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Nano Research 2024年第10期17卷 8893-8903页

作者： Jason koon-Lam Poon Sammual Yu-Lut Leung Eric Ka-Ho Wong Vivian wing-Wah Yam Institute of Molecular Functional Materials State Key Laboratory of Synthetic Chemistry and Department of ChemistryThe University of Hong KongHong Kong 999077China

A series of mononuclear complexes and unsymmetric dinuclear alkynylplatinum(II)terpyridine complexes with oligo(paraphenylene ethynylene)(OPE)-derived backbone with a variation of the lengths of alkoxy chains and OPE backbones was *** morphological properties,packing lattice and gelation behaviors of the mononuclear complexes were systematically studied,and the thermodynamic parameters and packing lattices of the dinuclear complexes were also investigated,providing further insights into the roles of the non-covalent interactions and their delicate balance in constructing sophisticated supramolecular *** and nanotube formation have been observed upon a delicate control of the intermolecular interactions by altering the lengths and structural dimensions of the complexes.

关键词： supramolecular chemistry self-assembled nanostructures platinum(II)complexes metallogel

伴有特殊表型的Wiskott-Aldrich综合征3例

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中国当代儿科杂志 2017年第2期19卷 250-253页

作者：贺建新 chan koon wing 徐保平刘秀云桂晋刚申昆玲江载芳 Lau Yu Lung 首都医科大学附属北京儿童医院呼吸科北京100045 香港大学儿童与青少年科学系首都医科大学附属北京儿童医院免疫研究室北京100045

病例1 患儿,男,4个月。因发现血小板减少4月余,咳嗽50 d,发热4 d入院。患儿4个月前（生后2 d）发现血小板减少（PLT 22×10^9/L）,外院经骨髓细胞学检查诊断为血小板减少性紫癜,口服泼尼松及静脉丙种球蛋白治疗,血小板正常后出院。出院... 详细信息

病例1 患儿,男,4个月。因发现血小板减少4月余,咳嗽50 d,发热4 d入院。患儿4个月前（生后2 d）发现血小板减少（PLT 22×10^9/L）,外院经骨髓细胞学检查诊断为血小板减少性紫癜,口服泼尼松及静脉丙种球蛋白治疗,血小板正常后出院。出院后不规律口服泼尼松,2个月前停用,血小板波动于50～60×10^9/L。

关键词： Wiskott-Aldrich综合征血小板减少性紫癜静脉丙种球蛋白表型骨髓细胞学检查诊断泼尼松出院后

A converged ubiquitin-proteasome pathway for the degradation of TOC and TOM tail-anchored receptors

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Journal of Integrative Plant Biology 2024年第5期66卷 1007-1023页

作者： Meijing Yang Shuai Chen Shey-Li Lim Lang Yang Jia Yi Zhong koon Chuen chan Zhizhu Zhao Kam-Bo Wong Junqi Wang Boon Leong Lim School of Biological Sciences University of Hong KongPokfulam 999077Hong KongChina Department of Biology Southern University of Science and TechnologyShenzhen 518055China School of Biomedical Engineering Shenzhen UniversityShenzhen 518060China School of Life Sciences The Chinese Universityof Hong KongShatin 999077HongKongChina State Key Laboratory of Agrobiotechnology The Chinese University of Hong KongShatin 999077Hong KongChina HKU Shenzhen Institute of Research and Innovation Shenzhen 518052China

In plants,thousands of nucleus-encoded proteins translated in the cytosol are sorted to chloroplasts and mitochondria by binding to specific receptors of the TOC(translocon on the outer chloroplast membrane)and the TOM(translocon on the outer mitochondrial membrane)complexes for import into those *** degradation pathways for these receptors are ***,we discovered a converged ubiquitin-proteasome pathway for the degradation of Arabidopsis thaliana TOC and TOM tail-anchored *** receptors are ubiquitinated by E3 ligase(s)and pulled from the outer membranes by the AAA+adenosine triphosphatase CDC48,after which a previously uncharacterized cytosolic protein,transmembrane domain(TMD)-binding protein for tail-anchored outer membrane proteins(TTOP),binds to the exposed TMDs at the C termini of the receptors and CDC48,and delivers these complexes to the 26S proteasome.

