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The generation of PD-L1 and PD-L2 in cancer cells: From nuclear chromatin reorganization to extracellular presentation

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1041-1053页

作者： zhiwei fan Changyue Wu Miaomiao Chen Yongying Jiang Yuanyuan Wu Renfang Mao Yihui fan Department of Pathogenic Biology School of MedicineNantong UniversityNantong 226001China Laboratory of Medical Science School of MedicineNantong UniversityNantong 226001China Department of Dermatology Affiliated Hospital of Nantong UniversityNantong UniversityNantong 226001China Department of Pathophysiology School of MedicineNantong UniversityNantong 226001China

The immune checkpoint blockade(ICB)targeting on PD-1/PD-L1 has shown remarkable promise in treating ***,the low response rate and frequently observed severe side effects limit its broad *** is partially due to less understanding of the biological regulation of ***,we systematically and comprehensively summarized the regulation of PD-L1 from nuclear chromatin reorganization to extracellular *** PD-L1 and PD-L2 highly expressed cancer cells,a new TAD(topologically associating domain)(chr9:5,400,000-5,600,000)around CD274 and CD273 was discovered,which includes a reported super-enhancer to drive synchronous transcription of PD-L1 and *** re-shaped TAD allows transcription factors such as STAT3 and IRF1 recruit to PD-L1 locus in order to guide the expression of *** transcription,the PD-L1 is tightly regulated by mi RNAs and RNA-binding proteins via the long 3’*** translational level,PD-L1 protein and its membrane presentation are tightly regulated by post-translational modification such as glycosylation and *** addition,PD-L1 can be secreted via exosome to systematically inhibit immune ***,fully dissecting the regulation of PD-L1/PD-L2 and thoroughly detecting PD-L1/PD-L2 as well as their regulatory networks will bring more insights in ICB and ICB-based combinational therapy.

关键词： Immune checkpoint blockade PD-L1 PD-L2 Topologically associating domain Transcription Post-transcriptional regulation Post-translational regulation Exosome

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The Integrative Studies on the Functional A-to-I RNA Editing Events in Human Cancers

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Genomics, Proteomics & Bioinformatics 2023年第3期21卷 619-631页

作者： Sijia Wu zhiwei fan Pora Kim Liyu Huang Xiaobo Zhou School of Life Science and Technology Xidian UniversityXi’an 710071China West China School of Public Health and West China Fourth Hospital Sichuan UniversityChengdu 610040China Center for Computational Systems Medicine School of Biomedical InformaticsThe University of Texas Health Science Center at HoustonHoustonTX 77030USA

Adenosine-to-inosine(A-to-I)RNA editing,constituting nearly 90%of all RNA editing events in humans,has been reported to contribute to the tumorigenesis in diverse ***,the comprehensive map for functional A-to-I RNA editing events in cancers is still *** fill this gap,we systematically and intensively analyzed multiple tumorigenic mechanisms of A-to-I RNA editing events in samples across 33 cancer types from The Cancer Genome *** individual candidate among1,500,000 quantified RNA editing events,we performed diverse types of downstream functional ***,we identified 24,236 potentially functional A-to-I RNA editing events,including the cases in APOL1,IGFBP3,GRIA2,BLCAP,and *** events might play crucial roles in the scenarios of tumorigenesis,due to their tumor-related editing frequencies or probable effects on altered expression profiles,protein functions,splicing patterns,and microRNA regulations of tumor *** functional A-to-I RNA editing events(https://***/CAeditome/)will help better understand the cancer pathology from the A-to-I RNA editing aspect.

关键词： A-to-I RNA editing Cancer Protein recoding Alternative splicing MicroRNA regulation

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Time-dependent mechanical behavior of tough hydrogels under multiaxial stretching

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International Journal of Smart and Nano Materials 2023年第4期14卷 460-473页

作者： Yong Liu Yang Chen Jie Zhu Mengze Lu Chuanxia Jiang zhiwei fan Taolin Sun South China Advanced Institute for Soft Matter Science and Technology School of Emergent Soft MatterSouth China University of TechnologyGuangzhou China Guangdong Provincial Key Laboratory of Functional and Intelligent Hybrid Materials and Devices South China University of TechnologyGuangzhouChina Guangdong Marubi Biotechnology Co LtdGuangzhouChina

