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Effects of intestine-specific deletion of fibroblast growth factor 15 on alcoholic liver disease development in mice

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liver Research 2022年第2期6卷 84-92页

作者： Bo Kong Mingxing huang Rulaiha E.Taylor daniel Rizzolo Katherine d.Otersen Grace l.Guo department of Pharmacology and Toxicology Ernest Mario School of PharmacyRutgersThe State University of New JerseyPiscatawayNJUSA department of Infectious diseases The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhaiGuangdongChina Environmental and Occupational Health Sciences Institute RutgersThe State University of New JerseyPiscatawayNJUSA Rutgers Center for lipid Research RutgersThe State University of New JerseyPiscatawayNJUSA VA New Jersey Health Care System Veterans Administration Medical CenterEast OrangeNJUSA

Background and aims:Alcoholic liver disease(Ald)is an important and growing cause for the development of chronic liver diseases in the *** acid(BA)levels are increased in patients with Ald anddysregulation of BA homeostasis worsens *** synthesis is critically regulated by fibroblast growthfactor(FGF)15 in mice and FGF19 in ***15/19 are mainly produced in the ileum and their mainfunction is to suppress BA synthesis in the liver through the activation of fibroblast growth factor receptor 4(FGFR4)on *** effects of intestine-specific Fgf15 deficiency on the development ofAld were determined in the current ***:Enterocyte-specific Fgf15 knockout mice(Fgf15intint^(-/-))and the established mouse model bychronic and binge ethanol feeding(NIAAA model)were adapted in this ***:The Fgf15intint^(-/-)mice had increased BA pool size,consistent with negative effects of FGF15-FGFR4signaling on BA *** were not obviously physical and hepatic histological abnormalitiespresented in Fgf15intint^(-/-)mice compared to wild-type *** alcohol treatment,the Fgf15intint^(-/-)mice exhibited a higher degree of liver injury,increased hepatic expression of Cd14,a receptor forlipopolysaccharide expressed in the liver,and increased hepatic lipid *** did not observe alterations in the levels of fibrosis in the liver or expression of genes involved in hepatic fibrosis,regardless ofgenotypes or following the alcohol ***:FGF15 may prevent hepatic steatosis in the development of Ald in mice,and maintainingFGF19/FGFR4 signaling may be critical in the prevention and/or treatment of Ald in humans in thefuture.

关键词： Fibroblast growth factor 15(FGF15) Farnesoid X receptor(FXR) Bile acid(BA) Alcoholic fatty liver disease Alcoholic steatohepatitis

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New genetic and epigenetic insights into the chemokine system: the latest discoveries aiding progression toward precision medicine

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Cellular & Molecular Immunology 2023年第7期20卷 739-776页

作者： Hanli Xu Shuye lin Ziyun Zhou duoduo li Xiting Zhang Muhan Yu Ruoyi Zhao Yiheng Wang Junru Qian xinyi li Bohan li Chuhan Wei Keqiang Chen Teizo Yoshimura Ji Ming Wang Jiaqiang huang College of life Sciences and Bioengineering School of Physical Science and EngineeringBeijing Jiaotong University3 ShangyuanCunHaidian District100044 BeijingP.R.China Cancer Research Center Beijing Chest HospitalCapital Medical UniversityBeijing Tuberculosis and Thoracic Tumor Institute101149 BeijingChina laboratory of Cancer Innovation Center for Cancer ResearchNational Cancer Institute at FrederickFrederickMD 21702USA.

Over the past thirty years,the importance of chemokines and their seven-transmembrane G protein-coupled receptors(GPCRs)has been increasingly *** interactions with receptors trigger signaling pathway activity to form a network fundamental to diverse immune processes,including host homeostasis and responses to *** and nongenetic regulation of both the expression and structure of chemokines and receptors conveys chemokine functional *** and defects in the system contribute to the pathogenesis of a variety of diseases,including cancer,immune and inflammatory diseases,and metabolic and neurological disorders,which render the system a focus of studies aiming to discover therapies and important *** integrated view of chemokine biology underpinning divergence and plasticity has provided insights into immune dysfunction in disease states,including,among others,coronavirus disease 2019(COVId-19).In this review,by reporting the latest advances in chemokine biology and results fromanalyses of a plethora of sequencing-based datasets,we outline recent advances in the understanding of the genetic variations and nongenetic heterogeneity of chemokines and receptors and provide an updated view of their contribution to the pathophysiological network,focusing on chemokine-mediated inflammation and *** of the molecular basis of dynamic chemokine-receptor interactions will help advance the understanding of chemokine biology to achieve precision medicine application in the clinic.

