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SRY-Box transcription factor 9 triggers YAP nuclear entry via direct interaction in tumors

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2285-2297页

作者： Hui Qian Chen-Hong Ding Fang Liu Shi-jie Chen Chen-Kai Huang Meng-Chao xiao Xia-Lu Hong Ming-Chen Wang Fang-Zhi Yan Kai Ding Ya-Lu Cui Bai-Nan Zheng jin Ding Cheng Luo Xin {3. Wei-Fen Xie Department of Gastroenterology Changzheng HospitalNaval Medical UniversityShanghaiChina Department of Gastroenterology Shanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina Drug Discovery and Design Center CAS Key Laboratory of Receptor ResearchState Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina Department of Gastroenterology First Affiliated Hospital of Nanchang UniversityNanchangChina Clinical Cancer institute Center for Translational MedicineNaval Medical UniversityShanghaiChina

The translocation of YAP from the cytoplasm to the nucleus is critical for its activation and plays a key role in tumor ***,the precise molecular mechanisms governing the nuclear import of YAP are not fully *** this study,we have uncovered a crucial role of SOX9 in the activation of ***9 promotes the nuclear translocation of YAP by direct ***,we have identified that the binding between Asp-125 of SOX9 and Arg-124 of YAP is essential for SOX9-YAP interaction and subsequent nuclear entry of ***,we have discovered a novel asymmetrical dimethylation of YAP at Arg-124(YAP-R124me2a)catalyzed by ***-R124me2a enhances the interaction between YAP and SOX9 and is associated with poor prognosis in multiple ***,we disrupted the interaction between SOX9 and YAP using a competitive peptide,S-A1,which mimics anα-helix of SOX9 containing Asp-125.S-A1 significantly inhibits YAP nuclear translocation and effectively suppresses tumor *** study provides the first evidence of SOX9 as a pivotal regulator driving YAP nuclear translocation and presents a potential therapeutic strategy for YAP-driven human cancers by targeting SOX9-YAP interaction.

关键词： interaction interaction precise

Searching for the Highest Energy of Pulsation and Critical Luminosity of Swift J0243.6+6124 Observed by Insight-HXMT

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Research in Astronomy and Astrophysics 2024年第5期24卷 61-69页

作者： Qing-Xia Zhao Xian Hou Ming-Yu Ge Shuang-Nan zhang Yun-Xiang xiao You-Li Tuo Zi-Xu Yang Ling-Da Kong jin-Lu Qu Shu zhang Jian-Cheng Wang Yunnan Observatories Chinese Academy of SciencesKunming 650216China Key Laboratory of Particle Astrophysics Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China University of chinese academy of sciences ChineseAcademy of SciencesBeijing 100049China Key Laboratory for the Structure and Evolution of Celestial Objects Chinese Academy of SciencesKunming 650216China Institut fur Astronomic und Astrophysik Sand 1D-72076 TabingenGemany School of Physics and Optoelectronic Engineering Shandong University of TechnologyZibo 255000China

Owing to the broad energy coverage of Insight-HXMT in the hard X-ray band,we detected the highest energy of pulsation exceeding 200 keV around the 2017–2018 outburst peak of the first Galactic pulsating ultraluminous X-ray source (PULX) Swift J0243.6+6124,which is the highest energy detected from PULXs to *** also obtained the highest energy of pulsation of every exposure during the outburst in 2017–2018,and found the highest energy is roughly positively correlated with *** our newly developed method,we identified the critical luminosity being {3.0^(3.)erg s^(-1) when the main peaks of the low and high energy pulse profiles became aligned,which separates the fan-beam dominated and pencil-beam dominated accretion *** the critical luminosity,the phase of the main peak shifted gradually from 0.5 to 0.8 until the outburst peak in al energy bands is reached,which is in agreement with the phase shift found previously at low *** result is consistent with what is derived from spectral analysis.

关键词： (stars:)pulsars-individual(Swift J0243.6+6124)-X-rays binaries–stars neutron

Development and performance evaluation of high temperature resistant strong adsorption rigid blocking agent

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Petroleum Science 2024年第4期21卷 2650-2662页

作者： Zhe Xu jin-Sheng Sun jing-Ping Liu Kai-He Lv xiao-Dong Dong Zong-Lun Wang Tai-Feng {3. Yuan-Wei Sun Zhi-Wen Dai School of Petroleum Engineering China University of Petroleum (East China) CNPC Engineering Technology R&D Company Limited

