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Current and emerging therapies for alcohol-associated hepatitis

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Liver Research 2023年第1期7卷 35-46页

作者： Francisco Idalsoaga gustavo Ayares Luis Antonio Díaz Jorge Arnold María Ayala-Valverde david Hudson Marco Arrese juan Pablo Arab Department of gastroenterology School of MedicinePontificia Universidad Catolica de ChileSantiagoChile Internal Medicine Service Hospital El PinoCritical Patient UnitClinica DavilaSantiagoChile Division of gastroenterology Department of MedicineSchulich School of MedicineWestern University&London Health Sciences CentreLondonOntarioCanada Department of Epidemiology and Biostatistics Schulich School of MedicineWestern UniversityLondonOntarioCanada Alimentiv LondonOntarioCanada

Alcohol-related liver disease(ALD)encompasses a spectrum of diseases caused by excessive alcohol *** includes hepatic steatosis,steatohepatitis,variable degrees of fibrosis,cirrhosis,and alcohol-associated hepatitis(AH),the latter being the most severe acute form of the *** AH is associated with high mortality(reaching up to 30%e50%)at 90 *** cornerstone of ALD,and particularly AH,treatment continues to be abstinence,accompanied by support measures such as nutritional supplementation and management of alcohol withdrawal syndrome(AWS).In severe AH with model for end-stage liver disease(MELD)score21,corticosteroids can be used,especially MELD score between 25 and 39,where the highest benefit is *** key aspects of treatment include the early identification of infections and their associated management and the proper identification of potential candidates for liver *** development of new therapies based on the pathophysiology and mechanisms of liver injury are *** includes the modulation and management of the innate immune response,gut dysbiosis,bacterial translocation,and bacteria-derived products from the *** hold promise for the future of AH treatment.

关键词： Alcohol-associated hepatitis(AH) Alcohol-related liver disease(ALD) Alcohol use disorder(AUD) AUD treatment Nutritional therapy Steroids therapy Cirrhosis Fibrosis

Intraoperative intracardiac thrombosis in a liver transplant patient

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World Journal of Hepatology 2010年第5期2卷 198-200页

作者： Lena Sibulesky Prith Peiris C Burcin Taner david J Kramer juan M Canabal Justin H Nguyen Department of Transplantation Division of Transplant SurgeryMayo ClinicJacksonvilleFL 32224United States Department of Anesthesiology Mayo ClinicJacksonvilleFL 32224United States Departments of Trans-plantation and Critical Care Mayo ClinicJacksonvilleFL32224United States

A 66-year-old female with cryptogenic cirrhosis complicated by ascites,hepatic encephalopathy,variceal bleeding and malnutrition with MELD of 34 underwent orthotopic deceased donor liver transplantation performed with piggyback *** eversion thromboendovenectomy was performed for a portal vein thrombus which resulted in an excellent portal vein *** liver graft was recirculated without any hemodynamic ***,the patient became hypotensive progressing to *** was resuscitated and a transesophageal probe was inserted which revealed a mobile right atrial thrombus and an underfilled poorly contractile right *** patient was noted to be coagulopathic at the *** became progressively more stable with a TEE showing complete resolution of the intracardiac thrombus.

关键词： Liver transplantation Cardiac thrombus Reperfusion injury Coagulopathy Transesophageal echocardiogram

Functional divergence of oligoadenylate synthetase 1(OAS1)proteins in Tetrapods

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Science China(Life Sciences) 2022年第7期65卷 1395-1412页

作者： Xiaoxue Wang Jiaxiang Hu Linfei Song Enguang Rong Chenghuai Yang Xiaoyun Chen juan Pu Honglei Sun Chuze gao david WBurt Jinhua Liu Ning Li Yinhua Huang State Key Laboratory for Agrobiotechnology College of Biology SciencesChina Agricultural UniversityBeijing 100193China China Institute of Veterinary Drug Control Beijing 100081China Key Laboratory of Animal Epidemiology and Zoonosis Ministry of AgricultureCollege of Veterinary MedicineChina Agricultural UniversityBeijing 100083China University of Queensland St.LuciaBrisbaneQLD 4072Australia

