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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 Genome Institute of Singapore 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 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 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

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： hepatocellular carcinoma intra-tumor heterogeneity phenotypic evolution tumor evolution

Betaine combined with traditional Chinese medicine ointment to treat skin wounds in microbially infected diabetic mice

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World Journal of Diabetes 2025年第1期16卷 104-120页

作者： Wen-Yan Xu Yuan-Yuan Dai Shi-Xian Yang Hao Chen Yan-qiang Huang Pei-Pei Luo Zhong-Heng wei Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance Youjiang Medical University for NationalitiesBaise 533000Guangxi Zhuang Autonomous RegionChina Guangxi Clinical Medical Research Center for Hepatobiliary Diseases Affiliated Hospital of Youjiang Medical University for NationalitiesBaise 533000Guangxi Zhuang Autonomous RegionChina Department of Pathology Wannan Medical CollegeWuhu 241002Anhui ProvinceChina Guangxi Zhuang Autonomous Region Engineering Research Center of Clinical Prevention and Control Technology and Leading Drug for Microorganisms with Drug Resistance in Border Ethnic Areas Youjiang Medical University for NationalitiesBaise 533000Guangxi Zhuang Autonomous RegionChina Department of Gastroenterology Wujin People’s Hospital Affiliated to Jiangsu UniversityChangzhou 213004Jiangsu ProvinceChina

BACKGROUND Skin wounds are highly common in diabetic patients,and with increasing types of pathogenic bacteria and antibiotic resistance,wounds and infections in diabetic patients are difficult to treat and *** To explore the effects of betaine ointment(BO)in promoting the healing of skin wounds and reducing the inflammation and apoptosis of skin cells in microbially infected diabetic *** By detecting the minimum inhibitory concentrations(MICs)of betaine and plant monomer components such as psoralen,we prepared BO with betaine as the main ingredient,blended it with traditional Chinese medicines such as gromwell root and psoralen,and evaluated its antibacterial effects and safety in vitro and in *** skin infection wound models of ordinary mice and diabetic mice were constructed,and the OTC drugs mupirocin ointment and Zicao ointment were used as controls to evaluate the antibacterial effects in vivo and the anti-inflammatory and anti-apoptotic effects of *** The MICs of betaine against microorganisms such as Staphylococcus aureus(***),Candida albicans and Cryptococcus neoformans ranged from 4 to 32μg/*** root and psoralea,both of which contain antimicrobial components,mixed to prepare BO with MICs ranging from 16 to 64μg/mL,which is 32-256 times lower than those of Zicao ointment,although the MIC is greater than that of *** 15 days of treatment with BO for USA300-infected ordinary mice,the wound scab removal rates were 83.3%,while those of mupirocin ointment and Zicao ointment were 66.7%and 0%,respectively,and the differences were statistically *** diabetic mice,the wound scab removal rate of BO and mupirolacin ointment was 80.0%,but BO reduced wound inflammation and the apoptosis of skin cells and facilitated wound *** The ointment prepared by mixing betaine and traditional Chinese medicine can effectively inhibit common skin microorganisms and has a strong effect on the skin wounds of sensit

关键词： Betaine ointment Staphylococcus aureus Drug resistance Skin infection Diabetes mellitus

Activin A receptor type 1C single nucleotide polymorphisms associated with esophageal squamous cell carcinoma risk in Chinese population

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 39-51页

作者： Si-Yun Lin Hou Huang Jin-Jie Yu Feng Su Tian Jiang Shao-Yuan Zhang Lu Lv Tao Long Hui-Wen Pan Jun-Qing Qi qiang Zhou wei-Feng Tang Guo-Wen Ding Li-Ming Wang Li-Jie Tan Jun Yin Department of Thoracic Surgery Zhongshan Hospital Affiliated to Fudan UniversityShanghai 200032China Shanghai Key Laboratory of Clinical Geriatric Medicine Huadong Hospital Affiliated to Fudan UniversityShanghai 200040China Department of Cardiothoracic Surgery The Affiliated People's Hospital of Jiangsu UniversityZhenjiang 212002Jiangsu ProvinceChina Department of Thoracic Surgery Sichuan Cancer Hospital&InstituteChengdu 610042Sichuan ProvinceChina Department of Cardiothoracic Surgery Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210000Jiangsu ProvinceChina Department of Respiratory and Critical Care Medicine Shanghai Xuhui Central HospitalShanghai 200032China

BACKGROUND Transforming growth factor-β(TGF-β)superfamily plays an important role in tumor progression and *** A receptor type 1C(ACVR1C)is a TGF-βtype I receptor that is involved in tumorigenesis through binding to dif-ferent *** To evaluate the correlation between single nucleotide polymorphisms(SNPs)of ACVR1C and susceptibility to esophageal squamous cell carcinoma(ESCC)in Chinese Han *** In this hospital-based cohort study,1043 ESCC patients and 1143 healthy controls were *** SNPs(rs4664229,rs4556933,rs77886248,rs77263459,rs6734630)of ACVR1C were assessed by the ligation detection reaction ***-weinberg equilibrium test,genetic model analysis,stratified analysis,linkage disequi-librium test,and haplotype analysis were *** Participants carrying ACVR1C rs4556933 GA mutant had significantly decreased risk of ESCC,and those with rs77886248 TA mutant were related with higher risk,especially in older male *** the haplotype analysis,ACVR1C Trs4664229Ars4556933Trs77886248Crs77263459Ars6734630 increased risk of ESCC,while Trs4664229Grs4556933Trs77886248Crs77263459Ars6734630 was associated with lower susceptibility to *** ACVR1C rs4556933 and rs77886248 SNPs were associated with the susceptibility to ESCC,which could provide a potential target for early diagnosis and treatment of ESCC in Chinese Han population.

