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Advances in immunotherapy for hepatitis B virus associated hepatocellular carcinoma patients

World Journal of Hepatology 2024年第10期16卷 1158-1168页

作者： Wei-Hua Cao Ya-Qin Zhang Xin-Xin Li Zi-Yu Zhang Ming-Hui Li Department of Hepatology division 2 Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China Department of Hepatology division 2 Beijing Ditan HospitalCapital Medical UniversityPeking University Ditan Teaching HospitalBeijing 100015China

Hepatitis B virus(HBV)infection plays an important role in the occurrence and development of hepatocellular carcinoma(HCC),and the rate of HBV infection in liver cancer patients in China is as high as 92.05%.Due to long-term exposure to chronic antigens from the gut,the liver needs to maintain a certain level of immune tolerance,both to avoid severe inflammation caused by non-pathogenic antigens and to maintain the possibility of rapid and violent responses to infection and ***,HBV infection interacts with the tumor microenvironment(TME)through a highly complex and intertwined signaling pathway,which results in a special TME in *** to changes in the TME,tumor cells can evade immune surveillance by inhibiting tumor-specific T cell function through cytotoxic T-lymphocy-associated protein-4(CTLA-4)and programmed cell death 1(PD-1)/programmed cell death ligand 1(PD-L1).Interferons,as a class of immune factors with strong biological activity,can improve the TME of HBV-HCC through various *** recent years,the systematic treatment of HCC has gradually come out of the *** addition to the continuous emergence of new multi-target anti-vascular tyrosine kinase inhibitor drugs,immune checkpoint inhibitors have opened up a new avenue for the systematic treatment of *** present,immunotherapy based on PD-1/L1 inhibitors has gradually become a new direction of systematic treatment for HCC,and the disease charac-teristics of patients included in global clinical studies are different from those of Chinese ***,whether a group of HCC patients with HBV background and poor prognosis in China can also benefit from immunotherapy is an issue of wide *** review aims to elucidate the advances of immuno-therapy for HBV related HCC patients with regard to:(1)Immunotherapy based on interferons;(2)Immunotherapy based on PD-1/L1 inhibitors;(3)Immunotherapy based on CTLA4 inhibitors;(4)Adoptive cell transfer;(5)Combination immunotherapy str

关键词： Hepatitis B virus Hepatocellular carcinoma Immune checkpoint inhibitors Peginterferon alpha Systematic treatment

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Spatial and Temporal Differences of Climate Suitability of Ice and Snow Sports in Major Ski Tourism Destinations in China

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Chinese Geographical Science 2024年第5期34卷 967-982页

作者： XIE Xia PANG Zhengjin ZHU Haiqiang GAO Jun ZHOU Qiaoya Key Laboratory of the Sustainable development of Xinjiang’s Historical and Cultural Tourism Xinjiang UniversityUrumqi 830046China College of Tourism Xinjiang UniversityUrumqi 830046China School of Tourism Management Sun Yat-sen UniversityZhuhai 519000China

Ice and snow tourism in China has grown significantly since the country successfully hosted the Beijing Winter *** conditions profoundly impact the development of ice and snow tourism;however,most studies have focused on constructing different climate suitability indicators for ice and snow tourism to evaluate individual regions,lacking horizontal comparative studies across multiple *** study aims to enrich the connotation of climate suitability for ice and snow sports,establish an evaluation model based on snowfall amount,temperature,and wind speed,and use daily meteorological data from 1991 to 2021 to horizontally compare the climate suitability for ice and snow sports in major ski tourism destinations in *** study boasts four major findings:1)the average ice and snow sports climate index of each region decreases over time,and the overall suitability of the climate for ice and snow sports is reducing;2)northern Xinjiang exhibits the most evident regional differentiation from‘very suitable’to‘generally suitable’;3)the spatial zoning of climate suitability for ice and snow sports exhibits heterogeneity,as northern Xinjiang is divided into two‘suitable and above’zones with rotating empirical orthogonal function(REOF).Correspondingly,the four provinces of Hebei,Heilongjiang,Jilin,and Liaoning are divided into three‘generally suitable and above’zones;4)snowfall amount is the main factor affecting the climate suitability of ice and snow sports in the major ski tourist destinations in China.

