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A multidimensional platform of patient-derived tumors identifies drug susceptibilities for clinical lenvatinib resistance

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Acta Pharmaceutica Sinica B 2024年第1期14卷 223-240页

作者： Lei Sun Arabella H.Wan Shijia Yan Ruonian Liu Jiarui Li Zhuolong Zhou Ruirui Wu Dongshi Chen Xianzhang Bu Jingxing Ou Kai Li Xiongbin Lu Guohui Wan Zunfu Ke Department of Pathology the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China National-Local Joint Engineering Laboratory of Druggability and New Drug Evaluation National Engineering Research Center for New Drug and Druggability(Cultivation)Guangdong Province Key Laboratory of New Drug Design and EvaluationSchool of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006China Department of Medical and Molecular Genetics Indiana University School of MedicineIndianapolisIN 46202USA Department of Medicine Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCA 90033USA Department of Hepatic Surgery and liver Transplantation Center Third Affiliated HospitalOrgan Transplantation InstituteSun Yat-sen UniversityOrgan Transplantation Research Center of Guangdong ProvinceGuangdong Province Engineering Laboratory for Transplantation MedicineGuangzhou 510630China Guangdong Provincial Key Laboratory of liver Disease Research Guangzhou 510630China Department of Ultrasound Third Affiliated HospitalSun Yat-sen UniversityGuangzhou 510630China Melvin and Bren Simon Comprehensive Cancer Center Indiana UniversityIndianapolisIN 46202USA

Lenvatinib,a second-generation multi-receptor tyrosine kinase inhibitor approved by the FDA for first-line treatment of advanced liver cancer,facing limitations due to drug ***,we applied a multidimensional,high-throughput screening platform comprising patient-derived resistant liver tumor cells(PDCs),organoids(PDOs),and xenografts(PDXs)to identify drug susceptibilities for conquering lenvatinib resistance in clinically relevant *** and passaging of PDCs and PDOs from resistant patient liver tumors retained functional fidelity to lenvatinib treatment,expediting drug repurposing *** screening identified romidepsin,YM155,apitolisib,NVP-TAE684 and dasatinib as potential antitumor agents in lenvatinib-resistant PDC and PDO ***,romidepsin treatment enhanced antitumor response in syngeneic mouse models by triggering immunogenic tumor cell death and blocking the EGFR signaling pathway.A combination of romidepsin and immunotherapy achieved robust and synergistic antitumor effects against lenvatinib resistance in humanized immunocompetent PDX ***,our findings suggest that patient-derived liver cancer models effectively recapitulate lenvatinib resistance observed in clinical settings and expedite drug discovery for advanced liver cancer,providing a feasible multidimensional platform for personalized medicine.

关键词： Lenvatinib Drug resistance High-throughput screening Drug discovery Patient-derived model Romidepsin EGFR liver cancer

Comprehensive insights into recent innovations:Magnesium-inclusive high-entropy alloys

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Journal of Magnesium and Alloys 2024年第4期12卷 1311-1345页

作者： Andrii Babenko Ehsan Ghasali Saleem Raza Kahila Baghchesaraee Ye Cheng Asif Hayat Peng Liu Shuaifei Zhao Yasin Orooji Shandong Vocational and Technical University of International studies Rizhao 276826China Zhejiang Normal University Jinhua 321004China Geelong Institute for Frontier MaterialsDeakin UniversityVIC 3216Australia

This review focuses on thermodynamic and physical parameters,synthesis methods,and reported phases of Magnesium(Mg)containing high-entropy alloys(HEAs).Statistical data of publications concerning Mg-containing HEAs were collected and *** on the chemical elements included in Mg-containing HEAs,their theoretical end experimental densities,thermodynamic parameters,physical parameters,fabricated techniques and reported phases were also collected and *** the basis of this information,a new classification for HEAs was *** is also shown that the existing thermodynamic parameters cannot accurately predict the formation of a single phase solid solution for Mg-containing *** physical parameters of Mg-containing HEAs are within a wide range,and most of the synthesized Mg-containing HEAs have a complex multiphase structure.

