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Dynamic phenotypic heterogeneity and the evolution of multiple RNA subtypes in hepatocellular carcinoma:the PLANET study

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National Science Review 2022年第3期9卷 96-109页

作者： Weiwei Zhai Hannah Lai Neslihan Arife Kaya Jianbin Chen Hechuan Yang Bingxin Lu Jia Qi Lim Siming Ma Sin Chi Chew Khi Pin Chua Jacob Josiah Santiago Alvarez Pauline Jieqi Chen Mei Mei Chang Lingyan Wu Brian K.P.Goh Alexander Yaw-Fui chung chung Yip Chan peng chung cheow Ser Yee Lee Juinn Huar Kam Alfred Wei-Chieh Kow Iyer Shridhar Ganpathi Rawisak Chanwat Jidapa Thammasiri Boon Koon Yoong Diana Bee-Lan Ong Vanessa H.de Villa Rouchelle D.Dela Cruz Tracy Jiezhen Loh Wei Keat Wan Zeng Zeng Anders Jacobsen Skanderup Yin Huei Pang Krishnakumar Madhavan Tony Kiat-Hon Lim Glenn Bonney Wei Qiang Leow Valerie Chew Yock Young Dan Wai Leong Tam Han Chong Toh Roger Sik-Yin Foo Pierce Kah-Hoe Chow Division of Pathology National Cancer Institute Department of Surgery Faculty of Medicine University of Malaya Department of Surgery and Center for Liver Disease Management and Transplantation The Medical City 13. Department of Laboratories The Medical City Department of Pathology Singapore General Hospital Institute for Infocomm Research ASTAR Department of Pathology National University Health System Translational Immunology Institute (TII) Sing Health Duke-NUS Academic Medical Centre Division of Gastroenterology and Hepatology University Medicine Cluster National University Hospital Department of Biochemistry Yong Loo Lin School of Medicine National University of Singapore Genome Institute of Singapore Agency for Science Technology and Research Cancer Science Institute of Singapore National University of Singapore Division of Medical Oncology National Cancer Center Singapore Cardiovascular Research Institute National University of Singapore National University Healthcare System Singhealth-Duke-NUS Academic Surgery Program Duke-NUS Graduate Medical School Institute of Molecular and Cell Biology Agency for Science Technology and Research Key Laboratory of Zoological Systematics and Evolution Institute of Zoology Chinese Academy of Sciences Center for Excellence in Animal Evolution and Genetics Chinese Academy of Sciences School of Biological Sciences Nanyang Technological University Division of Biosciences Faculty of Life Sciences Division of Surgery and Surgical Oncology National Cancer Centre Department of Hepato-Pancreato-Biliary and Transplant Surgery Singapore General Hospital Division of Hepatobiliary and Pancreatic Surgery Department of Surgery University Surgical Cluster National University Health System Hepato-Pancreato-Biliary Surgery Unit Department of Surgery National Cancer Institute

Intra-tumor heterogeneity(ITH) is a key challenge in cancer treatment, but previous studies have focused mainly on the genomic alterations without exploring phenotypic(transcriptomic and immune)heterogeneity. Using one of the largest prospective surgical cohorts for hepatocellular carcinoma(HCC)with multi-region sampling, we sequenced whole genomes and paired transcriptomes from 67 HCC patients(331 samples). We found that while genomic ITH was rather constant across stages, phenotypic ITH had a very different trajectory and quickly diversified in stage Ⅱ patients. Most strikingly, 30% of patients were found to contain more than one transcriptomic subtype within a single tumor. Such phenotypic ITH was found to be much more informative in predicting patient survival than genomic ITH and explains the poor efficacy of single-target systemic therapies in HCC. Taken together, we not only revealed an unprecedentedly dynamic landscape of phenotypic heterogeneity in HCC, but also highlighted the importance of studying phenotypic evolution across cancer types.

