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19篇 您的检索式:作者名="Manyu Wang"
    题名 作者 年代 出处 被引量
1Behaviors of Leucine and Isoleucine in Ion Mobility- Quadrupole Time of Flight Mass Spectrometry显示文摘在这研究,离子活动性分离结合了双人脚踏车团 spectrometry (IM 双人脚踏车 MS ) 被利用包括白氨酸和异白氨酸调查二氨基酸的电离行为。在 electrospray 电离(ESI ) 下面模式,在各分子的 sturcture 的二个 protonation 地点引起了 protomer 的二种形式。一个人产生了从氨基从 carboxyl 的 protonated (amino-protomer ) 和其它正在是 protonated (carboxyl-protomer ) 。在里面二维(飘移时间, m/z ) 光谱, protomers 有一样的团,而是可区分的飘移时间和破碎模式。为描述目的, protomers 的理论碰撞十字节(CCS ) 价值被计算并且证明与一致试验性。而且,在氨基酸之间的确定的关系和他们的 protomers 被评估。它证明 carboxyl-protomer 是的许多与氨基酸的集中成正比,而 amino-protomer 的没有一样的趋势。在气压化学药品电离(APCI ) 下面模式,仅仅 carboxyl-protomer 被观察。另外, amino-protomer 和在 ESI 下面观察的簇离子完全是不在的。结果证明电离模式不仅在 therir protomers 的形式上而且在确定的关系上重重地影响白氨酸和异白氨酸的电离行为。Su Guo Fang Zhang Haoyang Wang Manyu Zhang Zhixu Zhang Xiang Zhang Yinlong Guo 2015Chinese Journal of Chemistry2015,33,12:4
2The crystal structure of Ac-AChBP in complex with α-conotoxin LvlA reveals the mechanism of its selectivity towards different nAChR subtypes显示文摘3* nAChRs,被认为为象疼痛那样的问题正在答应药目标,嗜好,心血管的功能,认知混乱等等,在整个中央、外部的神经系统被发现。-conotoxin (-CTx) LvIA 作为迄今为止知道的 32 nAChRs 的最选择的禁止者被识别了,并且它能把 32 nAChR 子类型与 6/323 和 34 种 nAChR 子类型区分开来。然而,它向 32 的选择的机制, 6/323,和 34 nAChRs 留下逃犯。这里,我们在 3.4 的一个决定与 Aplysia californica 醋胆素绑定蛋白质(Ac-AChBP ) 在建筑群报导 LvIA 的合作水晶结构 ? 。基于这建筑群的结构,和基于另外的 nAChR 子类型和有约束力的亲密关系试金当模特儿的相同,我们断定 LvIA 的 Asp-11 在选择起一个重要作用向 32 的 LvIA 和由做盐的 3/623 nAChRs 与老鼠的 Lys-155 衔接 3 子单元。在被老鼠的 Met-36, Thr-59,和 Phe-119 形成的一个恐水病的衣袋以内的 Asn-9 谎言在 32 nAChR 模型的 2 子单元,向 32 nAChR 子类型为它的更多的有势力选择揭示原因。这些结果提供能被用来设计 ligands 的分子的卓见有选择地指向 32 nAChRs,与为新治疗学的 -CTxs 的设计的重要含意。Manyu Xu Xiaopeng Zhu Jinfang Yu Jinpeng Yu Sulan Luo Xinquan Wang 2017Protein & Cell2017,8,9:3
3Response of daily stem radial growth of Platycladus onentahs toenvironmental factors in a semi-arid area of North China显示文摘JIANG Yuan WANG Bingqin DONG Manyu 2015Trees2015,29,1:1
4Catalytic transfer hydrogenolysis of C–O bonds in lignin model compounds without arene hydrogenation显示文摘The shortage of resources and the destruction of the environment have caused serious resource and environmental problems shared by all countries around the world. As a ubiquitous renewable resource, biomass has great prospects for replacing fossil energy and attracted attention from the society. The use of catalytic approach to transform biomass into high-value chemicals is an effective way to use biomass efficiently. In this work, Nisupported catalysts has been developed for the selective cleavage of C–O bonds in lignin model compounds with 2-propanol as the hydrogen source solvent. Among these catalysts, it was indicated that zirconium phosphate(Zr P)-supported Ni catalysts were highly efficient and recyclable for alkyl-aryl ether(α-O-4 and β-O-4) cleavage in lignin model compounds. The further investigation demonstrated that the transfer hydrogenolysis of the C–O bond is highly selective, which afforded phenols and aromatics as dominant products without the products arising from hydrogenation of aromatic rings. Through a series of characterization of the catalyst, it was demonstrated that the medium strong acid sites of the Zr P support promoted the cleavage of alkyl-aryl ethers(α-O-4 and β-O-4),and Br?nsted acid sites favored for achieving high selectivity toward C–O bond cleavage. Additionally, Ni(0) sites on the Zr P catalysts were responsible for the catalytic transfer hydrogenolysis.Kai Cui Xiuge Zhao Qingpo Peng Honghui Gong Xinjia Wei Jiajia Wang Manyu Chen Zhenshan Hou 2022Green Chemical Engineering2022,3,1:1