关键词： Activin A receptor type 1C Single nucleotide polymorphisms Esophageal squamous cell carcinoma Genetic susceptibility Hospital-based cohort study

Coupled Lagrangian impingement spray model for doublet impinging injectors under liquid rocket engine operating conditions

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Chinese Journal of Aeronautics 2017年第4期30卷 1391-1406页

作者： qiang wei Guozhu LIANG School of Astronautics Beihang University Beoing 100083 China

To predict the effect of the liquid rocket engine combustion chamber conditions on the impingement spray, the conventional uncoupled spray model for impinging injectors is extended by considering the coupling of the jet impingement process and the ambient gas field. The new coupled model consists of the plain-orifice sub-model, the jet-jet impingement sub-model and the droplet collision sub-model. The parameters of the child droplet are determined with the jet-jet impingement sub-model using correlations about the liquid jet parameters and the chamber *** overall model is benchmarked under various impingement angles, jet momentum and offcenter ratios. Agreement with the published experimental data validates the ability of the model to predict the key spray characteristics, such as the mass flux and mixture ratio distributions in quiescent air. Besides, impinging sprays under changing ambient pressure and non-uniform gas flow are investigated to explore the effect of liquid rocket engine chamber conditions. First, a transient impingement spray during engine start-up phase is simulated with prescribed pressure profile. The minimum average droplet diameter is achieved when the orifices work in cavitation state, and is about 30% smaller than the steady single phase state. Second, the effect of non-uniform gas flow produces off-center impingement and the rotated spray fan by 38°. The proposed model suggests more reasonable impingement spray characteristics than the uncoupled one and can be used as the first step in the complex simulation of coupling impingement spray and combustion in liquid rocket engines.

关键词： Combustion chamber Doublet impinging injector Impingement spray model Lagrangian method Liquid rocket engine

Kinematics-based four-state trajectory tracking control of a spherical mobile robot driven by a 2-DOF pendulum

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Chinese Journal of Aeronautics 2019年第6期32卷 1530-1540页

作者： wei LI qiang ZHAN Robotics Institute Beihang UniversityBeijing 100083China Ecole Centrale de Pékin Beihang UniversityBeijing 100083China

Spherical mobile robot has compact structure, remarkable stability, and flexible motion,which make it have many advantages over traditional mobile robots when applied in those unmanned environments, such as outer planets. However, spherical mobile robot is a special highly under-actuated nonholonomic system, which cannot be transformed to the classic chained form. At present, there has not been a kinematics-based trajectory tracking controller which could track both the position states and the attitude states of a spherical mobile robot. In this paper, the four-state(two position states and two attitude states) trajectory tracking control of a type of spherical mobile robot driven by a 2-DOF pendulum was studied. A controller based on the shunting model of neurodynamics and the kinematic model was deduced, and its stability was demonstrated with Lyapunov’s direct method. The control priorities of the four states were allocated according to the magnification of each state tracking error in order to firstly ensure the correct tracking of the position states. The outputs(motor speeds) of the controller were regulated according to the maximum speeds and the maximum accelerations of the actuation motors in order to solve the speed jump problem caused by initial state errors, and continuous and bounded outputs were obtained. The effectiveness including the anti-interference ability of the proposed trajectory tracking controller was verified through MATLAB simulations.

关键词： Kinematics Lyapunov methods Neurodynamics Nonholonomic systems Spherical mobile robot Trajectory tracking

From Liquid to Solid‑State Lithium Metal Batteries:Fundamental Issues and Recent Developments

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Nano-Micro Letters 2024年第2期16卷 68-125页

作者： Zhao Zhang wei‑qiang Han School of Materials Science and Engineering Zhejiang UniversityHangzhou 310027People’s Republic of China

The widespread adoption of lithium-ion batteries has been driven by the proliferation of portable electronic devices and electric vehicles,which have increasingly stringent energy density *** metal batteries(LMBs),with their ultralow reduction potential and high theoretical capacity,are widely regarded as the most promising technical pathway for achieving high energy density *** this review,we provide a comprehensive overview of fundamental issues related to high reactivity and migrated interfaces in ***,we propose improved strategies involving interface engineering,3D current collector design,electrolyte optimization,separator modification,application of alloyed anodes,and external field regulation to address these *** utilization of solid-state electrolytes can significantly enhance the safety of LMBs and represents the only viable approach for advancing *** review also encompasses the variation in fundamental issues and design strategies for the transition from liquid to solid *** noteworthy is that the introduction of SSEs will exacerbate differences in electrochemical and mechanical properties at the interface,leading to increased interface inhomogeneity—a critical factor contributing to failure in all-solidstate lithium metal *** on recent research works,this perspective highlights the current status of research on developing high-performance LMBs.