Understanding the time-dependent mechanical behavior of tough and viscoelastic hydrogels under complex external loading is *** this study,we utilized tough and viscoelastic hydrogels synthesized through the copolymerization of methacrylic acid and methacrylamide as a model system to investigate their mechanical behavior under multiaxial stretching across a wide range of strain *** stretching modes examined were uniaxial,pure shear,and equal biaxial *** findings show that under equal biaxial stretching,the hydrogels exhibit higher mechanical properties and energy dissipation compared to uniaxial and pure shear stretching,owing to the greater contribution of hydrogen bonds to energy dissipation in the former stretching ***,employing the time-elongation separability method during the stretching process,we observed that the relaxation of dynamic hydrogen bonds in the hydrogels only depends on stretching time,independent of the elongation ratio and stretching *** anticipate that this study will yield valuable contributions to the design of durable load-bearing soft materials,particularly in dealing with complex deformation and strain rate responses.

关键词： Hydrogels Viscoelasticity Multiaxial stretching

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Seed,cutting and air-layering reproductive inefficiency of noxious woody vine Merremia biosiana and its implications for management strategy

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Frontiers in Biology 2009年第3期4卷 342-349页

作者： Mingguang LI Haiyang LIU Fenglan LI Xiuyuan CHENG Bin GUO zhiwei fan State Key Laboratory of Biocontrol Sun Yat-sen UniversityGuangzhou 510275China Environment and Plant Protection Institute Chinese Academy of Tropical Agricultural SciencesDanzhou 571737China

Merremia boisiana(Gagnep)van *** a noxious fast growing woody vine and is able to grow overtop other plants,causing the death of plants underneath and forming monospecies *** formulate management responses,we assessed its seed and vegetative reproduction efficacy through indoor and field *** number of flowers counted from bagged infructescences in Guangzhou ranged from 25 to 172,with an average of *** the seeds of bagged infructescences had shown that there were only 1.58 hard testa seeds in each *** vitality tests using red ink indicated that only 68.6%of hard testa and filled seeds were *** emergence rate of scarified hard testa seeds in the sand bed was 31.96%.Under imitated natural conditions,8%of hard testa seeds could germinate,and 9%still retained their germination potential in one ***,seedlings should be monitored and removed in a timely fashion after any attempt of *** soil or transplanting plant from infested patches should be strictly prohibited at least for several *** considered,an infructescence contributed 0.3 *** investigation in the field found no seedlings either inside or at the perimeter of the patch,suggesting scant expansion by means of seed ***,the elimination effort could be focused on a relatively restricted scale of *** 630 cuttings of young shoots,old shoots and old lying shoots with or without growth regulators,there were only four(or 0.63%)established ***-layering shoots all died in two *** cuttings and airlayering reproduction indicated that regeneration from fragments of removed stems or accidentally dropped ones was quite unlikely,and thus mechanical removal was safe.

关键词： Merremia boisiana seed vitality germination rate vegetative reproduction management

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Super-enhancer receives signals from the extracellular matrix to induce PD-L1-mediated immune evasion via integrin/ BRAF/TAK1/ERK/ETV4 signaling

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Cancer Biology & Medicine 2022年第5期19卷 669-684页

作者： Panpan Ma Xinxin Jin zhiwei fan Zhou Wang Suhui Yue Changyue Wu Shiyin Chen Yuanyuan Wu Miaomiao Chen Donghua Gu Siliang Zhang Renfang Mao Yihui fan Laboratory of Medical Science School of MedicineNantong UniversityNantong 226001China Department of Pathogenic Biology School of MedicineNantong UniversityNantong 226001China Department of Clinical Laboratory Yancheng No.1 People’s HospitalYancheng 224005China School of Life Sciences Nantong UniversityNantong 226001China Department of Dermatology Affiliated Hospital of Nantong UniversityNantong UniversityNantong 226001China The Department of Urology the Second Affiliated Hospital of Nantong UniversityNantong UniversityNantong 226001China The Department of Radiotherapy Oncology Harbin Medical University Cancer HospitalHarbin 150086China Department of Pathophysiology School of MedicineNantong UniversityNantong 226001China