5Numerical modelling of MOV with Voronoi network and finite element method显示文摘The electrical and thermal characteristics of metal oxide varistor(MOV)are essential for the study of MOV performance and degradation.This paper provides a modelling method of MOV to simulate its microstructure geometry with the Voronoi network and derive the electrical functions on the grain boundaries.A series of discrete data to describe the resistance-voltage(R-V)characteristics of MOV from experiments is applied to the pro-posed model.Through 8/20μs surge current experiments,the electrical conductivity of MOV is determined to achieve the simulation of the clamping voltage.With this model,the current distribution and temperature distribution over a MOV sample are simulated and analysed by the finite element method(FEM).The simulation results show good agreement with the experimental measurement and inherent feature of MOV.Qibin Zhou Hongxiang Yang Xin Huang Manyu Wang Xin Ren 2021High Voltage2021,6,4:1
6The effect of LyPRP/collagen composite hydrogel on osteogenic differentiation of rBMSCs显示文摘Although platelet-rich plasma(PRP)plays a significant role in the orthopedic clinical application,it still faces two major problems,namely,uncontrollable factors release,frequent preparation and extraction processes as well as the inconvenient form of usage.To overcome these shortcomings,freeze-dried PRP(LyPRP)was encapsulated into bioactive Col I hydrogel to induce osteogenic dif-ferentiation of rabbit bone marrow mesenchymal stem cells(rBMSCs).And PRP/Col I composite hydrogel was prepared as a control.Compared with Col I hydrogel,the introduction of platelets significantly improved the mechanical properties of hydrogels.Meanwhile,platelets were evenly distributed in the composite hydrogels network.The sustainable release of related factors in the composite hydrogels could last for more than 14days to maintain its long-term biological activity.Further cell experiments confirmed that PRP and LyPRP could effectively alleviate the contraction of collagen hydrogel in vitro,and promote the adhesion,proliferation and osteogenesis differentia-tion of rBMSCs.The results of osteogenic gene expression indicated that the 10%LyPRP/Col I composite hydrogel could facilitate the early expression of BMP-2 and late osteogenic associated protein formation with higher expression of alkaline phosphatase and Osteocalcin(OCN).These results might provide new insights for the clinical application of 10%LyPRP/Col I composite hydro-gel as practical bone repair injection.Manyu Chen Quanying Liu Yang Xu Yuxiang Wang Xiaowen Han Zhe Wang Jie Liang Yong Sun Yujiang Fan Xingdong Zhang 2021Regenerative Biomaterials2021,8,1:1
7Targeting fibrosis: mechanisms and clinical trials显示文摘Fibrosis is characterized by the excessive extracellular matrix deposition due to dysregulated wound and connective tissue repair response.Multiple organs can develop fibrosis,including the liver,kidney,heart,and lung.Fibrosis such as liver cirrhosis,idiopathic pulmonary fibrosis,and cystic fibrosis caused substantial disease burden.Persistent abnormal activation of myofibroblasts mediated by various signals,such as transforming growth factor,platelet-derived growth factor,and fibroblast growh factor,has been recongized as a major event in the occurrence and progression of fibrosis.Although the mechanisms driving organ-specific fibrosis have not been fully elucidated,drugs targeting these identified aberrant signals have achieved potent anti-fibrotic efficacy in clinical trials.In this review,we briefly introduce the aetiology and epidemiology of several fibrosis diseases,including liver fibrosis,kidney fibrosis,cardiac fibrosis,and pulmonary fibrosis.Then,we summarise the abnormal cells(epithelial cells,endothelial cells,immune cells,and fibroblasts)and their interactions in fibrosis.In addition,we also focus on the aberrant signaling pathways and therapeutic targets that regulate myofibroblast activation,extracellular matrix cross-linking,metabolism,and inflammation in fibrosis.Finally,we discuss the anti-fibrotic drugs based on their targets and clinical trials.This review provides reference for further research on fibrosis mechanism,drug development,and clinical trials.Manyu Zhao Liqun Wang Mengzhu Wang Shijie Zhou Ying Lu Huijie Cui Alexandra C.Racanelli Ling Zhang Tinghong Ye Bisen Ding Ben Zhang Jinliang Yang Yuqin Yao 2022Signal Transduction and Targeted Therapy2022,7,7:1
