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Immunoregulatory and Anti-cancer Activities of Combination Treatment of Novel Four-Herb Formula and Doxorubicin in 4T1-Breast Cancer Bearing Mice

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Chinese Journal of Integrative Medicine 2024年第4期30卷 311-321页

作者： Lea Ling-Yu Kan Ben Chung-Lap Chan Grace Gar-Lee Yue LI Pei-ting Sharon Sze-Man Hon HUANG Dan-qi Miranda Sin-Man Tsang Clara Bik-San Lau Ping-Chung leung Chun-Kwok Wong Institute of Chinese Medicine The Chinese University of Hong KongHong Kong SARChina State Key Laboratory of Research on Bioactivities and Clinical Applications of Medicinal Plants The Chinese University of Hong KongHong KongChina Department of Chemical Pathology The Chinese University of Hong KongHong Kong SARChina China-Australia International Research Centre for Chinese Medicine School of Health and Biomedical SciencesSTEM CollegeRMIT UniversityBundooraVictoriaAustralia Li Dak Sum Yip Yio Chin R&D Centre for Chinese Medicine The Chinese University of Hong Kong SARHong KongChina

Objective To investigate the in vivo immunomodulatory and anti-tumor mechanisms of the combined treatment of novel Four-Herb formula(4HF)and doxorubicin in triple-negative breast cancer(TNBC).Methods Murine-derived triple-negative mammary carcinoma cell line,4T1 cells,was cultured and inoculated into mouse mammary ***-six mice were randomly assigned into 6 groups(n=11 in ench):naive,control,LD 4HF(low dose 4HF),HD 4HF(high dose 4HF),LD 4HF+D(low dose and doxorubicin),and D(doxorubicin).Apart from the naive group,each mouse received subcutaneous inoculation with 5×10^(5)4T1 cells resuspended in 100µL of normal saline in the mammary fat *** from the day of tumor cell inoculation,tumors were grown for 6 *** LD and HD groups received daily oral gavage of 658 and 2,630 mg/kg 4HF,*** LD 4HF+D group received daily oral gavage of 658 mg/kg 4HF and weekly intraperitoneal injection of doxorubicin(5 mg/kg).The D group received weekly intraperitoneal injections of doxorubicin(5 mg/kg).The treatment naive mice received daily oral gavage of 0.2 mL double distilled water and 0.1 mL normal saline via intraperitoneal injection once a *** control group received daily oral gavage of 0.2 mL double-distilled *** treatment period was 30 *** the end of treatment,mice organs were harvested to analyze immunological activities via immunophenotyping,gene and multiplex analysis,histological staining,and gut microbiota *** Mice treated with the combination of 4HF and doxorubicin resulted in significantly reduced tumor and spleen burdens(P<0.05),altered the hypoxia and overall immune lymphocyte landscape,and manipulated gut microbiota to favor the anti-tumor immunological ***,immunosuppressive genes,cytokines,and chemokines such as C-C motif chemokine 2 and interleukin-10 of tumors were significantly downregulated(P<0.05).4HF-doxorubicin combination treatment demonstrated synergetic activities and was most effective

关键词： adjunctivetherapy breast cancer cytokines Chinese medicine tumor microenvironment

Quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: A comparison between Omicron BA.2 and non-VOC-D614G

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Virologica Sinica 2024年第2期39卷 218-227页

作者： Zigui Chen Rita Way Yin Ng Grace Lui Lowell Ling Agnes S.Y.leung Chit Chow Siaw Shi Boon Wendy C.S.Ho Maggie Haitian Wang Renee Wan Yi Chan Albert Martin Li David Shu Cheong Hui Paul Kay Sheung Chan Department of Microbiology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Medicine and Therapeutics Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Anaesthesia and Intensive Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Paediatrics Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Anatomical and Cellular Pathology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Jockey Club School of Public Health and Primary Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Stanley Ho Centre for Emerging Infectious Diseases Faculty of MedicineThe Chinese University of Hong KongHong KongChina

The SARS-CoV-2 Omicron variants are notorious for their transmissibility,but little is known about their subgenomic RNA(sgRNA)*** study applied RNA-seq to delineate the quantitative and qualitative profiles of canonical sgRNA of 118 respiratory samples collected from patients infected with Omicron BA.2 and compared with 338 patients infected with non-variant of concern(non-VOC)-D614G.A unique characteristic profile depicted by the relative abundance of 9 canonical sgRNAs was reproduced by both BA.2 and non-VOCD614G regardless of host gender,age and presence of ***,such profile was lost in samples with low viral load,suggesting a potential application of sgRNA pattern to indicate viral activity of individual patient at a specific time point.A characteristic qualitative profile of canonical sgRNAs was also reproduced by both BA.2 and *** presence of a full set of canonical sgRNAs carried a coherent correlation with crude viral load(AUC¼0.91,95%CI 0.88–0.94),and sgRNA ORF7b was identified to be the best surrogate marker allowing feasible routine application in characterizing the infection status of individual *** potentials in using sgRNA as a target for vaccine and antiviral development are worth pursuing.

