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| 1 | Oncogenic AURKA-enhanced N6-methyladenosine modification increases DROSHA mRNA stability to transactivate STC1 in breast cancer stem-like cells显示文摘RNase III DROSHA is upregulated in multiple cancers and contributes to tumor progression by hitherto unclear mechanisms.Here,we demonstrate that DROSHA interacts withβ-Catenin to transactivate STC1 in an RNA cleavage-independent manner,contributing to breast cancer stem-like cell(BCSC)properties.DROSHA mRNA stability is enhanced by N6-methyladenosine(m^(6)A)modification which is activated by AURKA in BCSCs.AURKA stabilizes METTL14 by inhibiting its ubiquitylation and degradation to promote DROSHA mRNA methylation.Moreover,binding of AURKA to DROSHA transcript further strengthens the binding of the m^(6)A reader IGF2BP2 to stabilize m^(6)A-modified DROSHA.In addition,wild-type DROSHA,but not an m^(6)A methylation-deficient mutant,enhances BCSC stemness maintenance,while inhibition of DROSHA m^(6)A modification attenuates BCSC traits.Our study unveils the AURKA-induced oncogenic m^(6)A modification as a key regulator of DROSHA in breast cancer and identifies a novel DROSHA transcriptional function in promoting the BCSC phenotype. | Fei Peng Jie Xu Bai Cui Qilan Liang Sai Zeng Bin He Hong Zou Manman Li Huan Zhao Yuting Meng Jin Chen Bing Liu Shasha Lv Peng Chu Fan An Zifeng Wang Junxiu Huang Yajing Zhan Yuwei Liao Jinxin Lu Lingzhi Xu Jin Zhang Zhaolin Su Zhiguang Li Fangjun Wang Eric W-FLam Quentin Liu | 2021 | Cell Research2021，31，3： | 9 |
| 2 | Host–guest materials with room temperature phosphorescence:Tunable emission color and thermal printing patterns显示文摘The research of purely organic materials with long afterglow has drawn more and more attention,especially for those with stimulus‐response characteristic.So far,this kind of material is really very scarce and their performance is not good enough.In this study,we successfully developed an efficient heatingresponsive room‐temperature phosphorescence material with phosphorescence efficiency and lifetime up to 13.4%and 2.08 s through the simple host–guest doping strategy.Further on,by introducing the additional energy acceptor of fluorescein with concentration‐dependent emission to construct ternary doping systems,the afterglow color was extended from blue to yellow.Accordingly,the multicolor thermal printings have been easily realized,showing the great practical application prospects. | Yunsheng Wang Jie Yang Yanxiang Gong Manman Fang Zhen Li Ben Zhong Tang | 2020 | SmartMat2020，1，1： | 8 |
| 3 | Microbial community structure and diversity in deep-sea hydrothermal vent sediments along the Eastern Lau Spreading Centre显示文摘The aim of this study is to investigate microbial structures and diversities in five active hydrothermal fields' sediments along the Eastern Lau Spreading Centre (ELSC) in the Lau Basin (southwest Pacific). Microbial communities were surveyed by denatured gradient gel electrophoresis (DGGE) and clone library analysis of 16S rRNA genes. The differences in microbial community structures among sediment samples from the five deep-sea hydrothermal sites were revealed by DGGE profiles. Cluster analysis of DGGE profiles separated the five hydrothermal samples into two groups. Four different 16S rRNA gene clone libraries, representing two selected hydrothermal samples (19-4TVG8 and 19-4TVG11), were constructed. Twenty-three and 32 phylotypes were identified from 166 and 160 bacterial clones respectively, including Proteobacteria, Bacteroidetes, Firmicutes, Nitrospirae and Planctomycetes. The phylum Proteobacteria is dominant in both bacterial libraries with a predominance of Gamma-Proteobacteria. A total of 31 and 25 phylotypes were obtained from 160 and 130 archaeal clones respectively, including Miscellaneous Crenarchaeotic Group, Marine Group Ⅰ and Ⅲ, Marine Benthic Group E, Terrestrial Hot Spring Crenarchaeota and Deep-sea Hydrothermal Vent Euryarchaeota. These results show a variety of clones related to those involved in sulfur cycling, suggesting that the cycling and utilization of sulfur compounds may extensively occur in the Lau Basin deep-sea hydrothermal ecosystem. | WEI Manman ZHANG Rubing WANG Yuguang JI Houguo ZHENG Jia CHEN Xinhua ZHOU Hongbo | 2013 | Acta Oceanologica Sinica2013，32，2： | 6 |