关键词： Lithium metal batteries All-solid-state lithium metal battery Li dendrite Solid electrolyte Interface

定向电场下W_(6)C_(6)团簇的超卤素调制及非线性光学特性

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原子与分子物理学报 2025年第3期42卷 72-76页

作者：蔡璧钧段宇静魏强重庆理工大学理学院重庆400050

本文采用密度泛函(DFT)方法研究了定向外电场(OEEF)对W_(6)C_(6)团簇几何结构、电子性质以及非线性光学响应(NLO)的影响.计算结果表明W_(6)C_(6)的结构在一定OEEF强度下可以保持稳定.OEEF可以增大W_(6)C_(6)团簇的电子亲和能(EA值),且... 详细信息

本文采用密度泛函(DFT)方法研究了定向外电场(OEEF)对W_(6)C_(6)团簇几何结构、电子性质以及非线性光学响应(NLO)的影响.计算结果表明W_(6)C_(6)的结构在一定OEEF强度下可以保持稳定.OEEF可以增大W_(6)C_(6)团簇的电子亲和能(EA值),且在特定强度下,OEEF可以将W_(6)C_(6)团簇转变为超卤素.通过对EA值的非线性拟合可以实现对W_(6)C_(6)团簇的连续调制.进一步对不同外电场下W_(6)C_(6)团簇的最高占据分子轨道(HOMO)和最低未占据分子轨道(LUMO)能级进行分析,发现OEEF降低了W_(6)C_(6)团簇LUMO能级是其EA值增大的主因.此外,OEEF可以显著增大W_(6)C_(6)团簇的平均极化率和第一超极化率,尤其是第一超极化率,改变其非线性光学性质.

关键词：定向外电场超原子密度泛函理论 NLO W_(6)C_(6)团簇

Recent Advances and Perspectives of Lewis Acidic Etching Route:An Emerging Preparation Strategy for MXenes

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Nano-Micro Letters 2023年第5期15卷 187-235页

作者： Pengfei Huang wei-qiang Han School of Materials Science and Engineering Zhejiang UniversityHangzhou 310027People’s Republic of China

Since the discovery in 2011,MXenes have become the rising star in the field of two-dimensional *** from the metallic-level conductivity,large and adjustable gallery spacing,low ion diffusion barrier,rich surface chemistry,superior mechanical strength,MXenes exhibit great application prospects in energy storage and conversion,sensors,optoelectronics,electromagnetic interference shielding and ***,two issues seriously deteriorate the further development of *** is the high experimental risk of common preparation methods such as HF etching,and the other is the difficulty in obtaining MXenes with controllable surface ***,Lewis acidic etching,as a brand-new preparation strategy for MXenes,has attracted intensive attention due to its high safety and the ability to endow MXenes with uniform ***,a comprehensive review of Lewis acidic etching method has not been reported ***,we first introduce the Lewis acidic etching from the following four aspects:etching mechanism,terminations regulation,in-situ formed metals and delamination of multi-layered ***,the applications of MXenes and MXene-based hybrids obtained by Lewis acidic etching route in energy storage and conversion,sensors and microwave absorption are carefully ***,some challenges and opportunities of Lewis acidic etching strategy are also presented.

关键词： Lewis acidic etching MXenes Etching mechanism Termination regulation In-situ formed metals Delamination Application

Sliding Dynamics of Slide-Ring Polymers Based on the Bead-Spring Model

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Chinese Journal of Polymer Science 2023年第9期41卷 1410-1424,I0007页

作者： Zhong-qiang Xiong wei Yu Advanced Rheology Institute Department of Polymer Science and EngineeringState Key Laboratory for Metal Matrix Composite MaterialsShanghai Jiao Tong UniversityShanghai200240China

Understanding the sliding dynamics is critical for developing rotaxane-based mechanically interlocked *** this work,we studied the sliding behavior of a sliding ring and its influence on the dynamics of attached polymer chains based on the heterogeneous beadspring *** sliding constraint was treated as direction-related confinement with the heterogeneous friction coefficient and constraint *** relaxation spectrum,the diffusion dynamics,and the sliding dynamics under/after drag were studied for typical sliding chain topologies,namely,the sliding dangling chain,the constraint sliding chain,and the sliding *** with the non-sliding chains(such as the free chain,the dangling chain,and the network strand),the slide of one or two chain ends induces an additional slow process in the transition from the Rouse-type behavior to the long-time terminal *** effect of the sliding-related process on the diffusion of specific chain segments relies on the chain *** slow sliding relaxation process is also observed in the sliding process during and after chain deformation,whose characteristic time is at least three times the terminal relaxation time of the free chain with the same length,and will increase with the friction coefficient(i.e.,the interaction)between the ring and the polymer *** results of this work will benefit the understanding of the sliding dynamics in experiments.

关键词： Sliding chain Bead-spring model Heterogeneity Diffusion Mean conformation