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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

Development of seismic fragility curves for low-rise masonry infilled reinforced concrete buildings by a coefficient-based method

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Earthquake Engineering and Engineering Vibration 2013年第2期12卷 319-332页

作者： Ray kai leung Su Chien-Liang Lee Department of Civil Engineering The University of Hong Kong

This study presents a seismic fragility analysis and ultimate spectral displacement assessment of regular low-rise masonry infilled （MI） reinforced concrete （RC） buildings using a coefficient-based method. The coefficient-based method does not require a complicated finite element analysis; instead, it is a simplifed procedure for assessing the spectral acceleration and displacement of buildings subjected to earthquakes. A regression analysis was first performed to obtain the best-fitting equations for the inter-story drift ratio （IDR） and period shift factor of low-rise MI RC buildings in response to the peak ground acceleration of earthquakes using published results obtained from shaking table tests. Both spectral acceleration- and spectral displacement-based fragility curves under various damage states （in terms of IDR） were then constructed using the coefficient-based method. Finally, the spectral displacements of low-rise MI RC buildings at the ultimate （or near- collapse） state obtained from this paper and the literature were compared. The simulation results indicate that the fragility curves obtained from this study and other previous work correspond well. Furthermore, most of the spectral displacements of low-rise MI RC buildings at the ultimate state from the literature fall within the bounded spectral displacements predicted by the coefficient-based method.

关键词： seismic fragility analysis masonry spectral displacement

R-Memcached: A Reliable In-Memory Cache for Big Key-Value Stores

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Tsinghua Science and Technology 2015年第6期20卷 560-573页

作者： Chengjian Liu kai Ouyang Xiaowen Chu Hai Liu Yiu-Wing leung Department of Computer Science Hong Kong Baptist University Institute of Research and Continuing Education Hong Kong Baptist University

Large-scale key-value stores are widely used in many Web-based systems to store huge amount of data as(key, value) pairs. In order to reduce the latency of accessing such(key, value) pairs, an in-memory cache system is usually deployed between the front-end Web system and the back-end database system. In practice, a cache system may consist of a number of server nodes, and fault tolerance is a critical feature to maintain the latency Service-Level Agreements(SLAs). In this paper, we present the design, implementation, analysis, and evaluation of R-Memcached, a reliable in-memory key-value cache system that is built on top of the popular Memcached software. R-Memcached exploits coding techniques to achieve reliability, and can tolerate up to two node *** experimental results show that R-Memcached can maintain very good latency and throughput performance even during the period of node failures.

关键词： in-memory cache fault tolerance key-value store

Anatomic and technical skill factor of gastroduodenal complication in post-transarterial embolization for hepatocellular carcinoma: A retrospective study of 280 cases

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World Journal of Gastroenterology 2005年第10期11卷 1554-1557页

作者： Ting-kai leung Chi-Ming Lee Hsin-Chi Chen Department of Diagnostic Radiology

AIM: To reduce the possibility of gastroduodenal complications. The purpose of this retrospective study was to survey the literature and compare and discuss the incidence of post-transarterial embolization (TAE)gastroduodenal ***: We found reports describing 280 cases of hepatocellular carcinoma with TAE procedures done during the past 4 years and selected all of them for our *** these cases, 86 were suspected of suffering gastroduodenal complications within one month of postTAE treatment. Fifteen of these cases were proved by pan-endoscopy to have gastroduodenal erosions or ulcerations. We reviewed the angiographic pictures in patient records to evaluate the possibility that anatomic and technical skill factors could explain the ***: Amongst the 15 cases, 9 were primary lesions of the antrum and prepylorus; 4 had duodenal ulcer or erosions; 2 had mid-body lesions; none showed a lesion at the fundus or cardia region. Three cases had not received TAEs using our ideal method, and may be associated with possible regurgitation of gel-foam pieces into the right or left gastric arteries. Two cases involved sub-selective embolization at a distal point on the hepatic artery; one case was found by angiography to have complete occlusion of the celiac ***: Comparing our results with past cases of post-TAE gastroduodenal complications, we surmise that our relatively low incidence (5.3%) of gastric complications might be explained by our concerted efforts to improve our technical skills in multi-sequential, selective and superselective approaches to the embolization of tumor vessels.

关键词： Post-TAE complication Transarterial embolization Gastroduodenal complication

Fatal thrombotic complications of hepatic cystic compression of the inferior vena: A case report

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World Journal of Gastroenterology 2005年第11期11卷 1728-1729页

作者： Ting-kai leung Chi-Ming Lee Hsin-Chi Chen Department of Diagnostic Radiology

Of 5% of patients who develop liver cysts, only 10-15%of them come for medical attention, typically because of dull right upper quadrant pain, abdominal bloating or early satiety. We treated a 77-year-old female with a rare complication of inferior vena cava thrombosis. The patient expired due to septic shock and multiple organ failure.