| 4 | Pharmacokinetics of H002, a novel S1PR_1 modulator, and its metabolites in rat blood using liquid chromatography–tandem mass spectrometry显示文摘A rapid and sensitive liquid chromatography–tandem mass spectrometry(LC–MS/MS) method was developed and validated for the simultaneous determination of H002 and its phosphorylated metabolite, H002-P and hydroxylated metabolite H002-M, in rat blood. H001, an analogue of H002, was used as the internal standard.Blood samples were prepared by simple protein precipitation. The analytes and internal standard were separated on a Zorbax SB-C18 column with a gradient mobile phase consisting of methanol and water containing 0.1% formic acid at a flow rate of 0.2 mL /min with an operating temperature of 20 1C. The detection was performed on a triple quadrupole tandem mass spectrometer with positive electrospray ionization in multiple-reaction monitoring mode.Linear detection responses were obtained from 0.2–100 ng/mL for H002 and H002-M, while 0.5–100 ng/mL for H002-P. The intra- and inter-day precision(RSD%) was within 11.76%, with the accuracy(RE%) ranging from –9.84% to 9.12%. The analytes were shown to be stable during sample storage, preparation and analytic procedures.The method was applied to determine the pharmacokinetics of H002 in rats, and a preliminary study showed that the pharmacokinetics of H002 correlated with its biological effect on peripheral blood lymphocytes. | Jiaqi Mi Manman Zhao Shu Yang Shuang Yang Jing Jin Xiaojian Wang Qiong Xiao Jinping Hu Yan Li | 2016 | Acta Pharmaceutica Sinica B2016，6，6： | 5 |
| 5 | Accumulation of carotenoids and expression of carotenoid biosynthesis genes in fruit flesh during fruit development in two Cucurbita maxima inbred lines显示文摘Mesocarp color is an important agronomic trait of Cucurbita maxima and is determined mainly by the contents and compositions of the carotenoids.The two inbred lines with significant differences in fruit flesh color were used in the study,the orange’312-1’and white’98-2’.Changes in seven carotenoid contents and compositions in the flesh of fruit produced by inbred lines’312-1’and’98-2’were analyzed during fruit development.The expression of eight key carotenoid biosynthesis genes in the fruit flesh were investigated during five fruit development stage in two inbred lines.As the flesh color intensified,the orange flesh color of’312-1’was determined mainly by the increased contents of lutein,β-carotene and zeaxanthin and the lack of carotenoid accumulation led to the formation of white flesh in’98-2’fruit.The expression of the LCY-e and CHYb genes was significantly stronger in’312-1’than in’98-2’,and their expression was strongly correlated with lutein andβ-carotene contents during fruit development.This study provides a deep understanding of the molecular mechanism of carotenoid biosynthesis in fruit flesh and provides a basis for additional studies on the highly refined improvement of squash quality. | Yusong Luo Chaojie Wang Manman Wang Yunli Wang Wenlong Xu Hongyu Han Zhichao Wang Yujuan Zhong Hexun Huang Shuping Qu | 2021 | Horticultural Plant Journal2021，7，6： | 3 |
