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  • 1
    Online Resource
    Online Resource
    Complete loss of miR-200 family induces EMT associated cellular senescence in gastric cancer
    Springer Science and Business Media LLC ; 2022
    In:  Oncogene Vol. 41, No. 1 ( 2022-01-03), p. 26-36
    Details
    In: Oncogene, Springer Science and Business Media LLC, Vol. 41, No. 1 ( 2022-01-03), p. 26-36
    Abstract: The EMT (epithelial-to-mesenchymal-transition) subtype of gastric cancer (GC) is associated with poor treatment responses and unfavorable clinical outcomes. Despite the broad physiological roles of the micro-RNA (miR)-200 family, they largely serve to maintain the overall epithelial phenotype. However, during late-stage gastric tumorigenesis, members of the miR-200 family are markedly suppressed, resulting in the transition to the mesenchymal state and the acquisition of invasive properties. As such, the miR-200 family represents a robust molecular marker of EMT, and subsequently, disease severity and prognosis. Most reports have studied the effect of single miR-200 family member knockdown. Here, we employ a multiplex CRISPR/Cas9 system to generate a complete miR-200 family knockout (FKO) to investigate their collective and summative role in regulating key cellular processes during GC pathogenesis. Genetic deletion of all miR-200s in the human GC cell lines induced potent morphological alterations, G1/S cell cycle arrest, increased senescence-associated β-galactosidase (SA-β−Gal) activity, and aberrant metabolism, collectively resembling the senescent phenotype. Coupling RNA-seq data with publicly available datasets, we revealed a clear separation of senescent and non-senescent states amongst FKO cells and control cells, respectively. Further analysis identified key senescence-associated secretory phenotype (SASP) components in FKO cells and a positive feedback loop for maintenance of the senescent state controlled by activation of TGF-β and TNF-α pathways. Finally, we showed that miR-200 FKO associated senescence in cancer epithelial cells significantly recruited stromal cells in the tumor microenvironment. Our work has identified a new role of miR-200 family members which function as an integrated unit serving to link senescence with EMT, two major conserved biological processes.
    Type of Medium: Online Resource
    ISSN: 0950-9232 , 1476-5594
    URL: Article
    DOI: 10.1038/s41388-021-02067-y
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2008404-3
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  • 2
    Online Resource
    Online Resource
    Blocking Pannexin1 Channels Alleviates Thalamic Hemorrhage-Induced Pain and Inflammatory Depolarization of Microglia in Mice
    American Chemical Society (ACS) ; 2023
    In:  ACS Chemical Neuroscience Vol. 14, No. 14 ( 2023-07-19), p. 2548-2559
    Details
    In: ACS Chemical Neuroscience, American Chemical Society (ACS), Vol. 14, No. 14 ( 2023-07-19), p. 2548-2559
    Type of Medium: Online Resource
    ISSN: 1948-7193 , 1948-7193
    URL: Article
    URL: Article
    DOI: 10.1021/acschemneuro.3c00217
    DOI: 10.1021/acschemneuro.3c00217.s001
    Language: English
    Publisher: American Chemical Society (ACS)
    Publication Date: 2023
    detail.hit.zdb_id: 2528493-9
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  • 3
    Online Resource
    Online Resource
    Inhibition of UBA6 by inosine augments tumour immunogenicity and responses
    Springer Science and Business Media LLC ; 2022
    In:  Nature Communications Vol. 13, No. 1 ( 2022-09-15)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2022-09-15)
    Abstract: Anti-cancer immunity and response to immune therapy is influenced by the metabolic states of the tumours. Immune checkpoint blockade therapy (ICB) is known to involve metabolic adaptation, however, the mechanism is not fully known. Here we show, by metabolic profiling of plasma samples from melanoma-bearing mice undergoing anti-PD1 and anti-CTLA4 combination therapy, that higher levels of purine metabolites, including inosine, mark ICB sensitivity. Metabolic profiles of ICB-treated human cancers confirm the association between inosine levels and ICB sensitivity. In mouse models, inosine supplementation sensitizes tumours to ICB, even if they are intrinsically ICB resistant, by enhancing T cell-mediated cytotoxicity and hence generating an immunologically hotter microenvironment. We find that inosine directly inhibits UBA6 in tumour cells, and lower level of UBA6 makes the tumour more immunogenic and this is reflected in favourable outcome following ICB therapy in human melanomas. Transplanted mouse melanoma and breast cancer cells with genetic ablation of Uba6 show higher sensitivity to ICB than wild type tumours. Thus, we provide evidence of an inosine-regulated UBA6-dependent pathway governing tumour-intrinsic immunogenicity and hence sensitivity to immune checkpoint inhibition, which might provide targets to overcome ICB resistance.