关键词： NADH oxidase H2O2 production oxidative phosphorylation

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Applying heteroatom co-doped carbon nanotube for manifesting high performance in the electrochemical reduction of aqueous nitrogen oxide by gold nanoparticles

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Nano Research 2024年第3期17卷 1151-1164页

作者： Jane chung Haibo Yin Rong Wang Yunlong Wang Junyang Zhang Yue peng Joung Woo Han Seongyun Ryu Junhua Li State Key Joint Laboratory of Environment Simulation and Pollution Control School of EnvironmentTsinghua UniversityBeijing 100084China EHS Research Center Samsung Electronics Co.Ltd.Gyeonggi-do 18448Republic of Korea

Electrochemical NO-to-NH_(3) under ambient conditions could be a viable alternative having advantages in terms of energy consumption and exhaust gas recycling of NO,replacing a traditional ammonia synthesis method of the Haber–Bosch process.In synthesizing boron(B-)and nitrogen(N-)co-doped carbon nanotube(CNT)based gold(Au)catalysts,B-dopants elevate the conductivity of carbon nanotube by sp2 hybridization on graphene and implant B–N domains within the graphene layer,and result in facilitating the embedding amount of Au accompanied by high dispersibility with low particle size.Theoretical density functional theory(DFT)calculations elucidate that the electron cloud transmitted from B-dopant to the active site of Au induces the Lewis acidic site,and the O-distal pathway occurs following a spontaneous reaction.Increment of the electron-deficient B-doping area accompanied by N-defects and B–O edges retains the major valence state of Au as Au^(δ+),and suppresses hydrogen evolution reaction(HER)by repulsing the hindrance of H*.This record exhibits the highest faradaic efficiency(FE)of 94.7%,and NH_(3) yield rate of 1877.4μg·h^(-1)·mg_(cat)^(-1),which is the optimal yield over energy consumption in the field of the ambient reduction of aqueous NO.

关键词： boron heteroatom nitrogen defect gold nanoparticles valence states of gold electrochemical NO-to-NH3

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Clinical values of Barcelona Clinic Liver Cancer subgroup and up-to-7 criteria in intermediate stage hepatocellular carcinoma with transcatheter arterial chemoembolization

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World Journal of Clinical Cases 2022年第21期10卷 7275-7284页

作者： Shou-Wu Lee Yen-Chun peng Han-chung Lien chung-Wang Ko Chun-Fang Tung Chi-Sen Chang Division of Gastroenterology and Hepatology Department of Internal MedicineTaichung Veterans General HospitalTaichung 40705Taiwan Department of Internal Medicine Yang Ming Chiao Tung UniversityTaipei 112304Taiwan Department of Post-Baccalaureate Medicine College of MedicineChung Hsing UniversityTaichung 40227Taiwan Department of Internal Medicine Chung Shan Medical UniversityTaichung 40201Taiwan

BACKGROUND Transarterial chemoembolization(TACE)is a recommended treatment for patients with intermediate stage hepatocellular carcinoma(HCC)but with variable treatment outcomes.AIM To determine factors for predicting outcomes of TACE in patients with intermediate stage B HCC.METHODS Patients with Barcelona Clinic Liver Cancer(BCLC)stage B HCC who underwent TACE as the primary treatment were enrolled at Taichung Veterans General Hospital from January 2005 to December 2009.Patients were assigned to either the objective responder(OR)group or the non-OR group according to mRECIST criteria.Clinical and radiological characteristics were compared between the 2 groups.The overall survival of enrolled subjects was analyzed.RESULTS In 128 enrolled patients,66(51.6%)were in the OR group and 62(48.4%)in the non-OR group.Compared with the non-OR group,the OR group had a significantly smaller HCC size(6.55 cm vs 9.50 cm,P=0.001)and was within the up-to-7 criteria(50%vs 26.7%,P=0.001).After multivariable analyses,these significant associations still existed.Overall survival rate of all the subjects averaged 20.65±13.26 mo.The survival rate at 1-year was 64.8%,2-year was 46.9%,and 3-year was 31.2%.For those patients with OR to TACE,smaller tumor size and within up-to-7 criteria were associated with significantly better overall survival.Those patients with subgroup B1 had the highest OR ratio(75%)and better overall survival(26.70±12.07 mo)after TACE.CONCLUSION BCLC stage B HCC patients with smaller tumor size or within up-to-7 criteria had better survival outcomes to TACE.BCLC stage B subgroup is useful to predict refractoriness to TACE.