关键词： ice and snow tourism climate suitability rotating empirical orthogonal function(REOF) spatial division China

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Heritable Chronic Cholestatic Liver Diseases:A Review

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Journal of Clinical and Translational Hepatology 2024年第8期12卷 726-738页

作者： Jasmine Tidwell George Y.Wu Department of Medicine University of Connecticut Health CenterFarmingtonCTUSA division of Gastroenterology-Hepatology University of Connecticut Health CenterFarmingtonCTUSA

Chronic cholestasis due to heritable causes is usually diagnosedin ***,many cases can present andsurvive into *** time course varies considerablydepending on the underlying *** data usuallyreveal elevated conjugated hyperbilirubinemia,alkalinephosphatase,and gamma-glutamyl *** be asymptomatic;however,when present,the typicalsymptoms are pruritus,jaundice,fatigue,and *** diagnostic methods and management requireddepend on the underlying *** development of genome-wide associated studies has allowed the identificationof specific genetic mutations related to the pathophysiologyof cholestatic liver *** aim of this review was tohighlight the genetics,clinical pathophysiology,presentation,diagnosis,and treatment of heritable etiologies of chroniccholestatic liver disease.

关键词： Chronic cholestasis Cholestatic liver disease Congenital hepatic fibrosis Caroli disease Caroli syndrome Alagille syndrome Biliary atresia

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Etiologies of Splenic Venous Hypertension:A Review

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Journal of Clinical and Translational Hepatology 2024年第6期12卷 594-606页

作者： Jasmine Tidwell Bianca Thakkar George Y.Wu Department of Medicine University of Connecticut Health CenterFarmingtonCTUSA division of Gastroenterology-Hepatology University of Connecticut Health CenterFarmingtonCTUSA

Splenic venous hypertension or left-sided portal hypertension is a rare condition caused by an obstruction of the splenic ***,it presents with upper gastrointestinal bleeding in the absence of liver *** can be classified based on the mechanism of development of splenic vein hypertension:compression,stenosis,inflammation,thrombosis,and surgically decreased splenic venous *** is established by various imaging modalities and should be suspected in patients with gastric varices in the absence of esophageal varices,splenomegaly,or *** management and prognosis vary depending on the underlying etiology but generally involve reducing splenic venous *** aim of this review was to summarize the etiologies of splenic venous hypertension according to the mechanism of development.

关键词： Splenic venous hypertension Left-sided portal hypertension Sinistral portal hypertension Splenic vein thrombosis Gastric varices Hematemesis Upper gastrointestinal bleeding

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Transparent and Accountable Training Data Sharing in Decentralized Machine Learning Systems

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Computers, Materials & Continua 2024年第6期79卷 3805-3826页

作者： Siwan Noh Kyung-Hyune Rhee Industrial Science Technology Research Center Pukyong National UniversityBusan48513South Korea division of Computer Engineering Pukyong National UniversityBusan48513South Korea

In Decentralized Machine Learning(DML)systems,system participants contribute their resources to assist others in developing machine learning *** malicious contributions in DML systems is challenging,which has led to the exploration of blockchain *** leverages its transparency and immutability to record the provenance and reliability of training ***,storing massive datasets or implementing model evaluation processes on smart contracts incurs high computational ***,current research on preventing malicious contributions in DML systems primarily focuses on protecting models from being exploited by workers who contribute incorrect or misleading ***,less attention has been paid to the scenario where malicious requesters intentionally manipulate test data during evaluation to gain an unfair *** paper proposes a transparent and accountable training data sharing method that securely shares data among potentially malicious system ***,we introduce a blockchain-based DML system architecture that supports secure training data sharing through the IPFS ***,we design a blockchain smart contract to transparently split training datasets into training and test datasets,respectively,without involving system *** the system,transparent and accountable training data sharing can be achieved with attribute-based proxy *** demonstrate the security analysis for the system,and conduct experiments on the Ethereum and IPFS platforms to show the feasibility and practicality of the system.

