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Oxidative spirolactonisation for modular access of γ-spirolactones via a radical tandem annulation pathway

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Chinese Chemical Letters 2024年第10期35卷 275-278页

作者： Jindian Duan Xiaojuan Ding pui ying Choy Binyan Xu Luchao Li Hong Qin Zheng Fang Fuk Yee Kwong Kai Guo College of Biotechnology and Pharmaceutical Engineering State Key Laboratory of Materials-Oriented Chemical Engineering Nanjing Tech University Department of Chemistry and State Key Laboratory of Synthetic Chemistry The Chinese University of Hong Kong

An oxidative annulation of 2-arylidene-1,3-indanediones with Meldrum's acid has been developed for the divergent syntheses of spirolactones with a spirocenter located at the γ-position with respect to the carbonyl group. This heteroannulation protocol tolerates various functional groups and delivers moderate-to-good product yields. Interestingly, the reaction outcomes are exclusively controlled by the reaction oxidant/medium. This annulation strategy can also be executed in the flow system with decent product yields. Control experiments revealed that the reaction proceeds via a radical tandem annulation pathway.

关键词： 2-Arylidene-1,3-indanediones Divergent synthesis Meldrum's acid Spirolactonisation γ-Spirolactones

ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating BCL2–BECN1 interaction

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2026-2038页

作者： Shiqiang Xu Qilian Ma Junwen Shen Ningning Li Shan Sun Nana Wang Yang Chen Chunsheng Dong Kin yip Tam Jochen H.M.Prehn Hongfeng Wang Zheng ying Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences Soochow UniversitySuzhou 215123China MOE Key Laboratory of Geriatric Diseases and Immunology College of Pharmaceutical SciencesSuzhou Medical College of Soochow UniversitySuzhou 215123China Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development Soochow UniversitySuzhou 215123China Dept.of Physiology&Medical Physics and FUTURE-NEURO Research Centre Royal College of Surgeons in IrelandDublin D02 YN77Ireland Faculty of Health Sciences University of MacaoTaipaMacao 999078China Insititutes of Biology and Medical Science Soochow UniversitySuzhou 215123China

Growing evidences indicate that dysfunction of autophagy contributes to the disease pathogenesis of amyotrophic lateral sclerosis(ALS)and frontotemporal dementia(FTD),two neurodegenerative *** GGGGCC·GGCCCC repeat RNA expansion in chromosome 9 open reading frame 72(C9orf72)is the most genetic cause of both ALS and *** to the previous studies,GGGGCC·GGCCCC repeat undergoes the unconventional repeat-associated non-ATG translation,which produces dipeptide repeat(DPR)*** there is a growing understanding that C9orf72 DPRs have a strong ability to harm neurons and induce C9orf72-linked ALS/FTD,whether these DPRs can affect autophagy remains *** the present study,we find that poly-GR and poly-PR,two arginine-containing DPRs which display the most cytotoxic properties according to the previous studies,strongly inhibit starvation-induced ***,our data indicate that arginine-rich DPRs enhance the interaction between BCL2 and BECN1/Beclin 1 by inhibiting BCL2 phosphorylation,therefore they can impair autophagic clearance of neurodegenerative disease-associated protein aggregates under starvation condition in ***,our study not only highlights the role of C9orf72 DPR in autophagy dysfunction,but also provides novel insight that pharmacological intervention of autophagy using SW063058,a small molecule compound that can disrupt the interaction between BECN1 and BCL2,may reduce C9orf72 DPR-induced neurotoxicity.

关键词： Amyotrophic lateral sclerosis Frontotemporal dementia C9orf72 Autophagy BCL2 BECN1/Beclin 1 Dipeptide repeat Neurodegeneration

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

Recent Expedition in Pd-Catalyzed Sonogashira Coupling and Related Processes

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Chinese Journal of Chemistry 2023年第9期41卷 1099-1118页

作者： pui ying Choy Kin Boon Gan Fuk Yee Kwong Department of Chemistry and State Key Laboratory of Synthetic Chemistry The Chinese University of Hong KongShatinNew TerritoriesHong Kong SARChina Shenzhen Center of Novel Functional Molecules Shenzhen Municipal Key Laboratory of Chemical Synthesis of Medicinal Organic MoleculesCUHK Shenzhen Research InstituteNo.10.Second Yuexing RoadShenzhenGuangdong 518507China