关键词： Hepatocellular carcinoma Objective response Overall survival Transcatheter arterial chemoembolization Barcelona Clinic Liver Cancer

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Comparison between multiple logistic regression and machine learning methods in prediction of abnormal thallium scans in type 2 diabetes

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World Journal of Clinical Cases 2023年第33期11卷 7951-7964页

作者： chung-Chi Yang chung-Hsin peng Li-Ying Huang Fang Yu Chen Chun-Heng Kuo chung-Ze Wu Te-Lin Hsia chung-Yu Lin Division of Cardiovascular Medicine Taoyuan Armed Forces General HospitalTaoyuan City 32551Taiwan Division of Cardiovascular Tri-service General HospitalTaipei City 114202TaiwanChina Department of Urology Cardinal Tien HospitalNew Taipei City 23148TaiwanChina School of Medicine Fu-Jen Catholic UniversityNew Taipei City 242062TaiwanChina Department of Internal Medicine Department of Medical EducationSchool of MedicineFu Jen Catholic University HospitalNew Taipei City 243TaiwanChina School of Medicine College of MedicineFu Jen Catholic UniversityNew Taipei City 243TaiwanChina Department of Endocrinology Fu Jen Catholic University HospitalNew Taipei City 243TaiwanChina Division of Endocrinology and Metabolism Department of Internal MedicineFu Jen Catholic University HospitalNew Taipei City 243TaiwanChina Division of Endocrinology Shuang Ho HospitalNew Taipei City 23561TaiwanChina School of Medicine Taipei Medical UniversityTaipei City 11031TaiwanChina Department of Internal Medicine Cardinal Tien HospitalNew Taipei City 23148TaiwanChina Department of Cardiology Fu Jen Catholic University HospitalNew Taipei City 24352TaiwanChina Graduate Institute of Business Administration Fu Jen Catholic UniversityNew Taipei City 242062TaiwanChina

BACKGROUND The prevalence of type 2 diabetes(T2D)has been increasing dramatically in recent decades,and 47.5%of T2D patients will die of cardiovascular disease.Thallium-201 myocardial perfusion scan(MPS)is a precise and noninvasive method to detect coronary artery disease(CAD).Most previous studies used traditional logistic regression(LGR)to evaluate the risks for abnormal CAD.Rapidly developing machine learning(Mach-L)techniques could potentially outperform LGR in capturing non-linear relationships.AIM To aims were:(1)Compare the accuracy of Mach-L methods and LGR;and(2)Found the most important factors for abnormal TMPS.METHODS 556 T2D were enrolled in the study(287 men and 269 women).Demographic and biochemistry data were used as independent variables and the sum of stressed score derived from MPS scan was the dependent variable.Subjects with a MPS score≥9 were defined as abnormal.In addition to traditional LGR,classification and regression tree(CART),random forest,Naïve Bayes,and eXtreme gradient boosting were also applied.Sensitivity,specificity,accuracy and area under the receiver operation curve were used to evaluate the respective accuracy of LGR and Mach-L methods.RESULTS Except for CART,the other Mach-L methods outperformed LGR,with gender,body mass index,age,low-density lipoprotein cholesterol,glycated hemoglobin and smoking emerging as the most important factors to predict abnormal MPS.CONCLUSION Four Mach-L methods are found to outperform LGR in predicting abnormal TMPS in Chinese T2D,with the most important risk factors being gender,body mass index,age,low-density lipoprotein cholesterol,glycated hemoglobin and smoking.

关键词： Myocardial perfusion scintigraphy Machine learning Type 2 diabetes Thallium-201

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Mesenchymal stromal cell-derived small extracellular vesicles modulate macrophage polarization and enhance angio-osteogenesis to promote bone healing

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Genes & Diseases 2022年第4期9卷 841-844页

作者： Shang Jiunn Chuah Chee Weng Yong Kristeen Ye Wen Teo Jacob Ren Jie Chew Yi Ann cheow Shipin Zhang Raymond chung Wen Wong Asher Ah Tong Lim Sai Kiang Lim Wei Seong Toh Faculty of Dentistry National University of Singapore119085Singapore Institute of Molecular and Cell Biology Agency for ScienceTechnology and Research138648Singapore Department of Orthopaedic Surgery Yong Loo Lin School of MedicineNational University of Singapore119288Singapore Department of Biomedical Engineering Faculty of EngineeringNational University of Singapore117583Singapore Tissue Engineering Program Life Sciences InstituteNational University of Singapore117456Singapore Integrative Sciences and Engineering Program NUS Graduate SchoolNational University of Singapore119077Singapore

Mesenchymal stem/stromal cells(MSCs)have demonstrated therapeutic efficacy for bone regeneration in animal and clinical studies.Although MSCs were initially thought to differentiate to various cell types to replace the injured/diseased tissue,it is now accepted that these cells secrete factors to promote tissue repair.1 Among these factors,small extracellular vesicles(sEVs)of size 50–200 nm,which include the exosomes,have been identified as the principal agent mediating the wide-ranging therapeutic efficacy of MSCs.2 Several studies have also reported the therapeutic effects of MSC-sEVs to enhance bone repair in animal models,as recently reviewed.3 However,the cellular processes and mechanisms mediated by MSC-sEVs in bone regeneration remain to be fully elucidated.