| 6 | Mechanisms of traditional Chinese medicines in the treatment of allergic rhinitis using a network biology approach显示文摘Objective:To systematically explore the effect and mechanism of traditional Chinese herbs in the treatment of allergic rhinitis.Methods:Magnolia flower,xanthium fruit,astragalus root,paniculate cynanchum,scutellaria root,cicada molting,stephania root,small centipeda herb,and licorice root as traditional Chinese herbs are widely used to treat allergic rhinitis.With multiple database integration and entity grammar systems,a molecular interaction network of traditional Chinese herbs for treating allergic rhinitis was established.Bioinformatics approaches were adopted to integrate relevant data and biological information by multiple databases.Molecular interaction network of Chinese herbs for treating allergic rhinitis was constructed based on entity grammar systems model.The network was then used for elucidating the antiallergic rhinitis mechanism of the Chinese herbs on the molecular level.The subnetworks were also extracted to explicitly display the pathway and targets where effective components acted on.Results:Traditional Chinese herbs could influence various pathological aspects in allergic rhinitis including the production of pro-inflammatory substances,such as histamine and cytokine interleukin-4(IL-4),interleukin-13(IL-13),lowering immunoglobulin E(IgE)level or blocking antigen binding,altering the biological processes of IgE,modulating the balance of T helper(Th)or other cells by cell proliferation and differentiation,mediating cellecell signaling and second-messenger-mediated signaling,stabilizing the cell membrane,and affecting regulation of cellular defense response.Conclusion:The research theoretically confirms the mechanism of anti-allergic rhinitis by traditional Chinese herbs,provides important fundamental research information for treatment of allergic rhinitis,and may serve as a reference for new drug development and effective ingredients of compatibility. | Li Du Xiaotong Ye Manman Li Huihui Wang Baixia Zhang Rao Zheng Yun Wang | 2021 | Journal of Traditional Chinese Medical Sciences2021，8，1： | 3 |
| 7 | AFF3-DNA methylation interplay in maintaining the mono-allelic expression pattern of XIST in terminally differentiated cells显示文摘X chromosome inactivation and genomic imprinting are two classic epigenetic regulatory processes that cause mono-allelic gene expression.In female mammals,mono-allelic expression of the long non-coding RNA gene X-inactive specific transcript(XIST)is essential for initiation of X chromosome inactivation upon differentiation.We have previously demonstrated that the central factor of super elongation complex-like 3(SEC-L3),AFF3,is enriched at gamete differentially methylated regions(DMRs)of the imprinted loci and regulates the imprinted gene expression.Here,we found that AFF3 can also bind to the DMR downstream of the XIST promoter.Knockdown of AFF3 leads to de-repression of the inactive allele of X IST in terminally differentiated cells.In addition,the binding of AFF3 to the XIST DMR relies on DNA methylation and also regulates DNA methylation level at DMR region.However,the KAP1-H3K9 methylation machineries,which regulate the imprinted loci,might not play major roles in maintaining the mono-aUelic expression pattern of XIST in these cells.Thus,our results suggest that the differential mechanisms involved in the X IST DMR and gDMR regulation,which both require AFF3 and DNA methylation. | Yue Zhang Chao Wang Xiaoxu Liu Qian Yang Hongliang Ji Mengjun Yang Manman Xu Yunyan Zhou Wei Xie Zhuojuan Luo Chengqi Lin | 2019 | Journal of Molecular Cell Biology2019，11，9： | 3 |
| 8 | A review of systematic evaluation and improvement in the big data environment显示文摘The era of big data brings unprecedented opportunities and challenges to management research.As one of the important functions of management decision-making,evaluation has been given more functions and application space.Exploring the applicable evaluation methods in the big data environment has become an important subject of research.The purpose of this paper is to provide an overview and discussion of systematic evaluation and improvement in the big data environment.We first review the evaluation methods based on the main analytic techniques of big data such as data mining,statistical methods,optimization and simulation,and deep learning.Focused on the characteristics of big data(association feature,data loss,data noise,and visualization),the relevant evaluation methods are given.Furthermore,we explore the systematic improvement studies and application fields.Finally,we analyze the new application areas of evaluation methods and give the future directions of evaluation method research in a big data environment from six aspects.We hope our research could provide meaningful insights for subsequent research. | Feng YANG Manman WANG | 2020 | Frontiers of Engineering Management2020，7，1： | 3 |