关键词： Coronavirus SARS-CoV-2 Omicron BA.2 Non-VOC-D614G RNA-seq Subgenomic RNA(sgRNA)

“中文+常识”在香港非华语小学生中文教学中的应用研究

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语言教学与研究 2024年第5期 26-36页

作者：梁慧敏王莎香港理工大学中文及双语学系中国香港999077

香港特区非华语学生在使用中文学习其他科目时面临着学科和语言的双重障碍。对非华语学生而言,中文是他们的第二语言或外语,如果中文欠佳,势必影响学科知识的学习。本研究采用“内容与语言整合学习”的4Cs模式,为香港地区的非华语小学... 详细信息

香港特区非华语学生在使用中文学习其他科目时面临着学科和语言的双重障碍。对非华语学生而言,中文是他们的第二语言或外语,如果中文欠佳,势必影响学科知识的学习。本研究采用“内容与语言整合学习”的4Cs模式,为香港地区的非华语小学三年级学生设计了一套融合常识科内容的中文学习材料和框架,聚焦于小学常识科的六大学习范畴,展开跨学科协作模式,统整学科与中文作为第二语言的学习内容。创新的“中文+常识”课程旨在融合学科教育来提升学生中文水平,同时透过针对性语言教学深化学科知识的掌握。本研究的意义在于,首先让香港非华语中文教学突破单一的语言课堂,平衡“目标语言”和“工具语言”的教学,增强学生通过中文学习常识等其他学科的能力﹔其次,亦希望本课题可以抛砖引玉,为国际中文教育中“中文+其他学科”的教学模式提供香港地区经验。

关键词：香港非华语小学生中文+常识内容与语言整合学习 4Cs教学框架

RNA m^(6)A reader YTHDF2 facilitates precursor miR-126 maturation to promote acute myeloid leukemia progression

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Genes & Diseases 2024年第1期11卷 382-396页

作者： Zheng Zhang Keren Zhou Li Han Andrew Small Jianhuang Xue Huilin Huang Hengyou Weng Rui Su Brandon Tan Chao Shen Wei Li Zhicong Zhao Ying Qing Xi Qin Kitty Wang Keith leung Mark Boldin Chun-Wei Chen David Ann Zhijian Qian Xiaolan Deng Jianjun Chen Zhenhua Chen Department of Systems Biology Beckman Research Institute of City of HopeMonroviaCA 91016USA Irell and Manella Graduate School of Biological Sciences Beckman Research Institute of City of HopeDuarteCA 91010USA Gehr Family Center for Leukemia Research City of HopeDuarteCA 91010USA Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdong 510060China Guangzhou Laboratory GuangzhouGuangdong 510005China Bioland Laboratory GuangzhouGuangdong 51005China Department of Liver Surgery Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China Department of Diabetes Complications and Metabolism Beckman Research Institute of City of HopeDuarteCA 91010USA Department of Biochemistry and Molecular Biology University of FloridaGainesvilleFL 32603USA Tongji Hospital Affiliated to Tongji University Frontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China School of Pharmacy China Medical UniversityShenyangLiaoning 110001China

As the most common internal modification of mRNA,Ne-methyladenosine(m^(6)A)and its regulators modulate gene expression and play critical roles in various biological and patholog-ical processes including *** was reported previously that m^(6)A methyltransferase(writer),methyltransferase-like 3(METTL3)adds m^(6)A in primary microRNAs(pri-miRNAs)and fa-cilitates its processing into precursor miRNAs(pre-miRNAs).However,it is unknown whether m^(6)A modification also plays a role in the maturation process of pre-miRNAs and(if so)whether such a function contributes to ***,we found that YTHDF2 is aberrantly overexpressed in acute myeloid leukemia(AML)patients,especially in relapsed patients,and plays an onco-genic role in ***,YTHDF2 promotes expression of miR-126-3p(also known as miR-126,as it is the main product of precursor miR-126(pre-miR-126)),a miRNA that was reported as an oncomiRNA in AML,through facilitating the processing of pre-miR-126 into mature ***,YTHDF2 recognizes m^(6)A modification in pre-miR-126 and recruits AGO2,a regulator of pre-miRNA processing,to promote the maturation of ***2 posi-tively and negatively correlates with miR-126 and miR-126's downstream target genes,respec-tively,in AML patients,and forced expression of miR-126 could largely rescue YTHDF2/Ythdf2 depletion-mediated suppression on AML cell growth/proliferation and leukemogenesis,indi-cating that miR-126 is a functionally important target of YTHDF2 in ***,our studies not only reveal a previously unappreciated YTHDF2/miR-126 axis in AML and highlight the ther-apeutic potential of targeting this axis for AML treatment,but also suggest that m^(6)A plays a role in pre-miRNA processing that contributes to tumorigenesis.