Sonogashira cross-coupling protocol,typically showing the reaction between aryl/vinyl halide and terminal alkyne,has been a widely used protocol for constructing C(sp2)-C(sp)*** resulting internal alkynes are highly versatile for reaching differently function-alized alkyne-containing scaffolds or serving as valuable synthetic synthons to many other functional *** is worth noting that products originated from this coupling reaction are mostly applicable to be transformed into corresponding Z-alkene,alkane,or het-erocyclic moieties in natural product *** reaction conditions and catalyst systems are able to be tweaked in order to facil-itate the activation of steric hindered and/or electron-rich ***-catalyzed copper-free Sonogashira coupling reaction has caught increasing attention as the improved method can be more environmentally *** is more,the conditions of the cou-pling reaction can be readily amended to allow the fusion of other carbonylation or decarboxylation step in the catalytic cycle,and thus allow more complex yet versatile convergent synthesis to proceed in an operationally simple one-pot manner.

关键词： Sonogashira Alkynylation Palladium Multicomponent reactions Cross-Coupling

Traditional Chinese medicine poisoning in the emergency departments in Hong Kong: Trend, clinical presentation and predictors for poor outcome

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World Journal of Emergency Medicine 2021年第2期12卷 143-150页

作者： Rex pui Kin Lam Eric Ho Yin Lau Wai Lam yip Joe Kai Shing Leung Matthew Sik Hon Tsui Emergency Medicine Unit Li Ka Shing Faculty of Medicinethe University of Hong KongHong KongChina Accident and Emergency Department Queen Mary HospitalHong KongChina Accident and Emergency Department Pamela Youde Nethersole Eastern HospitalHong KongChina School of Public Health Li Ka Shing Faculty of Medicinethe University of Hong KongHong KongChina

Dear editor,Traditional Chinese medicine (TCM) is popular in many countries,especially in the Chinese population.^([1,2]) In Hong Kong,it has been estimated that around 15%of the population consumed Chinese medicine products/herbs in the preceding *** reasons for consumption include regulating bodily functions,curing disease,and building up health.

关键词： has editor curing

HepG2 cells recovered from apoptosis show altered drug responses and invasiveness

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Hepatobiliary & Pancreatic Diseases International 2014年第3期13卷 293-300页

作者： Shan-Shan Wang Xin Xie Chung Sing Timothy Wong pui ying Choi Ming Chiu Fung School of Life Sciences the Chinese University of Hong Kong Department of Anatomical and Cellular Pathology Prince of Wales Hospital the Chinese University of Hong Kong

BACKGROUND: Cancer relapse, associated with increased drug resistance and rate of metastasis, often follows completion of chemotherapy but the cancer escape mechanisms are still incompletely understood. Percutaneous ethanol injection(PEI)has been used for treating hepatocellular carcinoma(HCC)for decades, while the recurrence after PEI treatment remains a major limitation. Recent evidence mounted that cancer cells could survive from chemical induced apoptosis, suggesting a potential route through which cancer relapse may occur. This study focuses on the consequence of HepG2 recovery from ethanol-induced apoptotic ***: The model of HepG2 recovery from ethanolinduced apoptotic event was established by live cell imaging,BrdU assay and Western blotting. MTT assay, wound healing assay and invasion assay were used to investigate the behavior of HepG2 after ***: HepG2 cells could recover from ethanol-induced apoptosis. These cells changed their behaviors such as drug resistance, mobility and invasiveness. On average, the recovered HepG2 cell clones were found to be 46% more resistant to ethanol and 84% higher in mobility. The recovered clones became 58.2% more sensitive to ***: HepG2 cells can recover from ethanolinduced apoptotic event. These cells became more resistant to ethanol and more invasive. Although the recovered cell clones were more resistant to ethanol, they became more sensitive to5-fluorouracil treatment.

