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Effects of 17-allylamino-17-demethoxygeldanamycin (17-AAG) in transgenic mouse models of frontotemporal lobar degeneration and Alzheimer’s disease

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Translational Neurodegeneration 2013年第1期2卷 174-182页

作者： Shuk Wai Ho Yuk Tung Chanel Tsui Ting Ting Wong Stanley Kwok-Kuen Cheung William B Goggins lau ming yi Kwok Kin Cheng Larry Baum Department of Surgery The University of Hong KongPokfulamHong KongChina School of Biomedical Sciences(Pharmacology) The University of NottinghamNottinghamUK Department of Microbiology The University of Hong KongPokfulamHong KongChina School of Public Health and Primary Care The Chinese University of Hong KongShatinHong KongChina School of Pharmacy The Chinese University of Hong KongShatinHong KongChina

Alzheimer’s disease(AD),the most common dementia,is characterized by potentially neurotoxic aggregation of Aβ peptide and tau protein,and their deposition as amyloid plaques and neurofibrillary tangles(NFTs).Tau aggregation also occurs in other common neurodegenerative *** dementia(FTD)can be caused by tau mutations that increase the susceptibility of tau to hyperphosphorylation and aggregation,which may cause neuronal dysfunction and deposition of NFTs.17-allylamino-17-demethoxygeldanamycin(17-AAG)is a potent inhibitor of heat shock protein 90(Hsp90),a cytosolic chaperone implicated in the proper folding and functions of a repertoire of client proteins.17-AAG binds to Hsp90 and enhances degradation of Hsp90 client *** sought to determine whether 17-AAG can reduce Aβ and tau pathology in the brains of AD and FTD model mice expressing Aβ or P301L mutant tau,*** were randomized to receive 25,5,or 0 mg/kg 17-AAG thrice weekly from age eight to 11 *** was performed by rotarod test on motor function,on the area occupied by plaques in hippocampus or NFTs in medulla tissue sections,and on mortality.A high dose of 17-AAG tended to decrease NFTs in male mice(p=0.08).Further studies are required to confirm the effect of 17-AAG in diseases of tau aggregation.

关键词： Dementia Mouse Tangles Plaques

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Biphasic Cholinergic Modulation of Reverberatory Activity in Neuronal

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Neuroscience Bulletin 2023年第5期39卷 731-744页

作者： Xiao-Wei Li yi Ren Dong-Qing Shi Lei Qi Fang Xu Yanyang Xiao Pak-ming lau Guo-Qiang Bi CAS Key Laboratory of Brain Function and Disease School of Life SciencesDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230027China CAS Key Laboratory of Brain Connectome and Manipulation Interdisciplinary Center for Brain Informationthe Brain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsShenzhen 518055China

Acetylcholine(ACh)is an important neuromod-ulator in various cognitive ***,it is unclear how ACh influences neural circuit dynamics by altering cellular ***,we investigated how ACh influ-ences reverberatory activity in cultured neuronal *** found that ACh suppressed the occurrence of evoked reverberation at low to moderate doses,but to a much lesser extent at high ***,high doses of ACh caused a longer duration of evoked reverberation,and a higher occur-rence of spontaneous *** whole-cell recording from single neurons,we found that ACh inhibited excita-tory postsynaptic currents(EPSCs)while elevating neu-ronal firing in a dose-dependent ***,all ACh-induced cellular and network changes were blocked by muscarinic,but not nicotinic receptor *** computational modeling,we found that simulated changes in EPSCs and the excitability of single cells mimicking the effects of ACh indeed modulated the evoked network reverberation similar to experimental ***,ACh modulates network dynamics in a biphasic fashion,probably by inhibiting excitatory synaptic transmission and facilitating neuronal excitability through muscarinic signaling pathways.

