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Identification of microbial metabolites that accelerate the ubiquitindependent degradation of c-Myc

Oncology Research 2023年第5期31卷 655-666页

作者： ZIYU LIU AKIKO OKANO EMIKO SANADA YUSHI FUTAMURA TOSHIHIKO NOGAWA KOSUKE ISHIKAWA KENTARO SEMBA JIANG LI XIAOMENG LI HIROYUKI OSADA NOBUMOTO WATANABE Bioprobe Application Research Unit RIKEN CSRSSaitama351-0198Japan graduate School of Medical and Dental Sciences Tokyo Medical and Dental UniversityTokyo113-8510Japan Chemical Biology Research Group RIKEN CSRSSaitama351-0198Japan Chemical Resource Development Research Unit RIKEN CSRSSaitama351-0198Japan Molecular Structure Characterization Unit RIKEN CSRSSaitama351-0198Japan Japan Biological Informatics Consortium(JBIC) Tokyo135-8073Japan Department of Life Science and Medical bioscience School of Advanced Science and EngineeringWaseda UniversityTokyo162-8480Japan Medical-Industrial Translational Research Center Fukushima Medical UniversityFukushima960-1295Japan Guangdong Engineering Research Center of Oral Restoration and Reconstruction Affiliated Stomatology Hospital of Guangzhou Medical UniversityGuangzhouChina KingMed School of Laboratory Medicine Guangzhou Medical UniversityGuangzhouChina Department of Pharmaceutical Sciences University of ShizuokaShizuoka422-8526Japan

Myc belongs to a family of proto-oncogenes that encode transcription *** overexpression of c-Myc causes many types of ***,we established a system for screening c-Myc inhibitors and identified antimycin A by screening the RIKEN NPDepo chemical *** specific mechanism of promoting tumor cell metastasis by high c-Myc expression remains to be *** this study,we screened approximately 5,600 microbial extracts using this system and identified a broth prepared from Streptomyces ***19-A0402 strongly inhibits c-Myc transcriptional *** purification of the hit broth,we identified compounds closely related to the aglycone of cytovaricin and had a structure similar to that of oligomycin *** to oligomycin A,the hit compounds inhibited mitochondrial complex *** mitochondria dysfunction caused by the compounds induced the production of reactive oxygen species(ROS),and the ROS activated GSK3α/βthat phosphorylated c-Myc for *** study provides a successful screening strategy for identifying natural products as potential c-Myc inhibitors as potential anticancer agents.

关键词： High-throughput screening Phosphorylation Reactive oxygen species

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Ectopic Tcf1 expression instills a stem-like program in exhausted CD8^(+) T cells to enhance viral and tumor immunity

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Cellular & Molecular Immunology 2021年第5期18卷 1262-1277页

作者： Qiang Shan Sheng’en Hu Xia Chen Derek B.Danahy Vladimir P.Badovinac Chongzhi Zang Hai-Hui Xue Center for Discovery and Innovation Hackensack Meridian HealthNutleyNJ07110USA Department of Microbiology and Immunology Carver College of MedicineUniversity of IowaIowa CityIA52242USA Center for Public Health Genomics University of Virginia School of MedicineCharlottesvilleVA22908USA Department of Pathology Carver College of MedicineUniversity of IowaIowa CityIA52242USA interdisciplinary Immunology graduate Program Carver College of MedicineUniversity of IowaIowa CityIA52242USA Iowa City Veterans Affairs Health Care System Iowa CityIA52246USA

