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Journal of Rare Earths 2024年第4期42卷 743-748页

作者： Hao Zhang Yi Bian Yuxuan xia yuchen Cui Ziang Li Fang Zhang Yiming Bai Nuofu Chen Jikun Chen School of New Energy North China Electric Power UniversityBeijing102206China School of Materials Science and Engineering University of Science and Technology BeijingBeijing100083China

While the metal to insulator transition(MIT)of d-band correlated perovskite nickelates(RENiO_(3))are widely adjustable via their rare-earth composition,the roles of potential valence variabilities associated with the rare-earth elements were rarely concerned.Herein,we demonstrate the material synthesis and MIT properties of RENiO_(3) containing valence variable rare-earth compositions,such as Ce,Pr,Sm,Eu and Tb.The metastable perovskite structure of SmNiO_(3) and EuNiO_(3) with a rare-earth valence states variable towards+2 can be effectively synthesized under high oxygen pressures as it is necessary to reduce their formation free energies.This is in contrast to Ce and Tb,in which situations the variable rare-earth valence state towards+4 reduces their ionic radius and prohibits their occupation or co-occupation of the rare-earth site within the perovskite structured RENiO_(3).Nevertheless,PrNiO_(3) with MIT properties can be effectively synthesized at lower oxygen pressures,owing to the higher stability to form a fully occupied 6s orbit associated Pr3+compared to the half-filled one related to Pr4+.The present work provides guidance for regulating the MIT properties of RENiO_(3).

关键词： Metal to insulator transition Metastable perovskites Rare-earth nickelates Oxides

Preclinical evaluation of cyclophosphamide and fludarabine combined with CD19 CAR-T in the treatment of B-cell hematologic malignancies in vivo

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Oncology Research 2024年第6期32卷 1109-1118页

作者： ZHIGANG xia MENGYAO TIAN YUCAI CHENG WENFANG YI ZEFAN DU TIANWEN LI yuchen WEN LINDI LI YONG LIU CHUN CHEN Pediatric Hematology Laboratory Division of Hematology/OncologyDepartment of PediatricsThe Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China Scientific Research Center The Seventh Affiliated Hospital of Sun Yat-sen UniversityShenzhen518107China

Background:Chimeric antigen receptor T(CAR-T)cell therapy has achieved marked therapeutic success in ameliorating hematological malignancies.However,there is an extant void in the clinical guidelines concerning the most effective chemotherapy regimen prior to chimeric antigen receptor T(CAR-T)cell therapy,as well as the optimal timing for CAR-T cell infusion post-chemotherapy.Materials and Methods:We employed cell-derived tumor xenograft(CDX)murine models to delineate the optimal pre-conditioning chemotherapy regimen and timing for CAR-T cell treatment.Furthermore,transcriptome sequencing was implemented to identify the therapeutic targets and elucidate the underlying mechanisms governing the treatment regimen.Results:Our preclinical in vivo evaluation determined that a combination of cyclophosphamide and fludarabine,followed by the infusion of CD19 CAR-T cells five days subsequent to the chemotherapy,exerts the most efficacious therapeutic effect in B-cell hematological malignancies.Concurrently,RNA-seq data indicated that the therapeutic efficacy predominantly perturbs tumor cell metabolism,primarily through the inhibition of key mitochondrial targets,such as C-Jun Kinase enzyme(C-JUN).Conclusion:In summary,the present study offers critical clinical guidance and serves as an authoritative reference for the deployment of CD19 CAR-T cell therapy in the treatment of B-cell hematological malignancies.

