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Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-βsignaling

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Frontiers of Medicine 2024年第1期18卷 128-146页

作者： Yuanyuan Hao Panpan Chen Shanshan Guo Mengyuan Li Xueli Jin Minghuan Zhang wenhai Deng Ping Li wen lei Aibin Liang wenbin Qian Department of Hematology The Second Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou310009China Department of Hematology Henan Provincial People’s HospitalZhengzhou University People’s HospitalZhengzhou450003China Key Laboratory of Laboratory Medicine Ministry of EducationSchool of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhou325000China Department of Hematology Tongji Hospital of Tongji UniversityShanghai200065China

Tumor-derived exosomes (TEXs) enriched in immune suppressive molecules predominantly drive T-cell dysfunction and impair antitumor immunity. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for refractory and relapsed hematological malignancies, but whether lymphoma TEXs have the same impact on CAR T-cell remains unclear. Here, we demonstrated that B-cell lymphoma-derived exosomes induce the initial activation of CD19-CAR T-cells upon stimulation with exosomal CD19. However, lymphoma TEXs might subsequently induce CAR T-cell apoptosis and impair the tumor cytotoxicity of the cells because of the upregulated expression of the inhibitory receptors PD-1, TIM3, and LAG3 upon prolonged exposure. Similar results were observed in the CAR T-cells exposed to plasma exosomes from patients with lymphoma. More importantly, single-cell RNA sequencing revealed that CAR T-cells typically showed differentiated phenotypes and regulatory T-cell (Treg) phenotype conversion. By blocking transforming growth factor β (TGF-β)-Smad3 signaling with TGF-β inhibitor LY2109761, the negative effects of TEXs on Treg conversion, terminal differentiation, and immune checkpoint expression were rescued. Collectively, although TEXs lead to the initial activation of CAR T-cells, the effect of TEXs suppressed CAR T-cells, which can be rescued by LY2109761. A treatment regimen combining CAR T-cell therapy and TGF-β inhibitors might be a novel therapeutic strategy for refractory and relapsed B-cell lymphoma.

关键词： tumor-derived exosome chimeric antigen receptor T-cell lymphoma TGF-β

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辐冠苣苔属(苦苣苔科)一新替代名称——Radiaticorollarus Y. G. Wei, F. wen & lei Cai

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广西植物 2024年第4期44卷 619-620页

作者：温放韦毅刚李晓娟熊驰蔡磊广西喀斯特植物保育与恢复生态学重点实验室广西壮族自治区中国科学院广西植物研究所广西桂林541006 广西植物研究所国家苦苣苔科种质资源库中国野生植物保护协会苦苣苔专委会中国苦苣苔科植物保育中心中国科学院桂林植物园广西桂林541006 中国科学院昆明植物研究所云南省极小种群野生植物综合保护重点实验室昆明650201

辐冠苣苔属为中国广东特有苦苣苔科单型属,因其具有苦苣苔科中相对比较少见的辐射状花冠裂片而得名。有学者提出因其属名Actinostephanus F.wen,Y.G.Wei&L.F.Fu和已灭绝的化石浮游植物属名Actinostephanos Khursevich极其相似而易于混淆... 详细信息

辐冠苣苔属为中国广东特有苦苣苔科单型属,因其具有苦苣苔科中相对比较少见的辐射状花冠裂片而得名。有学者提出因其属名Actinostephanus F.wen,Y.G.Wei&L.F.Fu和已灭绝的化石浮游植物属名Actinostephanos Khursevich极其相似而易于混淆,应处理为晚出同名。依据2018年《国际藻类、菌物和植物命名法规(深圳法规)》,该文为该晚出同名拟定了一个新名称,即Radiaticorollarus Y.G.Wei,F.wen&lei Cai,并将其属下辐冠苣苔Actinostephanus enpingensis F.wen,Y.G.Wei&Z.B.Xin处理为新组合Radiaticorollarus enpingensis(F.wen,Y.G.Wei&Z.B.Xin)F.wen,Y.G.Wei&lei Cai的异名。

关键词：辐冠苣苔属辐冠苣苔苦苣苔科新名称新组合

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Chord length sampling correction analysis for dispersion fuel in Monte Carlo simulation

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Nuclear Science and Techniques 2024年第4期35卷 57-64页

