechanisms and therapeutic strategies for Alzheimer's disease

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Neural Regeneration Research 2022年第3期17卷 543-549页

作者： Yaojun Ju kin yip tam Faculty of Health Sciences University of MacaoAvenida de UniversidadeTaipaMacao Special Adiministrative RegionChina

Alzheimer's disease is a rather complex neurodegenerative disease,which is attributed to a combination of multiple *** the many pathological pathways,synaptic dysfunctions,such as synapses loss and deficits in synaptic plasticity,were thought to be strongly associated with cognitive *** deficiencies in various sorts of neurotransmissions are responsible for the multifarious neurodegenerative symptoms in Alzheimer's disease,for example,the cholinergic and glutamatergic deficits for cognitive decline,the excitatory and inhibitory neurotransmission dyshomeostasis for synaptic plasticity deficits and epileptiform symptoms,and the monoamine neurotransmission for neuropsychiatric *** cascade hypothesis is the most popular pathological theory to explain Alzheimer's disease pathogenesis and attracts considerable *** lines of genetic and pathological evidence support the predominant role of amyloid beta in Alzheimer's disease *** tangles assembled by microtubule-associated protein tau are other important histopathological characteristics in Alzheimer's disease *** of tau toxicity was proved to lead to neuron damage,neuroinflammation and oxidative stress in *** is the main risk factor of neurodegenerative diseases,and is associated with inflammation,oxidative stress,reduced metabolism,endocrine insufficiencies and organ *** aging related risk factors were also proved to be some of the risk factors contributing to Alzheimer's *** Alzheimer's disease drug development,many good therapeutic strategies have been investigated in clinical ***,complex mechanism of Alzheimer's disease and the interplay among different pathological factors call for the come out of allpowerful therapies with multiple curing *** review seeks to summarize some of the representative treatments targeting different pathological pathways currently under clinical ***

关键词： Alzheimer's disease pathological pathways drug development multiple pathologies

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Analysis of an Unconditionally Stable Explicit Finite-difference Time-domain Method

Analysis of an Unconditionally Stable Explicit Finite-differ...

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2002海峡两岸三地无线科技研讨会

作者： Man-kin Sun, Wai-yip tam Department of Electronic and Information Engineering, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong, China

In this paper, an unconditionally stable explicit finite-difference time-domain (FDTD) method is proposed. The method is derived by applying the Durfort-Frankel method to approximate the spatial deri

关键词： FDTD stability numerical dispersion

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Peripheral corneal ulcer secondary to acquired eyelash trichomegaly following treatment with erlotinib in Asia:a case report

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International Journal of Ophthalmology(English edition) 2023年第3期16卷 468-469页

作者： kin-Man tam Iat-Fan Lai Department of Ophthalmic Center Kiang Wu HospitalMacao 999078China

Dear Editor,Erlotinib is an epidermal growth factor receptor (EGFR)inhibitor used in the treatment of non-small cell lung *** side effects of erlotinib include rash and diarrhea,while eyelash trichomegaly and hair dis... 详细信息

关键词： diarrhea treatment ulcer

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Cloaking nanosecond events at any time

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Frontiers of Optoelectronics 2020年第2期13卷 188-189页

作者： Bowen LI Kenneth kin-yip WONG Department of Electrical Computerand Energy EngineeringUniversity of ColoradoBoulderColoradoUSA Department of Electrical and Electronic Engineering The University of Hong KongHong KongChina

The concept of cloaking has never failed to fascinate scientific *** recent years,the idea has ignited a whole new trend of research effort when extended to temporal domain.A typical temporal cloak conceals events from probing light by creating a temporal intensity gap(cloaking time)that will later be closed back by manipulating the speed of light leveraging the chromatic dispersion in dielectric media.

关键词： domain. dielectric dispersion

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DYNAMIC MODEL AND SIMULATION OF A NOVEL ELECTRO-HYDRAULIC FULLY VARIABLE VALVE SYSTEM FOR FOUR-STROKE AUTOMOTIVE ENGINES

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Chinese Journal of Mechanical Engineering 2007年第5期20卷 80-86页

作者： WONG Pak-kin tam Lap-mou LI Ke Department of Electromechanical Engineering Faculty of Science and Technology University of Macao Macao China

在现代四击的引擎技术，可变阀门预定和电梯控制提议潜力为做一台高效的引擎受益。去四击的汽车的引擎的一列新奇电镀物品水力的充分可变的阀门火车被介绍。阀门火车系统和它的动态分析的非线性的数学模型的构造也被介绍。试验性并且模... 详细信息