关键词： 26S proteasome CDC48 SP1 TOC TOM ubiquitination

同一家族内IL-12β1受体缺陷引起的卡介苗播散性感染二例

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同一家族内IL-12β1受体缺陷引起的卡介苗播散性感染二例

Circadian rhythm dysfunction and psychopathology in the offspring of parents with bipolar disorder:a highrisk study in the Chinese population

中华医学会第十四次全国儿科学术会议

作者：王晓川章迁王晓红王莹吕志宝刘宇隆 chan koon wing 复旦大学附属儿科医院香港大学医学院

目的:报道同一家族中两例IL-12Rβ1受体缺陷引起的卡介苗播散性感染。方法:对第1例患儿进行的是回顾性诊断,对第2例患儿结合其家族史、临床表现和基因诊断进行诊断。结果:例1患儿男性,2000年9月27日出生,生后2小时接种卡介苗,4月龄时发...

目的:报道同一家族中两例IL-12Rβ1受体缺陷引起的卡介苗播散性感染。方法:对第1例患儿进行的是回顾性诊断,对第2例患儿结合其家族史、临床表现和基因诊断进行诊断。结果:例1患儿男性,2000年9月27日出生,生后2小时接种卡介苗,4月龄时发现其左腋下淋巴结结核,给予异烟肼+ 利福平+丁胺卡娜霉素治疗,于2001年4月17日行左腋下淋巴结团块切除术,同年8月行右侧腹股沟淋巴结清扫术,术后继续抗痨治疗。于2001年11月起,患儿出现发热、白蛋白降低并有腹水,继续给

关键词：

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General Psychiatry 2024年第3期37卷 388-400页

作者： Binbin Lei Hongliang Feng Lulu Yang Jing Wang Jie Chen Weidong Song Chao Jiang Kun Zhang Qunfeng Wang Jessie Chi Ching Tsang Ngan Yin chan Yaping Liu Joey W.Y.chan Jiyang Pan Bin Zhang Tao Li Kathleen Ries Merikangas Jihui Zhang Yun Kwok wing Guangdong Cardiovascular Institute Guangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhouGuangdongChina Guangdong Mental Health Center Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdongChina Li Chiu Kong Family Sleep Assessment Unit Department of PsychiatryFaculty of MedicineThe Chinese University of Hong KongHong KongChina Center for Sleep and Circadian Medicine The Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina Department of Psychiatry Faculty of MedicineThe Chinese University of Hong KongNew TerritoriesHong KongChina Key Laboratory of Neurogenetics and channelopathies of Guangdong Province and the Ministry of Education of China Guangzhou Medical UniversityGuangzhouGuangdongChina Shenzhen Nanshan Center for Chronic Diseases Control(Shenzhen Nanshan Mental Health Center) ShenzhenChina Department of Clinical Psychology Shenzhen Fuyong People's HospitalShenzhenChina Department of Mental Illness Prevention and Treatment Shenzhen Longgang Center for Chronic Diseases ControlShenzhenChina Department of Neurology Zhongnan Hospital of Wuhan UniversityWuhanHubeiChina Sleep Medical Center The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdongChina Department of Psychiatry Nanfang HospitalSouthern Medical UniversityGuangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired IntelligenceGuangzhouGuangdongChina Department of Neurobiology Affiliated Mental Health Center&Hangzhou Seventh People's HospitalZhejiang University School of MedicineHangzhouZhejiangChina Genetic Epidemiology Research Branch Intramural Research ProgramNational Institute of Mental HealthBethesdaMarylandUSA

Background Understanding the evolution of circadian rhythm dysfunction and psychopathology in the high-risk population has important implications for the prevention of bipolar ***,some of the previous studies on the emergence of psychopathologies and circadian dysfunction among high-risk populations were inconsistent and *** To examine the prevalence rates of sleep and circadian dysfunctions,mental disorders and their symptoms in the offspring of parents with(O-BD)and without bipolar disorder(O-control).Methods The study included 191 O-BD and 202 O-control subjects aged 6-21 years from the Greater Bay Area,*** diagnoses and symptoms of sleep/circadian rhythm and mental disorders were assessed by the Diagnostic Interview for Sleep Patterns and Disorders,and the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version,*** estimating equations and shared frailty proportional hazards models of survival analysis were applied to compare the outcomes in the *** Adjusting for age,sex and region of recruitment,there was a significantly higher risk of delayed sleep phase symptoms(9.55%vs 2.58%,adjusted OR:4.04)in O-BD than in O-control.O-BD had a nearly fivefold higher risk of mood disorders(11.70%vs 3.47%,adjusted OR:4.68)and social anxiety(6.28%vs 1.49%,adjusted OR:4.70),a fourfold higher risk of depressive disorders(11.17%vs 3.47%,adjusted OR:3.99)and a threefold higher risk of mood symptoms(20.74%vs 10.40%,adjusted OR:2.59)than *** analysis revealed that O-BD children(aged under 12 years)had a nearly 2-fold higher risk of any mental and behavioural symptoms than O-control,while there was a nearly 4-fold higher risk of delayed sleep phase symptoms,a 7.5-fold higher risk of social anxiety and a 3-fold higher risk of mood symptoms in O-BD adolescents(aged 12 years and over).Conclusions There was an increase in delayed sleep phase symptoms in O-BD