OASs play critical roles in immune response against virus infection by polymerizing ATP into 2-5 As,which initiate the classical OAS/RNase L pathway and induce degradation of viral *** members are functionally diverged in four known innate immune pathways(OAS/RNase L,OASL/IRF7,OASL/RIg-I,and OASL/cgAS),but how they functionally diverged is ***,we focus on evolutionary patterns and explore the link between evolutionary processes and functional divergence of Tetrapod *** show that Palaeognathae and Primate OAS1 genes are conserved in genomic and protein structures but differ in *** former(i.e.,ostrich)efficiently synthesized long 2-5 A and activated RNase L,while the latter(i.e.,human)synthesized short 2-5 A and did not activate RNase *** predicted and verified that two in-frame indels and one positively selected site in the active site pocket contributed to the functional divergence of Palaeognathae and Primate ***,we discovered and validated that an in-frame indel in the C-terminus of Palaeognathae OAS1 affected the binding affinity of ds RNA and enzymatic activity,and contributed to the functional divergence of Palaeognathae OAS1 *** findings unravel the molecular mechanism for functional divergence and give insights into the emergence of novel functions in Tetrapod OAS1.

关键词： functional divergence OAS1 molecular evolution primate palaeognathae

Abscisic Acid Connects Phytohormone Signaling with RNA Metabolic Pathways and Promotes an Antiviral Response that Is Evaded by a Self- Controlled RNA Virus

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Plant Communications 2020年第5期1卷 111-128页

作者： Fabio Pasin Hongying Shan Beatriz garcía Maren Müller david San León Márta Ludman david H.Fresno Károly Fátyol Sergi Munné-Bosch guillermo Rodrigo juan Antonio garcía Centro Nacional de Biotecnología(CNB-CSIC) 28049 MadridSpain Agricultural Biotechnology Research Center Academia Sinica11529 TaipeiTaiwan Departamento de Biologı´a Evolutiva Ecologı´a y Ciencias AmbientalesFacultad de Biologı´aUniversidad de Barcelona08028 BarcelonaSpain Agricultural Biotechnology Institute National Agricultural Research and Innovation Centre2100 Godoll}oHungary Institute for Integrative Systems Biology(I2SysBio) CSIC-University of Valencia46980 PaternaSpain Present address:College of Horticulture and gardening Tianjin Agricultural University300384 TianjinChina

A complex network of cellular receptors,RNA targeting pathways,and small-molecule signaling provides robust plant immunity and tolerance to *** maximize their fitness,viruses must evolve control mechanisms to balance host immune evasion and plant-damaging *** genus Potyvirus comprises plant viruses characterized by RNA genomes that encode large polyproteins led by the P1 protease.A P1 autoinhibitory domain controls polyprotein processing,the release of a downstream functional RNAsilencing suppressor,and viral ***,we show that P1Pro,a plum pox virus clone that lacks the P1 autoinhibitory domain,triggers complex reprogramming of the host transcriptome and high levels of abscisic acid(ABA)accumulation.A meta-analysis highlighted ABA connections with host pathways known to control RNA stability,turnover,maturation,and *** changes triggered by P1Pro infection or ABA showed similarities in host RNA abundance and *** and hormone treatment assays showed that ABA promotes plant resistance to potyviral ***,quantitative mathematical modeling of viral replication in the presence of defense pathways supported self-control of polyprotein processing kinetics as a viral mechanism that attenuates the magnitude of the host antiviral ***,our findings indicate that ABA is an active player in plant antiviral immunity,which is nonetheless evaded by a self-controlled RNA virus.

关键词： abscisic acid antiviral immune evasion mathematical modeling viral polyprotein processing Potyvirus RNA metabolism

Mid-mantle heterogeneities associated with Izanagi plate:Implications for regional mantle viscosity

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Mid-mantle heterogeneities associated with Izanagi plate:Imp...