关键词： Acetylcholine Neuronal network Reverberation Synaptic current Excitability

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Factors influencing the residence’s intention to adopt solar photovoltaic technology: a case study from Klang Valley, Malaysia

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Clean Energy 2021年第3期5卷 464-473页

作者： Wei-Yong Cheam Lin-Sea lau Chooi-yi Wei Universiti Tunku Abdul Rahman Kampus PerakFaculty of Business and FinanceNo 6Laluan Chemor Maju 16Taman Chemor Idaman Perak Chemor 31900Malaysia

Recently,the Malaysian government has targeted to achieve the 20%renewable-energy goal by *** the Malaysian government’s having taken initiatives in promoting the use of renewable energy for more than a decade,to date,more than three-quarters of the electricity supply in Peninsular Malaysia is generated from the burning of fossil ***,the development of renewable energy is still slow and in its *** current study intends to identify the predictors(environmentalism,cost,knowledge and personal innovativeness)that influence the residential intention to adopt solar photovoltaic(PV)in Klang *** study adopts the technology acceptance model as the theoretical framework to analyse the mediation effect on perceived ease of use and perceived usefulness between the determinants and the intention to adopt solar ***-administered questionnaires are used to collect data from non-solar PV users who stay in Klang *** equation modelling analysis was carried out on the 200 samples from data *** findings demonstrated that environmentalism is having a significant impact on the intention to adopt solar PV,followed by *** perceived usefulness mediates the relationship between the predictors and the intention to use solar PV,although no mediation effect was found for the perceived ease of ***,several implications are highlighted to the policymakers and solar-market practitioners to improve the existing policies and promote solar PV adoptions among residents.

关键词： determinants of public acceptance for solar PV public acceptance residence intention solar solar PV

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Repetitive transcranial magnetic stimulation for lower extremity motor function in patients with stroke:a systematic review and network meta-analysis

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Neural Regeneration Research 2021年第6期16卷 1168-1176页

作者： Yun-Juan Xie yi Chen Hui-Xin Tan Qi-Fan Guo Benson Wui-Man lau Qiang Gao Department of Rehabilitation Medicine West China HospitalSichuan UniversityChengduSichuan ProvinceChina Key Laboratory of Rehabilitation Medicine in Sichuan Province West China HospitalSichuan UniversityChengduSichuan ProvinceChina Department of Rehabilitation Sciences The Hong Kong Polytechnic UniversityHong Kong Special Administrative RegionChina

Transcranial magnetic stimulation,a type of noninvasive brain stimulation,has become an ancillary therapy for motor function *** previous studies have focused on the effects of repetitive transcranial magnetic stimulation(rTMS)on motor function in stroke *** have been relatively few studies on the effects of different modalities of rTMS on lower extremity motor function and corticospinal excitability in patients with *** MEDLINE,Embase,Cochrane Library,ISI Science Citation Index,Physiotherapy Evidence Database,China National Knowledge Infrastructure Library,and *** databases were *** or crossover randomized controlled trials that addressed the effectiveness of rTMS in patients with stroke,published from inception to November 28,2019,were *** pairwise meta-analysis was conducted using R version 3.6.1 with the“meta”*** network analysis using the Markov chain Monte Carlo algorithm was conducted to investigate the effectiveness of different rTMS protocol *** meta-analysis results of 18 randomized controlled trials regarding lower extremity motor function recovery revealed that low-frequency rTMS had better efficacy in promoting lower extremity motor function recovery than sham *** meta-analysis results of five randomized controlled trials demonstrated that highfrequency rTMS led to higher amplitudes of motor evoked potentials than low-frequency rTMS or sham *** findings suggest that rTMS can improve motor function in patients with stroke,and that low-frequency rTMS mainly affects motor function,whereas high-frequency rTMS increases the amplitudes of motor evoked *** highquality randomized controlled trials are needed to validate this *** work was registered in PROSPERO(registration ***42020147055)on April 28,2020.