关键词： prevention dysfunction bipolar

两种新型Wiskott-Aldrich综合征蛋白基因突变的鉴定

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中华儿科杂志 2003年第8期41卷 590-593,T002页

作者：蒋利萍徐酉华杨锡强刘恩梅王莉佳刘宇隆陈冠荣重庆医科大学儿童医院临床免疫室 400014 香港大学医学院儿科系

目的　明确 3例Wiskott Aldrich综合征 (WAS)患儿WAS蛋白 (WASP)基因突变的类型。方法　根据典型临床表现 (血小板减少、湿疹、反复感染 ) ,及淋巴细胞和血小板扫描电镜改变 ,采用PCR直接测序法 ,对 3例疑为WAS的患儿及其母亲的WASP基... 详细信息

目的　明确 3例Wiskott Aldrich综合征 (WAS)患儿WAS蛋白 (WASP)基因突变的类型。方法　根据典型临床表现 (血小板减少、湿疹、反复感染 ) ,及淋巴细胞和血小板扫描电镜改变 ,采用PCR直接测序法 ,对 3例疑为WAS的患儿及其母亲的WASP基因进行序列分析。结果　以正义、反义引物扩增的PCR产物分别测序 ,发现两种新型WASP基因突变 :2例WAS孪生兄弟WASP基因第 10外显子 ,第 984位核苷酸C缺失突变 (984delC) ,导致 317位密码子后移码突变 ,于 4 4 4位密码子提前出现终止密码 (H317fsX4 4 4 ) ;其母亲为此突变WASP基因携带者。另 1例WAS患儿WASP基因第 11外显子 ,第 1388位核苷酸由G替换为T(1388G→T) ,为无义突变 ,使第 4 5 2位密码子提前变为终止密码(E4 5 2X)。其母亲无此突变WASP基因。结论　鉴定出两种新型WASP基因突变 ,WASP基因序列分析对于不典型和散发WAS的诊断及WASP突变基因携带者的检出有重要作用。

关键词： Wiskott-Aldrich综合征基因突变鉴定 WAS蛋白 X-连锁隐性遗传免疫缺陷病小儿

Association of accelerometer-measured sleep duration and different intensities of physical activity with incident type 2 diabetes in a population-based cohort study

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Journal of Sport and Health Science 2024年第2期13卷 222-232页

作者： Xinyi Jin Yilin Chen Hongliang Feng Mingqing Zhou Joey W.Y.chang Yaping Liu Alice Pik Shan Kong Xiao Tan Yun-Kwok wing Yannis Yan Liang Jihui Zhang Guangdong Cardiovascular Institute Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention Guangdong Cardiovascular InstituteGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China School of Medicine South China University of TechnologyGuangzhou 510641China Center for Sleep and Circadian Medicine The Affiliated Brain Hospital of Guangzhou Medical UniversityGuangzhou 510180China The Second School of Clinical Medicine Southern Medical UniversityGuangzhou 510282China Guangdong Mental Health Center Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510120China Li Chiu Kong Family Sleep Assessment Unit Department of PsychiatryFaculty of MedicineThe Chinese University of Hong KongHong Kong 999077China Department of Psychiatry Faculty of MedicineThe Chinese University of Hong KongHong Kong 999077China Department of Medicine and Therapeutics Faculty of MedicineThe Chinese University of Hong KongHong Kong 999077China Department of Medical Sciences Uppsala UniversityUppsala 75185Sweden Department of Big Data in Health Science Zhejiang University School of Public HealthHangzhou 310058China Key Laboratory of Neurogenetics and channelopathies of Guangdong Province and the Ministry of Education of China Guangzhou 510260China