As drilling wells continue to move into deep ultra-deep layers, the requirements for temperature resistance of drilling fluid treatments are getting higher and higher. Among them, blocking agent, as one of the key treatment agents, has also become a hot spot of research. In this study, a high temperature resistant strong adsorption rigid blocking agent(QW-1) was prepared using KH570 modified silica,acrylamide(AM) and allyltrimethylammonium chloride(TMAAC). QW-1 has good thermal stability,average particle size of 1.46 μm, water contact angle of 10.5., has a strong hydrophilicity, can be well dispersed in water. The experimental results showed that when 2 wt% QW-1 was added to recipe A(4 wt% bentonite slurry+0.5 wt% DSP-1(filtration loss depressant)), the API filtration loss decreased from 7.8to 6.4 m L. After aging at 240.C, the API loss of filtration was reduced from 21 to 14 m L, which has certain performance of high temperature loss of filtration. At the same time, it is effective in sealing 80-100mesh and 100-120 mesh sand beds as well as 3.and 5 μm ceramic sand discs. Under the same conditions,the blocking performance was superior to silica(5 μm) and calcium carbonate(2.6 μm). In addition, the mechanism of action of QW-1 was further investigated. The results show that QW-1 with amide and quaternary ammonium groups on the molecular chain can be adsorbed onto the surface of clay particles through hydrogen bonding and electrostatic interaction to form a dense blocking layer, thus preventing further intrusion of drilling fluid into the formation.

关键词： High adsorption Rigid microsphere High temperature resistance Blocking performance

Inflammatory and Immunomodulatory Effects of Tripterygium wilfordii Multiglycoside in Mouse Models of Psoriasis Keratinocytes

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chinese Journal of Integrative Medicine 2024年第3期30卷 222-229页

作者： zhang Shuo LI Hong-jin YANG Chun-mei LIU Liu SUN xiao-ying WANG Jiao CHEN Si-ting LU Yi HU Man-qi YAN Ge ZHOU Ya-qiong MIAO xiao LI Xin LI Bin Department of Dermatology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai200437China institute of Dermatology Shanghai Academy of Traditional Chinese MedicineShanghai201203China Department of Integrated Traditional chinese and Western Medicine Shanghai Skin Disease HospitalTongji University School of MedicineShanghai200443China

Objective:To determine the role of Tripterygium wilfordii multiglycoside(TGW) in the treatment of psoriatic dermatitis from a cellular immunological ***:Mouse models of psoriatic dermatitis were established by imiquimod(IMQ).Twelve male BALB/c mice were assigned to MQ or IMQ+TGW groups according to a random number *** changes in vivo were assessed by hematoxylin and eosin *** of immune cells and cytokines in mice,as well as PAM212 cell proliferation in vitro were assessed by flow ***-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain ***:TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45^(+)cells,neutrophils and T lymphocytes(all P1).Moreover,TGW significantly attenuated keratinocytes(KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin(IL)-17A,IL-23.tumor necrosis factor α,and chemokine(C-X-C motif) ligand 1(P1 or P17 cells in skin lesion of mice and draining lymph nodes(P1).Conclusions:TGW improved psoriasis-like inflammation by inhibiting KCs proliferation,as well as the associated immune cells and cytokine *** inhibited IL-17 secretion from γδ T cells,which improved the immune-inflammatory microenvironment of psoriasis.

关键词： psoriasis Tripterygium wilfordii multiglycoside γδT cells inflammation chinese medicine

Profibrotic role of the SOX9-MMP10-ECM biosynthesis axis in the tracheal fibrosis after injury and repair

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Genes & Diseases 2024年第5期11卷 360-373页

作者： Lei Gu Anmao Li Chunyan He Rui xiao Jiaxin Liao Li Xu Junhao Mu xiaohui Wang Mingjin Yang jinyue Jiang Yang Bai Xingxing jin Meiling xiao Xia zhang Tairong Tan Yang xiao jing Lin Yishi Li Shuliang Guo Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Soochow UniversitySuzhou 215006China Department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Infection Disease The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang 325000China

Fibroblast activation and extracellular matrix(ECM)deposition play an important role in the tracheal abnormal repair process and *** a transcription factor,SOX9 is involved in fibroblast activation and ECM ***,the mechanism of how SOX9 regulates fibrosis after tracheal injury remains *** investigated the role of SOX9 in TGF-b1-induced fibroblast activation and ECM deposition in rat tracheal fibroblast(RTF)***9 overexpression adenovirus(Ad-SOX9)and siRNA were transfected into RTF *** found that SOX9 expression was up-regulated in RTF cells treated with ***9 overexpression activated fibroblasts and promoted ECM *** SOX9 inhibited cell proliferation,migration,and ECM deposition,induced G2 arrest,and increased apoptosis in RTF ***-seq and chromatin immunoprecipitation sequencing(ChIP-seq)assays identified MMP10,a matrix metalloproteinase involved in ECM deposition,as a direct target of SOX9,which promotes ECM degradation by increasing MMP10 expression through the Wnt/b-catenin signaling ***,in vivo,SOX9 knockdown ameliorated granulation proliferation and tracheal fibrosis,as manifested by reduced tracheal *** conclusion,our findings indicate that SOX9 can drive fibroblast activation,cell proliferation,and apoptosis resistance in tracheal fibrosis via the Wnt/b-catenin signaling *** SOX9eMMP10 eECM biosynthesis axis plays an important role in tracheal injury and *** SOX9 and its downstream target MMP10 may represent a promising therapeutic approach for tracheal fibrosis.