Objective:PD-L1 and PD-L2 expression levels determine immune evasion and the therapeutic efficacy of immune checkpoint *** factors that drive inducible PD-L1 expression have been extensively studied,but mechanisms that result in constitutive PD-L1 expression in cancer cells are largely ***:DNA elements were deleted in cells by CRISPR/Cas9-mediated *** function was inhibited by chemical *** levels were examined by Western blot,mRNA levels were examined by real-time RT-PCR,and surface protein expression was determined by cellular immunofluorescence and flow *** evasion was examined by in vitro T cell-mediated ***:We determined the core regions(chr9:5,496,378–5,499,663)of a previously identified PD-L1L2-super-enhancer(SE).Through systematic analysis,we found that the E26 transformation-specific(ETS)variant transcription factor(ETV4)bound to this core DNA region but not to DNA surrounding *** knockout of ETV4 dramatically reduced the expressions of both PD-L1 and ***4 transcription was dependent on ERK activation,and BRAF/TAK1-induced ERK activation was dependent on extracellular signaling fromαvβ3 integrin,which profoundly affected ETV4 transcription and PD-L1/L2 *** silencing or pharmacological inhibition of components of the PD-L1L2-SE-associated pathway rendered cancer cells susceptible to T cell-mediated ***:We identified a pathway originating from the extracellular matrix that signaled via integrin/BRAF/TAK1/ERK/ETV4 to PD-L1L2-SE to induce PD-L1-mediated immune *** results provided new insights into PD-L1L2-SE activation and pathways associated with immune checkpoint regulation in cancer.

关键词： PD-L1 super-enhancer ETV4 ERK αvβ3 integrin BRAF TAK1

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Wearable membranes from zirconium-oxo clusters cross-linked polymer networks for ultrafast chemical warfare agents decontamination

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Chinese Chemical Letters 2022年第6期33卷 3241-3244页

作者： Litao Ma Jiamin Xie Xiaoshan Yan zhiwei fan Heguo Li Lin Lu Likun Chen Yi Xin Panchao Yin South China Advanced Institute for Soft Matter Science and Technology&State Key Laboratory of Luminescent Materials and Devices University of Technology Guangzhou 510641China State Key Laboratory of NBC Protection for Civilian Research Institution of Chemical DefenseBeijing 100191China

The urgent need for immediate personal protection against chemical warfare agents(CWAs)spurs the requirement on robust and highly efficient catalytic systems that can be conveniently integrated to wearable ***,as a new concept for CWA decontamination catalyst design,sub-nanoscale,catalytically active zirconium-oxo molecular clusters are covalently integrated in flexible polymer network as crosslinkers for the full exposure of catalytic sites as well as robust framework *** obtained membrane catalysts exhibit high swelling ratio with aqueous content as 84 wt%and therefore,demonstrate quasi-homogeneous catalytic activity toward the rapid hydrolysis of both CWA,soman(GD)(t_(1/2)=5.0 min)and CWA simulant,methyl paraoxon(DMNP)(t_(1/2)=8.9 min).Meanwhile,due to the covalent nature of cross-linkages and the high flexibility of polymer strands,the membranes possess promising mechanical strength and toughness that can stand the impact of high gas pressures and show high permeation for both CO_(2)and O_(2),enabling their extended applications in the field of collective/personal protective materials with body comfort.

关键词： Molecular clusters Chemical warfare agents Catalysis Polymer nanocomposites Wearable devices

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Integrated analysis of changes in soil microbiota and metabolites following long-term fertilization in a subtropical maize-wheat agroecosystem

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Pedosphere 2023年第3期33卷 521-533页

作者： Guiru ZHAO Kaixian WU Tongxin AN Lu WEN Shuhui ZI zhiwei fan Feng ZHOU Chengren OUYANG Youqiong YANG Bozhi WU Michael AFULLEN Faculty of Agronomy and Biotechnology Yunnan Agricultural UniversityKunming 650201(China) Department of Resources and Environment Moutai InstituteRenhuai 564507(China) Soil and Fertilizer Station Puer 665000(China) College of Agronomy and Life Science Kunming UniversityKunming 650214(China) School of Architecture and the Built Environment Springfield Campus The University of WolverhamptonWolverhampton WV100JP(UK)

Although the application of inorganic fertilizer is a widespread agronomic practice used to boost soil productivity and crop yields,the effects on soil microbiome and the metabolic mechanisms involved in the high-yield response of crops to long-term fertilization remain poorly *** this study,combined metagenomic and metabolomic analyses were used to explore the mechanism of crop yield response to the 20-year application of nitrogen-phosphorus-potassium fertilizers in a subtropical agroecosystem in Southwest *** bacterial and fungal communities were monitored using16S r RNA(bacteria)and internal transcribed spacer 1(ITS1)full-length gene(fungi)amplicon sequencing technologies,and metabolites were detected using a liquid chromatograph mass *** results revealed that,in addition to providing nutrients,long-term fertilization shaped the compositions of bacteria and fungi to increase crop ***-term fertilization significantly increased the relative abundances of plant growth-promoting rhizobacteria and arbuscular mycorrhizal fungi and promoted the secretion of soil metabolites such as carbohydrates,organic acids,and organic nitrogen compounds,which were primarily enriched in amino acid metabolism *** increases in carbon and nitrogen sources and bioactive substances in soil promoted the increases in plant biomass and thereby maintained soil quality and production *** findings highlighted the importance of soil metabolites in maintaining soil productivity as well as crop yields,and suggested that regulating key metabolites could increase crop yields in agroecosystems.