Purpose:The aim of the current study was to investigate the association of accelerometer-measured sleep duration and different intensities of physical activity(PA)with the risk of incident type 2 diabetes in a population-based prospective cohort ***:Altogether,88,000 participants(mean age=62.2±7.9 years,mean±SD)were included from the UK *** duration(short:8 h/day)and PA of different intensities were measured using a wrist-won accelerometer over a 7-day period between 2013 and *** was classified according to the median or World Health Organization-recommendation:total volume of PA(high,low),moderate-to-vigorous PA(MVPA)(recommended,not recommended),and light-intensity PA(high,low).Incidence of type 2diabetes was ascertained using hospital records or death ***:During a median follow-up of 7.0 years,1615 incident type 2 diabetes cases were *** with normal sleep duration,short(hazard ratio(HR)=1.21,95%confidence interval(95%CI):1.03-1.41)but not long sleep duration(HR=1.01,95%CI:0.89-1.15)was associated with excessive type 2 diabetes *** increased risk among short sleepers seems to be protected against by *** with normal sleepers with high or recommended PA,short sleepers with low volume of PA(HR=1.81,95%CI:1.46-2.25),not recommended(below the World Health Organization-recommended level of)MVPA(HR=1.92,95%CI:1.55-2.36),or low light-intensity PA(HR=1.49,95%CI:1.13-1.90)had a higher risk of type 2 diabetes,while short sleepers with a high volume of PA(HR=1.14,95%CI:0.88-1.49),recommended MVPA(HR=1.02,95%CI:0.71-1.48),or high light-intensity PA(HR=1.14,95%CI:0.92-1.41)did ***:Accelerometer-measured short but not long sleep duration was associated with a higher risk of incident type 2 diabetes.A higher level of PA,regardless of intensity,potentially ameliorates this excessive risk.

关键词： Light physical activity Sleep duration Triaxial accelerometer Type 2 diabetes UK Biobank

Genomics-driven derivatization of the bioactive fungal sesterterpenoid variecolin:Creation of an unnatural analogue with improved anticancer properties

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Acta Pharmaceutica Sinica B 2024年第1期14卷 421-432页

作者： Dexiu Yan Jemma Arakelyan Teng Wan Ritvik Raina Tsz Ki chan Dohyun Ahn Vladimir Kushnarev Tsz Kiu Cheung Ho Ching chan Inseo Choi Pui Yi Ho Feijun Hu Yujeong Kim Hill Lam Lau Ying Lo Law Chi Seng Leung Chun Yin Tong Kai Kap Wong wing Lam Yim Nikolay S.Karnaukhov Richard Y.C.Kong Maria V.Babak Yudai Matsuda Department of Chemistry City University of Hong KongHong Kong SARChina iGEM Team“VarieCure” City University of Hong KongHong Kong SARChina Department of Biomedical Engineering City University of Hong KongHong Kong SARChina Moscow Clinical Research Center Named After A.S.Loginov Moscow 111123Russian Federation

A biosynthetic gene cluster for the bioactive fungal sesterterpenoids variecolin(1)and variecolactone(2)was identified in Aspergillus aculeatus ATCC *** production of 1 and 2 was achieved in Aspergillus oryzae by expressing the sesterterpene synthase VrcA and the cytochrome P450 ***,the replacement of VrcB with homologous P450s from other fungal terpenoid pathways yielded three new variecolin analogues(5-7).Analysis of the compounds’anticancer activity in vitro and in vivo revealed that although 5 and 1 had comparable activities,5 was associated with significantly reduced toxic side effects in cancer-bearing mice,indicating its potentially broader therapeutic *** study describes the first tests of variecolin and its analogues in animals and demonstrates the utility of synthetic biology for creating molecules with improved biological activities.

关键词： Animal studies Anticancer properties Biosynthesis Natural products Sesterterpenoids Synthetic biology Terpene synthases Variecolin

Identification of novel small-molecule inhibitors of SARS-CoV-2 by chemical genetics

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Acta Pharmaceutica Sinica B 2024年第9期14卷 4028-4044页

作者： Chris Chun-Yiu chan Qian Guo Jasper Fuk-Woo chan Kaiming Tang Jian-Piao Cai Kenn Ka-Heng Chik Yixin Huang Mei Dai Bo Qin Chon Phin Ong Allen wing-Ho Chu Wan-Mui chan Jonathan Daniel Ip Lei Wen Jessica Oi-Ling Tsang Tong-Yun Wang Yubin Xie Zhenzhi Qin Jianli Cao Zi-Wei Ye Hin Chu Kelvin Kai-Wang To Xing-Yi Ge Tao Ni Dong-Yan Jin Sheng Cui Kwok-Yung Yuen Shuofeng Yuan State Key Laboratory of Emerging Infectious Diseases Carol Yu Centre for InfectionDepartment of MicrobiologySchool of Clinical MedicineLi Ka Shing Faculty of Medicinethe University of Hong KongPokfulamHong Kong SAR 999077China Department of Infectious Diseases and Microbiology the University of Hong Kong-Shenzhen HospitalShenzhen 518000China Centre for Virology Vaccinology and TherapeuticsHong Kong Science and Technology ParkHong Kong SAR 999077China Academician Workstation of Hainan Province Hainan Medical University-the University of Hong Kong Joint Laboratory of Tropical Infectious DiseasesHaikou 571100China School of Biomedical Sciences Li Ka Shing Faculty of Medicinethe University of Hong KongPokfulamHong Kong SAR 999077China NHC Key Laboratory of Systems Biology of Pathogens Institute of Pathogen Biology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China College of Biology Hunan Provincial Key Laboratory of Medical VirologyHunan UniversityChangsha 410082China