关键词： healing clinical macrophage

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Applications of dynamical complexity theory in traditional Chinese medicine

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Frontiers of Medicine 2014年第3期8卷 279-284页

作者： Yan Mal Shuchen Sun chung-Kang peng Division of Interdisciplinary Medicine and Biotechnology Beth Israel Deaconess Medical Centel Harvard Medical School Boston MA 02215USA Sleep CenteR Eye Hospital China Academy of Chinese Medical Sciences Beijing 100040 China Department of Otolaryngology Guang 'anmen Hospital China Academy of Chinese Medical Sciences Beijing 100053 China Center for Dynamical Biomarkers and Translational Medicine National Central University Chung-Li Taiwan China

Traditional Chinese medicine （TCM） has been gradually accepted by the world. Despite its widespread use in clinical settings, a major challenge in TCM is to study it scientifically. This difficulty arises from the fact that TCM views human body as a complex dynamical system, and focuses on the balance of the human body, both internally and with its external environment. As a result, conventional tools that are based on reductionist approach arc not adequate. Methods that can quantify the dynamics of complex integrative systems may bring new insights and utilities about the clinical practice and evaluation of efficacy of TCM. The dynamical complexity theory recently proposed and its computational algorithm, Multiscale Entropy （MSE） analysis, are consistent with TCM concepts. This new system level analysis has been successfully applied to many health and disease related topics in medicine. We believe that there could be many promising applications of this dynamical complexity concept in TCM. In this article, we propose some promising applications and research areas that TCM practitioners and researchers can pursue.

关键词： traditional Chinese medicine Multiscale Entropy dynamical complexity system level applications

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Investigation of the genetic etiology in male infertility with apparently balanced chromosomal structural rearrangements by genome sequencing

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Asian Journal of Andrology 2022年第3期24卷 248-254页

作者： Matthew Hoi Kin Chau Ying Li peng Dai Mengmeng Shi Xiaofan Zhu Jacqueline Pui Wah chung Yvonne K Kwok Kwong Wai Choy Xiangdong Kong Zirui Dong Department of Obstetrics and Gynaecology The Chinese University of Hong KongHong KongChina Shenzhen Research Institute The Chinese University of Hong KongShenzhen 518057China Hong Kong Hub of Paediatric Excellence The Chinese University of Hong KongHong KongChina Genetics and Prenatal Diagnosis Center The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China The Chinese University of Hong Kong-Baylor College of Medicine Joint Center for Medical Genetics Hong KongChina

Apparently balanced chromosomal structural rearrangements are known to cause male infertility and account for approximately 1%of azoospermia or severe oligospermia.However,the underlying mechanisms of pathogenesis and etiologies are still largely unknown.Herein,we investigated apparently balanced interchromosomal structural rearrangements in six cases with azoospermia/severe oligospermia to comprehensively identify and delineate cryptic structural rearrangements and the related copy number variants.In addition,high read-depth genome sequencing(GS)(30-fold)was performed to investigate point mutations causative of male infertility.Mate-pair GS(4-fold)revealed additional structural rearrangements and/or copy number changes in 5 of 6 cases and detected a total of 48 rearrangements.Overall,the breakpoints caused truncations of 30 RefSeq genes,five of which were associated with spermatogenesis.Furthermore,the breakpoints disrupted 43 topological-associated domains.Direct disruptions or potential dysregulations of genes,which play potential roles in male germ cell development,apoptosis,and spermatogenesis,were found in all cases(n=6).In addition,high read-depth GS detected dual molecular findings in case MI6,involving a complex rearrangement and two point mutations in the gene DNAH1.Overall,our study provided the molecular characteristics of apparently balanced interchromosomal structural rearrangements in patients with male infertility.We demonstrated the complexity of chromosomal structural rearrangements,potential gene disruptions/dysregulation and single-gene mutations could be the contributing mechanisms underlie male infertility.