关键词： CD19 CAR-T B-cell hematologic malignancies Metabolism In vivo

Antibiotic-induced gut bacteria depletion has no effect on HBV replication in HBV immune tolerance mouse model

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Virologica Sinica 2023年第3期38卷 335-343页

作者： Yanan Bu Kaitao Zhao Zaichao Xu Yingcheng Zheng Rong Hua Chuanjian Wu Chengliang Zhu yuchen xia xiaoming Cheng State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology Hubei Jiangxia LaboratoryInstitute of Medical VirologyTaiKang Center for Life and Medical SciencesTaiKang Medical SchoolWuhan UniversityWuhan430071China Department of Clinical Laboratory Renmin Hospital of Wuhan UniversityWuhan430060China Department of Pathology Center for Pathology and Molecular DiagnosticsHubei Clinical Center and Key Laboratory of Intestinal and Colorectal DiseasesZhongnan Hospital of Wuhan UniversityTaiKang Medical SchoolWuhan UniversityWuhan430071China

Commensal microbiota is closely related to Hepatitis B virus(HBV)infection.Gut bacteria maturation accelerates HBV immune clearance in hydrodynamic injection(HDI)HBV mouse model.However,the effect of gut bacteria on HBV replication in recombinant adeno-associated virus(AAV)-HBV mouse model with immune tolerance remains obscure.We aim to investigate its role on HBV replication in AAV-HBV mouse model.C57BL/6 mice were administrated with broad-spectrum antibiotic mixtures(ABX)to deplete gut bacteria and intravenously injected with AAV-HBV to establish persistent HBV replication.Gut microbiota community was analyzed by fecal qPCR assay and 16S ribosomal RNA(rRNA)gene sequencing.HBV replication markers in blood and liver were determined by ELISA,qPCR assay and Western blot at indicated time points.Immune response in AAV-HBV mouse model was activated through HDI of HBV plasmid or poly(I:C)and then detected by quantifying the percentage of IFN-γ^(+)/CD8^(+)T cells in the spleen via flow cytometry as well as the splenic IFN-γmRNA level via qPCR assay.We found that antibiotic exposure remarkably decreased gut bacteria abundance and diversity.Antibiotic treatment failed to alter the levels of serological HBV antigens,intrahepatic HBV RNA transcripts and HBc protein in AAV-HBV mouse model,but contributed to HBsAg increase after breaking of immune tolerance.Overall,our data uncovered that antibiotic-induced gut bacteria depletion has no effect on HBV replication in immune tolerant AAV-HBV mouse model,providing new thoughts for elucidating the correlation between gut bacteria dysbiosis by antibiotic abuse and clinical chronic HBV infection.

关键词： Hepatitis B virus(HBV) Gut bacteria Antibiotic mixtures(ABX) Adeno-associated virus(AAV)-HBV mouse model Persistent HBV replication Chronic HBV infection

A small molecule cocktail breaks the bottleneck of human primary hepatocytes culture

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Science Bulletin 2019年第18期64卷 1293-1294页

作者： yuchen xia State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology School of Basic Medical Sciences and Renmin Hospital of Wuhan University

It is estimated that more than 300 million people in China are suffering from different liver diseases including viral hepatitis,fatty liver,alcoholic liver,liver fibrosis,cirrhosis and liver cancer,of which about 400,000 people die each year[1].The clinical resolution of these diseases relies largely on the breakthroughs from basic research.Human primary hepatocytes(PHHs)have long been considered as the"gold standard"for in vitro liver disease research models.However,there are still a number of limitations,like high donor variability,short life spans and limited availability.

关键词： diseases clinical culture

小浪底水库运用后黄河下游游荡段游荡程度变化特点及机理

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地理学报 2024年第5期79卷 1161-1176页

作者：刘雨晨夏军强周美蓉程亦菲武汉大学水资源工程与调度全国重点实验室武汉430072

为实现黄河下游游荡段游荡程度变化的定量评价,提出了游荡指数的计算方法;本文结合Landsat影像,分析了小浪底水库运用后游荡段游荡程度的变化特点及机理。研究表明,2000—2022年黄河下游游荡段整体游荡程度降低,游荡指数由0.918减至0.6... 详细信息

