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A robust luminescent assay for screening alkyladenine DNA glycosylase inhibitors to overcome DNA repair and temozolomide drug resistance

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Journal of Pharmaceutical Analysis 2023年第5期13卷 514-522页

作者： Ying-Qi Song Guo-Dong Li Dou Niu Feng Chen Shaozhen Jing Vincent Kam wai wong Wanhe Wang Chung-Hang Leung State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao999078China Department of Biomedical Sciences Faculty of Health SciencesUniversity of MacaoMacao999078China Institute of Medical Research Northwestern Polytechnical UniversityXi'an710072China Dr.Neher's Biophysics Laboratory for Innovative Drug Discovery State Key Laboratory of Quality Research in Chinese MedicineMacao University of Science and TechnologyMacao999078China

Temozolomide(TMZ)is an anticancer agent used to treat glioblastoma,typically following radiation therapy and/or surgical ***,despite its effectiveness,at least 50%of patients do not respond to TMZ,which is associated with repair and/or tolerance of TMZ-induced DNA *** have demonstrated that alkyladenine DNA glycosylase(AAG),an enzyme that triggers the base excision repair(BER)pathway by excising TMZ-induced N3-methyladenine(3meA)and N7-methylguanine lesions,is overexpressed in glioblastoma tissues compared to normal ***,it is essential to develop a rapid and efficient screening method for AAG inhibitors to overcome TMZ resistance in ***,we report a robust time-resolved photoluminescence platform for identifying AAG inhibitors with improved sensitivity compared to conventional steady-state spectroscopic *** a proof-of-concept,this assay was used to screen 1440 food and drug administration-approved drugs against AAG,resulting in the repurposing of sunitinib as a potential AAG *** restored glioblastoma(GBM)cancer cell sensitivity to TMZ,inhibited GBM cell proliferation and stem cell characteristics,and induced GBM cell cycle ***,this strategy offers a new method for the rapid identification of small-molecule inhibitors of BER enzyme activities that can prevent false negatives due to a fluorescent background.

关键词： Drug screening Alkyladenine DNA glycosylase N3-methyladenine Glioblastoma Temozolomide Sunitinib

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SMA molecular line survey towards the massive star-forming region G10.6-0.4in W31complex

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Research in Astronomy and Astrophysics 2018年第11期18卷 29-42页

作者： wai-Ho wong Tao An Key Laboratory of Radio Astronomy Shanghai Astronomical ObservatoryChinese Academy of SciencesShanghai 200030China University of Chinese Academy of Sciences Beijing 100049China

Line surveys of complex molecules with millimeter and sub-millimeter telescopes are important for probing the physical and chemical environments of massive star forming regions(MSFRs).We present a molecular line survey with the Submillimeter Array(SMA) in the frequency ranges of 220.3–222.3 GHz and 230.3–232.3 GHz toward G10.6-0.4, the brightest star forming core in the W31 complex. Ninety-nine transitions from 22 molecular species and their isotopologues are identified. The moment 0 images of typical molecules show a compact core which is concentrated at the continuum peak position. Based on the local thermodynamic equilibrium assumption, the molecular line data are modeled. The rotational temperatures of those molecular species range from 96 to 178 K and their column densities range from 2.0×1014to 3.7×1017cm-2. The observational data suggest that all complex molecules are located in a warm environment. Chemical environments of the molecules are discussed. We compared molecular abundances and gas temperatures in G10.6-0.4 with those in other MSFRs, and found that gas temperatures and fractional abundances of specific molecules in G10.6-0.4 are similar to the typical MSFR W51 North, suggesting that there are similar physical and chemical environments in these two MSFRs.

