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Tyrosine phosphatase SHP2 in ovarian granulosa cells balances follicular development by inhibiting PI3K/AKT signaling

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Journal of Molecular Cell Biology 2022年第7期14卷 23-36页

作者： Xiaoli Wei Lanping Zheng yingpu tian Haibin Wang Youqiang Su Gensheng Feng Chao Wang Zhongxian Lu School of Pharmaceutical Sciences State Key Laboratory of Cellular Stress BiologyXiamen UniversityXiamen 361005China Fujian Provincial Key Laboratory of Reproductive Health Research Medical College of Xiamen UniversityXiamen 361102China State Key Laboratory of Agrobiotechnology College of Biological SciencesChina Department of Pathology Division of Biological SciencesUniversity of California at San DiegoLa JollaCA 92093USA State Key Laboratory of Agrobiotechnology College of Biological SciencesChina Agricultural UniversityBeijing 100193China

In mammals,the growth and maturation of oocytes within growing follicles largely depends on ovarian granulosa cells(GCs)in response to gonadotropin stimulation.Many signals have been shown to regulate GC proliferation and apoptosis.However,whether the tyrosine phosphatase SHP2 is involved remains unclear.In this study,we identified the crucial roles of SHP2 in modulating GC proliferation and apoptosis.The production of both mature oocytes and pups was increased in mice with Shp2 specifically deleted in ovarian GCs via Fshr-Cre.Shp2 deletion simultaneously promoted GC proliferation and inhibited GC apoptosis.Furthermore,Shp2 deficiency promoted,while Shp2 overexpression inhibited,the proliferation of cultured primary mouse ovarian GCs and the human ovarian granulosa-like tumor cell line KGN in vitro.Shp2 deficiency promoted follicule-stimulating hormone(FSH)-activated phosphorylation of AKT in vivo.SHP2 deficiency reversed the inhibitory effect of hydrogen peroxide(H_(2)O_(2))on AKT activation in KGN cells.H_(2)O_(2) treatment promoted the interaction between SHP2 and the p85 subunit of PI3K in KGN cells.Therefore,SHP2 in GCs may act as a negative modulator to balance follicular development by suppressing PI3K/AKT signaling.The novel function of SHP2 in modulating proliferation and apoptosis of GCs provides a potential therapeutic target for the clinical treatment of follicle developmental dysfunction.

关键词： tyrosine phosphatase SHP2 granulosa cell follicular development PI3K/AKT signaling

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Deletion of Gab2 in mice protects against hepatic steatosis and steatohepatitis:a novel therapeutic target for fatty liver disease

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Journal of Molecular Cell Biology 2016年第6期8卷 492-504页

作者： Shuai Chen Yujia Kang Yan Sun Yanhong Zhong Yanli Li Lijuan Deng Jin Tao Yang Li yingpu tian Yinan Zhao Jianghong Cheng Wenjie Liu Gen-Sheng Feng Zhongxian Lu School of Pharmaceutical Sciences State Key Laboratory of Cellular Stress BiologyXiamen UniversityXiamenFujian 361005China Department of Pathology and Division of Biological SciencesUniversity of California San DiegoLa JollaCA 92093USA

Fatty liver disease is a serious health problem worldwide and is the most common cause for chronic liver disease and metabolic disorders.The major challenge in the prevention and intervention of this disease is the incomplete understanding of the underlying mechanism and thus lack of potent therapeutic targets due to multifaceted and interdependent disease factors.In this study,we investigated the role of a signaling adaptor protein,GRB2-associated-binding protein 2(Gab2),in fatty liver using an animal disease model.Gab2 expression in hepatocytes responded to various disease factor stimulations,and Gab2 knockout mice exhibited resistance to fat-induced obesity,fat-or alcohol-stimulated hepatic steatosis,as well as methionine and choline deficiency-induced steatohepatitis.Concordantly,the forced expression or knockdown of Gab2 enhanced or diminished oleic acid(OA)-or ethanol-induced lipid production in hepatocytes in vitro,respectively.During lipid accumulation in hepatocytes,both fat and alcohol induced the recruitment of PI3K or Socs3 by Gab2 and the activation of their downstream signaling proteins AKT,ERK,and Stat3.Therefore,Gab2 may be a disease-associated protein that is induced by pathogenic factors to amplify and coordinate multifactor-induced signals to govern disease development in the liver.Our research provides a novel potential target for the prevention and intervention of fatty liver disease.

关键词： alcoholic fatty liver disease non-alcoholic fatty liver disease knockout mouse disease-associated protein therapeutic target

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Tyrosine phosphatase Shp2 play a key role in meiosis of mice spermatogenesis

Tyrosine phosphatase Shp2 play a key role in meiosis of mice...

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中国生理学会生殖科学专业委员会—中国动物学会生殖生物学...