8Response of daily stem radial growth of Platycladus orientalis to environ- mental factors in a semi-add area of North China 显示文摘JIANG Yuan WANG Bingqin Dong Manyu 2015Trees2015,29,:1
9Perceptual Gradient Similarity Deviation for Full Reference Image Quality Assessment显示文摘Perceptual image quality assessment(IQA)is one of the most indispensable yet challenging problems in image processing and computer vision.It is quite necessary to develop automatic and efficient approaches that can accurately predict perceptual image quality consistently with human subjective evaluation.To further improve the prediction accuracy for the distortion of color images,in this paper,we propose a novel effective and efficient IQA model,called perceptual gradient similarity deviation(PGSD).Based on the gradient magnitude similarity,we proposed a gradient direction selection method to automatically determine the pixel-wise perceptual gradient.The luminance and chrominance channels are both took into account to characterize the quality degradation caused by intensity and color distortions.Finally,a multi-scale strategy is utilized and pooled with different weights to incorporate image details at different resolutions.Experimental results on LIVE,CSIQ and TID2013 databases demonstrate the superior performances of the proposed algorithm.Manyu Jin Tao Wang Zexuan Ji Xiaobo Shen 2018Computers, Materials & Continua2018,,9:1
10Maternal genetic structure of a neolithic population of the Yangshao culture显示文摘The Yangshao culture is one of the most influential Neolithic cultures in East Asia.The populations associated with the Yangshao culture were widely distributed along the Yellow River basin and were suggested to play a profound role in the present-day East Asians.To date,the population of the Yangshao culture is largely investigated through archaeological studies.Bo Miao Yichen Liu Wanfa Gu Qingli Wei Qian Wu Wenjun Wang Ming Zhang Manyu Ding Tianyi Wang Juncen Liu Feng Liu Peng Cao Qingyan Dai Ruowei Yang Xiaotian Feng Wanjing Ping Weihong Hou Haibing Yuan Qiaomei Fu 2021Journal of Genetics and Genomics2021,48,8:0
11Design,application and verification of a novel system utilizing bacteria and microalgae to treat swine farm wastewater and produce value-added biomass显示文摘Swine farm wastewater is extremely harmful to the environment if not treated before it is discharged.In this study,a system was developed and optimized for testing the high levels of organic matter in swine farm wastewater utilizing a microalgae/bacteria co-culture combined with a novel closed-loop extraction and dilution process.Importantly,the system produces biomass that also could be harvested and used in value-added applications.The efficacy of biomass as a biofertilizer was demonstrated by using a model plant of Arabidopsis.In addition,the analysis of biomass indicates that it also has potential as a source for biofuel.After a 20-d cultivation period,a yield of biomass was achieved to 2.063 g/L of wastewater.The highest removal rates recorded in steady state conditions were:13.8 mg/L·d of Total Nitrogen(TN);11.5 mg/L·d of Ammonia Nitrogen(NH_(4)^(+)-N);24.8 mg/L·d of Chemical Oxygen Demand(COD);and 16.9 mg/L·d of Total Phosphorus(TP).After cultivation,the composition of the biomass was analyzed on a dry basis;the major components were protein(44.9%),lipids(24.6%),carbohydrates(19.9%),Chlorophyll-A(2.75%),Chlorophyll-B(1.66%),and carotenoids(0.57%).This biomass was diluted with