| 9 | Level set-based isogeometric topology optimization for maximizing fundamental eigenfrequency显示文摘Maximizing the fundamental eigenfrequency is an efficient means for vibrating structures to avoid resonance and noises.In this study,we develop an isogeometric analysis(IGA)-based level set model for the fonnulation and solution of topology optimization in cases with maximum eigenfrequency.The proposed method is based on a combination of level set method and IGA technique,which uses the non-uniform rational B-spline(NURBS),description of geometry,to perfonn analysis.The same NURBS is used for geometry representation,but also for IGA-based dynamic analysis and parameterization of the level set surface,that is,the level set function.The method is applied to topology optimization problems of maximizing the fundamental eigenfrequency for a given amount of material.A modal track method,that monitors a single target eigenmode is employed to prevent the exchange of eigenmode order number in eigenfrequency optimization.The validity and efficiency of the proposed method are illustrated by benchmark examples. | Manman XU Shuting WANG Xianda XIE | 2019 | Frontiers of Mechanical Engineering2019，14，2： | 3 |
| 10 | Isogeometric topology optimization based on energy penalization for symmetric structure显示文摘We present an energy penalization method for isogeometric topology optimization using moving morphable components(ITO–MMC),propose an ITO–MMC with an additional bilateral or periodic symmetric constraint for symmetric structures,and then extend the proposed energy penalization method to an ITO–MMC with a symmetric constraint.The energy penalization method can solve the problems of numerical instability and convergence for the ITO–MMC and the ITO–MMC subjected to the structural symmetric constraint with asymmetric loads.Topology optimization problems of asymmetric,bilateral symmetric,and periodic symmetric structures are discussed to validate the effectiveness of the proposed energy penalization approach.Compared with the conventional ITO–MMC,the energy penalization method for the ITO–MMC can improve the convergence rate from 18.6%to 44.5%for the optimization of the asymmetric structure.For the ITO–MMC under a bilateral symmetric constraint,the proposed method can reduce the objective value by 5.6%and obtain a final optimized topology that has a clear boundary with decreased iterations.For the ITO–MMC under a periodic symmetric constraint,the proposed energy penalization method can dramatically reduce the number of iterations and obtain a speedup of more than 2. | Xianda XIE Shuting WANG Ming YE Zhaohui XIA Wei ZHAO Ning JIANG Manman XU | 2020 | Frontiers of Mechanical Engineering2020，15，1： | 3 |
| 11 | The initial attempt to reveal the emission processes of both mechanoluminescence and room temperature phosphorescence with the aid of circular dichroism in solid state显示文摘A phenothiazine derivative PtzChol containing non-conjugated chiral cholesterol group was designed and synthesized. By analyzing the single crystal structure of PtzChol carefully, coupled with the circular dichroism(CD) signals before and after grinding, it was found that the introduction of cholesterol produced a positive effect on the production of chiral space group, on mechanoluminescence(ML) and room temperature phosphorescence(RTP), and throughout the entire light-emitting process, the CD signal could well reflect the changes of molecular arrangement. | Yu Tian Xuekang Yang Yanbin Gong Yunsheng Wang Manman Fang Jie Yang Zhiyong Tang Zhen Li | 2021 | Science China Chemistry2021，64，3： | 2 |