作者： Yang Li Wensheng Liu Jia Yi Yinan Zhao yingpu tian Wen Liu Haibin Wang zhongxian Lu School of Pharmaceutical Sciences State Key Laboratory of Cellular Stress BiologyXiamen University Fujian Provincial Key Laboratory of Reproductive Health Research Medical College of Xiamen University

＜正＞SHP2,a nonreceptor tyrosine phosphatase,play key roles in the development of several organs.The somatic mutation of its gene PTPN11 leads to infertile in most of the patients.But the exact mechanism of SHP2 in germ cell development is largely unknown.Here,we found that SHP2 protein was abundant in the cytoplasm of spermatogonia,but was remarkably dropped and transferred into

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A Blockchain-Based Access Control Scheme for Reputation Value Attributes of the Internet of Things

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Computers, Materials & Continua 2024年第1期78卷 1297-1310页

作者： Hongliang tian Junyuan tian College of Electrical Engineering Northeast Electric Power UniversityJilin132012China

The Internet of Things(IoT)access controlmechanism may encounter security issues such as single point of failure and data tampering.To address these issues,a blockchain-based IoT reputation value attribute access control scheme is proposed.Firstly,writing the reputation value as an attribute into the access control policy,and then deploying the access control policy in the smart contract of the blockchain system can enable the system to provide more fine-grained access control;Secondly,storing a large amount of resources fromthe Internet of Things in Inter Planetary File System(IPFS)to improve system throughput;Finally,map resource access operations to qualification tokens to improve the performance of the access control system.Complete simulation experiments based on the Hyperledger Fabric platform.Fromthe simulation experimental results,it can be seen that the access control system can achieve more fine-grained and dynamic access control while maintaining high throughput and low time delay,providing sufficient reliability and security for access control of IoT devices.

关键词： Blockchain IoT access control Hyperledger Fabric

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Robust adaptive radar beamforming based on iterative training sample selection using kurtosis of generalized inner product statistics

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Journal of Systems Engineering and Electronics 2024年第1期35卷 24-30页

作者： tian Jing ZHANG Wei School of Information and Electronics Beijing Institute of TechnologyBeijing 100081China National Key Laboratory of Electromagnetic Space Security Chengdu 610036China

In engineering application,there is only one adaptive weights estimated by most of traditional early warning radars for adaptive interference suppression in a pulse reputation interval(PRI).Therefore,if the training samples used to calculate the weight vector does not contain the jamming,then the jamming cannot be removed by adaptive spatial filtering.If the weight vector is constantly updated in the range dimension,the training data may contain target echo signals,resulting in signal cancellation effect.To cope with the situation that the training samples are contaminated by target signal,an iterative training sample selection method based on non-homogeneous detector(NHD)is proposed in this paper for updating the weight vector in entire range dimension.The principle is presented,and the validity is proven by simulation results.

关键词： adaptive radar beamforming training sample selection non-homogeneous detector electronic jamming jamming suppression

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Transformer and GAN-Based Super-Resolution Reconstruction Network for Medical Images

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Tsinghua Science and Technology 2024年第1期29卷 197-206页

作者： Weizhi Du Shihao tian Arts&Sciences College Washington University in St.LouisSt.LouisMO 63130USA Department of Electric and Computing Engineering Cornell UniversityIthacaNY 14850USA

Super-resolution reconstruction in medical imaging has become more demanding due to the necessity of obtaining high-quality images with minimal radiation dose,such as in low-field magnetic resonance imaging(MRI).However,image super-resolution reconstruction remains a difficult task because of the complexity and high textual requirements for diagnosis purpose.In this paper,we offer a deep learning based strategy for reconstructing medical images from low resolutions utilizing Transformer and generative adversarial networks(T-GANs).The integrated system can extract more precise texture information and focus more on important locations through global image matching after successfully inserting Transformer into the generative adversarial network for picture reconstruction.Furthermore,we weighted the combination of content loss,adversarial loss,and adversarial feature loss as the final multi-task loss function during the training of our proposed model T-GAN.In comparison to established measures like peak signal-to-noise ratio(PSNR)and structural similarity index measure(SSIM),our suggested T-GAN achieves optimal performance and recovers more texture features in super-resolution reconstruction of MRI scanned images of the knees and belly.

关键词： super-resolution image reconstruction Transformer generative adversarial network(GAN)

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DeepSI:A Sensitive-Driven Testing Samples Generation Method of Whitebox CNN Model for Edge Computing

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Tsinghua Science and Technology 2024年第3期29卷 784-794页

作者： Zhichao Lian Fengjun tian School of Cyber Science and Engineering Nanjing University of Science and TechnologyNanjing 210094China

In recent years,Deep Learning(DL)technique has been widely used in Internet of Things(IoT)and Industrial Internet of Things(IIoT)for edge computing,and achieved good performances.But more and more studies have shown the vulnerability of neural networks.So,it is important to test the robustness and vulnerability of neural networks.More specifically,inspired by layer-wise relevance propagation and neural network verification,we propose a novel measurement of sensitive neurons and important neurons,and propose a novel neuron coverage criterion for robustness testing.Based on the novel criterion,we design a novel testing sample generation method,named DeepSI,which involves definitions of sensitive neurons and important neurons.Furthermore,we construct sensitive-decision paths of the neural network through selecting sensitive neurons and important neurons.Finally,we verify our idea by setting up several experiments,then results show our proposed method achieves superior performances.

