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Genomic,transcriptomic,and metabolomic analysis of Oldenlandia corymbosa reveals the biosynthesis and mode of action of anti-cancer metabolites

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Journal of integrative Plant Biology 2023年第6期65卷 1442-1466页

作者： irene Julca Daniela Mutwil-Anderwald Vaishnervi Manoj Zahra Khan Soak Kuan Lai Lay K.Yang ing T.Beh Jerzy Dziekan Yoon P.Lim Shen K.Lim Yee W.Low yuen i.lam Seth Tjia Yuguang Mu Qiao W.Tan Przemyslaw Nuc Le M.Choo Gillian Khew Loo Shining Antony Kam James P.Tam Zbynek Bozdech Maximilian Schmidt Bjoern Usadel Yoganathan Kanagasundaram Saleh Alseekh Alisdair Fernie Hoi Y.Li Marek Mutwil School of Biological Sciences Nanyang Technological UniversitySingapore 639798Singapore Shared Analytics Singapore Institute of Food and Biotechnology Innovation(SIFBI)Agency for ScienceTechnology and Research(A*STAR)Singapore 138671Singapore Department of Biochemistry National University of SingaporeSingapore 117596Singapore Singapore Botanic Gardens Singapore 259569Singapore Department of Gene Expression Faculty of BiologyInstitute of Molecular Biology and BiotechnologyAdam Mickiewicz UniversityPoznan 61-614Poland iBG-4 Bioinformatics Forschungszentrum JülichJülich 52428Germany Max-Planck-institut für Molekulare Pflanzenphysiologie Potsdam-Golm 14476Germany Center of Plant Systems Biology and Biotechnology Plovdiv 4000Bulgaria

Plants accumulate a vast array of secondary metabolites,which constitute a natural resource for *** corymbosa belongs to the Rubiaceae family,and has been used in traditional medicine to treat different diseases,including ***,the active metabolites of the plant,their biosynthetic pathway and mode of action in cancer are *** fill these gaps,we exposed this plant to eight different stress conditions and combined different omics data capturing gene expression,metabolic profiles,and anti-cancer *** results show that *** extracts are active against breast cancer cell lines and that ursolic acid is responsible for this ***,we assembled a high-quality genome and uncovered two genes involved in the biosynthesis of ursolic ***,we also revealed that ursolic acid causes mitotic catastrophe in cancer cells and identified three high-confidence protein binding targets by Cellular Thermal Shift Assay(CETSA)and reverse ***,these results constitute a valuable resource to further characterize the biosynthesis of active metabolites in the Oldenlandia group,while the mode of action of ursolic acid will allow us to further develop this valuable compound.

关键词： genome medicinal metabolomics mode of action transcriptome

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A Detailed Study on the Equal Arrival Time Surface Effect in Gamma-Ray Burst Afterglows

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Chinese Journal of Astronomy and Astrophysics 2007年第3期7卷 397-404页

作者： Yong-Feng Huang Ye Lu Anna yuen lam Wong Kwong Sang Cheng Department of Astronomy Nanjing University Nanjing 210093 Department of Physics The University of Hong Kong Pokfulam Road Hong Kong National Astronomical Observatories Chinese Academy of Sciences Beijing 100012

Due to the relativistic motion of gamma-ray burst remnant and its deceleration in the circumburst medium, the equal arrival time surfaces at any moment are not spherical, rather, they are distorted ellipsoids. This will leave some imprints in the afterglows. We study the effect of equal arrival time surfaces numerically for various circumstances, i.e., isotropic fireballs, collimated jets, density jumps and energy injection events. For each case, a direct comparison is made between including and not including the effect. For isotropic fireballs and jets viewed on axis, the effect slightly hardens the spectra and postpones the peak time of the afterglows, but does not change the shapes of the spectra and light curves significantly. in the cases of a density jump or an energy injection, the effect smears out the variations in the afterglows markedly.