关键词： Extracellular matrix deposition Fibroblast activation MMP10 SOX9 Tracheal fibrosis

A human-specific insertion promotes cell proliferation and migration by enhancing TBC1D8B expression

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Science China(Life sciences) 2024年第4期67卷 765-777页

作者： Hui Zhao Lin-Lin Liu Jian Sun Lian jin Hai-Bing Xie Jian-Bo Li Hui Xu Dong-Dong Wu xiao-Lin Zhuang Min-Sheng Peng Ya-Jun Guo Wei-Zhu Qian Newton OOtecko Wei-jie Sun Liang-Hu Qu jie He Zhao-Li Chen Rong Liu Ce-Shi Chen Ya-Ping zhang State Key Laboratory for Conservation and Utilization of Bio-resource School of Life SciencesSchool of Ecology and Environmental ScienceYunnan UniversityKunming 650091China School of Forensic Medicine Kunming Medical UniversityKunming 650500China academy of Biomedical Engineering Kunming Medical UniversityKunming 650500China The Third Affiliated Hospital Kunming Medical UniversityKunming 650118China Key Laboratory of Animal Models and Human Disease Mechanisms of the chinese academy of sciences and Yunnan Province Kunming Institute of ZoologyChinese Academy of SciencesKunming 650201China State Key Laboratory of Genetic Resources and Evolution Yunnan Laboratory of Molecular Biology of Domestic AnimalsKunming Institute of ZoologyChinese Academy of SciencesKunming 650201China The Key Laboratory of Gene Engineering of the Ministry of Education State Key Laboratory for BiocontrolSun Yat-sen UniversityGuangzhou 510275China National Engineering Research Center for Antibody Medicine and Shanghai Key Laboratory of Cell Engineering and Antibody Shanghai 201203China Department of Thoracic Surgery Cancer Institute and HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

Human-specific insertions play important roles in human phenotypes and *** we reported a 446-bp insertion(Insert-446)in intron 11 of the TBC1D8B gene,located on chromosome X,and traced its origin to a portion of intron 6 of the EBF1 gene on chromosome ***,Insert-446 was present in the human Neanderthal and Denisovans genomes,and was fixed in humans after human-chimpanzee *** have demonstrated that Insert-446 acts as an enhancer through binding transcript factors that promotes a higher expression of human TBC1D8B gene as compared with orthologs in *** addition,over-expression TBC1D8B promoted cell proliferation and migration through“a dual finger”catalytic mechanism(Arg53. and Gln573.in the TBC domain in vitro and knockdown of TBC1D8B attenuated tumorigenesis in *** of Insert-446 prevented cell proliferation and migration in cancer and normal *** results reveal that the human-specific Insert-446 promotes cell proliferation and migration by upregulating the expression of TBC1D8B *** findings provide a significant insight into the effects of human-specific insertions on evolution.

关键词： human-specific insertion enhancer gene expression cell proliferation and migration

Mitigated reaction kinetics between lithium metal anodes and electrolytes by alloying lithium metal with low-content magnesium

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Journal of Energy Chemistry 2024年第8期95卷 644-650,I0014页

作者： Yang-Yang Wang Ya-Nan Wang Nan Yao Shu-Yu Sun xiao-Qing Ding Chen-Xi Bi Qian-Kui zhang Zhao Zheng Cheng-Bin jin Bo-Quan Li Xue-Qiang zhang Jia-Qi Huang School of Materials Science and Engineering Beijing Institute of TechnologyBeijing 100081China Advanced Research institute of Multidisciplinary Science Beijing Institute of TechnologyBeijing 100081China Beijing Key Laboratory of Green Chemical Reaction Engineering and Technology Department of Chemical EngineeringTsinghua UniversityBeijing 100084China College of Materials and Chemistry China Jiliang UniversityHangzhou 310018ZhejiangChina