water(5%by weight)and used as a biofertilizer to grow Arabidopsis.The results showed that the average root and stem lengths of Arabidopsis were 43.0%and 55.0%longer compared to those of the control group.Additionally,the number of leaves and the maximum leaf length increased by 30.2%and 39.7%;and the fresh and dry leaf weights increased by 44.0%and 33.7%,respectively.These results demonstrate the efficacy of this system for treating swine farm wastewater whilst simultaneously producing a value-added microalgae/bacteria biomass.This paper also demonstrated the use of biomass as a fertilizer for cultivating a value-added crop and,based on the compositional analyses,propose that the biomass could be used as a raw material for biofuel production due to its high lipid content of 24.6%.By constructing a microalgae/bacteria symbiosis system,Swine farm wastewater can be treated as resources utilizing producing value-added biomass with demonstrated efficacy as a biofertilizer.Xin Zhen Yali Li Jingwen Qiang Manyu Tang Wei Hua Wanqing Wang Shuang Wu Phil Perkins Roger Ruan Yanling Cheng 2023International Journal of Agricultural and Biological Engineering2023,16,4:0
12Effects of manufactured nanomaterials on algae:Implications and applications显示文摘The wide application of manufactured nanomaterials(MNMs)has resulted in the inevitable release of MNMs into the aquatic environment along their life cycle.As the primary producer in aquatic ecosystems,algae play a critical role in maintaining the balance of ecosystems’energy flow,material circulation and information transmission.Thus,thoroughly understanding the biological effects of MNMs on algae as well as the underlying mechanisms is of vital importance.We conducted a comprehensive review on both positive and negative effects of MNMs on algae and thoroughly discussed the underlying mechanisms.In general,exposure to MNMs may adversely affect algae’s gene expression,metabolites,photosynthesis,nitrogen fixation and growth rate.The major mechanisms of MNMs-induced inhibition are attributed to oxidative stress,mechanical damages,released metal ions and light-shielding effects.Meanwhile,the rational application of MNMs-algae interactions would promote valuable bioactive substances production as well as control biological and chemical pollutants.Our review could provide a better understanding of the biological effects of MNMs on algae and narrow the knowledge gaps on the underlying mechanisms.It would shed light on the investigation of environmental implications and applications of MNMs-algae interactions and meet the increasing demand for sustainable nanotechnology development.Yuxiong Huang Manyu Gao Wenjing Wang Ziyi Liu Wei Qian Ciara Chun Chen Xiaoshan Zhu Zhonghua Cai 2022Frontiers of Environmental Science & Engineering2022,16,9:0
13Growth differentiation factor 11 promotes macrophage polarization towards M2 to attenuate myocardial infarction via inhibiting Notch1 signaling pathway显示文摘Background:Myocardial infarctions(MI)is a major threat to human health especially in people exposed to cold environment.The polarization of macrophages towards different functional phenotypes(M1 macrophages and M2 macrophages)is closely related to MI repairment.The growth differentiation factor 11(GDF11)has been reported to play a momentous role in inflammatory associated diseases.In this study,we examined the regulatory role of GDF11 in macrophage polarization and elucidated the underlying mechanisms in MI.Methods:In vivo,the mice model of MI was induced by permanent ligation of the left anterior descending coronary artery(LAD),and mice were randomly divided into the sham group,MI group,and MI+GDF11 group.The protective effect of GDF11 on myocardial infarction and its effect on macrophage polarization were verified by echocardiography,triphenyl tetrazolium chloride