关键词： gamma rays bursts -- relativity -- shock waves -- iSM clouds

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Constitutive androstane receptor:A tumor suppressor and a biomarker for favorable prognosis of liver diseases

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Genes & Diseases 2024年第6期11卷 88-90页

作者： Sarah Da Won Bae Romario Nguyen Lawrence yuen Vincent lam Jacob George Liang Qiao Storr Liver Centre Westmead institute for Medical ResearchUniversity of Sydneyand Westmead HospitalWestmeadNSW2145Australia Department of Surgery Westmead HospitalWestmeadNSW2145Australia

Constitutive androstane receptor(CAR)is a nuclear receptor that is encoded by the gene NR113(nuclear receptor subfamily 1 group i member 3)and is almost exclusively expressed in the liver.1 As reported in our recent publication,CAR is well established as a xenosensor for drugs and energy metabolism with newer implications in the regulation of normal liver physiology and liver regeneration.

关键词： metabolism drugs liver

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Comprehensive analysis of results of surgical treatment of oraltongue carcinoma in Hong Kong

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Chinese Medical Journal 1997年第11期 43-48页

作者： Po Wing yuen, William i. Wei, Yue Ming Wong, Kwong Chi Tang and Lai Kun lam

Objective To evaluate the results of primary surgical treatment of carcinoma of oral tongue in Hong Kong. Methods Patients who had undergone primary surgical treatment of oral tongue carcinoma in Queen Mary Hospital were reviewed. Results There were 112 patients in this study. The first sites of tumor recurrence were 10 (9%) local, 25 (22%) nodal, 3 (3%) locoregional, 5 (5%) distant, 1 (1%) local and distant, 3 (3%) nodal and distant, and 1 (1%) neck extranodal site. Of the 63 T1 2 N0 M0 patients, the regional recurrence rate was 9% for elective neck dissection compared with 47% for “watchful waiting” (Chi square test, [WTBX]P=0.0008). The regional recurrence related mortality was 3% for elective neck dissection compared with 23% for “watchful waiting” (Fisher's test, P=0.02). The 5 year actuarial survival rate was 86% for elective neck dissection compared with 55% for “watchful waiting” (Wilcoxon, P=0.01). Conclusions Local and regional recurrences were the main sites of treatment failure. Elective neck dissection has significant benefits in the reduction of regional failure and improvement of survival. Elective selective Ⅰ Ⅲ neck dissection have to be considered in patients with stage Ⅰ and stage Ⅱ oral tongue carcinoma.

关键词： analysis results oraltongue Hong Comprehensive

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Far-infrared and submillimeter properties of SDSS galaxies in the Herschel ATLAS science demonstration phase field

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Research in Astronomy and Astrophysics 2013年第2期13卷 179-196页

作者： Man i.lam Hong Wu Yi-Nan Zhu Zhi-Min Zhou National Astronomical Observatories Chinese Academy of Science Graduate University of Chinese Academy of Sciences Key Laboratory of Optical Astronomy National Astronomical ObservatoriesChinese Academy of Sciences

Using the Herschel ATLAS science demonstration phase data cross- identified with SDSS DR7 spectra, we select 297 galaxies with F250μm 〉 5σ. The sample galaxies are classified into five morphological types, and more than 40% of the galaxies are peculiar/compact galaxies. The peculiar galaxies show higher far- infrared/submillimeter luminosity-to-mass ratios than the other types. We perform and analyze the correlations of far-infrared/submillimeter and Hα luminosities for differ- ent morphological types and different spectral types. The Spearman rank coefficient decreases and the scatter increases with the wavelength increasing from 100 μm to 500 μm. We conclude that a single Herschel SPiRE band is not good for tracing star formation activities in galaxies. AGNs contribute less to the far-infrared/submillimeter luminosities and do not show a difference from star-forming galaxies. However, the earlier type galaxies present significant deviations from the best fit of star-forming galaxies.