MicroRNAs dysregulation in hepatocellular carcinoma: Insights in genomic medicine

中国科学院地质与地球物理研究所2014年度（第14届）学术年会

作者： juan Li david A.Yuen Key Laboratory of the Earth's Deep Interior Institute of Geology and GeophysicsChinese Academy of Sciences School of Environment Sciences China University of Geosciences Department of Earth Sciences University of Minnesota

We employed S-to-P converted waveforms to detect mid-mantle scattering beneath northeastern China and the adjacent Japan *** and short-period waveforms recorded by seismic arrays for eight moderate-sized deep earthquakes were analyzed using a non-linear array stacking technique,and midmantle scatterers within the depth range 930–1120 km were clearly *** heterogeneities have an overall lateral extent of～800 km,and mostly occur within a region with a high velocity *** accumulation of MORB-like slab materials at mid-mantle depths might cause a different chemical composition than that of the surrounding peridotitic *** spatial isolation of the heterogeneities from the stagnant Pacific slab suggests an origin related to the subduction of ancient Izanagi *** combination with the reconstruction history of plate motions,we estimate the viscosity of the topmost lower mantle to vary from 1.0×1022to 1.6×1023Pa s,which can be used as an independent constraint on the rheology of the lower mantle on a regional scale.

关键词： mid-mantle discontinuity subduction Izanagi plate viscosity

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World Journal of Hepatology 2015年第11期7卷 1530-1540页

作者： Iván Lyra-gonzález Laura E Flores-Fong Ignacio gonzález-garcía david Medina-Preciado juan Armendáriz-Borunda Departamento de Biología Molecular y genómica CUCS Universidad de Guadalajara Instituto de Biología Molecular en Medicina y Terapia Génica O.P.D. Hospital Civil de guadalajara "Fray Antonio Alcalde" O.P.D. Hospital Civil de guadalajara "juan I. Menchaca" Departamento de Biología Molecular y genómica CUCS Universidad de Guadalajara

Hepatocellular carcinoma(HCC) is the leading primary liver cancer and its clinical outcome is still poor. MicroRNAs(mi RNAs) have demonstrated an interesting potential to regulate gene expression at post-transcriptional level. Current findings suggest that mi RNAs deregulation in cancer is caused by genetic and/or epigenetic, transcriptional and post-transcriptional modifications resulting in abnormal expression and hallmarks of malignant transformation: aberrant cell growth, cell death, differentiation, angiogenesis, invasion and metástasis. The important role of mi RNAs in the development and progression of HCC has increased the efforts to understand and develop mechanisms of control overt this single-stranded RNAs. Several studies have analyzed tumoral response to the regulation and control of deregulated mi RNAs with good results in vitro and in vivo, proving that targeting aberrant expression of mi RNAs is a powerful anticancer therapeutic. Identification of up and/or down regulated mi RNAs related to HCC has led to the discovery of new potential application for detection of their presence in the affected organism. Mi RNAs represent a relevant new target for diagnosis, prognosis and treatment in a wide variety of pathologic entities, including HCC. This manuscript intends to summarize current knowledge regarding mi RNAs and their role in HCC development.

关键词： Hepatocellular carcinoma MicroRNAs Regulation Therapeutic targets

Einstein Probe discovery of EP240408a: A peculiar X-ray transient with an intermediate timescale

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Science China(Physics,Mechanics & Astronomy) 2025年第1期Mechanics & Astronomy) .卷 222-240页