There are only eight approved small molecule antiviral drugs for treating *** them,four are nucleotide analogues(remdesivir,JT001,molnupiravir,and azvudine),while the other four are protease inhibitors(nirmatrelvir,ensitrelvir,leritrelvir,and simnotrelvir-ritonavir).Antiviral resistance,unfavourable drug‒drug interaction,and toxicity have been reported in previous *** there is a dearth of new treatment options for *** this work,a three-tier cell-based screening was employed to identify novel compounds with anti-SARS-CoV-2 *** compound,designated 172,demonstrated broad-spectrum antiviral activity against multiple human pathogenic coronaviruses and different SARS-CoV-2 variants of *** studies validated by reverse genetics showed that compound 172 inhibits the 3-chymotrypsin-like protease(3CLpro)by binding to an allosteric site and reduces 3CLpro dimerization.A drug synergistic checkerboard assay demonstrated that compound 172 can achieve drug synergy with nirmatrelvir in *** vivo studies confirmed the antiviral activity of compound 172 in both Golden Syrian Hamsters and K18 humanized ACE2 ***,this study identified an alternative druggable site on the SARS-CoV-23CLpro,proposed a potential combination therapy with nirmatrelvir to reduce the risk of antiviral resistance and shed light on the development of allosteric protease inhibitors for treating a range of coronavirus diseases.

关键词： SARS-CoV-2 High throughput screening Broad-spectrum antiviral treatment 3CLpro inhibitor Allosteric-site inhibitor Animal models Chemical genetics Reverse genetics

Variable outcome in infantile-onset inflammatory bowel disease in an Asian cohort

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World Journal of Gastroenterology 2016年第48期22卷 10653-10662页

作者： Way Seah Lee Ruey Terng Ng koon-wing chan Yu-Lung Lau Department of Paediatrics University Malaya Medical Center University Malaya Paediatric and Child Health Research Group University Malaya Department of Paediatrics and Adolescent Medicine Queen Mary Hospital LKS Faculty of Medicine The University of Hong Kong

AIM Infantile-onset inflammatory bowel disease(IO-IBD) with the onset of disease before 12 mo of age, is a different disease entity from childhood IBD. We aimed to describe the clinical features, outcome and role of mutation in interleukin-10(IL-10) and interleukin-10 receptors(IL-10R) in Asian children with IO-IBD. METHODS All cases of IO-IBD, defined as onset of disease before 12 mo of age, seen at University Malaya Medical Center, Malaysia were reviewed. We performed mutational analysis for IL10 and IL10 R genes in patients with presenting clinical features of Crohn's disease(CD).RESULTS Six [13%; CD = 3, ulcerative colitis(UC) = 2, IBDunclassified(IBD-U) = 1] of the 48 children(CD = 25; UC = 23) with IBD have IO-IBD. At final review [median(range) duration of follow-up: 6.5(3.0-20) years], three patients were in remission without immunosuppression [one each for post-colostomy(IBD-U), after standard immunosuppression(CD), and after total colectomy(UC)]. Three patients were on immunosuppression:one(UC) was in remission while two(both CD) had persistent disease. As compared with later-onset disease, IO-IBD were more likely to present with bloody diarrhea(100% vs 55%, P = 0.039) but were similar in terms of an associated autoimmune liver disease(0% vs 19%, P = 0.31), requiring biologics therapy(50% vs 36%, P = 0.40), surgery(50% vs 29%, P = 0.27), or achieving remission(50% vs 64%, P = 0.40). No mutations in either IL10 or IL10 R in the three patients with CD and the only patient with IBD-U were *** The clinical features of IO-IBD in this Asian cohort of children who were negative for IL-10 or IL-10 R mutations were variable. As compared to childhood IBD with onset of disease after 12 mo of age, IO-IBD achieved remission at a similar rate.

关键词： Infantile-onset inflammatory bowel disease Pediatric