关键词： cancer recurrence apoptosis recovery liver cancer percutaneous ethanol injection 5-fluorouracil

Attenuating innate immunity and facilitating β-coronavirus infection by NSP1 of SARS-CoV-2 through specific redistributing hnRNP A2/B1 cellular localization

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Signal Transduction and Targeted Therapy 2021年第11期6卷 3174-3176页

作者： Fanghang Zhou Qianya Wan Sheng Chen ying Chen pui-Hui Wang Xi Yao Ming-liang He Department of Biomedical Sciences City University of Hong KongKowloonHong Kong SARChina Advanced Medical Research Institute Cheeloo College of MedicineShandong University250012JinanShandongChina CityU Shenzhen Research Institute NanshanShenzhenChina

Dear Editor,Evidence shows the NSP1’s crucial roles of theβ-coronavirus SARS-CoV-2 in promoting cellular mRNA degradation,inhibiting host cell translation,innate immunity,and inducing inflammatory cytokine storm in the pathogenesis of COVID-19.1,2 More interestingly,NSP1 deletion in infectious clones prevents virus infection.3 However,little is known how NSP1 interacts with host factors to disrupt the host’s innate immunity for facilitating virus infection and *** a(+)ssRNA virus,SARS-CoV-2 completes its life cycle in the cytosol;viral RNA processing is the key for controlling and regulating the virus reproduction and *** ribonucleoproteins hnRNPs are the main factors responsible for RNA processing,including RNA splicing,maturation,decay,and translation,and even innate immunity in some cases.

关键词： NSP1 immunity infection

Young adults’perceptions of breastfeeding in public:a focus group study

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Frontiers of Nursing 2020年第3期7卷 217-226页

作者： Ka-Huen yip Yuk-Chiu yip Catherine Man-Yin Lee Mei-Yi Siu Shu-ying Ngai Mei-Kuen Chow School of Health Sciences Caritas Institute of Higher EducationHong KongChina School of Nursing The University of Hong KongHong KongChina

Objective:To elucidate the perceptions of young Chinese adults aged 18–25 toward adopting breastfeeding in public in Hong Kong Special Administrative Region(Hong Kong),***:A descriptive and exploratory study design was *** were recruited by convenience *** group data were collected from three semi-structured *** from 18 participants were audiotaped,transcribed verbatim,coded,and analyzed using content ***:Four themes emerged that described the young adults’perceptions and barriers toward breastfeeding practices:(1)adaptability of self and others,(2)cultural deem and practice,(3)convenience and connection,and(4)education and ***,all respondents(male and female)are aware of the benefits of *** negative perceptions toward breastfeeding initiation and continuation originate from factors that are essentially extraneous to the mother-infant dyads(such as the breadth and intensity of sociopolitical support,the dominant social beliefs and norms,and the inadequacy of breastfeeding education in adolescent years).Conclusions:In general,the young adult’s perception of breastfeeding is dominated by sociopolitical and cultural-related *** particular,sexualization of breasts as a deep-rooted belief in the Chinese context negatively affects young adults’perceptions and limits their breastfeeding practices.

关键词： breastfeeding young adult perceptions Chinese Hong Kong

Searching for Susceptibility Genes in Age-related Macular Degeneration： An Evolutionary Process

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首都医科大学学报 2010年第1期31卷 51-59页

作者： WANG Jing-ying CHEN Hao-yu CHEN Li-jia PANG Chi-pui Joint Shantou International Eye Center Shantou University and the Chinese University of Hong Kong Department of Ophthalmology and Visual Sciences the Chinese University of Hong Kong

Age-related macular degeneration(AMD) is a complex disease with multiple risk *** the pathogenesis and etiology remain largely unclear,systematic investigation into the genetics of this disease has cumulated during the past two decades that leads to putative mechanisms and genes associated with *** this review,the development of genetic studies on AMD was *** we intend to perform a comprehensive citation of all published works on AMD genetics,we find that we have to filter out some reference papers and focus on those reports bearing more information and insight into AMD genetics and its molecular *** have worked on a selection of observations and supporting references that illustrate a picture of the genetic processes that eventually lead to the development of AMD and related complications.

关键词：医学期刊 AMD 摘要编辑部编辑工作