关键词： Chemokine Chemokine receptor Migration Homeostasis Genetics Epigenetics

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Effects of imidacloprid and thiamethoxam as seed treatments on the early seedling characteristics and aphid-resistance of oilseed rape

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Journal of Integrative Agriculture 2015年第12期14卷 2581-2589页

作者： huang liang ZHAO Chun-lin huang Fang BAI Run-e lü Yao-bin YAN Feng-ming HAO Zhong-ping School of Agricultural and Food Science Zhejiang A & F University Institute of Plant Protection and Microbiology Zhejiang Academy of Agricultural Sciences College of Plant Protection Henan Agricultural University Key laboratory of Crop Quality Improvement of Anhui Province Crop Research Institute Anhui Academy of Agricultural Sciences

Seed treatments with the neonicotinoid insecticides imidacloprid and thiamethoxam were evaluated to determine whether the chemicals at effective concentrations for aphid control would influence the germination and early growth of oilseed rape,Brassica *** with imidacloprid or thiamethoxam did not affect the cumulative germination rate,but significantly inhibited establishment potential by suppressing root system development in the cotyledon ***,these alterations in seedling development in the thiamethoxam-treated seeds appeared not to be detrimental as leaves developed;in contrast,for the seedlings with imidacloprid as seed treatment agent,a significantly decreased shoot/root ratio was still evident at the late two-leaf *** two leaves developed,chlorophyll content per leaf in the thiamethoxam treatment was significantly higher than that of the control,while chlorophyll content per leaf in the imidacloprid treatment remained close to that in the *** other parameters,i.e.,height,leaf area,weight of stem,leaf or root,and other growth indexes,between the treatments and the control showed no significant ***,it was found that storage time of the treated seeds had a significant effect on cumulative germination *** 30 d before planting significantly reduced germination relative to that of the *** of the plants treated with neonicotinoids were shown to have significant anti-aphid characteristics that persisted until the end of the trial.

关键词： oilseed rape seed coating agent imidacloprid thiamethoxam seedling growth germination aphid

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Constructing two-scale network microstructure with nano-Ti5Si3 for superhigh creep resistance

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Journal of Materials Science & Technology 2019年第8期35卷 1532-1542页

作者： Y.Jiao l.J.huang S.l.Wei H.X.Peng Q.An S.Jiang l.Geng State Key laboratory of Advanced Welding and Joining Harbin Institute of TechnologyHarbin 150001 China Center of Analysis and Measurement Harbin Institute of TechnologyHarbin 150001 China department of Materials Science and Engineering Massachusetts Institute of TechnologyCambridge MA02139 USA Institute for Composites Science Innovation (InCSI) School of Materials Science and EngineeringZhejiang UniversityHangzhou 310027 China

The improvement of mechanical properties must be achieved by designing and constructing more suitable microstructure,such as hierarchical *** order to significantly enhance the creep resistance of titanium matrix composites(TMCs),two-scale network microstructure was constructed including the first-scale network(d the second-scale network(der metallurgy and in-situ *** results showed that the creep rate of the composite was remarkably reduced by an order of magnitude compared with the Ti6Al4V alloy at 550℃,600℃,650℃ under the stresses between 100 MPa and 350 ***,the rupture time of the composite was increased by 20 times,compared with that of the Ti6Al4 Valloy at 550℃/300 *** superior creep resistance could be attributed to the hierarchical *** micro-TiBw reinforcement in the first-scale network boundary contributed to creep resistance primarily by blocking grain boundary sliding,while the nano-Ti5Si3 particle in the second-scale network boundary mainly by hindering phase boundary *** addition,the nano-Ti5Si3 particle was dissolved,and precipitated with smaller size than the primary *** phenomenon was attributed to Si element diffusion under high temperature and external stress,which could further continuously enhance the creep ***,the creep rate during steady-state stage was significantly decreased,which manifested superior creep resistance of the composite.

关键词： Titanium matrix composite Two-scale network microstructure Nano-Ti5Si3 Creep Powder metallurgy

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Practical automatic background substitution for live video

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Computational Visual Media 2017年第3期3卷 273-284页

作者： Haozhi huang Xiaonan Fang Yufei Ye Songhai Zhang Paul l.Rosin department of Computer Science Tsinghua University School of Computer Science and Informatics Cardiff University

In this paper we present a novel automatic background substitution approach for live video. The objective of background substitution is to extract the foreground from the input video and then combine it with a new background. In this paper, we use a color line model to improve the Gaussian mixture model in the background cut method to obtain a binary foreground segmentation result that is less sensitive to brightness differences. Based on the high quality binary segmentation results, we can automatically create a reliable trimap for alpha matting to refine the segmentation boundary. To make the composition result more realistic, an automatic foreground color adjustment step is added to make the foreground look consistent with the new background. Compared to previous approaches, our method can produce higher quality binary segmentation results, and to the best of our knowledge, this is the first time such an automatic and integrated background substitution system has been proposed which can run in real time, which makes it practical for everyday applications.