staining and immunofluorescence staining of heart tissue.In vitro,based on the RAW264.7 cell line,the effect of GDF11 in promoting macrophage polarization toward the M2 type by inhibiting the Notch1 Signaling pathway was validated by qRT-PCR,Western blot,and flow cytometry.Results:We found that GDF11 was significantly downregulated in the cardiac tissue of MI mice.And GDF11 supplementation can improve the cardiac function.Moreover,GDF11 could reduce the proportion of M1 macrophages and increase the accumulation of M2 macrophages in the heart tissue of MI mice.Furthermore,the cardioprotective effect of GDF11 on MI mice was weakened after macrophage clearance.At the cellular level,application of GDF11 could inhibit the expression of M1 macrophage(classically activated macrophage)markers iNOS,interleukin(IL)-1β,and IL-6 in a dose-dependent manner.In contrast,GDF11 significantly increased the level of M2 macrophage markers including IL-10,CD206,arginase 1(Arg1),and vascular endothelial growth factor(VEGF).Interestingly,GDF11 could promote M1 macrophages polarizing to M2 macrophages.At the molecular level,GDF11 significantly down-regulated the Notch1 signaling pathway,the activation of which has been demonstrated to promote M1 polarization in macrophages.Conclusions:GDF11 promoted macrophage polarization towards M2 to attenuate myocardial infarction via inhibiting Notch1 signaling pathway.Manyu Gong Xuewen Yang Yaqi Wang Yanying Wang Dongping Liu Haodong Li Yunmeng Qu Xiyang Zhang Yanwei Zhang Han Sun Lei Jiao Ying Zhang 2023Frigid Zone Medicine2023,3,1:0
14Long non-coding RNA-AK138945 regulates myocardial ischemia-reperfusion injury via the miR-1-GRP94 signaling pathway显示文摘Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)regulate MIRI through multiple mechanisms.This study explored the regulatory effect of lncRNA-AK138945 on myocardial ischemia-reperfusion injury and its mechanism.Methods:In vivo,8-to 12-weeks-old C57BL/6 male mice underwent ligation of the left anterior descending coronary artery for 50 minutes followed by reperfusion for 48 hours.In vitro,the primary cultured neonatal mouse ventricular cardiomyocytes(NMVCs)were treated with 100μmol/L hydrogen peroxide(H_(2)O_(2)).The knockdown of lncRNA-AK138945 was evaluated to detect cardiomyocyte apoptosis,and a glucose-regulated,endoplasmic reticulum stress-related protein 94(GRP94)inhibitor was used to detect myocardial injury.Results:We found that the expression level of lncRNA-AK138945 was reduced in MIRI mouse heart tissue and H2O2-treated cardiomyocytes.Moreover,the proportion of apoptosis in cardiomyocytes increased after lncRNA-AK138945 was silenced.The expression level of Bcl2 protein was decreased,and the expression level of Bad,Caspase 9 and Caspase 3 protein was increased.Our further study found that miR-1a-3p is a direct target of lncRNA-AK138945,after lncRNA-AK138945 was silenced in cardiomyocytes,the expression level of miR-1a-3p was increased while the expression level of its downstream protein GRP94 was decreased.Interestingly,treatment with a GRP94 inhibitor(PU-WS13)intensified H2O2-induced cardiomyocyte apoptosis.After overexpression of FOXO3,the expression levels of lncRNA-AK138945 and GRP94 were increased,while the expression levels of miR-1a-3p were decreased.Conclusion:LncRNA-AK138945 inhibits GRP94 expression by regulating miR-1a-3p,leading to cardiomyocyte apoptosis.The transcription factor Forkhead Box Protein O3(FOXO3)participates in cardiomyocyte apoptosis induced by endoplasmic reticulum stress through up-regulation of lncRNA-AK138945.Yanying Wang Jian Huang Han Sun Jie Liu Yingchun Shao Manyu Gong Xuewen Yang Dongping Liu Zhuo Wang Haodong Li Yanwei Zhang Xiyang Zhang Zhiyuan Du Xiaoping Leng Lei Jiao Ying Zhang 2024Frigid Zone Medicine2024,4,1:0