作者： Zhao-Yu Liang Ding She Yu-Tong wen lei Shi Institute of Nuclear and New Energy Technology(INET) Key Laboratory of Advanced Reactor Engineering and Safety of Ministry of EducationTsinghua UniversityBeijing 100084China

Dispersion fuels,knowned for their excellent safety performance,are widely used in advanced reactors,such as hightemperature gas-cooled reactors.Compared with deterministic methods,the Monte Carlo method has more advantages in the geometric modeling of stochastic media.The explicit modeling method has high computational accuracy and high computational cost.The chord length sampling(CLS)method can improve computational efficiency by sampling the chord length during neutron transport using the matrix chord length?s probability density function.This study shows that the excluded-volume effect in realistic stochastic media can introduce certain deviations into the CLS.A chord length correction approach is proposed to obtain the chord length correction factor by developing the Particle code based on equivalent transmission probability.Through numerical analysis against reference solutions from explicit modeling in the RMC code,it was demonstrated that CLS with the proposed correction method provides good accuracy for addressing the excludedvolume effect in realistic infinite stochastic media.

关键词： Stochastic media Monte Carlo Chord length sampling Excluded-volume effect Chord length correction

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N-glycan biosignatures as a potential diagnostic biomarker for earlystage pancreatic cancer

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 659-669页

作者： Yan-Rong wen Xia-wen Lin Yu-wen Zhou lei Xu Jun-Li Zhang Cui-Ying Chen Jian He Department of Nuclear Medicine Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008Jiangsu ProvinceChina Department of Research and Development Sysdiagno(Nanjing)Biotech Co.LtdNanjing 210008Jiangsu ProvinceChina

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)has a poor prognosis,with a 5-year survival rate of less than 10%,owing to its late-stage diagnosis.Early detection of pancreatic cancer(PC)can significantly increase survival rates.AIM To identify the serum biomarker signatures associated with early-stage PDAC by serum N-glycan analysis.METHODS An extensive patient cohort was used to determine a biomarker signature,in-cluding patients with PDAC that was well-defined at an early stage(stages I and II).The biomarker signature was derived from a case-control study using a case-cohort design consisting of 29 patients with stage I,22 with stage II,4 with stage III,16 with stage IV PDAC,and 88 controls.We used multiparametric analysis to identify early-stage PDAC N-glycan signatures and developed an N-glycan sig-nature-based diagnosis model called the“Glyco-model”.RESULTS The biomarker signature was created to discriminate samples derived from patients with PC from those of controls,with a receiver operating characteristic area under the curve of 0.86.In addition,the biomarker signature combined with cancer antigen 19-9 could discriminate patients with PDAC from controls,with a receiver operating characteristic area under the curve of 0.919.Glyco-model demonstrated favorable diagnostic performance in all stages of PC.The diagnostic sensitivity for stage I PDAC was 89.66%.Core Tip:This study employed a patient cohort to investigate the N-glycan signature of early-stage pancreatic cancer(PC).Serum N-glycans analysis was conducted to identify the serum biomarker signature associated with early-stage pancreatic ductal adenocarcinoma(PDAC),resulting in the identification of nine early-stage PDAC N-glycan signatures.Subsequently,utilizing these biosignatures,a diagnostic model named the“Glyco-model”was developed,demonstrating promising diagnostic performance across all stages of PC.The study revealed that the diagnostic sensitivity for stage I PDAC was determined to be 89.66%.Consequently,this diagnostic model exhibits potent

关键词： Glycomics N-glycans Biomarkers Pancreatic cancer Predictive modeling

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Geochemical identification of a source rock affected by migrated hydrocarbons and its geological significance:Fengcheng Formation,southern Mahu Sag,Junggar Basin,NW China

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Petroleum Science 2024年第1期21卷 100-114页

作者： wen-Long Dang Gang Gao Xin-Cai You Ke-Ting Fan Jun Wu De-wen lei wen-Jun He Yong Tang State Key Laboratory of Petroleum Resource and Prospecting China University of Petroleum(Beijing)Beijing102249China School of GeoSciences China University of Petroleum(Beijing)Beijing102249China Exploration&Development Institute Xinjiang Oil Field CompanyKaramay834000XinjiangChina