| 12 | Experimental and theoretical studies on the removal mechanism of formaldehyde from water by mesoporous calcium silicate显示文摘Most porous materials with high specific surface area and diverse internal structures possess good adsorption ability.In this work,a tremella-like mesoporous calcium silicate hydrate(CSH)with high adsorption capacity was successfully prepared via a facile hydrothermal method.The adsorption effect and adsorption mechanism of the as-prepared calcium silicate hydrate(APCSH)towards formaldehyde from water were investigated systematically.Results indicate that AP-CSH has high Ca/Si ratio(1.95),large specific surface area(122.83 m2 g-1)and exhibits excellent adsorption capacity.The results of batch adsorption experiments show that AP-CSH can remove formaldehyde from water rapidly and effectively with the maximum removal efficiency of 98.94%.The adsorption process agrees well with the pseudo-second-order and Freundlich isotherm model.Furthermore,regeneration can be achieved by simply immersing AP-CSH in absolute ethanol and the removal efficiency can still reach about 99.50%after five cycles.The adsorption mechanism was also studied by experimental analyses and molecular dynamics simulation.Both experimental results and theoretical simulation support that formaldehyde adsorption over AP-CSH belongs to chemical adsorption. | WANG ManMan FAN BaoMin WEN BianYing JIANG Chao | 2020 | Science China(Technological Sciences)2020，63，10： | 1 |
| 13 | Actin-depolymerizing factor of sec- ond-generation merozoite in Eimeria tenella : clone, pro- karyotic expression and dlclazuril-induced mRNA ex- pression显示文摘 | Bianhua Zhou Hongwei Wang Feiqun Xue Xiaoyang Wang Fengkun Yang Manman Ban Ruixiang Xin Congcong Wang | 2010 | Parasitology Research2010，，106： | 1 |
| 14 | Genipin improves lipid metabolism and sperm parameters in obese mice via regulation of miR-132 expression显示文摘Obesity has now surpassed malnutrition and infectious diseases as the most significant contributor to health problems worldwide.In particular,obesity is associated with several metabolic disorders,including hyperlipidemia,hepatic steatosis,and subfertility.Genipin(GNP),the aglycone of geniposide,is isolated from the extract of the traditional Chinese medicine Gardenia jasminoides Ellis and has been used in traditional oriental medicine against several inflammation-driven diseases.However,the effect and molecular mechanism of GNP on obesityassociated dyslipidemia and sperm dysfunction still need to be explored.In this study,we detect the effects of GNp on hyperlipidemia,hepatic lipid accumulation and sperm function using a high-fat diet(HFD)-induced obese mouse model.We find that obese mice treated with GNP show an improvement in body weight,serum triglyceride levels,serum hormone levels,serum inflammatory cytokines,hepatic steatosis and sperm function.At the molecular level,HFD/GNP diversely regulates the expression of miR-132 in a tissue-specific manner.miR-132 further targets and regulates the expression of SREBP-1c in liver cells,as well as the expressions of SREBP-1c and StAR in Leydig cells in the testis,thus modifying lipogenesis and steroidogenesis,respectively.Collectively,our data demonstrate that GNP shows a broad effect on the improvement of HFD-induced metabolic disorder and sperm dysfunction in male mice by tissue-specific regulation of miR-132.Our findings reveal the function GNP in ameliorating hepatic lipid metabolism and sperm function and suggest that this compound is a versatile drug to treat metabolic disorders. | Li Wangi Ge Chen Shuyao Wu YihuaXul Chenxi Guo Manman Wang Tingming Liang Zhigang Guo Hong-Jie Di Zhigang Hu | 2022 | Acta Biochimica et Biophysica Sinica2022，54，9： | 1 |