Lithium(Li)metal is regarded as a promising anode candidate for high-energy-density rechargeable ***,Li metal is highly reactive against electrolytes,leading to rapid decay of active Li metal ***,alloying Li metal with low-content magnesium(Mg)is proposed to mitigate the reaction kinetics between Li metal anodes and *** atoms enter the lattice of Li atoms,forming solid solution due to the low amount(5 wt%)of *** atoms mainly concentrate near the surface of Mg-alloyed Li metal *** reactivity of Mg-alloyed Li metal is mitigated kinetically,which results from the electron transfer from Li to Mg atoms due to the electronegativity *** on quantitative experimental analysis,the consumption rate of active Li and electrolytes is decreased by using Mgalloyed Li metal anodes,which increases the cycle life of Li metal batteries under demanding ***,a pouch cell(1.25 Ah)with Mg-alloyed Li metal anodes delivers an energy density of 3.0 Wh kg^(-1)and a cycle life of 100 *** work inspires the strategy of modifying Li metal anodes to kinetically mitigate the side reactions with electrolytes.

关键词： Lithium metal anodes Alloying Anode/electrolyte interface Reaction kinetics Pouch cell

The GECAM Real-time Burst Alert System

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Research in Astronomy and Astrophysics 2024年第10期24卷 36-47页

作者： Yue Huang Dongli Shi xiaolu zhang Xiang Ma Peng zhang Shi{3. Zheng Liming Song xiaoyun Zhao Wei Chen Rui Qiao Xinying Song jin Wang Ce Cai Shuo xiao Yanqiu zhang Shaolin Xiong Key Laboratory of Particle Astrophysics Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China Southwest Jiaotong University Chengdu 611756China Qufu Normal University Qufu 273165China College of Electronic and Information Engineering Tongji UniversityShanghai 201804China College of Physics and Hebei Key Laboratory of Photophysics Research and Application Hebei Normal UniversityShijiazhuang 050024China Guizhou Provincial Key Laboratory of Radio Astronomy and Data Processing Guizhou Normal UniversityGuiyang 550001China University of chinese academy of sciences Chinese Academy of SciencesBeijing 100049China

Gravitational wave high-energy Electromagnetic Counterpart All-sky Monitor(GECAM),consisting of two microsatellites,is designed to detect gamma-ray bursts associated with gravitational-wave ***,we introduce the real-time burst alert system of GECAM,with the adoption of the BeiDou-3.short message communication *** present the post-trigger operations,the detailed ground-based analysis,and the performance of the *** the first year of the in-flight operation,GECAM was triggered by 42 gamma-ray *** GECAM real-time burst alert system has the ability to distribute the alert within~1 minute after being triggered,which enables timely follow-up observations.

关键词： (stars:)gamma-ray burst:general gravitational waves methods:data analysis

Detection of Novel BEST1 Variations in Autosomal Recessive Bestrophinopathy Using Third-generation Sequencing

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Current Medical Science 2024年第2期44卷 419-425页

作者： Jia-xun LI Ling-rui MENG Bao-ke HOU xiao-lu HAO Da-jiang WANG Ling-hui QU Zhao-hui LI Lei zhang Xin jin Department of Senior Ophthalmology the Third Medical Center of PLA General HospitalBeijing 100853China Department of Ophthalmology the 74th Army Group HospitalGuangzhou 510318China

Objective:Autosomal recessive bestrophinopathy(ARB),a retinal degenerative disease,is characterized by central visual loss,yellowish multifocal diffuse subretinal deposits,and a dramatic decrease in the light peak on *** potential pathogenic mechanism involves mutations in the BEST1 gene,which encodes Ca2+-activated Cl−channels in the retinal pigment epithelium(RPE),resulting in degeneration of RPE and *** this study,the complete clinical characteristics of two chinese ARB families were ***:Pacific Biosciences(PacBio)single-molecule real-time(SMRT)sequencing was performed on the probands to screen for disease-causing gene mutations,and Sanger sequencing was applied to validate variants in the patients and their family ***:Two novel mutations,c.202T>C(chr11:61722628,p.Y68H)and c.867+97G>A,in the BEST1 gene were identified in the two chinese ARB *** novel missense mutation BEST1 c.202T>C(p.Y68H)resulted in the substitution of tyrosine with histidine in the N-terminal region of transmembrane domain{3. of *** novel variant,BEST1 c.867+97G>A(chr11:61725867),located in intron 7,might be considered a regulatory variant that changes allele-specific binding affinity based on motifs of important transcriptional ***:Our findings represent the first use of third-generation sequencing(TGS)to identify novel BEST1 mutations in patients with ARB,indicating that TGS can be a more accurate and efficient tool for identifying mutations in specific *** novel variants identified further broaden the mutation spectrum of BEST1 in the chinese population.

关键词： autosomal recessive bestrophinopathy BEST1 gene third-generation sequencing mutation