关键词： stars: formation ISM: abundances ISM: individual objects: G10.6-0.4 ISM: molecules radio lines: ISM

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Investigation of the genetic etiology in male infertility with apparently balanced chromosomal structural rearrangements by genome sequencing

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Asian Journal of Andrology 2022年第3期24卷 248-254页

作者： Matthew Hoi kin Chau Ying Li Peng Dai Mengmeng Shi Xiaofan Zhu Jacqueline Pui Wah Chung Yvonne K Kwok Kwong wai Choy Xiangdong Kong Zirui Dong Department of Obstetrics and Gynaecology The Chinese University of Hong KongHong KongChina Shenzhen Research Institute The Chinese University of Hong KongShenzhen 518057China Hong Kong Hub of Paediatric Excellence The Chinese University of Hong KongHong KongChina Genetics and Prenatal Diagnosis Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China The Chinese University of Hong Kong-Baylor College of Medicine Joint Center for Medical Genetics Hong KongChina

Apparently balanced chromosomal structural rearrangements are known to cause male infertility and account for approximately 1%of azoospermia or severe ***,the underlying mechanisms of pathogenesis and etiologies are still largely ***,we investigated apparently balanced interchromosomal structural rearrangements in six cases with azoospermia/severe oligospermia to comprehensively identify and delineate cryptic structural rearrangements and the related copy number *** addition,high read-depth genome sequencing(GS)(30-fold)was performed to investigate point mutations causative of male ***-pair GS(4-fold)revealed additional structural rearrangements and/or copy number changes in 5 of 6 cases and detected a total of 48 ***,the breakpoints caused truncations of 30 RefSeq genes,five of which were associated with ***,the breakpoints disrupted 43 topological-associated *** disruptions or potential dysregulations of genes,which play potential roles in male germ cell development,apoptosis,and spermatogenesis,were found in all cases(n=6).In addition,high read-depth GS detected dual molecular findings in case MI6,involving a complex rearrangement and two point mutations in the gene ***,our study provided the molecular characteristics of apparently balanced interchromosomal structural rearrangements in patients with male *** demonstrated the complexity of chromosomal structural rearrangements,potential gene disruptions/dysregulation and single-gene mutations could be the contributing mechanisms underlie male infertility.

关键词： azoospermia balanced structural rearrangements genome sequencing male infertility severe oligospermia

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Novel role of STAT3 in microglia-dependent neuroinflammation after experimental subarachnoid haemorrhage

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Stroke & Vascular Neurology 2022年第1期7卷 62-70页

作者： Zhiyuan Vera Zheng Junfan Chen Hao Lyu Sin Yu Erica Lam Gang Lu wai Yee Chan George K C wong Department of Surgery The Chinese University of Hong KongShatinHong Kong Department of Surgery Hainan General HospitalHaikouHainanChina School of Biomedical Science The Chinese University of Hong KongShatinHong Kong

Background and purpose Signal transducer and activator of transcription 3(STAT3)may contribute to the proinflammation in the central nervous system diseases by modulating the microglial ***,this study was intended to investigate the effect of STAT3 on microglia-dependent neuroinflammation and functional outcome after experimental subarachnoid haemorrhage(SAH).Methods The SAH model was established by endovascular perforation in the ***-time PCR(RtPCR)and western blot were used to examine the dynamic STAT3 signalling pathway responses after *** clarify the role of the STAT3 signalling pathway in the microglia-dependent neuroinflammation after SAH,the microglia-specific STAT3 knockout(KO)mice were generated by the Cre-LoxP *** neurological functions were assessed by Catwalk and Morris water maze *** loss after SAH was determined by immunohistochemistry *** polarisation status after STAT3 KO was then examined by RtPCR and *** The STAT3 and Janus kinase-signal transducer 2 activated immediately with the upregulation and phosphorylation after *** factors and related mediators altered dynamically and *** STAT3 deletion ameliorated the neurological impairment and alleviated the early neuronal loss after *** investigate the underlying mechanism,we examined the microglial reaction after STAT3 ***3 deletion reversed the increase of microglia after *** of STAT3 triggered the early morphological changes of microglia and primed microglia from M1 to M2 ***,microglial STAT3 deletion suppressed the SAH-induced proinflammation and promoted the anti-inflammation in the early *** STAT3 is closely related to the microglial polarisation transition and modulation of microglia-dependent *** STAT3 deletion improved neurological function and neuronal survival probably through promoting M2 polarisation and anti-inf

关键词： STAT3 inflammation reversed

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Is "Winter Coming" for International Arbitration?