| 15 | A Tremella-like Mesoporous Calcium Silicate Loaded by TiO_(2) with Robust Adsorption and Photocatalytic Degradation Capabilities显示文摘A titanium dioxide loaded tremella-like mesoporous calcium silicate hydrate(TiO_(2)@CSH)with both adsorption and photocatalytic degradation activity was successfully prepared by a hydrothermal method combined with sol-gel strategy in two steps in this work.Tremella-shaped CSH provides abundant active sites for accommodating of TiO_(2),thus the corresponding TiO_(2)@CSH achieved a high loading ratio of 36.73%.Such a special shaped TiO_(2)@CSH exhibits excellent pre-enrichment capacity and photocatalytic degradation capacity for organic pollutants.Bisphenol A(BPA)removal experiments show that TiO_(2)@CSH can remove 91.17%of BPA from aqueous solutions.Studies on removal mechanism suggest that BPA tends to bind on the interface between CSH and TiO_(2) and the pre-enrichment process conforms to the intraparticle diffusion model;and then,it is decomposed to harmless substances of CO_(2) and H_(2)O during the photocatalytic process.The experimental results show that loading functional nanoparticles such as TiO_(2) on the surface of inorganic porous materials can endow inert porous materials with new functions such as photocatalytic degradation,which effectively expands the application range of inorganic porous materials. | 姜超 温变英 樊保民 WANG Manman | 2022 | Journal of Wuhan University of Technology(Materials Science)2022，37，2： | 1 |
| 16 | A Highly Efficient and Selective Water-Soluble Bimetallic Catalyst for Hydrogenation of Chloronitrobenzene to Chloroaniline显示文摘Selective hydrogenation of chloronitrobenzene(CNB) to chloroaniline(CAN) catalyzed by water-soluble Ru/Pt bimetallic catalyst in an aqueous-organic biphasic system was studied. It was found that the catalytic activity increased obviously due to the addition of platinum. Ru/Pt bimetallic catalysts exhibited a strong synergistic effect when the molar ratio of Pt was in the range of 5%—80%. Under the mild conditions including a temperature of 25 ℃, a hydrogen pressure of 1.0 MPa and a Pt molar ratio of 20%, the conversion of p-chloronitrobenzene(p-CNB) reached 99.9%, with the selectivity to p-chloroaniline(p-CAN) equating to 99.4%. The Ru/Pt catalyst also showed high activity and selectivity for the hydrogenation of other chloro- and dichloro-nitrobenzenes with different substituted positions. In addition, the catalyst can be recycled five times without significant loss of activity. | Zhou Yafen Yang Wenjuan Zhou Limei Wang Manman Ma Xiaoyan | 2015 | China Petroleum Processing & Petrochemical Technology2015，17，2： | 1 |
| 17 | In situ fabrication of Na3V2(PO4)3 quantum dots in hard carbon nanosheets by using lignocelluloses for sodium ion batteries显示文摘The rational assembly of quantum dots on two-dimensional(2 D) carbonaceous materials is very promising to produce materials, but remains a challenge. Here, we develop an assembly strategy of growing Na3 V2(PO4)3 quantum dots with superlattice structure(NVP-QDs-SL) for obtaining precise control of the size, distribution and crystallinity. The multifunctional lignocelluloses(LCs) used as a hard carbon source induce heterogeneous nucleation and confined growth of NVP-QDs-SL, leading to the uniform distribution of NVP-QDs-SL in H/S-doped hard carbon ultra-thin nanosheets(HCS). Detailed electrochemical analysis results from sodium-ion batteries of NVP-QDs-SL show that NVP-QDs-SL could trap the electrons inside HCS, significantly enhancing Na ion storage and transfer kinetics. Compared to the common Na3 V2(PO4)3 nanoparticle cathode, the NVP-QDs-SL/HCS cathode exhibits a high reversible capacity of 149.2 m A h g^-1 at a 0.1 C rate, which is far beyond the theoretical capacity of Na3 V2(PO4)3(117.6 m A h g^-1).At the ultrahigh current rate of 100 C, this cathode still remains a high discharge capacity of 40 m A h g-1.Even after cycling at 20 C over 3000 cycles, an ultrahigh coulombic efficiency close to 100% is still obtained,highlighting its excellent long cycling life, remarkable rate performance and energy density. | Qihao Zhang Xudong Zhang Wen He Guogang Xu Manman Ren Jinhua Liu Xuena Yang Feng Wang | 2019 | Journal of Materials Science & Technology2019，35，10： | 1 |
