The interaction of viral nucleic acid with protein factors is a crucial process for initiating viral polymerase-mediated viral genome replication while activating pattern recognition receptor (PRR)-mediated innate immune responses. It has previously been reported that a hydrolysate of Ge-132, 3-(trihydroxygermyl) propanoic acid (THGP), shows a modulatory effect on microbial infections, inflammation, and immune responses. However, the detailed mechanism by which THGP can modify these processes during viral infections remained unknown. Here, we show that THGP can specifically downregulate type I interferon (IFN) production in response to stimulation with a cytosolic RNA sensor RIG-I ligand 5′-triphosphate RNA (3pRNA) but not double-stranded RNA, DNA, or lipopolysaccharide. Consistently, treatment with THGP resulted in the dose-dependent suppression of type I IFN induction upon infections with influenza virus (IAV) and vesicular stomatitis virus, which are known to be mainly sensed by RIG-I. Mechanistically, THGP directly binds to the 5′-triphosphate moiety of viral RNA and competes with RIG-I-mediated recognition. Furthermore, we found that THGP can directly counteract the replication of IAV but not EMCV (encephalitismyocarditis virus), by inhibiting the interaction of viral polymerase with RNA genome. Finally, IAV RNA levels were significantly reduced in the lung tissues of THGP-treated mice when compared with untreated mice. These results suggest a possible therapeutic implication of THGP and show direct antiviral action, together with the suppressive activity of innate inflammation.
In this paper, a database of the identically-distributed inherent strain within mechanical melting zone is developed and then applied for simplified distortion analysis in multi-layer and multi-pass welding of heavy section plate. First, numerical and experimental investigations of weld angular distortion were performed for multi-layer and multi-pass welding of heavy section plate to verify the simplified weld distortion analysis based on the theory of inherent strain. Next, the effect of residual stress due to precedent welding pass on inherent strain produced in current welding pass was investigated based on the fundamental bead-on-plate model to improve a database of the identically-distributed inherent strain within mechanical melting zone, which was already developed for single pass welding, for multi-layer and multi-pass welding. The usefulness of the developed database of inherent strain was validated for simplified distortion analysis in multi-layer and multi-pass welding of heavy section plate. Then, the simplified weld distortion analysis based on developed database of inherent strain was applied to quantify the effect of weld pass sequence on angular distortion in multi-layer and multi-pass welding of heavy section plate. Based on the results, the developed system can be expected to be a useful weld design support tool for accurately predicting weld distortion and managing construction quality in welded large structures.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.