关键词： Magnesium High-entropy alloys Classification Thermodynamic parameters Physical parameters

A literature review of genetics and epigenetics of HCV-related hepatocellular carcinoma: translational impact

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Hepatobiliary Surgery and Nutrition 2024年第4期13卷 650-661页

作者： Ziyan Pan Wai-Kay Seto Chun-Jen Liu Yilei Mao Saleh A.Alqahtani Mohammed Eslam Storr liver Centre Westmead Institute for Medical ResearchWestmead Hospital and University of SydneySydneyNSWAustralia Department of Medicine The University of Hong KongHong KongChina State Key Laboratory of liver Research The University of Hong KongHong KongChina Department of Internal Medicine National Taiwan University HospitalTaipei Hepatitis Research Center National Taiwan University HospitalTaipei Graduate institute of Clinical Medicine National Taiwan University College of MedicineTaipei Department of liver Surgery Peking Union Medical College(PUMC)HospitalPUMC&Chinese Academy of Medical SciencesBeijingChina Organ Transplant Center of Excellence King Faisal Specialist Hospital&Research CenterRiyadhSaudi Arabia Division of Gastroenterology&Hepatology Johns Hopkins UniversityBaltimoreMDUSA

Background and Objective:Hepatocellular carcinoma(HCC)poses a significant global health burden and ranks as the fifth most prevalent cancer on a global *** C virus(HCV)infection remains one of the major risk factors for HCC *** is a heterogeneous disease,and the development of HCC caused by HCV is intricate and involves various factors,including genetic susceptibility,viral factors,immune response due to chronic inflammation,alcohol abuse,and metabolic dysfunction associated with fatty liver *** this review,we provide a comprehensive and updated review of research on the genetics and epigenetic mechanisms implicated in developing HCC associated with HCV *** also discuss the potential translational implications,including novel biomarkers and drugs for ***:A comprehensive literature search was conducted in June 2023 in PubMed and Embase *** Content and Findings:Recent findings indicate that a variety of genetic and epigenetic processes are involved in the pathogenesis and continue to exist even after the complete elimination of *** deregulation of the epigenome has been identified as a significant factor in the deletrious effects of liver disease,especially during the initial stages when genetic alterations are *** enduring“epigenetic memory”of gene expression is believed to be regulated by epigenetic mechanisms,indicating that alterations caused by HCV infection continue to exist and are linked to the risk of development of liver cancer even after successful *** biology analytical methods will be required to delineate the magnitude and significance of both genetic and epigenomic alterations in tumor ***:By facilitating a more profound understanding of these aspects,this will ultimately foster the advancement of novel therapies and ultimately improve outcomes for patients.

关键词： Epigenetics genetics hepatitis C virus-related hepatocellular carcinoma(HCV-related HCC) translational implications

Trends in Mortality of Cirrhosis in China: An Analysis of the China Death Surveillance Database from 2008 to 2020

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Journal of Clinical and Translational Hepatology 2024年第3期12卷 236-244页

作者： Xiaoxiao Wang Huixin Liu Jinlei Qi Lijun Wang Peng Yin Feng Liu Lai Wei Yu Wang Maigeng Zhou Huiying Rao Peking University People’s Hospital Peking University Hepatology InstituteBeijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseasesBeijing International Cooperation Base for Science and Technology on NAFLD DiagnosisBeijingChina Department of Clinical Epidemiology and Biostatistics Peking University People’s HospitalBeijingChina National Center for Chronic Noncommunicable Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijingChina Beijing Tsinghua Changgung Hospital Tsinghua UniversityBeijingChina Chinese Foundation for Hepatitis Prevention and Control BeijingChina

Background and Aims:China accounts for 14.9%of total cirrhosis deaths worldwide.A detailed and comprehensive understanding of the contemporary status of cirrhosis mortality in China is crucial for establishing strategies for intervention and decreasing the disease burden of cirrhosis *** study aimed to report the cirrhosis mortality rates in our whole country or province over ***:Mortality data from 2008 to 2020 were retrieved from the Disease Surveillance Point System(DSPs)of the Chinese Center for Disease Control and *** crude mortality rate and age-standardized mortality rate of patients with cirrhosis were stratified by sex,residential location,and *** average annual percentage change(AAPC)in cirrhosis mortality rates from 2008 to 2020 was also ***:The crude mortality rate of cirrhosis was 4.57/100,000 people in *** with females and individuals living in urban areas,males and people living in rural areas had greater age-standardized *** crude mortality rate and age-standardized mortality rate in provinces in Southwest China(Guangxi,Yunnan,Guizhou,and Qinghai)were greater than those in other ***,with increasing age,the age-specific mortality rate increased *** 2008 to 2020,the mortality rate of cirrhosis in China decreased except for in males aged 50–59 years,females aged 45–49 years and females aged 80–84 ***:The mortality rate of patients with cirrhosis in China decreased from 2008 to *** the future,interventions of cirrhosis mortality control need to pay more attention to all males,females aged 45–49 and 80–84 years,and people living in rural areas and in provinces in Southwest China.