关键词： neuron sensitivity Layer-wise Relevance Propagation(LRP) neural network verification deeplearning testing

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Revisiting East Asian monsoon change during the Last Glacial Maximum using PMIP4 simulations

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Atmospheric and Oceanic Science Letters 2024年第3期17卷 47-52页

作者： Zhiping tian Institute of Atmospheric Physics Chinese Academy of SciencesBeijingChina

利用PMIP4多模式试验数据,本文重新检查了末次冰盛期(距今约21000年)东亚季风变化.结果表明:相对于工业革命前期,所有5个模式一致模拟显示末次冰盛期东亚季风减弱,冬季和夏季减幅分别为1%-18%和2-32%;不同模式中东亚季风环流变化的空间... 详细信息

利用PMIP4多模式试验数据,本文重新检查了末次冰盛期(距今约21000年)东亚季风变化.结果表明:相对于工业革命前期,所有5个模式一致模拟显示末次冰盛期东亚季风减弱,冬季和夏季减幅分别为1%-18%和2-32%;不同模式中东亚季风环流变化的空间分布存在差异,这主要源于该时期大尺度变冷和海平面气压梯度变化的空间分布不同;由于模式之间的差异和重建记录之间的不确定性,未来有待开展更多模拟和重建工作以更好地理解冰期东亚季风变化.

关键词：末次冰盛期东亚冬季风东亚夏季风 PMIP4试验

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Chemical derivatization strategies for enhancing the HPLC analytical performance of natural active triterpenoids

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Journal of Pharmaceutical Analysis 2024年第3期14卷 295-307页

作者： Xiao-Feng Huang Ying Xue Li Yong tian-tian Wang Pei Luo Lin-Sen Qing Chengdu Institute of Biology Chinese Academy of SciencesChengdu610041China State Key Laboratory for Quality Research in Chinese Medicines Macao University of Science and TechnologyMacaoChina Sichuan Center for Disease Control and Prevention Chengdu610041China University of Chinese Academy of Sciences Beijing100049China

riterpenoids widely exist in nature,displaying a variety of pharmacological activities.Determining triterpenoids in different matrices,especially in biological samples holds great significance.High-performance liquid chromatography(HPLC)has become the predominant method for triterpenoids analysis due to its exceptional analytical performance.However,due to the structural similarities among botanical samples,achieving effective separation of each triterpenoid proves challenging,necessitating significant improvements in analytical methods.Additionally,triterpenoids are characterized by a lack of ultraviolet(UV)absorption groups and chromophores,along with low ionization efficiency in mass spectrometry.Consequently,routine HPLC analysis suffers from poor sensitivity.Chemical derivatization emerges as an indispensable technique in HPLC analysis to enhance its performance.Considering the structural characteristics of triterpenoids,various derivatization reagents such as acid chlorides,rhodamines,isocyanates,sulfonic esters,and amines have been employed for the derivatization analysis of triterpenoids.This review comprehensively summarized the research progress made in derivatization strategies for HPLC detection of triterpenoids.Moreover,the limitations and challenges encountered in previous studies are discussed,and future research directions are proposed to develop more effective derivatization methods.

关键词： Triterpenoid HPLC Derivatization Quantification

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Frequency Domain Fatigue Evaluation on SCR Girth-Weld Based on Structural Stress

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China Ocean Engineering 2024年第2期38卷 255-270页

作者： ZHANG Long ZHAO tian-feng College of Safety and Ocean Engineering China University of Petroleum(Beijing)Beijing 102249China

The Steel Catenary Riser(SCR)is a vital component for transporting oil and gas from the seabed to the floating platform.The harsh environmental conditions and complex platform motion make the SCR’s girth-weld prone to fatigue failure.The structural stress fatigue theory and Master S-N curve method provide accurate predictions for the fatigue damage on the welded joints,which demonstrate significant potential and compatibility in multi-axial and random fatigue evaluation.Here,we propose a new frequency fatigue model subjected to welded joints of SCR under multiaxial stress,which fully integrates the mesh-insensitive structural stress and frequency domain random process and transforms the conventional welding fatigue technique of SCR into a spectrum analysis technique utilizing structural stress.Besides,a full-scale FE model of SCR with welds is established to obtain the modal structural stress of the girth weld and the frequency response function(FRF)of modal coordinate,and a biaxial fatigue evaluation about the girth weld of the SCR can be achieved by taking the effects of multi-load correlation and pipe-soil interaction into account.The research results indicate that the frequency-domain fatigue results are aligned with the time-domain results,meeting the fatigue evaluation requirements of the SCR.

关键词： SCR girth weld random vibration self(cross)power spectrum structural stress method biaxial fatigue damage

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