关键词： azoospermia balanced structural rearrangements genome sequencing male infertility severe oligospermia

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Experimental and numerical studies of micro PEM fuel cell

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Acta Mechanica Sinica 2011年第5期27卷 627-635页

作者： Rong-Gui peng Chen-chung chung Chiun-Hsun Chen Department of Mechanical Engineering National Chiao Tung UniversityHsinchu Taiwan China

A single micro proton exchange membrane fuel cell （PEMFC） has been produced using Micro-electromechanical systems （MEMS） technology with the active area of 2.5 cm 2 and channel depth of about 500 μ m.A theoretical analysis is performed in this study for a novel MEMS-based design of a micro PEMFC.The model consists of the conservation equations of mass,momentum,species and electric current in a fully integrated finite-volume solver using the CFD-ACE＋ commercial code.The polarization curves of simulation are well correlated with experimental data.Three-dimensional simulations are carried out to treat prediction and analysis of micro PEMFC temperature,current density and water distributions in two different fuel flow rates （15 cm 3 /min and 40 cm 3 /min）.Simulation results show that temperature distribution within the micro PEMFC is affected by water distribution in the membrane and indicate that low and uniform temperature distribution in the membrane at low fuel flow rates leads to increased membrane water distribution and obtains superior micro PEMFC current density distribution under 0.4 V operating voltage.Model predictions are well within those known for experimental mechanism phenomena.

关键词： Micro PEMFC · MEMS · Simulation · Fuel flow rate

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An Observational Analysis of the Oceanic and Atmospheric Structure of Global-Scale Multi-decadal Variability

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Advances in Atmospheric Sciences 2014年第2期31卷 316-330页

作者： peng LIU chung-Hsiung SUI Key Laboratory of Meteorological Disaster of Ministry of Education Nanjing University of Information Science & Technology Department of Atmospheric Sciences NTU Taipei 10617

The aim of the present study was to identify multi-decadal variability （MDV） relative to the current centennial global warming trend in available observation data.The centennial global wanning trend was first identified in the global mean surface temperature （STgm） data.The MDV was identified based on three sets of climate variables,including sea surface temperature （SST）,ocean temperature from the surface to 700 m,and the NCEP and ERA40 reanalysis datasets,respectively.All variables were detrended and low-pass filtered.Through three independent EOF analyses of the filtered variables,all results consistently showed two dominant modes,with their respective temporal variability resembling the Pacific Decadal Oscillation/Inter-decadal Pacific Oscillation （PDO/IPO） and the Atlantic Multi-decadal Oscillation （AMO）.The spatial structure of the PDO-like oscillation is characterized by an ENSO-like structure and hemispheric symmetric features.The structure associated with the AMO-like oscillation exhibits hemispheric asymmetric features with anomalous warm air over Eurasia and warm SST in the Atlantic and Pacific basin north of 10°S,and cold SST over the southern oceans.The Pacific and Atlantic MDV in upper-ocean temperature suggest that they are mutually linked.We also found that the PDO-like and AMO-like oscillations are almost equally important in global-scale MDV by EOF analyses.In the period 1975-2005,the evolution of the two oscillations has given rise to strong temperature trends and has contributed almost half of the STgm warming.Hereon,in the next decade,the two oscillations are expected to slow down the global warming trends.

关键词： global-scale multi-decadal variation global mean surface temperature PDO-like oscillation AMO-like oscillation

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FLO-2D Simulation of Mudflow Caused by Large Landslide Due to Extremely Heavy Rainfall in Southeastern Taiwan during Typhoon Morakot

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Journal of Mountain Science 2013年第2期10卷 207-218页

作者： peng Szu-Hsien LU Shih-chung Department of Spatial Design Chienkuo Technology University

Daniau Village in Daniau Creek Watershed,Taitung County,Taiwan,sustained damages from landslides and mudflows during Typhoon Morakot in 2009.The purpose of this study is to adopt the FLO2D numerical model recognized by Federal Emergency Management Agency(FEMA) to simulate the mudflow,and the Daniau Village was used as a case study,along with rainfall and digital terrain data for this simulation.On the basis of sediment yields,the residual sediment volume in the landslide area was determined to be 33,276 m 3 by comparison of digital elevation models(DEMs) and by using the universal soil loss equation(USLE).In addition,this study performed a hydrological frequency analysis of rainfall to estimate the flow discharge as conditions of the simulation.Results of disaster surveys were collected to compare with outputs of the numerical model.Results of the simulation conducted with FLO2D indicated that if the countermeasure was not destroyed,the drainage work would function without overflow.This study aimed to review the effectiveness of countermeasure on the basis of simulation results obtained by using the model to provide references for future disaster prevention and resident evacuation plans.

关键词：山体滑坡模拟台风台湾地区土石流暴雨期东南部通用土壤流失方程

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