关键词： Cirrhosis Mortality Trend China

High-order Autler–Townes splitting in electrically tunable photonic molecules

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Photonics Research 2024年第8期12卷 1794-1801页

作者： YIHAO CHEN JUNTAO DUAN JIN LI YAN CHEN JIEWEN LI JIANAN DUAN XIAOCHUAN XU JIAWEI WANG School of Integrated Circuit Harbin Institute of Technology(Shenzhen)Shenzhen 518055China College of Advanced Interdisciplinary studies National University of Defense TechnologyChangsha 410073China National Key Laboratory of Laser Spatial Information Harbin Institute of Technology(Shenzhen)Shenzhen 518055China

Whispering gallery mode optical microresonators represent a promising avenue for realizing optical analogs of coherent light–atom interactions,circumventing experimental ***-optical analogs of Autler–Townes splitting have been widely demonstrated,harnessing coupled optical microresonators,also known as photonic molecules,wherein the strong coupling between resonant fields enables energy level ***,we report the characterizations of Autler–Townes splitting in waveguide-coupled microring dimers featuring mismatched *** exploiting backscattering-induced coupling via Rayleigh and Mie scatterers in individual rings,high-order Autler–Townes splitting has been realized,yielding supermode hybridization in a multi-level *** resonance detuning using an integrated phase shifter,intra-cavity coupling-induced splitting becomes almost indistinguishable at the zero-detuning point where the strong inter-cavity coupling counteracts the imbalance of backscattering strengths in individual *** demonstrations on the maturing silicon photonics platform,our findings establish a framework of electrically tunable photonic molecules for coupling-mediated Autler–Townes splitting,offering promising prospects for on-chip signal generation and processing across classical and quantum regimes.

关键词： tunable tuning waveguide

Fundamental Challenges,Differentiated Approaches and Prospects for Making Rules for Global Digital Economy

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Contemporary World 2024年第3期 14-19页

作者： Wang Zhongmei the institute for World Economy studies at the Shanghai institutes for International studies

We are now at a crucial moment of developing digital ***tries around the world are striving to strike a balance between enabling innovation and enhancing regula*** digital economy,which is cross-border in nature,calls for higher-level regulatory integration and network effects,digital technology-related security issues have caused widespread concerns and regulation remains fragmented or even contradictory.

关键词： border network integration

Mortality Burden of liver Cancer in China: An Observational Study From 2008 to 2020

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Journal of Clinical and Translational Hepatology 2024年第4期12卷 371-380页

作者： Huixin Liu Xiaoxiao Wang Lijun Wang Peng Yin Feng Liu Lai Wei Yu Wang Maigeng Zhou Jinlei Qi Huiying Rao Department of Clinical Epidemiology and Biostatistics Peking University People's HospitalBeijingChina Peking University People’s Hospital Peking University Hepatology InstituteBeijing Key Laboratory of Hepatitis C and Immunotherapy for Liver DiseasesBeijing International Cooperation Base for Science and Technology on NAFLD DiagnosisBeijingChina National Center for Chronic Noncommunicable Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijingChina Beijing Tsinghua Changgung Hospital Tsinghua UniversityBeijingChina Chinese Foundation for Hepatitis Prevention and Control BeijingChina