Exhausted CD8^(+)T(Tex)cells are dysfunctional due to persistent antigen exposure in chronic viral infection and tumor contexts.A stem cell-like Tex(Tex-stem)subset can self-renew and differentiate into terminally exhausted(Tex-term)***,we show that ectopic Tcf1 expression potently promoted the generation of Tex-stem cells in both a chronic viral infection and preclinical tumor ***1 overexpression diminished coinhibitory receptor expression and enhanced polycytokine-producing capacity while retaining a heightened responses to checkpoint blockade,leading to enhanced viral and tumor ***,ectopically expressed Tcf1 exploited existing and novel chromatin accessible sites as transcriptional enhancers or repressors and modulated the transcriptome by enforcing pre-existing expression patterns in Tex-stem cells,such as enhanced suppression of Blimp1 and Bim and acquisition of new downstream genes,including Mx1,Tox2,and *** findings reveal a pronounced impact of ectopic Tcf1 expression on Tex functional restoration and highlight the therapeutic potential of harnessing Tcf1-enforced transcriptional programs.

关键词： T cell exhaustion Tcf1 Stem cell features

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Molecular Dynamics Simulation of Bombardment of Hydrogen Atoms on Graphite Surface

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Communications in Computational Physics 2008年第8期4卷 592-610页

作者： A.Ito H.Nakamura Department of Physics Graduate School of ScienceNagoya UniversityFuro-choChikusa-kuNagoya 464-8602Japan Department of Simulation Science National Institute for Fusion Science322-6 Oroshi-choToki 509-5292Japan

The new potential model of interlayer intermolecular interaction was proposed to represent“ABAB”stacking of *** bombardment of hydrogen atoms on the graphite surface was investigated using molecular dynamics *** the first graphene fromthe surface side was broken,the hydrogen atoms caused the following *** the case of the incident energy of 5 eV,many hydrogen atoms were adsorbed on the front of the first *** the case of the incident energy of 15 eV,almost all hydrogen atoms were reflected by the first *** the case of the incident energy of 30 eV,the hydrogen atoms were adsorbed between the first and second *** radial distribution function and the animation of the MD simulation demonstrated that the graphenes were peeled off one by one,which is called graphite *** C2H2 was generated in such chemical *** the other yieldedmolecules often had chain structures terminated by the hydrogen *** erosion yield increased linearly with time.

关键词： Plasma surface interaction chemical sputtering graphite graphene hydrogen atom

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A study on the interaction between ferric ion and silicic acid in hydrosphere: Si-containing ferruginous deposits formed in neutral hot spring waters

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Chinese Journal Of Geochemistry 2013年第1期32卷 27-34页

作者： Gaowa Naren Akane Miyazaki Motoyuki Matsuo BAI Shuqin Kotaro Yonesu Yoshihiro Okaue Takushi Yokoyama Department of Chemistry Faculty of Science Kyushu University Department of Chemical and Biological Sciences Faculty of Science Japan Women's University Department of Chemistry Graduate School of Arts and Sciences University of Tokyo College of Environment and Resources Inner Mongolia University Department of Earth Resources Engineering Faculty of Engineering Kyushu University

Five ferruginous deposit samples formed from neutral hot springs were analyzed to determine whether they consisted of a mixture of silica, hydrous iron oxide or iron silicate by differential thermal analysis (DTA), infrared (IR) spectroscopy, powder X-ray diffraction (XRD), and 57Fe Mssbauer spectroscopy. The Si/Fe atomic ratios of the deposits ranged from 0.25 to 0.45, and were smaller than those of hisingerite (12), but apparently close to those of siliceous ferrihydrite (0.250.5). Si was confirmed to be present as monomeric or oligomeric silicate from the Si-O stretching vibration frequencies on the IR spectra. Judging from the results of DTA, which minerals starting to produce after heating, and a relationship between Si-O stretching vibration frequency and Si/Fe atomic ratio proposed by Henmi et al. (1981), all the deposits in this study were concluded to be mixtures of various siliceous ferri-hydrites with low and high Si/Fe atomic ratios. Moreover, by comparing the chemical properties of hot spring waters, the formation conditions of siliceous ferrihydrite were also discussed.

关键词：温泉水硅酸盐三价铁离子 Si 相互作用中性铁质伸缩振动频率

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