关键词： background substitution background replacement background subtraction alpha matting

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Multi-length scale bioprinting towards simulating microenvironmental cues

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Bio-design and Manufacturing 2018年第2期1卷 77-88页

作者： Elisabeth l Gill Xia li Mark A. Birch Yan Yan Shery huang department of Engineering University of CambridgeTrumpington Street Cambridge CB2 1PZ UK division of Trauma and Orthopaedic Surgery Department of Surgery University of Cambridge Cambridge UK

It is envisaged that the creation of cellular environments at multiple length scales, that recapitulate in vivo bioactive and structural roles, may hold the key to creating functional, complex tissues in the laboratory. This review considers recent advances in biofabrication and bioprinting techniques across different length scales. Particular focus is placed on 3d printing of hydrogels and fabrication of biomaterial fibres that could extend the feature resolution and material functionality of soft tissue constructs. The outlook from this review discusses how one might create and simulate microenvironmental cues in vitro. A fabrication platform that integrates the competencies of different biofabrication technologies is proposed. Such a multi-process, multiscale fabrication strategy may ultimately translate engineering capability into an accessible life sciences toolkit, fulfilling its potential to deliver in vitro disease models and engineered tissue implants.

关键词： 3d bioprinting Electrospinning Additive manufacturing Microenvironment disease modelling Tissueengineering

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FUNdAMENTAl PROBlEMS IN PUlSEd-BIAS ARC dEPOSITION

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Acta Metallurgica Sinica(English letters) 2002年第1期15卷 91-103页

作者： G.Q. lin Z.F. ding d. Qi N.H. Wang M.d. huang d.Z. Wang Y.N. Wang C. dong l.S. Wen The State Key laboratory for Materials Modification by laser Ion and Electron Beams Dalian Uni-versity of Technology Dalian 116024 China department of Electromagnetic Engineering Dalian University of Technology Dalian 116024 China The State Key laboratory for Materials Modification by laser Ion and Electron Beams Dalian Uni-versity of Technology Dalian 116024 China Institute of Metals Research The Chinese Academy of Sciences Shenyang 110016 China Institute of Metals Research The Chinese Academy of Sciences Shenyang 110016 China

Arc deposition, a widely used surface coating technique, has disadvantages such as large droplet size and high deposition temperature. Recent trend in its renovation is the introduction of pulsed bias at the. substrate. The present paper attempts to describe the deposition process of TiN films using this technique with emphasis laid on the understanding of the basic problems such as discharge plasma properties, temperature calculation, and droplet size reduction. We show that this technique improves the film micro structure and quality, lowers deposition temperature, and allows coatings on insulating substrates. After analyzing load current oscillation behaviors, we have determined that the plasma load is of capacitance nature due to plasma sheath and that it is equivalent to a circuit element consisting of parallel capacitance and resistance. At last, we point out the remaining problems and future development of the pulsed-bias arc deposition technique.

关键词： arc deposition pulsed bias plasma

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Tumor initiation and early tumorigenesis:molecular mechanisms and interventional targets

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2900-2935页

作者： Shaosen Zhang xinyi Xiao Yonglin Yi Xinyu Wang lingxuan Zhu Yanrong Shen dongxin lin Chen Wu department of Etiology and Carcinogenesis National Cancer Center/National Clinical Research Center/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical College100021 BeijingChina Key laboratory of Cancer Genomic Biology Chinese Academy of Medical Sciences and Peking Union Medical College100021 BeijingChina Changping laboratory 100021 BeijingChina Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaGuangzhou 510060China CAMS Oxford Institute Chinese Academy of Medical Sciences100006 BeijingChina

Tumorigenesis is a multistep process,with oncogenic mutations in a normal cell conferring clonal advantage as the initial ***,despite pervasive somatic mutations and clonal expansion in normal tissues,their transformation into cancer remains a rare event,indicating the presence of additional driver events for progression to an irreversible,highly heterogeneous,and invasive ***,researchers are emphasizing the mechanisms of environmental tumor risk factors and epigenetic alterations that are profoundly influencing early clonal expansion and malignant evolution,independently of inducing ***,clonal evolution in tumorigenesis reflects a multifaceted interplay between cell-intrinsic identities and various cell-extrinsic factors that exert selective pressures to either restrain uncontrolled proliferation or allow specific clones to progress into ***,the mechanisms by which driver events induce both intrinsic cellular competency and remodel environmental stress to facilitate malignant transformation are not fully *** this review,we summarize the genetic,epigenetic,and external driver events,and their effects on the co-evolution of the transformed cells and their ecosystem during tumor initiation and early malignant evolution.A deeper understanding of the earliest molecular events holds promise for translational applications,predicting individuals at high-risk of tumor and developing strategies to intercept malignant transformation.

