Objective: Tofacitinib (TOF) is a Janus kinase (JAK) inhibitor used in the treatment of rheumatoid arthritis (RA), but the mechanism of its action remains unclear. In this study, we investigated the influence of TOF on gamma delta regulatory T-cell (γδTreg)/γδT17 cell balance in RA and the role of the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome in this process. Methods: We detected levels of inflammatory factors in the serum of RA patients before and after administration of TOF using an enzyme-linked immunosorbent assay (ELISA). A collagen-induced arthritis (CIA) model was constructed to investigate the effect of TOF on arthritis symptoms, γδTreg/γδT17 cell balance and the NLRP3 inflammasome. We used bone marrow-derived macrophages (BMDMs) to study the effect of TOF on NLRP3 inflammasome activation. Nlrp 3 -/- mice were introduced to assess the influence of NLRP3 on γδT17 cell activation in RA. Results: TOF treatment decreased levels of γδT17 cell-related cytokine interleukin-17 (IL-17) in RA patients. In addition, TOF intervention in the CIA model reduced joint inflammation and damage, rebalanced the γδTreg/γδT17 cell ratio and inhibited excessive NLRP3 inflammasome activation in draining lymph nodes and arthritic joints. BMDM intervention experiments demonstrated that TOF decreased the level of secreted IL-1β via downregulation of NLRP3. Furthermore, experiments using Nlrp3 -/- mice verified that the NLRP3 inflammasome mediated the effect of TOF on γδT17 cell activation. Conclusions: Recovery of γδTreg/γδT17 cell balance was a novel mechanism by which TOF alleviated RA. Meanwhile, NLRP3 played a pivotal role in the process of TOF-mediated γδT17 cell activation.

In order to improve the response ability of journalists to public emergencies, this study uses the computer simulation research method, based on Shannon’s information theory and the basic theory of journalism and communication, constructs the general model of public emergencies based on the statistical results of big data, and constructs the irrational natural person game model of four types of news communication participants. In the simulation analysis, it is found that in the face of public emergencies, journalists, on the one hand, firmly implement the publicity caliber, strengthen the amount of creation, and improve the forwarding amount and approval amount of manuscripts under the artificial intelligence news system. On the other hand, they should achieve effective interaction with nonofficial news media such as we media, and the subjective news department should provide effective guidance and guidance to the media.

The entanglement witness is an important tool to detect entanglement. In 2017 an idea considering a pair of Hermitian operators in product form was published, which is called ultrafine entanglement witnessing. In 2018 some rigorous results were given. Here we improve their work. First we point this idea can be directly derived from an earlier concept named joint separable numerical range and explain how it works as a series of witnesses. Second by a simple method we present a sufficient condition for an effective pair. Finally we prove this condition is necessary for optimization. [M Gachechiladze et al 2018 J. Phys. A: Math. Theor. 51 36].

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