关键词： Liver cyst Inferior vena cava thrombosis Non-parasitic cyst Cellulitis IVC compression Sepsis

Glial cells and glaucomatous neuropathy

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Chinese Medical Journal 2007年第4期120卷 326-335页

作者： ZHONG Yi-sheng Christopher kai-shun leung Chi-pui Pang Department of Ophthalmology Ruijin Hospital Shanghai JiaotongUniversity Shanghai 200025 China Department of-Ophthalmology and Visual Sciences ChineseUniversity of Hong Kong Hong Kong China

Glaucomatous optic neuropathy is characterized by progressive loss of retinal ganglion cells associated with visual functional deficits. As the ganglion cells die in glaucoma, there is a progressive thinning of the nerve fibre layer （NFL）.l The underlying pathophysiological mechanisms, however, remain unclear. Many mechanisms are involved in the initiation and process of irreversible ganglionic cell death in glaucoma. These include reduced axoplasmic transport, accumulation of toxic levels of neurotransmitter, increased nitric oxide and endothelin syntheses, and remodelling of the extracellular matrix, among others.

关键词： OPTIC-NERVE HEAD RETINAL GANGLION-CELLS NITRIC-OXIDE SYNTHASE NECROSIS-FACTOR-ALPHA OPEN-ANGLE GLAUCOMA CILIARY NEUROTROPHIC FACTOR ASTROCYTE PRECURSOR CELLS MULLER CELLS IN-VITRO REACTIVE ASTROCYTES

Safety of high-carbohydrate fluid diet 2 h versus overnight fasting before non-emergency endoscopic retrograde cholangiopancreatography:A single-blind,multicenter,randomized controlled trial

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Chinese Medical Journal 2024年第12期137卷 1437-1446页

作者： Wenbo Meng Joseph W.leung Zhenyu Wang Qiyong Li Leida Zhang kai Zhang Xuefeng Wang Meng Wang Qi Wang Yingmei Shao Jijun Zhang Ping Yue Lei Zhang Kexiang Zhu Xiaoliang Zhu Hui Zhang Senlin Hou kailin Cai Hao Sun Ping Xue Wei Liu Haiping Wang Li Zhang Songming Ding Zhiqing Yang Ming Zhang Hao Weng QingyuanWu Bendong Chen Tiemin Jiang Yingkai Wang Lichao Zhang Ke Wu Xue Yang Zilong Wen Chun Liu LongMiao Zhengfeng Wang Jiajia Li Xiaowen Yan Fangzhao Wang Lingen Zhang Mingzhen Bai Ningning Mi XianzhuoZhang Wence Zhou Jinqiu Yuan Azumi Suzuki Kiyohito Tanaka Jiankang Liu Ula Nur Elisabete Weiderpass Xun Li Department of General Surgery The First Hospital of Lanzhou UniversityLanzhouGansu 730000China Key Laboratory of Biological Therapy and Regenerative Medicine Transformation Gansu Province LanzhouGansu 730000China Division of Gastroenterology and Hepatology UC Davis Medical CenterSacramentoCA 95816USA Department of Minimally Invasive Surgery Tianjin Nankai HospitalTianjin 300100China Division of Hepatobiliary and Pancreatic Surgery Department of SurgeryShulan(Hangzhou)Hospital Affiliated to Zhejiang Shuren UniversityHangzhouZhejiang 310000China Department of Hepatobiliary Surgery Southwest HospitalArmy Medical UniversityChongqing 400000China Hepatobiliary Surgery Department Shandong Provincial Third HospitalJinanShandong 250000China Department of General Surgery Xinhua HospitalAffiliated to Shanghai Jiao Tong University School of MedicineShanghai Key Laboratory of Biliary Tract Disease ResearchShanghai 200000China Department of Hepatobiliary and Pancreatic Surgery The First Hospital of Jilin UniversityChangchunJilin 130000China Department of Hepatobiliary Surgery The General Hospital of Ningxia Medical UniversityYinchuanNingxia 750000China Department of Hepatobiliary&Hydatid Digestive and Vascular Surgery CenterXinjiang Key Laboratory of Echinococcosis and Liver Surgery ResearchThe First Affiliated Hospital of Xinjiang Medical UniversityUrumqiXinjiang 830000China Department of Hepatobiliary and Pancreatic Surgery The First Hospital of Shanxi Medical UniversityTaiyuanShanxi 030000China Department of General Surgery The Second Hospital of Lanzhou UniversityLanzhouGansu 730000China Department of Biliopancreatic Endoscopic Surgery The Second Hospital of Hebei Medical UniversityShijiazhuangHebei 050000China Gastrointestinal Surgery Department Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430000China Department of Hepatobiliary Surgery The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’anShaanxi 710000China Depart