关键词： Decentralized machine learning data accountability dataset sharing

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Blocking the PD-1 signal transduction by occupying the phosphorylated ITSM recognition site of SHP-2

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Science China Life Sciences 2024年

作者： Wenjie Li Wenyi Mei Hewei Jiang Jie Wang Xiaoli Li Lina Quan Yanyan Diao Yanni Ma Sisi Fan Zhuwei Xie Mengdie Gong Huan Zhu Dewen Bi Feng Zhang Lei Ma Jian Zhang Yufeng Gao Aris Paschalidis Honghuang Lin Fangfang Liu Kangdong Liu Mingliang Ye Zhenjiang Zhao Yajun Duan Zhuo Chen Yufang Xu Weilie Xiao Shengce Tao Lili Zhu Honglin Li Innovation Center for AI and Drug Discovery East China Normal University Shanghai Key Laboratory of New Drug Design School of PharmacyEast China University of Science&Technology Shanghai Center for Systems biomedicine Key Laboratory of Systems Biomedicine (Ministry of Education)Shanghai Jiao Tong University Lingang Laboratory Key Laboratory of Medicinal Chemistry for Natural Resource Ministry of EducationYunnan Characteristic Plant Extraction LaboratoryYunnan Provincial Center for Research&Development of Natural ProductsState Key Laboratory for Conservation and Utilization of Bio-Resources in YunnanSchool of Pharmacy and School of Chemical Science and TechnologyYunnan University CAS Key Laboratory of Separation Sciences for Analytical Chemistry National Chromatographic R&A CenterDalian Institute of Chemical PhysicsChinese Academy of Sciences Department of Cardiology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of China Department of Infectious Diseases The First Affiliated Hospital of Anhui Medical University Department of Medicine University of Massachusetts Chan Medical School Department of Pathophysiology School of Basic Medical SciencesAcademy of Medical ScienceCollege of MedicineZhengzhou University

Targeting the PD-1/PD-L1 axis with small-molecular inhibitors is a promising approach for immunotherapy. Here, we identify a natural pentacyclic triterpenoid, Pygenic Acid A(PA), as a PD-1 signaling inhibitor. PA exerts anti-tumor activity in hPD-1 knock-in C57BL/6 mice and enhances effector functions of T cells to promote immune responses by disrupting the PD-1 signaling transduction. Furthermore, we identify SHP-2 as the direct molecular target of PA for inhibiting the PD-1 signaling transduction. Subsequently, mechanistic studies suggest that PA binds to a new druggable site in the phosphorylated PD-1 ITSM recognition site of SHP-2, inhibiting the recruitment of SHP-2 by PD-1. Taken together, our findings demonstrate that PA has a potential application in cancer immunotherapy and occupying the phosphorylated ITSM recognition site of SHP-2 may serve as an alternative strategy to develop PD-1 signaling inhibitors. In addition, our success in target recognition provides a paradigm of target identification and confirmation for natural products.

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Anisotropy measurements and characterization of the Qingshankou shale

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Applied Geophysics 2024年第3期21卷 468-478,617页

作者： Li Qing-feng Yan Xue-hong Yan Wei-lin Ren Li Wang Peng Han Jian-qiang Xia Xue Chen Hao Daqing Oilfield Exploration division Daqing163000HeilongjiangChina Daqing Branch Company of CNPC Logging Daqing163000HeilongjiangChina Exploration and development Research Institute of Daqing Oilfield Co. Ltd.Daqing163712China State Key Laboratory of Acoustics Institute of AcousticsChinese Academy of SciencesBeijing100190China

Qingshankou shale(Gulong area,China)exhibits strong acoustic anisotropy characteristics,posing significant challenges to its exploration and *** this study,the five full elastic constants and multipole response law of the Qingshankou shale were studied using experimental *** show that the anisotropy parametersϵandγin the study region are greater than 0.4,whereas the anisotropy parameterδis smaller,generally *** simulations show that the longitudinal and transverse wave velocities of these strong anisotropic rocks vary significantly with inclination angle,and significant differences in group velocity and phase velocity are also *** logging measures the group velocity in dipped boreholes;this differs from the phase velocity to some *** the dip angle increases,the longitudinal and SH wave velocities increase accordingly,while the qSV-wave velocity initially increases and then decreases,reaching its maximum value at a dip of approximately 40°.These results provide an effective guide for the correction and modeling of acoustic logging time differences in the region.