15A pH Sensitive Fluorescence Probe Based on Tricarbocyanine显示文摘Medical imaging technologies consist of X-ray imagingtechnology, computed tomography(CT), positron emissioncomputed tomography(PET), ultrasound imaging(USG), mag-netic resonance imaging(MRI) and optical imaging(OI)ill. Theyplay an increasingly important role in diagnosis of disease anddrag research.YAN Luomei ZHOU Hua WU Cunqi WANG Lidan YANG Wei JIN Manyu ZHAO Yongxia XU Jingwei 2016Chemical Research in Chinese Universities2016,32,6:0
16Vinous-throated parrotbills breed in invasive smooth cordgrass habitat:Can native birds avoid the potential ecological trap?显示文摘Native animals are facing long-term coexistence with invasive plants worldwide,the impacts of which on animal behavior remain poorly known.Potential ecological traps could threaten native birds breeding in invasive plant habitats,but behavioral strategies for birds to avoid such risks are few concerned.The invasion of Smooth Cordgrass(Spartina alterniflra) has seriously varied the vegetation landscape in the coastal wetlands of eastern China,and affected the habitat selection of native birds.Here,we investigated the nesting and breeding characteristics of a common native passerine,the Vinous-throated Parrotbill(Sinosuthora webbiana),in habitats dominated by native Common Reed(Phragmites australis) and exotic cordgrass.We found that parrotbills could complete their breeding cycle in cordgrass habitat.Most nest failure was attributed to predation in native habitat but tide inundation in cordgrass habitat.However,the nest success rate and daily survival rate(DSR) in cordgrass habitat were higher.Moreover,nest height was markedly higher in cordgrass habitat and was the most important influencing variable(positively correlated with the DSR).These results suggest that cordgrass habitat is a potential ecological trap due to the tide inundation,but some parrotbills seem to effectively avoid this risk by increasing nest height.Our study reveals that a native passerine changes its nesting behavior to accommodate invasive plant habitat and highlights that habitat changes caused by invasive plants may drive the adaptive evolution of native animal behavior.The limitation of these results must be acknowledged for the small sample size,and there is a need for a larger sample and long-term data for further verification.Pan Chen Yanhong Chen Huimin Chen Taiyu Chen Bin Liu Manyu Zhang Silu Wang Changhu Lu 2023Avian Research2023,14,3:0
17Using nonparametric modeling approaches and remote sensing imagery to estimate ecological welfare forest biomass显示文摘The spatial distribution of forest biomass is closely related with carbon cycle, climate change, forest productivity, and biodiversity. Efficient quantification of biomass provides important information about forest quality and health. With the rising awareness of sustainable development, the ecological benefits of forest biomass attract more attention compared to traditional wood supply function. In this study, two nonparametric modeling approaches, random forest(RF) and support vector machine were adopted to estimate above ground biomass(AGB) using widely used Landsat imagery in the region,especially within the ecological forest of Fuyang District in Zhejiang Province, China. Correlation analysis was accomplished and model parameters were optimized during the modeling process. As a result, the best performance modeling method RF was implemented to produce an AGB estimation map. The predicted map of AGB in the study area showed obvious spatial variability and demonstrated that within the current ecological forest zone, as well as the protected areas, the average of AGB were higher than the ordinary forest. The quantification of AGB was proven to have a close relationship with the local forest policy and management pattern, which indicated that combining remote-sensing imagery and forest biophysical property would provide considerable guidance for making beneficial decisions.Chaofan Wu Hongxiang Tao Manyu Zhai Yi Lin Ke Wang Jinsong Deng Aihua Shen Muye Gan Jun Li Hong Yang 2018Journal of Forestry Research2018,29,1:0