关键词： cortical excitability lower extremity motor function network meta-analysis noninvasive brain stimulation stroke systematic review transcranial magnetic stimulation

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Exogenous neural stem cell transplantation for cerebral ischemia

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Neural Regeneration Research 2019年第7期14卷 1129-1137页

作者： Ling-yi Liao Benson Wui-Man lau Dalinda Isabel Sánchez-Vidana Qiang Gao Department of Rehabilitation Medicine West China HospitalSichuan University Department of Rehabilitation Sciences The Hong Kong Polytechnic University

Cerebral ischemic injury is the main manifestation of stroke,and its incidence in stroke patients is 70–80%.Although ischemic stroke can be treated with tissue-type plasminogen activator,its time window of effectiveness is ***,the incidence of paralysis,hypoesthesia,aphasia,dysphagia,and cognitive impairment caused by cerebral ischemia is *** tissue regeneration can promote the recovery of the aforementioned *** stem cells can participate in the reconstruction of the damaged nervous system and promote the recovery of nervous function during self-repair of damaged brain *** stem cell transplantation for ischemic stroke has been a hot topic for more than 10 *** review discusses the treatment of ischemic stroke with neural stem cells,as well as the mechanisms of their involvement in stroke treatment.

关键词： nerve regeneration stem cell therapy neural stem cells cell transplantation ischemic stroke cerebral ischemia neuroplasticity functional recovery neural regeneration

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Extremely low frequency electromagnetic fields promote cognitive function and hippocampal neurogenesis of rats with cerebral ischemia

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Neural Regeneration Research 2021年第7期16卷 1252-1257页

作者： Qiang Gao Aaron Leung Yong-Hong Yang Benson Wui-Man lau Qian Wang Ling-yi Liao Yun-Juan Xie Cheng-Qi He Department of Rehabilitation Medicine West China Hospital of Sichuan UniversityChengduSichuan ProvinceChina Institute of Disaster Management and Reconstruction Sichuan University–The Hong Kong Polytechnic UniversityChengduSichuan ProvinceChina Department of Biomedical Engineering The Hong Kong Polytechnic UniversityHong Kong Special Administrative RegionChina Department of Rehabilitation Sciences The Hong Kong Polytechnic UniversityHong Kong Special Administrative RegionChina

Extremely low frequency electromagnetic fields(ELF-EMF) can improve the learning and memory impairment of rats with Alzheimer's disease, however, its effect on cerebral ischemia remains poorly *** this study, we established rat models of middle cerebral artery occlusion/*** day after modeling, a group of rats were treated with ELF-EMF(50 Hz, 1 mT) for 2 hours daily on 28 successive *** results showed that rats treated with ELF-EMF required shorter swimming distances and latencies in the Morris water maze test than those of untreated *** number of times the platform was crossed and the time spent in the target quadrant were greater than those of untreated *** number of BrdU~+/NeuN~+ cells, representing newly born neurons, in the hippocampal subgranular zone increased more in the treated than in untreated ***-regulation in the expressions of Notch1, Hes1, and Hes5 proteins, which are the key factors of the Notch signaling pathway, was greatest in the treated *** findings suggest that ELF-EMF can enhance hippocampal neurogenesis of rats with cerebral ischemia, possibly by affecting the Notch signaling *** study was approved by the Institutional Ethics Committee of Sichuan University, China(approval No.2019255A) on March 5, 2019.