关键词： galaxies: formation -- galaxies statistics -- galaxies structure -- in-frared: galaxies

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Answering Reachability Queries on incrementally Updated Graphs by Hierarchical Labeling Schema

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Journal of Computer Science & Technology 2016年第2期31卷 381-399页

作者： Tak-lam Wong Department of Mathematics and information Technology The Hong Kong Institute of Education Hong Kong China

We proposed a novel solution schema called the Hierarchical Labeling Schema （HLS） to answer reachability queries in directed graphs. Different from many existing approaches that focus on static directed acyclic graphs （DAGs）, our schema focuses on directed cyclic graphs （DCGs） where vertices or arcs could be added to a graph incrementally. Unlike many of the traditional approaches, HLS does not require the graph to be acyclic in constructing its index. Therefore, it could, in fact, be applied to both DAGs and DCGs. When vertices or arcs are added to a graph, the HLS is capable of updating the index incrementally instead of re-computing the index from the scratch each time, making it more efficient than many other approaches in the practice. The basic idea of HLS is to create a tree for each vertex in a graph and link the trees together so that whenever two vertices are given, we can immediately know whether there is a path between them by referring to the appropriate trees. We conducted extensive experiments on both real-world datasets and synthesized datasets. We compared the performance of HLS, in terms of index construction time, query processing time and space consumption, with two state-of-the-art methodologies, the path-tree method and the 3-hop method. We also conducted simulations to model the situation when a graph is updated incrementally. The performance comparison of different algorithms against HLS on static graphs has also been studied. Our results show that HLS is highly competitive in the practice and is particularly useful in the cases where the graphs are updated frequently.

关键词： graph indexing reachability query Hierarchical Labeling Schema (HLS) incremental update directed cyclic graph

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Oncogene GAEC1 regulates CAPN10 expression which predicts survival in esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2013年第18期19卷 2772-2780页

作者： Dessy Chan Miriam yuen-Tung Tsoi Christina Di Liu SauHing Chan Simon Ying-Kit Law Kwok-Wah Chan yuen-Piu Chan Vinod Gopalan Alfred King-Yin lam Johnny Cheuk-On Tang State Key Laboratory of Chirosciences Lo Ka Chung Centre for Natural Anti-cancer Drug Development Department of Applied Biology and Chemical Technology the Hong Kong Polytechnic University Department of Surgery Li Ka Shing Faculty of Medicine the University of Hong Kong Department of Pathology Li Ka Shing Faculty of Medicine the University of Hong Kong Department of Pathology Griffith Medical School and Griffith Health Institute Griffith University

AiM: To identify the downstream regulated genes of GAEC1 oncogene in esophageal squamous cell carcinoma and their clinicopathological significance. METHODS: The anti-proliferative effect of knocking down the expression of GAEC1 oncogene was stud-ied by using the RNA interference (RNAi) approach through transfecting the GAEC1 -overexpressed esophageal carcinoma cell line KYSE150 with the pSilencer vector cloned with a GAEC1 -targeted sequence, followed by MTS cell proliferation assay and cell cycle analysis using flow cytometry. RNA was then extracted from the parental, pSilencer-GAEC1 -targeted sequence transfected and pSilencer negative control vector transfected KYSE150 cells for further analysis of different patterns in gene expression. Genes differentially expressed with suppressed GAEC1 expression were then determined using Human Genome U133 Plus 2.0 cDNA microarray analysis by comparing with the parental cells and normalized with the pSilencer negative control vector transfected cells. The most prominently regulated genes were then studied by immunohistochemical staining using tissue microarrays to determine their clinicopathological correlations in esophageal squamous cell carcinoma by statistical analyses. RESULTS: The RNAi approach of knocking down gene expression showed the effective suppression of GAEC1 expression in esophageal squamous cell carcinoma cell line KYSE150 that resulted in the inhibition of cell proliferation and increase of apoptotic population. cDNA microarray analysis for identifying differentially expressed genes detected the greatest levels of downregulation of calpain 10 (CAPN10 ) and upregulation of trinucleotide repeat containing 6C (TNRC6C ) transcripts when GAEC1 expression was suppressed. At the tissue level, the high level expression of calpain 10 protein was significantly associated with longer patient survival (month) of esophageal squamous cell carcinoma compared to the patients with low level of calpain 10 expression (37.73 ±

关键词： Esophageal squamous cell carcinoma Oncogene RNA interference Calpain 10 Tissue microarray

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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

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Design and mathematical analysis of activating transcriptional amplifiers that enable modular temporal control in synthetic juxtacrine circuits

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Synthetic and Systems Biotechnology 2023年第4期8卷 654-672页

作者： Calvin lam Department of Biochemistry and Molecular Biology University of Nebraska Medical CenterOmahaNE68198USA.