The Fengcheng Formation is a crucial source rock and the primary reservoir for oil accumulation in the Mahu Sag.Crude oils are distributed throughout the Fengcheng Formation,ranging from the edge to the interior of the sag in the southern Mahu Sag.These crude oils originate from in-situ source rocks in shallowly buried areas and the inner deep sag.During migration,the crude oil from the inner deep sag affects the source rocks close to carrier beds,leading to changes in the organic geochemical characteristics of the source rocks.These changes might alter source rock evaluations and oil-source correlation.Based on data such as total organic carbon(TOC),Rock-Eval pyrolysis of source rocks,and gas chromatography-mass spectrometry(GC-MS)of the saturated fraction,and considering the geological characteristics of the study area,we define the identification characteristics of source rock affected by migrated hydrocarbons and establish the various patterns of influence that migrated hydrocarbons have on the source rock of the Fengcheng Formation in the southern Mahu Sag.The source rocks of the Fengcheng Formation are mostly fair to good,containing mainly Type II organic matter and being thermally mature enough to generate oil.Source rocks affected by migrated hydrocarbons exhibit relatively high hydrocarbon contents(S1/TOC>110 mg HC/g TOC,Extract/TOC>30%,HC:hydrocarbon),relatively low Rock-Eval Tmax values,and relatively high tricyclic terpane contents with a descending and mountain-shaped distribution.Furthermore,biomarker composition parameters indicate a higher thermal maturity than in-situ source rocks.Through a comparison of the extract biomarker fingerprints of adjacent reservoirs and mudstones in different boreholes,three types of influence patterns of migrated hydrocarbons are identified:the edge-influence of thin sandstone-thick mudstone,the mixed-influence of sandstone-mudstone interbedded,and the full-influence of thick sandstone-thin mudstone.This finding reminds us that the influence of migrated hydrocarbons

关键词： Organic geochemistry Source rock Influence of migrated hydrocarbons Fengcheng Formation Southern Mahu Sag

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Metallothionein 1E Alleviates Cadmium-induced Renal Cytotoxicity through Promoting Mitochondrial Functional Recovery

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Biomedical and Environmental Sciences 2024年第1期37卷 117-121页

作者： wen Si Hui LI Lu Bei HUANG Hui Dan XIE Ying LUO lei Key Laboratory of Molecular Epidemiology of Hunan Province School of MedicineHunan Normal UniversityChangsha 410081HunanChina Department of Occupational Health Changsha Centre for Disease Control and PreventionChangsha 410004HunanChina The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province Hunan Normal University School of MedicineChangsha 410013HunanChina

The pervasive utilization of industrial substances has escalated human exposure to cadmium(Cd),a metal associated with long-term negative health outcomes such as renal dysfunction,neurological disorders,and various cancers^([1]).Once ingested by humans,Cd interacts with cysteine-rich metallothioneins(MTs)which have metal-binding and antioxidant properties and is subsequently transported to the kidney^([2]).

关键词： Renal kidney cadmium

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A semi-analytical model for coupled flow in stress-sensitive multi-scale shale reservoirs with fractal characteristics

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Petroleum Science 2024年第1期21卷 327-342页

作者： Qian Zhang wen-Dong Wang Yu-Liang Su Wei Chen Zheng-Dong lei lei Li Yong-Mao Hao Key Laboratory of Unconventional Oil&Gas Development(China University of Petroleum(East China)) Ministry of EducationQingdao266580ShandongChina School of Petroleum Engineering China University of Petroleum(East China)Qingdao266580ShandongChina Shale Oil Development Branch Changqing Oilfield CompanyPetroChinaQingyang745708GansuChina PetroChina Research Institute of Petroleum Exploration&Development Beijing100083China

A large number of nanopores and complex fracture structures in shale reservoirs results in multi-scale flow of oil. With the development of shale oil reservoirs, the permeability of multi-scale media undergoes changes due to stress sensitivity, which plays a crucial role in controlling pressure propagation and oil flow. This paper proposes a multi-scale coupled flow mathematical model of matrix nanopores, induced fractures, and hydraulic fractures. In this model, the micro-scale effects of shale oil flow in fractal nanopores, fractal induced fracture network, and stress sensitivity of multi-scale media are considered. We solved the model iteratively using Pedrosa transform, semi-analytic Segmented Bessel function, Laplace transform. The results of this model exhibit good agreement with the numerical solution and field production data, confirming the high accuracy of the model. As well, the influence of stress sensitivity on permeability, pressure and production is analyzed. It is shown that the permeability and production decrease significantly when induced fractures are weakly supported. Closed induced fractures can inhibit interporosity flow in the stimulated reservoir volume (SRV). It has been shown in sensitivity analysis that hydraulic fractures are beneficial to early production, and induced fractures in SRV are beneficial to middle production. The model can characterize multi-scale flow characteristics of shale oil, providing theoretical guidance for rapid productivity evaluation.