关键词： AML miR-126 N^(6)-methyladenosine Pre-miRNA maturation YTHDF2

Individual consistency in spatiotemporal characteristics of migratory Whimbrels in the East Asian–Australasian Flyway

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Avian Research 2024年第3期 308-315页

作者： Siwei An Fenliang Kuang Wei Wu Chris J.Hassell Jonathan T.Coleman Zijing Gao Xuena Sun Yue Yuan Grace Maglio Kar-Sin K.leung Xuesong Feng Zhijun Ma Ministry of Education Key Laboratory for Biodiversity Science and Ecological Engineering Coastal Ecosystems Research Station of the Yangtze River Estuary Institute of Biodiversity Science School of Life Sciences Fudan University School of Chemistry and Environment Yunnan Minzu University Shanghai Chongming Dongtan Nature Reserve Administration Center Global Flyway Network Australasian Wader Studies Group Queensland Wader Study Group Hong Kong Waterbirds Ringing Group

Many migratory birds exhibit interannual consistency in migration schedules, routes and stopover sites. Detecting the interannual consistency in spatiotemporal characteristics helps understand the maintenance of migration and enables the implementation of targeted conservation measures. We tracked the migration of Whimbrel(Numenius phaeopus) in the East Asian–Australasian Flyway and collected spatiotemporal data from individuals that were tracked for at least two years. Wilcoxon non-parametric tests were used to compare the interannual variations in the dates of departure from and arrival at breeding/nonbreeding sites, and the interannual variation in the longitudes when the same individual across the same latitudes. Whimbrels exhibited a high degree of consistency in the use of breeding, nonbreeding, and stopover sites between years. The variation of arrival dates at nonbreeding sites was significantly larger than that of the departure dates from nonbreeding and breeding sites. Repeatedly used stopover sites by the same individuals in multiple years were concentrated in the Yellow Sea coast during northward migration, but were more widespread during southward migration. The stopover duration at repeatedly used sites was significantly longer than that at sites used only once. When flying across the Yellow Sea, Whimbrels breeding in Sakha(Yakutia) exhibited the highest consistency in migration routes in both autumn and spring. Moreover, the consistency in migration routes of Yakutia breeding birds was generally higher than that of birds breeding in Chukotka. Our results suggest that the northward migration schedule of the Whimbrels is mainly controlled by endogenous factors, while the southward migration schedule is less affected by endogenous factors. The repeated use of stopover sites in the Yellow Sea coast suggests this region is important for the migration of Whimbrel, and thus has high conservation value.

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Beyond ribosomal function: RPS6 deficiency suppresses cholangiocarcinoma cell growth by disrupting alternative splicing

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ACTA PHARMACEUTICA SINICA B 2024年第9期14卷 3931-3948页

作者： Fu, Wenkang Lin, Yanyan Bai, Mingzhen Yao, Jia Huang, Chongfei Gao, Long Mi, Ningning Ma, Haidong Tian, Liang Yue, Ping Zhang, Yong Zhang, Jinduo Ren, Yanxian Ding, Liyun Dai, Lunzhi leung, Joseph W. Yuan, Jinqiu Zhang, Wenhua Meng, Wenbo Lanzhou Univ Sch Clin Med 1 Lanzhou 730030 Peoples R China Lanzhou Univ Hosp 1 Key Lab Biotherapy & Regenerat Med Gansu Prov Lanzhou 730000 Gansu Peoples R China Lanzhou Univ Hosp 1 Dept Gen Surg Lanzhou 730030 Peoples R China Lanzhou Univ Sch Phys Sci & Technol Lanzhou 730000 Peoples R China Sichuan Univ West China Hosp Natl Clin Res Ctr Geriatr Chengdu 610041 Peoples R China Sichuan Univ West China Hosp Dept Gen Practice State Key Lab Biotherapy Chengdu 610041 Peoples R China UC Davis Med Ctr Div Gastroenterol Sacramento CA 95817 USA Sacramento VA Med Ctr Sacramento CA 95817 USA Sun Yat Sen Univ Affiliated Hosp 7 Clin Res Ctr Big Data Ctr Shenzhen 518107 Guangdong Peoples R China Lanzhou Univ Sch Life Sci Lanzhou 730000 Peoples R China