关键词： Transverse isotropy anisotropy parameter sonic logging group velocity phase velocity

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Rhamnus crenata leaf extracts exhibit anti-inflammatory activity via modulating the Nrf2/HO-1 and NF-κB/MAPK signaling pathways

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Asian Pacific Journal of Tropical biomedicine 2022年第10期12卷 430-436页

作者： Hyun Ji Eo Da Som Kim Gwang Hun Park Special Forest resources division Department of Forest Bio-ResourcesNational Institute of Forest ScienceSuwon 16631Korea Forest Medicinal resources Research Center National Institute of Forest ScienceYeongju 36040Korea

Objective:To elucidate the potential anti-inflammatory mechanisms of Rhamnus crenata leaf extracts using RAW264.7 ***:We used 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay to measure cell *** oxide(NO)production was measured using Griess *** blotting and RT-PCR assays were carried out for analyzing the protein and gene expressions of pro-inflammatory mediators,***,PD98059(ERK1/2 inhibitor),SB203580(p38 inhibitor),SP600125(JNK inhibitor),and BAY11-7082(NF-κB inhibitor)were used to evaluate the anti-inflammatory mechanism of Rhamnus crenata leaf ***:Rhamnus crenata leaf extracts significantly inhibited the production of the pro-inflammatory mediators such as NO,iNOS,COX-2,IL-1β,and TNF-αin lipopolysaccharide(LPS)-stimulated RAW264.7 *** crenata leaf extracts also suppressed LPS-induced degradation of IκB-αand nuclear accumulation of p65,which resulted in the inhibition of NF-κB activation in RAW264.7 ***,the extracts attenuated the phosphorylation of p38,ERK1/2,and JNK in LPS-stimulated RAW264.7 ***,HO-1 expression induced by Rhamnus crenata leaf extracts was significantly downregulated by SB230580,PD98059,SP600125 and ***:Rhamnus crenata leaf extract may upregulate HO-1 expression through inhibition of p38,ERK1/2,and NF-κB activation,which may contribute to the anti-inflammatory activity of the *** crenata leaf extracts may have great potential for the development of anti-inflammatory drugs to treat acute and chronic inflammatory diseases.

关键词： Anti-inflammatory activity Heme oxygenase-1 Nrf2 Mitogen-activated protein kinase Nuclear factor kappa B Rhamnus crenata

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Cav3.2 channel regulates cerebral ischemia/reperfusion injury:a promising target for intervention

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Neural Regeneration Research 2024年第11期19卷 2480-2487页

作者： Feibiao Dai Chengyun Hu Xue Li Zhetao Zhang Hongtao Wang Wanjun Zhou Jiawu Wang Qingtian Geng Yongfei Dong Chaoliang Tang Graduate School Wannan Medical CollegeWuhuAnhui ProvinceChina Department of Anesthesiology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Core Facility Center for Medical Sciences The First Affiliated Hospital of USTC(Anhui Provincial Hospital)HefeiAnhui ProvinceChina Department of Pharmacy The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina Department of Neurosurgery The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui ProvinceChina