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仲裁与法律 2022年第2期 181-203页

作者： Crystal wong wai Chin Lee Hishammuddin Allen & Gledhill

An effective and efficient arbitral process is essential for the viability and sustainability of international arbitration as the preferred dispute resolution *** a well-functioning,independent,and productive justice system,decisions are taken within a reasonable time and predictably,are effectively enforced,and commercial rights are adequately *** has shown that the costs and time of international arbitration are rising and generated negative feedbacks and criticism from the *** issue has been brought to the forefront and become internationally *** essay is authored as a result of major dissatisfaction with the complaints launched and with a hope to retain the golden summer of international *** essay first evaluates the reasons for the complaint of delay and cost and offers practical measures and solutions in addressing these *** essay further prophesies and welcome International Arbitration 4.0( "IA 4.0"),by setting out the innovative technological solutions,such as e-briefs,visual data room,and automated case management system,which should be adopted in arbitral processes and the framework to design and pilot a successful revolution of IA 4.0.

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Novel insights into the role of anti-inflammatory IL-38 in immunity against infection

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Cellular & Molecular Immunology 2022年第11期19卷 1322-1324页

作者： Xun Gao Guoqiu Wu Miranda Sin-Man Tsang Danqi Huang Christopher wai-Kei Lam Chun Kwok wong Department of Chemical Pathology The Chinese University of Hong KongHong KongChina Center of Clinical Laboratory Medicine Zhongda HospitalSoutheast UniversityNanjingChina Institute of Chinese Medicine and State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Faculty of Medicine and State Key Laboratory of Quality Research in Chinese Medicines Macao University of Science and TechnologyMacaoChina Li Dak Sum Yip Yio Chin R and D Centre for Chinese Medicine The Chinese University of Hong KongHong KongChina

Since the identification and cloning of interleukin(IL)-38 in 2001,a plethora of studies have focused on its essential roles as a novel IL-1 family cytokine in both innate and acquired *** on the shared traits with IL-36 receptor antagonist(IL-36Ra)and IL-1 receptor antagonist(IL-1Ra),IL-38 constitutes one of the most important anti-inflammatory cytokines within the IL-36 subfamily and thus elicits its antagonistic effects through binding to IL-36 receptor(IL-36R)and to IL-R1 with a relatively low affinity[1,2].IL-38 has been proven to bind to X-linked interleukin-1 receptor accessory protein-like 1(IL1RAPL1)[1],and IL1RAPL1 therefore serves as a novel receptor of IL-38.

关键词： immunity antagonist insight

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空气悬架客车横向动力学建模和稳定性分析

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汽车工程 2022年第11期44卷 1746-1754页

作者：陈龙陈明孙晓强蔡英凤 Pak kin wong 吴子强江苏大学汽车工程研究院镇江212013 澳门大学机电工程系中国澳门999078 扬州市奥特瑞汽车电子科技有限公司扬州225299

针对特殊行驶工况下空气悬架客车横向动力学失稳现象的揭示问题,本文中提出一种系统非线性动力学建模和稳定性分析方法。为准确反映空气悬架客车横向动力学演化规律,建立了考虑空气弹簧和轮胎非线性力学特性的系统3自由度动力学模型。... 详细信息

针对特殊行驶工况下空气悬架客车横向动力学失稳现象的揭示问题,本文中提出一种系统非线性动力学建模和稳定性分析方法。为准确反映空气悬架客车横向动力学演化规律,建立了考虑空气弹簧和轮胎非线性力学特性的系统3自由度动力学模型。为实现复杂高维动力学系统的稳定性分析,首先基于中心流形理论对系统进行降维处理,而后对得到的约化系统进行定性性态分析,确定了系统满足鞍结分岔的充分必要条件。设置4种工况对空气悬架客车横向动力学系统在平衡点处的分岔行为进行了相平面分析,掌握了空气悬架客车在不同路面条件下随车速及前轮转角变化的横向动力学失稳演化规律,最后基于整车动力学进行仿真验证表明解析分析结果与仿真分析结果一致,证明本文提出的非线性稳定性分析方法有效可行。