作者： Wenda Zhang Weimin Yuan Zhixing Ling Yong Chen Nanda Rea Arne Rau Zhiming Cai Huaqing Cheng Francesco Coti Zelati Lixin Dai Jingwei Hu Shumei Jia Chichuan Jin Dongyue Li Paul O’Brien Rongfeng Shen Xinwen Shu Shengli Sun Xiaojin Sun Xiaofeng Wang Lei Yang Bing Zhang Chen Zhang Shuang-Nan Zhang Yonghe Zhang Jie An david Buckley Alexis Coleiro Bertrand Cordier Liming Dou Rob Eyles-Ferris Zhou Fan Hua Feng Shaoyu Fu Johan P.U.Fynbo Lluis galbany Saurabh W.Jha Shuaiqing Jiang Albert Kong Erik Kuulkers Weihua Lei Wenxiong Li Bifang Liu Mingjun Liu Xing Liu Yuan Liu Zhu Liu Chandreyee Maitra Alessio Marino Itumeleng Monageng Kirpal Nandra Jeremy Sanders Roberto Soria Lian Tao Junfeng Wang Song Wang Tinggui Wang Zhongxiang Wang Qingwen Wu Xuefeng Wu Dong Xu Yanjun Xu Suijian Xue Yongquan Xue Zijian Zhang Zipei Zhu Hu Zou Congying Bao Fansheng Chen Houlei Chen Tianxiang Chen Wei Chen Yehai Chen Yifan Chen Chenzhou Cui Weiwei Cui Yanfeng Dai Dongwei Fan Ju guan Dawei Han Dongjie Hou Haibo Hu Maohai Huang Jia Huo Zhenqing Jia Bowen Jiang ge Jin Chengkui Li Junfei Li Longhui Li Maoshun Li Wei Li Zhengda Li Tianying Lian Congzhan Liu Heyang Liu Huaqiu Liu Fangjun Lu Laidan Luo Jia Ma Xuan Mao Haiwu Pan Xin Pan Liming Song Hui Sun Yunyin Tan Qingjun Tang Yihan Tao Hao Wang juan Wang Lei Wang Wenxin Wang Yilong Wang Yusa Wang Qinyu Wu Haitao Xu Jingjing Xu Xinpeng Xu Yunfei Xu Zhao Xu Changbin Xue Yulong Xue Ailiang Yan Haonan Yang Xiongtao Yang Yanji Yang juan Zhang Mo Zhang Wenjie Zhang Zhen Zhang Zhen Zhang Ziliang Zhang Donghua Zhao Haisheng Zhao Xiaofan Zhao Zijian Zhao Hongyan Zhou Yilin Zhou Yuxuan Zhu Zhencai Zhu National Astronomical Observatories Chinese Academy of Sciences School of Astronomy and Space Sciences University of Chinese Academy of Sciences Key Laboratory of Particle Astrophysics Institute of High Energy Physics Chinese Academy of Sciences Institute of Space Sciences (ICE) CSIC Institut d’Estudis Espacials de Catalunya (IEEC) Max Planck Institute for Extraterrestrial Physics Innovation Academy for Microsatellites Chinese Academy of Sciences Department of Physics University of Hong Kong School of Physics and Astronomy University of Leicester School of Physics and Astronomy Sun Yat-sen University Department of Physics Anhui Normal University Shanghai Institute of Technical Physics Chinese Academy of Sciences Physics Department Tsinghua University Nevada Center for Astrophysics University of Nevada Las Vegas Department of Physics and Astronomy University of Nevada Las Vegas South African Astronomical Observatory Department of Astronomy University of Cape Town Department of Physics University of the Free State Université Paris Cité CNRS Astroparticule et Cosmologie Université Paris Cité CEA Paris-Saclay IRFU/DAp-AIM Department of Astronomy guangzhou University Cosmic Dawn Center (DAWN) Niels Bohr Institute University of Copenhagen Department of Physics and Astronomy Rutgers the State University of New Jersey Institute for Cosmic Ray Research The University of Tokyo ESA/ESTEC Department of Astronomy School of Physics Huazhong University of Science and Technology INAF-Osservatorio Astrofisico di Torino Sydney Institute for Astronomy School of Physics The University of Sydney Department of Astronomy Xiamen University Institute for Frontiers in Astronomy and Astrophysics Beijing Normal University Department of Astronomy University of Science and Technology School of Astronomy and Space Sciences University of Science and Technology of China Institute of Deep Space Sciences Deep Space Exploration Laboratory Department of Astronomy School of Physics and Astronomy Yunnan University Shanghai Astronomical Observatory Chi