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-022-33116-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2553671-0
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  • 4
    Online Resource
    Online Resource
    Solving Generalized Column Subset Selection With Heuristic Search
    Association for the Advancement of Artificial Intelligence (AAAI) ; 2018
    In:  Proceedings of the AAAI Conference on Artificial Intelligence Vol. 32, No. 1 ( 2018-04-29)
    Details
    In: Proceedings of the AAAI Conference on Artificial Intelligence, Association for the Advancement of Artificial Intelligence (AAAI), Vol. 32, No. 1 ( 2018-04-29)
    Abstract: We address the problem of approximating a matrix by the linear combination of a column sparse matrix and a low rank matrix. Two variants of a heuristic search algorithm are described. The first produces an optimal solution but may be slow, as these problems are believed to be NP-hard. The second is much faster, but only guarantees a suboptimal solution. The quality of the approximation and the optimality criterion can be specified in terms of unitarily invariant norms.
    Type of Medium: Online Resource
    ISSN: 2374-3468 , 2159-5399
    URL: Article
    DOI: 10.1609/aaai.v32i1.12197
    Language: Unknown
    Publisher: Association for the Advancement of Artificial Intelligence (AAAI)
    Publication Date: 2018
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  • 5
    Online Resource
    Online Resource
    Research on the Sensitivity of Automotive Sensors under the Background of 5G
    IOP Publishing ; 2021
    In:  Journal of Physics: Conference Series Vol. 1744, No. 2 ( 2021-02-01), p. 022028-
    Details
    In: Journal of Physics: Conference Series, IOP Publishing, Vol. 1744, No. 2 ( 2021-02-01), p. 022028-
    Abstract: With the continuous development of automotive electronics, automotive sensing technology has also appeared and has been more and more widely used. As an important part of the automotive electronic control system, automotive sensors not only need to collect information, but also transmit information. The automobile sensor first needs to convert the automobile operating condition information into electrical signals and then transmit it to the central control unit, in order to make the engine reach the best working condition. In addition, automotive sensors can also perform accurate and real-time measurement and control for information such as pressure, temperature, speed, photoelectricity and flow rate, which greatly improves the effectiveness of information processing. As a factor that can affect the safe operation of a car, the quality of the car sensor plays a direct role. Therefore, in order to ensure the safe operation of automobiles, strict requirements on the accuracy, stability, responsiveness, shock resistance and service life of automobile sensors are required. The development of modern cars is moving towards a safer and more comfortable perspective and the key to achieving this goal lies in the development of sensors. At present, the development of sensors mainly depends on the development of new sensors and the integration, intelligence and multifunction of sensors. Realize the improvement of the sensor’s working accuracy and response speed and the ability to adapt to different environments. Therefore, studying the application of sensors in the current automotive field is of great significance to the future development of the automotive field and the sensor field.
    Type of Medium: Online Resource
    ISSN: 1742-6588 , 1742-6596
    URL: Article
    DOI: 10.1088/1742-6596/1744/2/022028
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 2021
    detail.hit.zdb_id: 2166409-2
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