为实现黄河下游游荡段游荡程度变化的定量评价,提出了游荡指数的计算方法;本文结合Landsat影像,分析了小浪底水库运用后游荡段游荡程度的变化特点及机理。研究表明,2000—2022年黄河下游游荡段整体游荡程度降低,游荡指数由0.918减至0.674,且游荡程度降低速率先快后慢。其中铁谢—伊洛河口河段和花园口—夹河滩河段游荡程度显著降低,伊洛河口—花园口河段游荡程度基本不变,夹河滩—高村河段游荡程度有所增加。此外,游荡段游荡特性演变与水沙、河床边界条件变化以及局部河势调整密切相关。从水沙条件来看,小浪底水库运用后黄河下游输沙锐减、洪峰调平,使得河道全线冲刷、流路集中,以致游荡段游荡特性减弱,且丰水年较枯水年更有利于河势归顺;从河床边界条件来看,沿程河岸约束性强的河段游荡特性趋于减弱,且河床纵向稳定性增加是游荡段游荡程度降低及降低速率减慢的因素之一;从局部河势调整的影响来看,朱寨—东坝头河段河势变化是夹河滩—高村河段后期切滩频发的重要原因。

关键词：游荡程度时空变化演变机理游荡指数 Landsat影像黄河下游

基于LDA主题模型的中国学前融合教育研究主题分析及热点特征研判

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渭南师范学院学报 2024年第3期39卷 80-87页

作者：夏巍范宇辰西华师范大学学前与初等教育学院四川南充637000

学前融合教育是我国教育事业中不可或缺的一环和重要组成部分。运用LDA主题模型,对学前融合教育研究中的525篇文献摘要的内容进行挖掘与分析,抽取研究主题,进行特征分析并识别热点主题。结果显示,呈现出四大聚类主题:主题1聚焦于课程建... 详细信息

学前融合教育是我国教育事业中不可或缺的一环和重要组成部分。运用LDA主题模型,对学前融合教育研究中的525篇文献摘要的内容进行挖掘与分析,抽取研究主题,进行特征分析并识别热点主题。结果显示,呈现出四大聚类主题:主题1聚焦于课程建设,主题2突出儿童本位,主题3侧重于专业程度,主题4表达了三位联动趋向。在后续研究中应坚持深度挖掘本土资源,系统提炼学前融合教育课程意蕴;恪守儿童本位理念,突破实践活动的思想桎梏;夯实教师专业素养,深化学前融合教育研究层次;打造多方协同机制,践行家园社整体观的理论关照。

关键词：学前融合教育研究热点 LDA主题模型文本挖掘

Insights into Hepatitis B Virus DNA Integration-55 Years after Virus Discovery

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The Innovation 2020年第2期1卷 49-58页

作者： Kaitao Zhao Andrew Liu yuchen xia State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology School of Basic Medical SciencesWuhan UniversityWuhan 430071China Laboratory of Molecular Cardiology National Heart Lung Blood InstituteNational Institutes of HealthBethesdaMD 20814USA

Hepatitis B virus(HBV),which was discovered in 1965,is a threat to global public health.HBV infects human hepatocytes and leads to acute and chronic liver diseases,and there is no cure.In cells infected by HBV,viral DNA can be integrated into the cellular genome.HBV DNA integration is a complicated process during the HBV life cycle.Although HBV integration normally results in replication-incompetent transcripts,it can still act as a template for viral protein expression.Of note,it is a primary driver of hepatocellular carcinoma(HCC).Recently,with the development of detection methods and research models,the molecular biology and the pathogenicity of HBV DNA integration have been better revealed.Here,we review the advances in the research of HBV DNA integration,including molecular mechanisms,detection methods,research models,the effects on host and viral gene expression,the role of HBV integrations in the pathogenesis of HCC,and potential treatment strategies.Finally,we discuss possible future research prospects of HBV DNA integration.

