The NLRP3 inflammasome has a fundamental role in host defence against microbial pathogens and its deregulation may cause diverse inflammatory diseases. NLRP3 protein expression is a rate-limiting step for inflammasome activation, thus its expression must be tightly controlled to maintain immune homeostasis and avoid detrimental effects. However, how NLRP3 expression is regulated remains largely unknown. In this study, we identify E3 ubiquitin ligase TRIM31 as a feedback suppressor of NLRP3 inflammasome. TRIM31 directly binds to NLRP3, promotes K48-linked polyubiquitination and proteasomal degradation of NLRP3. Consequently, TRIM31 deficiency enhances NLRP3 inflammasome activation and aggravates alum-induced peritonitis in vivo. Furthermore, TRIM31 deficiency attenuates the severity of dextran sodium sulfate (DSS)-induced colitis, an inflammatory bowel diseases model in which NLRP3 possesses protective roles. Thus, our research describes a mechanism by which TRIM31 limits NLRP3 inflammasome activity under physiological conditions and suggests TRIM31 as a potential therapeutic target for the intervention of NLRP3 inflammasome related diseases.

TBK1 is essential for interferon-β (IFN-β) production and innate antiviral immunity. Here we identified the T cell anergy-related E3 ubiquitin ligase RNF128 as a positive regulator of TBK1 activation. RNF128 directly interacted with TBK1 through its protease-associated (PA) domain and catalyzed the K63-linked polyubiquitination of TBK1, which led to TBK1 activation, IRF3 activation and IFN-β production. Deficiency of RNF128 expression attenuated IRF3 activation, IFN-β production and innate antiviral immune responses to RNA and DNA viruses, in vitro and in vivo. Our study identified RNF128 as an E3 ligase for K63-linked ubiquitination and activation of TBK1 and delineated a previously unrecognized function for RNF128.

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The low permeability of silty hydrate reservoirs in the South China Sea is a critical issue that threatens safe, efficient, and long‐term gas production from these reservoirs. Hydraulic fracturing is a potentially promising stimulation technology for such low‐permeability reservoirs. Here, we assess the gas production potential of a depressurization horizontal well that is assisted by the hydraulic fracturing using numerical simulation according to field data at site SH2 in this area. In addition, the number of horizontal wells drilled is discussed if commercial production is to be performed at this site. The results show that the production potential can be significantly stimulated at the early production stage by adopting hydraulic fracturing in this reservoir due to a better depressurization effect. However, the increase in gas recovery gradually decreases with the continuous dissociation of gas hydrates, and the evolution trend is similar to that in a reservoir without stimulation during later periods of gas production because the dissociation front gradually moves away from the fractures. From the perspective of production potential, using a horizontal well scheme assisted by the hydraulic fracturing technology for gas recovery from a hydrate deposit can sharply reduce the number of operation wells, shorten the drilling operation time, and boost the economic efficiency. The horizontal well scheme may be an effective way to increase the gas yield if the application of quickly deployed horizontal wells and hydraulic fracturing techniques in such hydrate reservoirs greatly increases in the near future.

MicroRNAs (miRNAs) are small, non-coding RNAs found throughout the eukaryotes that control the expression of a number of genes involved in commitment and differentiation of hematopoietic stem cells and tumorigenesis. Widespread dysregulation of miRNAs have been found in hematological malignancies, including human acute myeloid leukemia (AML). A comprehensive understanding of the role of miRNAs within the complex regulatory networks that are disrupted in malignant AML cells is a prerequisite for the development of therapeutic strategies employing miRNA modulators. Herein, we review the roles of emerging miRNAs and the miRNAs regulatory networks in AML pathogenesis, prognosis, and miRNA-directed therapies.