The ability to control mammalian cells such that they self-organize or enact therapeutic effects as desired has incredible *** only would it further our understanding of native processes such as development and the immune response,but it would also have powerful applications in medical fields such as regenerative medicine and *** control is typically obtained by synthetic circuits that use synthetic receptors,but control remains *** synthetic juxtacrine receptors(SJRs)are widely used as they are fully modular and enable spatial control,but they have limited gene expression amplification and temporal *** these are integral facets to cell control,i therefore designed transcription factor based amplifiers that amplify gene expression and enable unidirectional temporal control by prolonging duration of target gene *** a validated in silico framework for SJR signaling,i combined these amplifiers with SJRs and show that these SJR amplifier circuits can direct spatiotemporal patterning and improve the quality of self-organization.i then show that these circuits can improve chimeric antigen receptor(CAR)T cell tumor killing against various heterogenous antigen expression *** amplifiers are flexible tools that improve control over SJR based circuits with both basic and therapeutic applications.

关键词： Synthetic biology Synthetic development Synthetic immunotherapy synNotch SNiPR Amplifiers Self-organization Temporal control Spatiotemporal control CAR T cell Synthetic receptors

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Carvedilol Versus Other Nonselective Beta Blockers for Variceal Bleeding Prophylaxis and Death: A Network Meta-analysis

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Journal of Clinical and Translational Hepatology 2023年第5期11卷 1143-1149页

作者： Ka-Shing Cheung Chiu-Hang Mok Lok-Ka lam Xian-Hua Mao Lung-Yi Mak Wai-Kay Seto Man-Fung yuen Department of Medicine School of Clinical MedicineThe University of Hong KongQueen Mary HospitalHong KongChina Department of Medicine The University of Hong Kong-Shenzhen HospitalShenzhenGuangdongChina School of Clinical Medicine The University of Hong KongHong KongChina State Key Laboratory of Liver Research The University of Hong KongHong KongChina

Background and Aims:We aimed to perform a network meta-analysis(NWM)to examine comparative effectiveness of non-selective beta blockers(NSBBs)on prophylaxis of gastroesophageal variceal bleeding(GVB)and mortality ***:MEDLiNE(OViD)and EMBASE databases were searched for eligible randomized clinical trials(RCTs)from inception to July 3,*** of interest included primary/secondary prophylaxis of GVB,failure to achieve hepatic venous pressure gradient(HVPG)decremental response,liver-related and all-cause mortality.A Bayesian NWM was performed to derive relative risk(RR)with 95%credible intervals(Cris).The ranking probability of each NSBB was assessed by surface under cumulative ranking curve(SUCRA).Results:Thirty-three RCTs including 3,188 cirrhosis patients with gastroesophageal varices were *** with placebo,nadolol ranked first for reducing variceal bleeding[RR:0.25,(95%Cri:0.11–0.51);SUCRA:0.898],followed by carvedilol[RR:0.33,(95%Cri:0.11–0.88);SUCRA:0.692]and propranolol[RR:0.52,(95%Cri:0.37–0.75);SUCRA:0.405].Carvedilol was more effective than propranolol in achieving HVPG decremental response[RR:0.43,(95%Cri:0.26–0.69)].Carvedilol ranked first for reducing all-cause mortality[RR:0.32,(95%Cri:0.17–0.57);SUCRA:0.963],followed by nadolol[RR:0.48,(95%Ci:0.29–0.77);SUCRA:0.688],and propranolol[RR:0.77,(95%Ci:0.58–1.02);SUCRA:0.337].Similar findings were observed for liver-related *** ranked the *** RR of adverse events was 4.38,(95%Cri:0.33–161.4);SUCRA:0.530,followed by propranolol[RR:7.54,(95%Cri:1.90–47.89);SUCRA:0.360],and nadolol[RR:18.24,(95%Cri:91.51–390.90);SUCRA:0.158].Conclusions:Carvedilol is the preferred NSBB with better survival benefit and lower occurrence of adverse events among patients with gastroesophageal varices.

关键词： NSBB Carvedilol Nadolol Propranolol Varices Cirrhosis CPSH

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