在现代四击的引擎技术，可变阀门预定和电梯控制提议潜力为做一台高效的引擎受益。去四击的汽车的引擎的一列新奇电镀物品水力的充分可变的阀门火车被介绍。阀门火车系统和它的动态分析的非线性的数学模型的构造也被介绍。试验性并且模拟结果证明新奇电镀物品水力的阀门火车能完成充分可变的阀门预定和电梯控制。因而，不同负担和速度上的引擎表演将显著地被增加。技术也允许消除传统在汽油引擎和增加引擎设计灵活性扼杀阀门。

关键词：变速发动机动力模型模拟实验电镀

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Surgical outcomes for unilateral superior oblique palsy in Chinese population: a retrospective study

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International Journal of Ophthalmology(English edition) 2015年第1期8卷 107-112页

作者： Gordon Shing kin Yau Victor Tak Yau tam Jacky Wai yip Lee Theo Tak Kwong Chan Can Yin Fun Yuen Department of Ophthalmology Caritas Medical Centre Department of Anatomy Faculty of MedicineUniversity of Hong Kong

AIM: To evaluate the outcome after surgery for unilateral superior oblique(SO) palsy in ***: The medical records of 39 patients that underwent surgery for unilateral SO palsy between January 2003 and December 2012 at Caritas Medical Centre, Hong Kong, were retrospectively reviewed. All surgeries were performed by a single surgeon. Pre-operative assessments for vertical deviation, cyclo-deviation, and Knapp’s classification were obtained to determine the nature and degree of surgical *** deviation was measured at 1wk; 1, 6mo and on last follow-up day post-operatively. Cyclo-deviation was measured on last follow-up day ***: During the 10 y period, 39 subjects were recruited. The most common etiology was congenital(94.9%). Knapp’s Type III(66.7%) and Type I(12.8%)classifications were the most common subtypes. To treat SO palsy, the most common surgical procedures were:isolated inferior oblique(IO) anteriorization(41.0%),isolated IO myectomy(10.3%), and isolated IO recession(10.3%). At 3.5 ±2.1y post-operatively, the vertical deviation was significantly reduced(15.1 ±6.2 PD versus0.5±1.4 PD, P <0.0001) without significant improvement in cyclo-deviation(P =0.5). Initial vertical deviation was correlated with cyclo-torsion(r =0.4, P =0.007). Those with over-correction had greater initial vertical deviation(19.4±7.2 PD versus 13.2±4.3 PD, P =0.003). After a single operation, 84.6% of subjects achieved a vertical deviation within ±3 PD.· CONCLUSION: The majority of subjects achieved corrected vertical deviation after a single surgery although there was no improvement in *** with over-correction of primary position deviation had greater preoperative vertical deviation and it may be related to simultaneous multiple muscle surgery.

关键词： superior oblique palsy vertical deviation surgery diplopia

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Ignition Pattern Analysis for Automotive Engine Trouble Diagnosis Using Wavelet Packet Transform and Support Vector Machines

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Chinese Journal of Mechanical Engineering 2011年第5期24卷 870-878页

作者： VONG Chi-man WONG Pak-kin tam Lap-mou ZHANG Zaiyong Department of Computer and Information Science Faculty of Science and Technology University of Macao Macao China Department of Electromechanical Engineering Faculty of Science and Technology University of Macao Macao China

Engine spark ignition is an important source for diagnosis of engine *** on the waveform of the ignition pattern,a mechanic can guess what may be the potential malfunctioning parts of an engine with his/her experience and ***,this manual diagnostic method is imprecise because many spark ignition patterns are very ***,a diagnosis needs many trials to identify the malfunctioning *** the mechanic needs to disassemble and assemble the engine parts for *** tackle this problem,an intelligent diagnosis system was established based on ignition ***,the captured patterns were normalized and *** wavelet packet transform（WPT） was employed to extract the representative features of the ignition ***,a classification system was constructed by using multi-class support vector machines（SVM） and the extracted *** classification system can intelligently classify the most likely engine fault so as to reduce the number of diagnosis *** results show that SVM produces higher diagnosis accuracy than the traditional multilayer feedforward neural *** is the first trial on the combination of WPT and SVM to analyze ignition patterns and diagnose automotive engines.

关键词： automotive engine ignition pattern diagnosis pattern classification wavelet packet transform support vector machines.