关键词： Multi-scale coupled flow Stress sensitivity Shale oil Micro-scale effect Fractal theory

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Polymer ionogels and their application in flexible ionic devices

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SmartMat 2024年第2期5卷 4-42页

作者： Jinqiao wen lei Zhou Tengling Ye Department of Applied Chemistry School of Chemistry and Chemical EngineeringHarbin Institute of TechnologyHarbinChina State Key Laboratory of Luminescent Materials and Devices South China University of TechnologyGuangzhouChina

Polymer ionogel(PIG)is a new type of flexible,stretchable,and ion-conductive material,which generally consists of two components(polymer matrix materials and ionic liquids/deep eutectic solvents).More and more attention has been received owing to its excellent properties,such as nonvolatility,good ionic conductivity,excellent thermal stability,high electrochemical stability,and transparency.In this review,the latest research and developments of PIGs are comprehensively reviewed according to different polymer matrices.Particularly,the development of novel structural designs,preparation methods,basic properties,and their advantages are respectively summarized.Furthermore,the typical applications of PIGs in flexible ionic skin,flexible electrochromic devices,flexible actuators,and flexible power supplies are reviewed.The novel working mechanism,device structure design strategies,and the unique functions of the PIG-based flexible ionic devices are briefly introduced.Finally,the perspectives on the current challenges and future directions of PIGs and their application are discussed.

关键词： electrochromism device flexible ionic devices flexible ionic skin ionic liquid ionogel

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Mo@PANI-catalyzed oxidative deoximation reaction

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Chinese Chemical Letters 2024年第2期35卷 407-410页

作者： Yiyang Zhang wen Li Zuofeng Hu Xiaobi Jing lei Yu School of Mechanical Engineering Yangzhou UniversityYangzhou 225127China School of Chemistry and Chemical Engineering Yangzhou UniversityYangzhou 225002China Yangzhou Yangzi Auto Interior & Exterior Co. Ltd.Yangzhou 225119China

Deoximation is an important transformation in synthetic industry.It can be employed in protection,characterization and purification of the carbonyls,and in the synthesis of ketones from non-carbonyl molecules.In the field,oxidative deoximation reaction can utilize the driving force caused by the oxidation process so that the reaction can occur under relatively mild conditions.Recently,we designed and prepared polyaniline-supported molybdenum(Mo@PANI)just by immersing PANI into the EtOH/H_(2)O solution of MoCl_(5).The material was successfully applied as the efficient catalyst for oxidative deoximation reactions,which were performed in ethanol using H_(2)O_(2)as the clean oxidant.The substrate scope of the reaction was wide.It could be applied on heterocycle-containing substrates,making this protocol preferable for pharmaceutical intermediate synthesis.Since Mo is a necessary trace element for both animals and plants,this method is environment-friendly and is suitable for large-scale preparation.This work as the first example of Mo-catalyzed oxidative deoximation reaction may inspire novel ideas for both catalyst design and synthetic process development.

关键词： Molybdenum Polyaniline Oxidation Deoximation Carbonyl

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Divergent defluorocarboxylation of α-CF_(3) alkenes with formate via photocatalyzed selective mono-or triple C-F bond cleavage

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Science China Chemistry 2024年第1期67卷 368-373页

作者： Xing-Yu Wang Pei Xu wen-wen Liu Hao-Qiang Jiang Song-lei Zhu Dong Guo Xu Zhu Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy School of PharmacyXuzhou Medical UniversityXuzhou 22100China

Unprecedented divergent synthesis of gem-difluorovinylacetic acid and glutaric acid derivatives fromα-CF_(3)alkenes with formate as the carbonyl source was disclosed.The reaction can undergo selective mono-or triple C-F bond cleavage by simply switching the photocatalyst and hydrogen atom transfer(HAT)catalyst under visible-light-induced conditions at room temperature.Foramte acts as both the C1 source and the reductant through the generation of CO_(2)^(·-)species,which underwent Giese radical addition to electron-deficient alkenes to trigger the consecutive C-F bond cleavage and carboxylation process.

关键词： C-F bond activation defluorocarboxylation carbon dioxide radical anion visible light

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