Type-I interferons (IFN-I) are used as common antiviral drugs for a range of viral diseases in clinic. However, the antiviral efficacy of IFN-I is largely restricted by negative regulators of IFN-I signaling in cells. Therefore, identification of intracellular inhibitors of IFN-I signaling is important for developing novel targets to improve IFN-I antiviral therapy. In this study, we report that the deubiquitinase ubiquitin-specific protease 7 (USP7) negatively regulates IFN-I-mediated antiviral activity. USP7 physically interacts with suppressor of cytokine signaling 1 (SOCS1) and enhances SOCS1 protein stability by deubiquitination effects, which in turn restricts IFN-I-induced activation of Janus kinase-signal transducer and activator of transcription 1 signaling. Interestingly, viral infection up-regulates USP7 and therefore facilitates viral immune evasion. Importantly, the USP7 small-molecule inhibitors P5091 and P22077 inhibit SOCS1 expression and enhance IFN-I antiviral efficacy. Our findings identify a novel regulator of IFN-I antiviral activity and reveal that USP7 inhibitors could be potential enhancement agents for improving IFN-I antiviral therapy.
Chlorine fluxing is widely used in the aluminum industry for the removal of magnesium from molten aluminum. Typically, it consists of bubbling a nitrogen/chlorine or argon/chlorine mixture into the melt. This Part I of a two-part article describes laboratory-scale experiments on the kinetics of the reactions and emissions during chlorine fluxing for magnesium removal. Bubble frequency, size, and residence time were measured by a two-microphone detection system, which lead to an estimate of the melt-gas interfacial area. Emissions were found to be low, provided the melt temperature was above the melting point of magnesium chloride and provided the magnesium content was above a critical level. Experimental results suggested the chlorine supply to be the rate-determining factor above this critical level and magnesium mass transport to be the rate-determining factor below the critical level.
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