关键词：空气悬架客车动力学建模横向稳定性鞍结分岔点

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Hospital admissions from alcohol-related acute pancreatitis during the COVID-19 pandemic:A single-centre study

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World Journal of Clinical Cases 2022年第25期10卷 8837-8843页

作者： wai kin Mak Davide Di Mauro Eleanor Pearce Laura Karran Aye Myintmo Jessica Duckworth Amira Orabi Rebekah Lane Sophie Holloway Antonio Manzelli Somayyeh Mossadegh Upper GI Surgery Royal Devon and Exeter HospitalExeter EX25DWUnited Kingdom General Surgery Torbay HospitalTorquay TQ27AAUnited Kingdom General Surgery Chelsea and Westminster HospitalLondon SW109NHUnited Kingdom General Surgery Royal Cornwall Hospital TreliskeTruro TR13LJUnited Kingdom

BACKGROUND The United kingdom government introduced lockdown restrictions for the first time on 23 March 2020 due to coronavirus disease 2019(COVID-19)*** were partially lifted on 15 June and further eased on 4 *** in social behaviour,including increased alcohol consumption were described at the ***,there were no data available to consider the impact of these changes on the number of alcohol-related disease admissions,specifically alcoholrelated acute pancreatitis(AP).This study evaluated the trend of alcohol-related AP admissions at a single centre during the initial COVID-19 *** To evaluate the trend in alcohol-related AP admissions at a single centre during the initial COVID-19 lockdown in the United *** All patients admitted with alcohol-related AP from March to September 2016 to 2020 were considered in this *** demographics,their initial presentation with AP,any recurrent admissions,disease severity and length of stay,were evaluated using ANOVA andχ^(2)and Kruskal–Wallis *** One hundred and thirty-six patients were included in the *** highest total number of AP admissions was seen in March–September 2019 and the highest single-month period was in March–May *** for first-time presentations of AP were highest in 2020 compared to other year groups and were significantly higher compared to previous years,for example,2016(P<0.05).Furthermore,the rate of admissions decreased by 38.89%between March–May 2020 and June–September 2020(P<0.05),coinciding with the easing of lockdown *** significant decrease was not observed in the previous year groups during those same time *** for recurrent AP were highest in *** median length of hospital stay did not differ between patients from each of the year *** An increased number of admissions for alcohol-related AP were observed during months when lockdown restrictions were enforced;a fall in figur

关键词： Alcohol abuse Alcohol-related acute pancreatitis COVID-19 pandemic

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Successful capture of red thrombus in acute inferior ST-elevation myocardial infarction

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Journal of Geriatric Cardiology 2018年第10期15卷 647-648页

作者： wai-kin CHI Chi-Yuen CHAN Division of Cardiology Department of Medicine and TherapeuticsPrince of Wales Hospitalthe Chinese University of Hong KongHong KongChina

A 50-year-old gentleman with past medical history of hypertension presented with acute inferior ST-segment elevation myocardial infarction (STEMI).He complained severe chest pain despite onset time was more than *** p... 详细信息

关键词： Embolic protection device Successful capture Thrombus

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Molecular Advances in Severe Acute Respiratory Syndrome-associated Coronavirus (SARS-CoV)

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Genomics, Proteomics & Bioinformatics 2003年第4期1卷 247-262页

作者： Raymond kin Hi Hui Raymond Tsz Yeung wong Chi wai Yip Frederick Chi Ching Leung Department of Zoology The University of Hong Kong Hong Kong SAR China.Department of Zoology The University of Hong Kong Hong Kong SAR China.Department of Zoology The University of Hong Kong Hong Kong SAR China.Department of Zoology The University of Hong Kong Hong Kong SAR China.

The sudden outbreak of severe acute respiratory syndrome (SARS) in 2002 prompted the establishment of a global scientific network subsuming most of the traditional rivalries in the competitive field of virology. Within months of the SARS outbreak, collaborative work revealed the identity of the disastrous pathogen as SARS-associated coronavirus (SARS-CoV). However, although the rapid identifi-

关键词： severe acute respiratory syndrome SARS-CoV genome phylogenetics human leukocyte antigen (HLA) system molecular epidemiology

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