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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

Hair growth-promotion effects and antioxidant activity of the banana flower extract HappyAngel^(■):double-blind, placebo-controlled trial

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Food Science and Human Wellness 2023年第5期12卷 1917-1923页

作者： Chia-Hua Liang yung-Hsiang Lin yung-kai Lin Chi-Fu Chiang Department of Cosmetic Science and Institute of Cosmetic Science Chia Nan University of Pharmacy and ScienceTainan 71710China Research&Design Center TCI CO.Ltd.Taipei 114722China Institute of Food Safety and Risk Management Department of Food ScienceTaiwan Ocean UniversityKeelung 202301China Graduate Institute of Biomedical Engineering Chung Hsing UniversityTaichung 202301China

Banana flowers contain various bioactive components, including several antioxidants with anti-inflammatory effects. However, it is unclear whether they can reduce and prevent hair loss. This study examines the effect of banana flower extracts on preventing hair loss and strengthening hair roots. The banana flower extract(HappyAngel^(■))was used to treat human hair follicle dermal papilla cells(HFDPCs)and the expression of reactive oxygen species(ROS), dihydrotestosterone(DHT), and hair-related genes(SRD5A1, SRD5A2, AR, and KROX20)were monitored. Fifty subjects were divided into a placebo group and a banana flower group. The experimental group consumed banana flower extract daily for twelve weeks and then underwent hair testing, hair-related genes analysis, collection of hair loss, and questionnaires. The results showed that the banana flower extract significantly increased hair cell growth and decreased the expression of ROS, DHT, and hair follicle growth inhibition-related SRD5A1, SRD5A2, and AR genes, and significantly increased the expression of hair growth-related KROX20 gene in HFDPCs. Consuming banana flower extract for twelve weeks increased the hair root diameter and reduced hair loss and scalp redness compared to the placebo group. Thus, banana flower extract(HappyAngel^(■))can stimulate hair growth and inhibit the activation of hair loss genes.

关键词： Banana flower Dihydrotestosterone Hair loss ROS Follicle dermal papilla cells

Data Hiding in AMBTC Images Using Selective XOR Hiding Scheme

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Computers, Materials & Continua 2022年第6期71卷 5167-5182页

作者： yung-Yao Chen Yu-Chen Hu Ting-kai Yang You-An Wang Department Electronic and Computer Engineering National Taiwan U.Science and TechnologyTaipei106Taiwan Department Computer Science and Information Management Providence UniversityTaichung433Taiwan Grad.Inst.Automation Technology National Taipei University of TechnologyTaipei106Taiwan

Nowadays since the Internet is ubiquitous,the frequency of data transfer through the public network is *** secure data in these transmitted data has emerged broad security issue,such as authentication and copyright *** the other hand,considering the transmission efficiency issue,image transmission usually involves image compression in Internet-based *** address both issues,this paper presents a data hiding scheme for the image compression method called absolute moment block truncation coding(AMBTC).First,an image is divided into nonoverlapping blocks through AMBTC compression,the blocks are classified four types,namely smooth,semi-smooth,semi-complex,and *** secret data are embedded into the smooth blocks by using a simple replacement *** proposed method respectively embeds nine bits(and five bits)of secret data into the bitmap of the semi-smooth blocks(and semicomplex blocks)through the exclusive-or(XOR)*** secret data are embedded into the complex blocks by using a hidden *** the embedding phase,the direct binary search(DBS)method is performed to improve the image qualitywithout damaging the secret *** experimental results demonstrate that the proposed method yields higher quality and hiding capacity than other reference methods.

关键词： Content protection technology security for image data absolute moment block truncation coding(AMBTC) direct binary search(DBS)

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

Development of an orally bioavailable selective inhibitor of the menin-MLL

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Genes & Diseases 2023年第5期10卷 1735-1738页

作者： Hai-Jing Zhong Wanhe Wang Wei Zhou Jia-Xin Liang yung-Chi Cheng Dik-Lung Ma Chung-Hang leung State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao SARChina Department of Chemistry Hong Kong Baptist UniversityKowloon TongHong Kong SARChina Department of Pharmacology Yale University School of MedicineNew HavenCT 06520USA Department of Biomedical Sciences Faculty of Health SciencesUniversity of MacaoMacao SARChina International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education(MOE) College of PharmacyJinan UniversityGuangzhouGuangdong 510632China

The protein–protein interaction between menin and mixed lineage leukemia(MLL)plays an important role in the development of human hepatocellular carcinogenesis(HCC)and is associated with poor prognosis of HCC patients.1,2 Hence,interrupting the menin-MLL interaction is an attractive strategy in cancer treatment,particularly for liver cancer.3,4 In this study,we identified complex C1 as the first rhodium(III)-based orally bioavailable selective inhibitor of the menin-MLL interaction for HCC.