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Photoelectrochemical degradation of Methylene Blue with β-PbO_2 electrodes driven by visible light irradiation

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Journal of Environmental Sciences 2011年第6期23卷 998-1003页

作者： Guoting Li HoYin yip kin Hang Wong Chun Hu Jiuhui Qu Po Keung Wong Department of Environmental and Municipal Engineering North China University of Water Conservancy and Electric Power Zhengzhou 450011 China School of Life Sciences The Chinese University of Hong Kong Shatin N.T. Hong Kong SAR China State Key Laboratory of Environmental Aquatic Chemistry Research Center for Eco-Environmental Sciences Chinese Academy of Sciences Beifing 100085 China

β-PbO2 electrodes were prepared by electro-deposition and characterized by scanning electron microscopy,X-ray diffraction,X-ray photoelectron spectroscopy,and linear sweep *** confirmed pure β-PbO2 crystals were on the electrode and it had a high oxygen evolution *** photoactivity and photoelectrochemical（PEC） properties of the β-PbO2 electrode were investigated under visible light irradiation（λ 〉 420 nm） for the decolorization of Methylene *** first-order kinetics parameter（Kapp） for dye decolorization using the β-PbO2 electrode achieved 6.71×10-4 min-1 under visible light irradiation,which indicated its excellent visible light-induced *** Kapp of the PEC process was as much as 1.41×10-3 min-1 and was 1.71 times that of visible light irradiation or electrolysis even in the presence of the β-PbO2 electrode.A significant synergetic effect was observed in the PEC *** also employed TiO2 modified β-PbO2 electrodes in this test,which revealed that the TiO2 immobilized on the β-PbO2 electrode inhibited the visible light-induced PEC efficiency despite the amount of TiO2 used for electrode *** β-PbO2 electrode was also superior to the dimensionally stable anode（Ti/Ru0.3Ti0.7O2） in visible light-induced photoactivity and PEC efficiency.

关键词： photocatalysis photoelectrochemical process visible light β-PbO2 electrode

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Virtual reality based multiple life skill training for intellectual disability:A multicenter randomized controlled trial

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Engineered Regeneration 2022年第2期3卷 121-130页

作者： James Chung-Wai Cheung Ming Ni Andy Yiu-Chau tam Tim Tin-Chun Chan Alyssa Ka-Yan Cheung Ocean Yu-Hong Tsang Chi-Bun yip Wing-Kai Lam Duo Wai-Chi Wong Department of Biomedical Engineering Faculty of EngineeringThe Hong Kong Polytechnic UniversityHong Kong 999077China Research Institute for Smart Ageing The Hong Kong Polytechnic UniversityHong Kong 999077China Jockey Club Smart Ageing Hub Department of Biomedical EngineeringFaculty of EngineeringThe Hong Kong Polytechnic UniversityHong Kong 999077China Department of Orthopaedics Pudong New Area People’s Hospital Affiliated to Shanghai Jiaotong UniversityShanghai 201299China Social Service Department Yan Chai HospitalHong Kong 999077China C2 Innovations and Research Limited Hong Kong 999077China Department of kinesiology Shenyang Sport UniversityShenyang 110102China Sports Information and External Affairs Centre Hong Kong Sports InstituteHong Kong 999077China

Life skill-based training is essential for intellectual disabled individuals to regain autonomy and social *** reality(VR)could deliver a nascent application that is more engaging and *** objective of this study was to evaluate the training effects of the VR-based multiple life skill training program on life skill perfor-mance,self-efficacy,memory,cognitive and behavioral functions via a multicenter randomized controlled trial.A total of 145 intellectual disabled participants were recruited for a randomized controlled trial with three in-tervention arms:VR(n=42);traditional(n=53);and control(n=50).The life skill tasks for the interventions included 1)grocery shopping,2)cooking,and 3)kitchen *** measures were performance scores for the three tasks,self-efficacy scale,digit span score,and Frontal Assessment Battery score,graded by blinded ***-after effects of each group were evaluated using separated Wilcoxon Signed-rank *** sig-nificantly improved cooking,cleaning performance,and memory span,while traditional training significantly improved shopping,cooking,and cleaning *** generalized estimating equation evaluated effects between groups adjusted for age,gender and intelligence quotient(IQ).VR had significantly larger improvement effects in cooking and cleaning than the control group and memory span compared to traditional training and controls *** appeared to be a significant confounder on the training *** work may consider developing artificial intelligence to customize programs depending on IQ level.

关键词： Mental retardation Intellectual development X-reality Immersive rehabilitation Metaverse

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