18Scalable Core–Sheath Yarn for Boosting Solar Interfacial Desalination Through Engineering Controllable Water Supply显示文摘Tailoring water supply to achieve confined heating has proven to be an effective strategy for boosting solar interfacial evaporation rates.However,because of salt clogging during desalination,a critical point of constriction occurs when controlling the water rate for confined heating.In this study,we demonstrate a facile and scalable weaving technique for fabricating core-sheath photothermal yarns that facilitate controlled water supply for stable and efficient interracial solar desalination.The core-sheath yarn comprises modal fibers as the core and carbon fibers as the sheaths.Because of the core-sheath design,remarkable liquid pumping can be enabled in the carbon fiber bundle of the dispersed superhydrophilic modal fibers.Our woven fabrics absorb a high proportion(92%)of the electromagnetic radiation in the solar spectrum because of the weaving structure and the carbon fiber sheath.Under one-sun(1 kW·m^(-2))illumination,our woven fabric device can achieve the highest evaporation rate(of 2.12kg·m^(-2)·h^(-1) with energy conversion efficiency:93.7%)by regulating the number of core-sheath yarns.Practical application tests demonstrate that our device can maintain high and stable desalination performance in a 5 wt%NaCl solution.Xingfang Xiao Luqi Pan Tao Chen Manyu Wang Lipei Ren Bei Chen Yingao Wang Qian Zhang Weilin Xu 2023Engineering2023,,11:0
19Phosphorylation of PB2 at serine 181 restricts viral replication and virulence of the highly pathogenic H5N1 avian influenza virus in mice显示文摘Influenza A virus(IAV)continues to pose a pandemic threat to public health,resulting a high mortality rate annually and during pandemic years.Posttranslational modification of viral protein plays a substantial role in regulating IAV infection.Here,based on immunoprecipitation(IP)-based mass spectrometry(MS)and purified virus-coupled MS,a total of 89 phosphorylation sites distributed among 10 encoded viral proteins of IAV were identified,including 60 novel phosphorylation sites.Additionally,for the first time,we provide evidence that PB2 can also be acetylated at site K187.Notably,the PB2 S181 phosphorylation site was consistently identified in both IP-based MS and purified virus-based MS.Both S181 and K187 are exposed on the surface of the PB2 protein and are highly conserved in various IAV strains,suggesting their fundamental importance in the IAV life cycle.Bioinformatic analysis results demonstrated that S181E/A and K187Q/R mimic mutations do not significantly alter the PB2 protein structure.While continuous phosphorylation mimicked by the PB2 S181E mutation substantially decreases viral fitness in mice,PB2 K187Q mimetic acetylation slightly enhances viral virulence in mice.Mechanistically,PB2 S181E substantially impairs viral polymerase activity and viral replication,remarkably dampens protein stability and nuclear accumulation of PB2,and significantly weakens IAV-induced inflammatory responses.Therefore,our study further enriches the database of phosphorylation and acetylation sites of influenza viral proteins,laying a foundation for subsequent mechanistic studies.Meanwhile,the unraveled antiviral effect of PB2 S181E mimetic phosphorylation may provide a new target for the subsequent study of antiviral drugs.Jiao Hu Zixiong Zeng Xia Chen Manyu Zhang Zenglei Hu Min Gu Xiaoquan Wang Ruyi Gao Shunlin Hu Yu Chen Xiaowen Liu Daxin Peng Xiufan Liu 2024Virologica Sinica2024,39,1:0
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