关键词： alterations mechanisms restrain

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Phase Transitions and Structures of Poly(ethylene-co-chlorotrifluoroethylene)

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应用化学 2001年第5期18卷 301-309页

作者： J.M.dEITZEl Bojie WANG Ping huang l.lawrence CHAPOY Stephen Z.d.CHENG The Maurice Morton Institute and department of Polymer Science The University of AkronAkron Ohio 44325-3909U.S.A.

Poly(ethylene- co -chlorotrifluoroethylene) with a 1∶1 molar ratio of ethylene and chlorotrifluoroethylene in composition, PECTFE, is a statistically alternating copolymer widely used in cable coating industry. PECTFE has been commonly characterized as a semicrystalline polymer with crystals melting at 238 ℃. differential scanning calorimetry, thermal mechanical analysis and dynamic mechanical analysis indicated that PECTFE undergoes a reversible solid-solid transition during cooling and heating in the temperature range between 100 ℃ and 200 ℃. Based on detailed structural analysis via wide angle X-ray diffraction and electron diffraction techniques, we proposed that PECTFE possesses a hexagonal phase above 200 ℃( a =0 60 nm, c =0 49 nm) and an orthorhombic phase( a =0 99 nm, b =0 57 nm, c =0 49 nm) at room temperature.

关键词：乙烯 1-氯-3氟乙烯共聚物结构

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MEK inhibition prevents CAR-T cell exhaustion and differentiation via downregulation of c-Fos and JunB

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SIGNAl TRANSdUCTION ANd TARGETEd THERAPY 2024年第1期9卷 1-19页

作者： Wang, Xiujian Tao, Xiao Chen, Pengjie Jiang, Penglei li, Wenxiao Chang, Hefeng Wei, Cong lai, xinyi Zhang, Hao Pan, Yihan ding, lijuan liang, Zuyu Cui, Jiazhen Shao, Mi Teng, xinyi Gu, Tianning Wei, Jieping Kong, delin Si, Xiaohui Han, Yingli Fu, Huarui lin, Yu Yu, Jian li, Xia Wang, dongrui Hu, Yongxian Qian, Pengxu huang, He Zhejiang Univ Affiliated Hosp 1 Bone Marrow Transplantat Ctr Sch Med Hangzhou 310003 Peoples R China Zhejiang Univ Med Ctr Liangzhu Lab Liangzhu Lab 1369 West Wenyi Rd Hangzhou 311121 Peoples R China Zhejiang Univ Inst Hematol Hangzhou 310003 Peoples R China Zhejiang Prov Engn lab Stem Cell & Immun Therapy Hangzhou 310003 Peoples R China Zhejiang Univ Ctr Stem Cell & Regenerat Med Sch Med Hangzhou 310058 Peoples R China Wenzhou Med Univ Affiliated Hosp 3 Dept Hematol Wenzhou 325200 Peoples R China

Clinical evidence supports the notion that T cell exhaustion and terminal differentiation pose challenges to the persistence and effectiveness of chimeric antigen receptor-T (CAR-T) cells. MEK1/2 inhibitors (MEKIs), widely used in cancer treatment due to their ability to inhibit aberrant MAPK signaling, have shown potential synergistic effects when combined with immunotherapy. However, the impact and mechanisms of MEKIs on CAR-T cells remain uncertain and controversial. To address this, we conducted a comprehensive investigation to determine whether MEKIs enhance or impair the efficacy of CAR-T cells. Our findings revealed that MEKIs attenuated CAR-T cell exhaustion and terminal differentiation induced by tonic signaling and antigen stimulation, thereby improving CAR-T cell efficacy against hematological and solid tumors. Remarkably, these effects were independent of the specific scFvs and costimulatory domains utilized in CARs. Mechanistically, analysis of bulk and single-cell transcriptional profiles demonstrates that the effect of MEK inhibition was related to diminish anabolic metabolism and downregulation of c-Fos and JunB. Additionally, the overexpression of c-Fos or JunB in CAR-T cells counteracted the effects of MEK inhibition. Furthermore, our Cut-and-Tag assay revealed that MEK inhibition downregulated the JunB-driven gene profiles associated with exhaustion, differentiation, anergy, glycolysis, and apoptosis. In summary, our research unveil the critical role of the MAPK-c-Fos-JunB axis in driving CAR-T cell exhaustion and terminal differentiation. These mechanistic insights significantly broaden the potential application of MEKIs to enhance the effectiveness of CAR-T therapy.

关键词： JunB metabolism stimulation

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