We report the discovery of a peculiar X-ray transient,EP240408a,by Einstein Probe （EP） and follow-up studies made with EP,Swift,NICER,gROND,ATCA and other ground-based multiwavelength *** new transient was first detected with Wide-field X-ray Telescope （WXT） on board EP on April 8th,2024,manifested in an intense yet brief X-ray flare lasting for *** flare reached a peak flux of 3.9×10-9erg cm-2s-1in 0.5-4 ke V,～300 times brighter than the underlying X-ray emission detected throughout the *** and more precise follow-up observations by EP/FXT,Swift and NICER confirmed the finding of this new *** X-ray spectrum is non-thermal in 0.5-10 ke V,with a power-law photon index varying *** X-ray light curve shows a plateau lasting for ～4 d,followed by a steep decay till becoming undetectable ～10 d after the initial *** on its temporal property and constraints from previous EP observations,an unusual timescale in the range of 7-23 d is found for EP240408a,which is intermediate between the commonly found fast and long-term *** counterparts have been found in optical and near-infrared,with the earliest observation at 17 h after the initial X-ray detection,suggestive of intrinsically weak emission in these *** demonstrate that the remarkable properties of EP240408a are inconsistent with any of the transient types known so far,by comparison with,in particular,jetted tidal disruption events,gamma-ray bursts,X-ray binaries and fast blue optical *** nature of EP240408a thus remains an *** suggest that EP240408a may represent a new type of transients with intermediate timescales of the order of～10 *** detection and follow-ups of more of such objects are essential for revealing their origin.

关键词： X-ray transients ${\bm~{Einstein~~Probe}}$

Highly sensitive phototransistors based on twodimensional gaTe nanosheets with direct bandgap

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Nano Research 2014年第5期7卷 694-703页

作者： Pingan Hu Jia Zhang Mina Yoon Xiao-Fen Qiao Xin Zhang Wei Feng Pingheng Tan Wei Zheng Jingjing Liu Xiaona Wang juan C. Idrobo david B. geohegan Kai Xiao Key Lab of Microsystem and Microstructure Harbin Institute of Technology Ministry of Education No. 2 Yikuang Street Harbin 150080 China Center for Nanophase Materials Sciences Oak Ridge National Laboratory One Bethel Valley Road Oak Ridge TN 37831 USA State Key Laboratory of Superlattices and Microstructures Institute of Semiconductors Chinese Academy of Sciences Beijing 100083 China

Highly sensitive phototransistors based on two-dimensional （2D） gaTe nanosheet have been demonstrated. The performance （photoresponsivity, detectivity） of the gaTe nanosheet phototransistor can be efficiently adjusted by using the applied gate voltage. The devices exhibit an ultrahigh photoresponsivity of 274.3 AW^-1. The detectivity of 2D gaTe devices is -10^12 Jones, which surpasses that of currently-exploited IngaAs photodetectors （10^11-10^12 Jones）. To reveal the origin of the enhanced photocurrent in gaTe nanosheets, theoretical modeling of the electronic structures was performed to show that gaTe nanosheets also have a direct bandgap structure, which contributes to the promotion of photon absorption and generation of excitons. This work shows that gaTe nanosheets are promising materials for high performance photodetectors.

关键词： photodetector gallium telluride two-dimensional semiconductor nanosheet

Identifcation of Immunity-related genes in Arabidopsis and Cassava Using genomic Data

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genomics, Proteomics & Bioinformatics 2013年第6期11卷 345-353页

作者： Luis guillermo Leal A'lvaro Perez Andre's Quintero A'ngela Bayona juan Felipe Ortiz Anju gangadharan david Mackey Camilo Lo'pez Liliana Lo'pez-Kleine Department of Statistics Universidad Nacional de Colombia Department of Biology Universidad Nacional de Colombia Department of Molecular genetics The Ohio State University

Recent advances in genomic and post-genomic technologies have provided the opportu- nity to generate a previously unimaginable amount of information. However, biological knowledge is still needed to improve the understanding of complex mechanisms such as plant immune responses. Better knowledge of this process could improve crop production and management. Here, we used holistic analysis to combine our own microarray and RNA-seq data with public genomic data from Arabidopsis and cassava in order to acquire biological knowledge about the relationships between proteins encoded by immunity-related genes （IRgs） and other genes. This approach was based on a kernel method adapted for the construction of gene networks. The obtained results allowed us to propose a list of new IRgs. A putative function in the immunity pathway was predicted for the new IRgs. The analysis of networks revealed that our predicted IRgs are either well documented or recognized in previous co-expression studies. In addition to robust relationships between IRgs, there is evidence suggesting that other cellular processes may be also strongly related to immunity.

关键词： Arabidopsis Cassava Functional gene prediction genomic data Kernel canonical correlation ajalysi Plant immunity