关键词： cerebral ischemia cognitive function electromagnetic fields hippocampus neurogenesis plasticity repair signaling pathway stroke rat

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Protein induced by vitamin K absence or antagonist-Ⅱ versus alpha-fetoprotein in the diagnosis of hepatocellular carcinoma: A systematic review with meta-analysis

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Hepatobiliary & Pancreatic Diseases International 2018年第6期17卷 487-495页

作者： Hao Xing yi-Jie Zheng Jun Han Han Zhang Zhen-Li Li Wan-Yee lau Feng Shen Tian Yang Department of Hepatic Surgery Eastern Hepatobiliary Surgery Hospital Naval Medical University Medical Scientific Affairs Abbott Diagnostics Faculty of Medicine The Chinese University of Hong Kong

Background: As a promising biomarker of hepatocellular carcinoma(HCC), protein induced by vitamin K absence or antagonist-Ⅱ(PIVKA-Ⅱ) has been studied extensively. However, its diagnostic capability varies across HCC studies. This study aimed to compare the performance of PIVKA-Ⅱ with alpha-fetoprotein(AFP) in the diagnosis of HCC. Data sources: A systematic literature search was conducted to identify the studies from MEDLINE, Embase and Cochrane Library Databases, which were published up to December 20, 2017 to compare the diagnostic capability of PIVKA-Ⅱ and AFP for HCC. The data were pooled using random effects model. Pooled sensitivity and specificity were calculated. Summary receiver operating characteristic curve(ROC) was employed to evaluate the diagnostic accuracy of each marker. Results: Thirty-one studies were included. The pooled sensitivity(95% CI) of PIVKA-Ⅱ and AFP was 0.66(0.65–0.68) and 0.66(0.65–0.67), respectively in diagnosis of HCC; and the corresponding pooled specificity(95% CI) was 0.89(0.88–0.90) and 0.84(0.83–0.85), respectively. The area under the ROC curve(AUC) of PIVKA-Ⅱ and AFP was 0.856(0.817–0.895) and 0.770(0.728–0.811), respectively. Subgroup analysis showed that PIVKA-Ⅱ was superior to AFP in terms of the AUC for both small HCC( < 3 cm) [0.863(0.825–0.901) vs 0.717(0.658–0.776)] and large HCC( ≥ 3 cm) [0.854(0.811–0.897) vs 0.729(0.682–0.776)]; for American [0.926(0.897–0.955) vs 0.698(0.594–0.662)], European [0.772(0.743–0.801) vs 0.628(0.594–0.662)], Asian [0.838(0.812–0.864) vs 0.785(0.764–0.806)] and African [0.812(0.794–0.840) vs 0.721(0.675–0.767)] HCC patients; and for HBV-related [0.909(0.866–0.951) vs 0.714(0.673–0.755)] and mixed-etiology [0.847(0.821–0.873) vs 0.794(0.772–0.816)] HCC. Conclusion: This meta-analysis indicates that PIVKA-Ⅱ is better than AFP in terms of the accuracy for diagnosing HCC, regardless of tumor size, patient ethnic group, or HCC etiology.

关键词： Hepatocellular carcinoma Meta-analyses Protein induced by vitamin K absence or antagonist-Ⅱ Alpha-fetoprotein

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Ultrafast laser-scanning time-stretch imaging at visible wavelengths

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Light(Science & Applications) 2016年第1期5卷 303-312页

作者： Jiang-Lai Wu yi-Qing Xu Jing-Jiang Xu Xiao-ming Wei Antony CS Chan Anson HL Tang Andy KS lau Bob MF Chung Ho Cheung Shum Edmund Y Lam Kenneth KY Wong Kevin K Tsia Department of Electrical and Electronic Engineering The University of Hong KongPokfulam RoadHong Kong 999077China Department of Bioengineering University of WashingtonSeattleWashington 98195USA Department of Mechanical Engineering The University of Hong KongPokfulam RoadHong Kong 999077China