Calcium influx into neurons triggers neuronal death during cerebral ischemia/reperfusion *** calcium channels are involved in cerebral ischemia/reperfusion ***3.2 channel is a main subtype of T-type calcium channels.T-type calcium channel blockers,such as pimozide and mibefradil,have been shown to prevent cerebral ischemia/reperfusion injury-induced brain ***,the role of Cav3.2 channels in cerebral ischemia/reperfusion injury remains ***,in vitro and in vivo models of cerebral ischemia/reperfusion injury were established using middle cerebral artery occlusion in mice and high glucose hypoxia/reoxygenation exposure in primary hippocampal *** results showed that Cav3.2 expression was significantly upregulated in injured hippocampal tissue and primary hippocampal *** further established a Cav3.2 gene-knockout mouse model of cerebral ischemia/reperfusion ***3.2 knockout markedly reduced infarct volume and brain water content,and alleviated neurological dysfunction after cerebral ischemia/reperfusion ***,Cav3.2 knockout attenuated cerebral ischemia/reperfusion injury-induced oxidative stress,inflammatory response,and neuronal *** the hippocampus of Cav3.2-knockout mice,calcineurin overexpression offset the beneficial effect of Cav3.2 knockout after cerebral ischemia/reperfusion *** findings suggest that the neuroprotective function of Cav3.2 knockout is mediated by calcineurin/nuclear factor of activated T cells 3 *** from this study suggest that Cav3.2 could be a promising target for treatment of cerebral ischemia/reperfusion injury.

关键词： calcineurin Cav3.2 channel cerebral ischemia/reperfusion hippocampus hypoxia/reoxygenation inflammatory response nuclear factor of activated T cells 3 oxidative stress primary hippocampal neurons stroke

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Sedimentary records of contaminant inputs in Frobisher Bay,Nunavut

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Environmental Science and Ecotechnology 2024年第2期18卷 28-42页

作者： Meaghan C.Bartley Tommy Tremblay Amila O.De Silva CMichelle Kamula Stephen Ciastek Zou Zou A.Kuzyk Centre for Earth Observation Science Clayton H.Riddell Faculty of EnvironmentEarth and ResourcesUniversity of ManitobaWinnipegManitobaR3T 2N2Canada Department of Environment and Geography Clayton H.Riddell Faculty of EnvironmentEarth and ResourcesUniversity of ManitobaWinnipegManitobaR3T 2N2Canada Canada-Nunavut Geoscience Office IqaluitNunavutX0A 0H0Canada Environment and Climate Change Canada BurlingtonOntarioL7S 1A1Canada Department of Earth Sciences Clayton H.Riddell Faculty of EnvironmentEarth and ResourcesUniversity of ManitobaWinnipegManitobaR3T 2N2Canada

Contaminants,such as polychlorinated biphenyls(PCBs),polycyclic aromatic hydrocarbons(PAHs),heavy metals,and per and polyfluoroalkyl substances(PFASs),primarily reach the Arctic through long-range atmospheric and oceanic ***,local sources within the Arctic also contribute to the levels observed in the environment,including legacy sources and new sources that arise from activities associated with increasing commercial and industrial *** City of Iqaluit in Frobisher Bay,Nunavut(Canada),has seen rapid population growth and associated development during recent decades yet remains a site of interest for ocean protection,where Inuit continue to harvest country *** the present study,seven dated marine sediment cores collected in Koojesse Inlet near Iqaluit,and from sites in inner and outer Frobisher Bay,respectively,were analyzed for total mercury(THg),major and trace elements,PAHs,PCBs,and *** sedimentary record in Koojesse Inlet shows a period of Aroclor 1260-like PCB input concurrent with military site presence in the 1950e60s,followed by decades of input of pyrogenic PAHs,averaging about ten times background ***-surface sediments in Koojesse Inlet also show evidence of transient local-source inputs of THg and PFASs,and recycling or continued slow release of PCBs from legacy land-based *** in PFAS congener composition clearly distinguish the local sources from long-range *** Koojesse Inlet but still in inner Frobisher Bay,9.2 km from Iqaluit,sediments showed evidence of both local source(PCB)and longrange *** outer Frobisher Bay,an up-core increase in THg and PFASs in sediments may be explained by ongoing inputs of these contaminants from long-range *** context for ocean protection and country food harvesting in this region of the Arctic clearly involves both local sources and long-range transport,with past human activities leaving a long legacy insofar as levels of persistent o

关键词： Arctic sediments Mercury Polycyclic aromatic hydrocarbons(PAHs) Polychlorinated biphenyls(PCBs) Per and polyfluoroalkyl substances(PFASs) Persistent organic pollutants(POPs)

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