关键词： carbohydrate crop yield metabolomics metagenomics organic acid organic nitrogen compound plant growth-promoting rhizobacteria soil fertility

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元坝气田雷口坡组古溶沟展布及其对气藏的控制

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石油实验地质 2014年第5期36卷 562-566页

作者：范志伟中国石化勘探南方分公司

在详细论述元坝气田雷口坡组古溶沟形成条件、识别方法及展布特征的基础上，重点剖析了古溶沟对储层、圈闭、流体及油气富集区的影响，提出有利的勘探目标区。剥蚀作用、早期断裂及湿热气候控制了古溶沟的形成；溶沟区具有残留地层薄、... 详细信息

在详细论述元坝气田雷口坡组古溶沟形成条件、识别方法及展布特征的基础上，重点剖析了古溶沟对储层、圈闭、流体及油气富集区的影响，提出有利的勘探目标区。剥蚀作用、早期断裂及湿热气候控制了古溶沟的形成；溶沟区具有残留地层薄、上覆地层增厚及潜流带发育等特征，地震剖面上可见“下凹”及“双向上超”等现象。工区内发育4个主要溶沟区，单条溶沟宽度一般在2～3 km，切割深度为30～60 m；岩溶残丘地层保存较全，储集空间发育，为有利目标区。

关键词：气藏古溶沟雷口坡组中三叠统元坝地区四川盆地

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近十年我国农民信息需求研究综述

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情报杂志 2012年第5期31卷 150-154页

作者：樊志伟西南大学计算机与信息科学学院信息管理系重庆400715

我国正处在农村信息化快速发展的时期,农民信息需求的满足程度是我国农村信息化发展的决定性评判标准。在调查统计近十年来国内外有关我国农民信息需求研究文献的基础上,从我国农民信息需求研究状况、研究热点两个方面,对我国农民信息... 详细信息

我国正处在农村信息化快速发展的时期,农民信息需求的满足程度是我国农村信息化发展的决定性评判标准。在调查统计近十年来国内外有关我国农民信息需求研究文献的基础上,从我国农民信息需求研究状况、研究热点两个方面,对我国农民信息需求状况调查、特征及影响因素等方面的研究进行了综述,并对我国农民信息需求研究的发展趋势进行了展望。

关键词：农民信息需求农民信息需求信息服务图书馆

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Native Expanding <i>Merremia boisiana</i>Is Not More Allelopathic than Its Non-Expanding Congener <i>M. vitifolia</i>in the Expanded Range in Hainan

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American Journal of Plant Sciences 2013年第4期4卷 774-779页

作者： Qiaoqiao Huang Yide Shen Xiaoxia Li zhiwei fan Mingguang Li Hanting Cheng Environment and Plant Protection Institute Chinese Academy of Tropical Agricultural Sciences Haikou China State Key Laboratory of Biocontrol School of Life Sciences Sun Yat-sen University Guangzhou China

Exotic invaders may possess novel biochemical weapons that native plants do not have, and these novel biochemical weapons may be more allelopathic than those from native plants to other native competitors. During range expansion, native species also encounter many new plant competitors. Thus, allelochemicals from native expanding species may also be more novel and allelopathic than those from non-expanding species to other plant competitors in the expanded range. We test this hypothesis using the native expanding Merremia boisiana and its non-expanding congener M. vitifolia in year 2012 inthe expanded range inHainan. In petridish bioassays, we found that aqueous extracts of M. boisiana leaves were often less inhibitory or more stimulatory to seed germination and seedling growth of five vegetable species than those of M. vitifolia leaves. In pot culture, we also found that aqueous leaf extracts of the two congeners could both inhibit the growth of a naturally co-occurring plant Paederia scanden, but their effects did not differ from each other. These results indicate that while allelopathy may contribute to the competitive ability of M. boisiana, it may not act as a novel weapon explaining its success in the expanded range in Hainan.

关键词： Allelopathy Expansion Invasion Merremia boisiana Native Expanding Species Novel Weapons

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