Background and Aims:China accounts for nearly half of liver cancer deaths globally.A better understanding of the current liver cancer mortality will be helpful to establishing priorities for intervention and to decreasing the disease burden of liver *** study aimed to explore and predict the mortality burden of liver cancer in ***:Data were extracted from the Disease Surveillance Point system of the Chinese Center for Disease Control and Prevention from 2008 to *** and age-standardized liver cancer mortality rates were reported by sex,urban or rural residence,and *** in liver cancer mortality rates from 2008 to 2020 were estimated as average annual percentage change(AAPC).The changing trend of live cancer mortality in the future is also ***:In 2020,the crude mortality of liver cancer was 25.57/100,000,and males and people lived in rural areas had higher age-standardized liver cancer mortality rates than females and people lived in people in urban *** mortality and age-standardized mortality rates in southwest provinces(Guangxi,Sichuan,Tibet)and in a northeast province(Heilongjiang)were higher than that in other provinces,and age-specific mortality rates increased with *** 2008 to 2020,liver cancer mortality rates decreased,but people under 50 years of age had a higher AAPC than those over 50 years of age,possibly because of the adoption of hepatitis B virus vaccination in newborns and ***,the mortality of liver cancer in 2021–2030 is predicted to have a downward ***:liver cancer mortality rates declined in China from 2008 to *** interventions to control liver cancer mortality need to focus on people of male sex,older age,and living in rural areas or less developed provinces.

关键词： liver cancer Mortality Burden Trend China Prediction

Cryptanalysis of DBST, a lightweight block cipher

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Frontiers of Computer Science 2024年第4期18卷 219-221页

作者： Sadegh SADEGHI Nasour BAGHERI Department of Mathematics Institute for Advanced Studies in Basic Sciences(IASBS)Zanjan 45137-66731Iran Research Center for Basic Sciences and Modern Technologies(RBST) Institute for Advanced Studies in Basic Sciences(IASBS)Zanjan 45137-66731Iran Electrical Engineering Department Shahid Rajaee Teacher Training UniversityTehran 16788-15811Iran School of Computer Science(SCS) Institute for Research in Fundamental Sciences(IPM)Tehran 19395-5531Iran

1 Introduction Conventional cryptographic primitives are not suitable for resource-constrained ***,numerous lightweight primitives have been proposed over the past decade,specifically tailored for such ***,such ciphers would not be used in a real-world application unless they were thoroughly tested for security against existing *** this direction,DBST[1]cipher has been recently proposed by Yan et *** balance security,cost,and efficiency,DBST has implemented a novel 4-branch generalized Feistel variant *** this structure,a 2-branch XOR operation has been incorporated in the middle section,establishing interconnections between all *** the other hand,by leveraging the bit-slice technique and subkeys,the algorithm introduces an innovative approach to constructing a dynamic S-box *** designers of DBST cipher have extensively investigated its resistance to known attacks such as linear and differential cryptanalysis,as well as impossible differential cryptanalysis,among *** them,the objective of differential cryptanalysis[2]is to identify high-probability characteristics in the plaintext that are transmitted to the ciphertext,known as distinguishers.

关键词： structure. primitive branch

AI Fairness-From Machine Learning to Federated Learning

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Computer Modeling in Engineering & Sciences 2024年第5期139卷 1203-1215页

作者： Lalit Mohan Patnaik Wenfeng Wang Consciousness studies Program School of HumanitiesNational Institute of Advanced StudiesBangalore560012India Research institute of Intelligent Engineering and Data Applications Shanghai Institute of TechnologyShanghai201418China Research Center of Ecology and Environment of Central Asia Chinese Academy of SciencesUrumqi830011China Applied Nonlinear Science Lab Anand International College of EngineeringJaipur391320India London institute of Technology The ASE-London CTI of SCOLondonCR26EQUK Sino-Indian Joint Research Center of AI and Robotics The IMT InstituteBhubaneswar752054India

This article reviews the theory of fairness in AI-frommachine learning to federated learning,where the constraints on precision AI fairness and perspective solutions are also *** a reliable and quantitative evaluation of AI fairness,many associated concepts have been proposed,formulated and ***,the inexplicability of machine learning systems makes it almost impossible to include all necessary details in the modelling stage to ensure *** privacy worries induce the data unfairness and hence,the biases in the datasets for evaluating AI fairness are *** imbalance between algorithms’utility and humanization has further reinforced *** for federated learning systems,these constraints on precision AI fairness still *** solution is to reconcile the federated learning processes and reduce biases and imbalances accordingly.

关键词： Formulation evaluation classification constraints imbalance biases