Cholangiocarcinoma (CCA) is a bile duct malignancy with a dismal prognosis. This study systematically investigated the role of the ribosomal protein S6 ( RPS6 ) gene, which is dependent in CCA. We found that RPS6 upregulation in CCA tissues was correlated with a poor prognosis. Functional investigations have shown that alterations in RPS6 expression, both gain- and loss-of function could affect the proliferation of CCA cells. In xenograft tumor models, RPS6 overexpression enhances tumorigenicity, whereas RPS6 silencing reduces it. Integration analysis using RNA-seq and proteomics elucidated downstream signaling pathways of RPS6 depletion by affecting the cell cycle, especially DNA replication. Immunoprecipitation followed by mass spectrometry has identified numerous spliceosome complex proteins associated with RPS6. Transcriptomic profiling revealed that RPS6 affects numerous alternative splicing (AS) events, and combined with RNA immunoprecipitation sequencing, revealed that minichromosome maintenance complex component 7 ( MCM7 ) binds to RPS6, which regulates its AS and increases oncogenic activity in CCA. Targeting RPS6 with vivo phosphorodiamidate morpholino oligomer (V-PMO) significantly inhibited the growth of CCA cells, patient-derived organoids, and subcutaneous xenograft tumor. Taken together, the data demonstrate that RPS6 is an oncogenic regulator in CCA and that RPS6-V-PMO could be repositioned as a promising strategy for treating CCA.

关键词： Cholangiocarcinoma Ribosomal protein S6 Alternative splicing p53 Minichromosome maintenance complex component 7 Vivo morpholino Patient-derived organoids PROTEIN S6 PHOSPHORYLATION PRE-MESSENGER-RNA EXPRESSION CANCER BINDING BIOGENESIS ACTIVATION GENERATION IMPAIRMENT THERAPIES

Message from Deputy Editor-in-Chief Gabriel M leung—International Trade and Global Health Protection

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China CDC weekly 2019年第4期1卷 45-46页

作者： Gabriel M leung China CDC Weekly Dean of Medicine The University of Hong KongHong Kong SARChina

It was external trade that first prompted the collection and reporting of surveillance data at the foreign ports from which the US imported *** established Bulletin of the Public Health—the first precursor to the US ... 详细信息

关键词： Trade prompt Health

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纪恩绵泽圆明园的建筑与亲情

紫禁城 2024年第4期351卷 94-113页

作者：梁慧淇香港故宫文化博物馆

圆明园原是康熙帝玄烨赐给其子胤禛的园林。胤禛继位后,圆明园升格为御园,历经雍正、乾隆、嘉庆、道光、咸丰五朝皇帝经营。在一百五十余年中,君臣父子的事迹在园内一再上演,通过艺术及文学创作,流传后世。

关键词：胤禛玄烨圆明园康熙帝咸丰雍正嘉庆

An Evaluation of Tropical Cyclone Genesis Forecast over the Western North Pacific and the South China Sea from the CMA-TRAMS

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Journal of Tropical Meteorology 2024年第1期30卷 20-28页

作者：李梦婕陈子通戴光丰田群梁卓轩林青张艳霞 Guangzhou Institute of Tropical and Marine Meteorology/Guangdong Provincial Key Laboratory of Regional Numerical Weather Prediction CMAGuangzhou 510641 China State Key Laboratory of Severe Weather Chinese Academy of Meteorological SciencesBeijing 100081 China Guangdong Meteorological Observatory Guangzhou 510641 China

Tropical cyclone(TC) genesis forecasting is essential for daily operational practices during the typhoon *** updated version of the Tropical Regional Atmosphere Model for the South China Sea(CMA-TRAMS) offers forecasters reliable numerical weather prediction(NWP) products with improved configurations and fine resolution. While traditional evaluation of typhoon forecasts has focused on track and intensity, the increasing accuracy of TC genesis forecasts calls for more comprehensive evaluation methods to assess the reliability of these predictions. This study aims to evaluate the effectiveness of the CMA-TRAMS for cyclogenesis forecasts over the western North Pacific and South China Sea. Based on previous research and typhoon observation data over five years, a set of localized, objective criteria has been proposed. The analysis results indicate that the CMA-TRAMS demonstrated superiority in cyclogenesis forecasts, predicting 6 out of 22 TCs with a forecast lead time of up to 144 h. Additionally, over 80% of the total could be predicted 72 h in advance. The model also showed an average TC genesis position error of 218.3 km, comparable to the track errors of operational models according to the annual evaluation. The study also briefly investigated the forecast of Noul(2011). The forecast field of the CMA-TRAMS depicted thermal and dynamical conditions that could trigger typhoon genesis, consistent with the analysis field. The 96-hour forecast field of the CMA-TRAMS displayed a relatively organized threedimensional structure of the typhoon. These results can enhance understanding of the mechanism behind typhoon genesis,fine-tune model configurations and dynamical frameworks, and provide reliable forecasts for forecasters.

关键词： CMA-TRAMS cyclogenesis numerical weather prediction tropical cyclone