关键词： HEPATITIS B VIRUS INTEGRATION NON-HOMOLOGOUS END JOINING INSERTIONAL MUTAGENESIS HEPATOCELLULAR CARCINOMA

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速效抗抑郁药的作用靶点研究进展

现代药物与临床 2024年第3期39卷 775-784页

作者：张宇琛郑明琳郭毅夏琴樊萍四川大学华西医院临床药学部四川成都610041 四川大学华西医院上锦医院药剂科四川成都611730

抑郁症是一种慢性复发性精神疾病,传统抗抑郁药通常需要连续几周的治疗才能发挥显著的治疗效果。N-甲基-D-天冬氨酸受体拮抗剂氯胺酮的上市为速效抗抑郁药物的研发打开了一个全新的视角,胆碱能受体阻滞剂东莨菪碱、5-HT2A受体激动剂赛... 详细信息

抑郁症是一种慢性复发性精神疾病,传统抗抑郁药通常需要连续几周的治疗才能发挥显著的治疗效果。N-甲基-D-天冬氨酸受体拮抗剂氯胺酮的上市为速效抗抑郁药物的研发打开了一个全新的视角,胆碱能受体阻滞剂东莨菪碱、5-HT2A受体激动剂赛洛西宾也表现出快速抗抑郁的作用潜力。归纳了谷氨酸能速效抗抑郁药、胆碱能受体拮抗剂、5-HT2A受体激动剂(致幻剂)速效抗抑郁药的药理学靶点研究,分析了新靶点的可能策略,以期对未来抗抑郁药物研究方向有所启示。

关键词：速效抗抑郁药抑郁症氯胺酮东莨菪碱赛洛西宾

水电梯级开发真的破坏下游河段营养盐情势吗?

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Science Bulletin 2024年第5期69卷 661-670页

作者：陈求稳陈宇琛林育青张建云倪晋仁夏军肖琳冯韬马宏海 State Key Laboratory of Hydrology-Water Resources&Hydraulic Engineering Nanjing Hydraulic Research InstituteNanjing 210029China Center for Eco-Environment Research Nanjing Hydraulic Research InstituteNanjing 210029China Yangtze Institute for Conservation and Green Development Nanjing 210024China School of the Environment Nanjing UniversityNanjing 210008China The Key Laboratory of Water and Sediment Sciences Ministry of EducationPeking UniversityBeijing 100091China State Key Laboratory of Water Resources and Hydropower Engineering Sciences Wuhan UniversityWuhan 430072China

River damming is believed to largely intercept nutrients,particularly retain more phosphorus(P)than nitrogen(N),and thus harm primary productivity,fishery catches,and food security downstream,which seriously constrain global hydropower development and poverty relief in undeveloped regions and can drive geo-political disputes between nations along trans-boundary rivers.In this study,we investigated whether reservoirs can instead improve nutrient regimes downstream.We measured different species of N and P as well as microbial functions in water and sediment of cascade reservoirs in the upper Mekong River over 5 years and modelled the influx and outflux of N and P species in each reservoir.Despite partially retaining total N and total P,reservoirs increased the downstream flux of ammonium and soluble reactive phosphorus(SRP).The increase in ammonium and SRP between outflux and influx showed positive linear relationships with the hydraulic residence time of the cascade reservoirs;and the ratio of SRP to dissolved inorganic nitrogen increased along the reservoir cascade.The lentic environment of reservoirs stimulated algae-mediated conversion of nitrate into ammonium in surface water;the hypoxic condition and the priming effect of algae-induced organic matter enhanced release of ammonium from sediment;the synergy of microbial phosphorylation,reductive condition and sediment geochemical properties increased release of SRP.This study is the first to provide solid evidence that hydropower reservoirs improve downstream nutrient bioavailability and N-P balance through a process of retention-transformation-transport,which may benefit primary productivity.These findings could advance our understanding of the eco-environmental impacts of river damming.

关键词： River damming Biogeochemical cycle Nitrogen Phosphorus Ecological impacts