Background:Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography(ERCP),the benefits and safety of high-carbohydrate fluid diet(CFD)intake 2 h before ERCP remain *** study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’***:This prospective,multicenter,randomized controlled trial involved 15 tertiary ERCP centers.A total of 1330 patients were randomized into CFD group(n=665)and fasting group(n=665).The CFD group received 400 mL of maltodextrin orally 2 h before ERCP,while the control group abstained from food/water overnight(>6 h)before *** ERCP procedures were performed using deep sedation with intravenous *** investigators were blinded but not the *** primary outcomes included postoperative fatigue and abdominal pain score,and the secondary outcomes included complications and changes in metabolic *** outcomes were analyzed according to a modified intention-to-treat ***:The post-ERCP fatigue scores were significantly lower at 4 h(4.1±2.6 vs.4.8±2.8,t=4.23,P<0.001)and 20 h(2.4±2.1 vs.3.4±2.4,t=7.94,P<0.001)in the CFD group,with least-squares mean differences of 0.48(95%confidence interval[CI]:0.26-0.71,P<0.001)and 0.76(95%CI:0.57-0.95,P<0.001),*** 4-h pain scores(2.1±1.7 vs.2.2±1.7,t=2.60,P=0.009,with a least-squares mean difference of 0.21[95%CI:0.05-0.37])and positive urine ketone levels(7.7%[39/509]vs.15.4%[82/533],χ^(2)=15.13,P<0.001)were lower in the CFD *** CFD group had significantly less cholangitis(2.1%[13/634]vs.4.0%[26/658],χ^(2)=3.99,P=0.046)but not pancreatitis(5.5%[35/634]vs.6.5%[43/658],χ^(2)=0.59,P=0.444).Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla(odds ratio[OR]:0.61,95%CI:0.39-0.95,P=0.028)in the multivariable ***:Ingesting 400 mL of CFD 2 h before ERCP is safe,with a reduction in post-ERCP fatigue,

关键词： Endoscopic retrograde cholangiopancreatography ERCP Carbohydrate Fasting Safety Complications Enhanced recovery after surgery Randomized controlled trial

Adaptive optics two-photon microscopy enables near-diffraction-limited and functional retinal imaging in vivo

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Light(Science & Applications) 2020年第1期9卷 1298-1308页

作者： Zhongya Qin Sicong He Chao Yang Jasmine Sum-Yee Yung Congping Chen Christopher kai-Shun leung kai Liu Jianan Y.Qu Department of Electronic and Computer Engineering The Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina Division of Life Science The Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina Department of Ophthalmology and Visual Sciences The Chinese University of Hong KongHong KongChina State Key Laboratory of Molecular Neuroscience The Hong Kong University of Science and TechnologyClear Water BayKowloonHongKongChina Center of Systems Biology and Human Health The Hong Kong University of Science and TechnologyClear Water BayKowloonHong KongChina

In vivo fundus imaging offers non-invasive access to neuron structures and biochemical processes in the ***,optical aberrations of the eye degrade the imaging resolution and prevent visualization of subcellular retinal *** developed an adaptive optics two-photon excitation fluorescence microscopy(AO-TPEFM)system to correct ocular aberrations based on a nonlinear fluorescent guide star and achieved subcellular resolution for in vivo fluorescence imaging of the mouse *** accurate wavefront sensing and rapid aberration correction,AOTPEFM permits structural and functional imaging of the mouse retina with submicron ***,simultaneous functional calcium imaging of neuronal somas and dendrites was ***,the timelapse morphological alteration and dynamics of microglia were characterized in a mouse model of retinal *** addition,precise laser axotomy was achieved,and degeneration of retinal nerve fibres was *** highresolution AO-TPEFM is a promising tool for non-invasive retinal imaging and can facilitate the understanding of a variety of eye diseases as well as neurodegenerative disorders in the central nervous system.

关键词： optics functional photon

Soft Computing Based Procurement Planning of Time-variable Demand in Manufacturing Systems

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International Journal of Automation and computing 2007年第1期4卷 80-87页

作者： kai leung Yung Wai Hung Ip Ding-Wei Wang Department of Industrial and Systems Engineering Hong Kong Polytechnic University Hung Horn Kowloon Hong Kong PRC School of Information Science and Engineering Northeastern University Shenyang 110004 PRC

Procurement planning with discrete time varying demand is an important problem in Enterprise Resource Planning （ERP）. It can be described using the non-analytic mathematical programming model proposed in this paper. To solve the model we propose to use a fuzzy decision embedded genetic algorithm. The algorithm adopts an order strategy selection to simplify the original real optimization problem into binary ones. Then, a fuzzy decision quantification method is used to quantify experience from planning experts. Thus, decision rules can easily be embedded in the computation of genetic operations. This approach is applied to purchase planning problem in a practical machine tool works, where satisfactory results have been achieved.

关键词： Purchase planning Enterprise Resource Planning (ERP) soft computing genetic algorithm fuzzy decision inventory control.