| 18 | Altering membrane structure to enhance water permeability and performance of anion exchange membrane fuel cell显示文摘Water management has been proven significant for enhancing both performance and durability of anion exchange membrane fuel cell. Besides searching new material, decreasing membrane thickness and modifying operation parameters, a simple and universal method of altering membrane structure is proposed in this work. Composite membranes made by unique processing method that includes both casting and electrospinning processes were compared with traditional casting membrane, all with the same thickness of 40 μm. Comparing to traditional casting membrane, the composite membrane put at proper position shows a higher water permeability, thus even more than 50% enhancement of the peak performance. | YANG Yue GAO XueQiang SONG Wei YU HongMei LI WenBin QI ManMan HUANG He WANG PengHao FAN ZhiXuan SHAO ZhiGang | 2021 | Science China(Technological Sciences)2021，64，2： | 1 |
| 19 | Tea Polyphenols Reducing Lipopolysaccharide-induced Inflammatory Responses in RAW264.7 Macrophages via NF-κB Pathway显示文摘The anti-inflammatory activity of tea polyphenols(TPs)in RAW264.7 macrophages stimulated by lipopolysaccharide(LPS)was investigated in this paper.RAW264.7 macrophages were treated with different concentrations of TP(0,12.5,25,50,100,and 200μg/mL)and then stimulated by LPS.Another blank control group was set up.The expression of pro-inflammatory cytokines associated with the nuclear factor-kappa B(NF-κB)signaling pathway was investigated before and after TP treatment.Pretreatment of RAW264.7 cells with TP decreased the expression of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin 1 beta(IL-1β)pro-inflammatory cytokines.In addition,TP inhibited the phosphorylation of p65 and IκB by blocking the phosphorylation and the degradation of NF-κB inhibitor protein.In conclusion,TP exerts anti-inflammatory effects by regulating the release of inflammatory mediators via the NF-κB signaling pathway. | SU Siyi LI Xiaoyu GUO Xu ZHOU Ruiming LI Manman MING Pengfei HUANG Yingying Sajid Ur RAHMAN DING Hongyan FENG Shibin LI Jinchun WANG Xichun LI Yu WU linjie | 2019 | Chemical Research in Chinese Universities2019，35，6： | 1 |
| 20 | The ubiquitin ligase Pelil inhibits ICOS and thereby Tfh-mediated immunity显示文摘T follicular helper(Tfh)cells are crucial for regulating autoimmune inflammation and protective immunity against viral infection.However,the molecular mechanism controlling Tfh cell differentiation is poorly understood.Here,through two mixed bone marrow chimeric experiments,we identified Peli1,a T cell-enriched E3 ubiquitin ligase,as an intrinsic regulator that inhibits Tfh cell differentiation.Peli1 deficiency significantly promoted c-Rel-mediated inducible T-cell costimulator(ICOS)expression,and PELI1 mRNA expression was negatively associated with ICOS expression on human CD4^(+)T cells.Mechanistically,increased ICOS expression on Peli1-KO CD4^(+)T cells enhanced the activation of PI3K-AKT signaling and thus suppressed the expression of Klf2,a transcription factor that inhibits Tfh differentiation.Therefore,reconstitution of Klf2 abolished the differences in Tfh differentiation and germinal center reaction between WT and Peli1-KO cells.As a consequence,Peli1-deficient CD4^(+)T cells promoted lupus-like autoimmunity but protected against H1N1 influenza virus infection in mouse models.Collectively,our findings established Peli1 as a critical negative regulator of Tfh differentiation and indicated that targeting Peli1 may have beneficial therapeutic effects in Tfhrelated autoimmunity or infectious diseases. | Xinfang Huang Shumeng Hao Junli Liu Yuanyuan Huang Manman Liu Chunyuan Xiao Yan Wang Siyu Pei Tao Yu Jing Xu Haikun Wang Dongfang Dai Xiao Su Yichuan Xiao | 2021 | Cellular & Molecular Immunology2021，18，4： | 1 |
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