关键词： MLL prognosis carcinogenesis

A near-infrared plasma membrane-specific AIE probe for fluorescence lifetime imaging of phagocytosis

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Science China Chemistry 2022年第5期65卷 979-988页

作者： Ming-Yu Wu Jong-kai leung Chuen Kam Tsu Yu Chou Jia-Li Wang Xueqian Zhao Shun Feng Sijie Chen Ming Wai Lau Centre for Reparative Medicine Karolinska InstitutetHong KongChina Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China

Phagocytosis is a biological process that plays a key role in host defense and tissue *** approaches for real-time imaging of phagocytosis are highly desired but ***,an AIE-active near-infrared fluorescent probe,named TBTCP,was developed for fluorescence lifetime imaging of *** could selectively label the cell plasma membrane with fast staining,wash-free process,high signal-to-background ratio,and excellent *** membrane statuses under different osmolarities as well as macrophage phagocytosis of bacteria or large silica particles in early stages could be reported by the fluorescence lifetime changes of *** with current fluorescence imaging methods,which target the bioenvironmental changes in the late phagocytosis stage,this approach detects the changes in the cell membrane,thus giving a faster response to *** article provides a functional tool to report the phagocytic dynamics of macrophages which may greatly contribute to the studies of phagocytic function-related diseases.

关键词： fluorescence lifetime imaging phagocytosis plasma membrane aggregation-induced emission near-infrared

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

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

Peptidic defective interfering gene nanoparticles against Omicron,Delta SARS-CoV-2 variants and influenza A virus in vivo

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Signal Transduction and Targeted Therapy 2022年第9期7卷 3484-3493页

作者： Hanjun Zhao Chuyuan Zhang Hoiyan Lam Xinjie Meng Zheng Peng Man Lung Yeung Jasper Fuk-Woo Chan Kelvin kai-Wang To Kwok-yung Yuen State Key Laboratory of Emerging Infectious Diseases Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Department of Microbiology School of Clinical MedicineLi Ka Shing Faculty of MedicineThe University of Hong KongHong Kong Special Administrative RegionChina Centre for Virology Vaccinology and TherapeuticsHong Kong Science and Technology ParkHong Kong Special Administrative RegionChina Department of Infectious Disease and Microbiology The University of Hong Kong-Shenzhen HospitalShenzhenGuangdong ProvinceChina Carol Yu Centre for Infection The University of Hong KongPokfulamHong Kong Special Administrative RegionChina Guangzhou Laboratory GuangzhouGuangdong ProvinceChina

Defective interfering genes(DIGs)are short viral genomes and interfere with wild-type viral ***,we demonstrate that the new designed SARS-CoV-2 DIG(CD3600)can significantly inhibit the replication of SARS-CoV-2 including Alpha,Delta,Kappa and Omicron variants in human HK-2 cells and influenza DIG(PAD4)can significantly inhibit influenza virus replication in human A549 *** dose of influenza DIGs prophylactically protects 90%mice from lethal challenge of A(H1N1)pdm09 virus and CD3600 inhibits SARS-CoV-2 replication in hamster lungs when DIGs are administrated to lungs one day before viral *** further investigate the gene delivery vector in the respiratory tract,a peptidic TAT2-P1&LAH4,which can package genes to form small spherical nanoparticles with high endosomal escape ability,is demonstrated to dramatically increase gene expression in the lung ***2-P1&LAH4,with the dual-functional TAT2-P1(gene-delivery and antiviral),can deliver CD3600 to significantly inhibit the replication of Delta and Omicron SARS-CoV-2 in hamster *** peptide-based nanoparticle system can effectively transfect genes in lungs and deliver DIGs to inhibit SARS-CoV-2 variants and influenza virus in vivo,which provides the new insight into the drug delivery system for gene therapy against respiratory viruses.

关键词： influenza vivo Delta