Optical time-stretch imaging enables the continuous capture of non-repetitive events in real time at a line-scan rate of tens of MHz—a distinct advantage for the ultrafast dynamics monitoring and high-throughput screening that are widely needed in biological ***,its potential is limited by the technical challenge of achieving significant pulse stretching(that is,high temporal dispersion)and low optical loss,which are the critical factors influencing imaging quality,in the visible spectrum demanded in many of these *** present a new pulse-stretching technique,termed free-space angular-chirpenhanced delay(FACED),with three distinguishing features absent in the prevailing dispersive-fiber-based implementations:(1)it generates substantial,reconfigurable temporal dispersion in free space(41 ns nm^(−1))with low intrinsic loss(o6 dB)at visible wavelengths;(2)its wavelength-invariant pulse-stretching operation introduces a new paradigm in time-stretch imaging,which can now be implemented both with and without spectral encoding;and(3)pulse stretching in FACED inherently provides an ultrafast all-optical laser-beam scanning mechanism at a line-scan rate of tens of *** FACED,we demonstrate not only ultrafast laser-scanning time-stretch imaging with superior bright-field image quality compared with previous work but also,for the first time,MHz fluorescence and colorized time-stretch *** results show that this technique could enable a wider scope of applications in high-speed and high-throughput biological microscopy that were once out of reach.

关键词： optical time-stretch imaging pulse stretching ultrafast laser scanning

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Shifting curves based on the detector integration effect for x-ray phase contrast imaging

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Chinese Physics B 2017年第2期26卷 512-515页

作者： Jun Yang Jin-ChuanGuo Yao-HuLei ming-Hao yi Li Chen Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province College of Optoelectronic Engineering Shenzhen University Shenzhen 518060 China

In theory, we find that the actual function of the analyzer grating in the Talbot–lau interferometer is segmenting the self-images of the phase grating and choosing integral areas, which make sure that each period of self-images in one detector pixel contributes the same signal to the detector. Furthermore, in the case of the lack of an analyzer grating, the shifting curves are still existent in theory as long as the number of fringes is non-integral in a detector pixel, which is a sufficient condition for creating shifting curve. The sufficient condition is available for not only the Talbot–lau interferometer and the inverse geometry of Talbot–lau interferometer, but also the x-ray phase contrast imaging system based on geometrical optics. In practical applications, we propose a method to improve the performances of the existing systems by employing the sufficient condition. This method can shorten the system length, is applicable to large period gratings, and can use the detectors with large pixels and large field of view. In addition, the experimental arrangement can be simplified due to the lack of an analyzer grating. In order to improve detection sensitivity and resolution, we also give an optimal fringe *** believe that the theory and method proposed here is a step forward for x-ray phase contrast imaging.

关键词： x-ray phase contrast imaging Talbot–lau interferometer x-ray imaging

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Expert insights on Malaysia’s residential solar-energy policies:shortcomings and recommendations

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Clean Energy 2022年第4期6卷 619-631页

作者： Lin-Sea lau Yuen-Onn Choong Suet-Ling Ching Chooi-yi Wei Abdelhak Senadjki Chee-Keong Choong Ai-Na Seow Faculty of Business and Finance Universiti Tunku Abdul RahmanMalaysia

Malaysia has a long way before achieving the 20%renewable-energy penetration by ***,merely 2%of the country’s electricity is generated by renewable energy sources including solar *** the abundant literature about solar energy,qualitative studies that focus on experts’opinions on the weaknesses of residential solar-energy policies have received less attention,particularly in the context of *** the flaws in the existing policies would lead to creating a better policy framework for solar-energy ***,this study aims to identify the shortcomings of the current government initiatives and policies that deter solar photovoltaic adoption among households from experts’*** also provide recommendations for better future policy design and *** study employs a qualitative research approach(via semi-structured interviews)in collecting experts’*** concerns emerging from the interviews include insufficient financial support,lack of awareness programmes and subsidized electricity ***,interviewed experts suggest sufficient financial incentives,increased public awareness programmes and comprehensive legislation aimed at safeguarding consumer interests as a means to raising solar-energy adoption in the *** underlines the need for policymakers to create public awareness,provide financial support and develop regulatory measures aimed at managing solar companies for the sake of solar development in Malaysia.

关键词： qualitative study interview expert insights solar energy households policy shortcomings policy recommendations

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