CircRNA_0075723 protects against pneumonia-induced sepsis through inhibiting macrophage pyroptosis by sponging miR-155-5p and regulating SHIP1 expression

IntroductionCircular RNAs (circRNAs) have been linked to regulate macrophage polarization and subsequent inflammation in sepsis. However, the underlying mechanism and the function of circRNAs in macrophage pyroptosis in pneumonia-induced sepsis are still unknown.MethodsIn this study, we screened the differentially expressed circRNAs among the healthy individuals, pneumonia patients without sepsis and pneumonia-induced sepsis patients in the plasma by RNA sequencing (RNA-seq). Then we evaluated macrophage pyroptosis in sepsis patients and in vitro LPS/nigericin activated THP-1 cells. The lentiviral recombinant vector for circ_0075723 overexpression (OE-circ_0075723) and circ_0075723 silence (sh-circ_0075723) were constructed and transfected into THP-1 cells to explore the potential mechanism of circ_0075723 involved in LPS/nigericin induced macrophage pyroptosis.ResultsWe found circ_0075723, a novel circRNA that was significantly downregulated in pneumonia-induced sepsis patients compared to pneumonia patients without sepsis and healthy individuals. Meanwhile, pneumonia-induced sepsis patients exhibited activation of NLRP3 inflammasome and production of the pyroptosis-associated pro-inflammatory cytokines IL-1β and IL-18. circ_0075723 inhibited macrophage pyroptosis via sponging miR-155-5p which promoted SHIP1 expression directly. Besides, we found that circ_0075723 in macrophages promoted VE-cadherin expression in endothelial cells through inhibiting the release of NLRP3 inflammasome-related cytokines, IL-1β and IL-18, and protects endothelial cell integrity.DiscussionOur findings propose a unique approach wherein circ_0075723 suppresses macrophage pyroptosis and inflammation in pneumonia-induced sepsis via sponging with miR-155-5p and promoting SHIP1 expression. These findings indicate that circRNAs could be used as possible potential diagnostic and therapeutic targets for pneumonia-induced sepsis

Thermomechanical fatigue damage mechanism and life assessment of a single crystal Ni-based superalloy

The thermomechanical fatigue (TMF) of single-crystal air-cooled turbine blades is critical for accurately evaluating the lifetimes of advanced aero-engines. The present work focuses on the mechanical behavior and damage mechanism of a single-crystal Ni-based superalloy (DD6) under stress-controlled TMF loading, and in-phase (IP) and out-of-phase (OP) mode of TMF were conducted and compared with low cycle fatigue (LCF) loading. A ratcheting effect is observed during the deformation of DD6 under TMF loading, and the direction and size of the ratcheting strain are considerably influenced by the phase angle and mechanical load. The ratcheting strain increases with mechanical load and dwell time at high temperature, consequently shortening the lifetime of the material. The key factors affecting the TMF damage of DD6 are identified through a SEM analysis, which shows that the damage under IP TMF loading mainly comes from creep and fatigue, whereas that under OP TMF loading is dominated by oxidation and fatigue. Based on the critical plane approach, a fatigue life prediction model is proposed considering the ratcheting effect to predict the fatigue life of DD6 under TMF loading. The good agreement between the proposed model and experimental data indicates that the model has the potential to predict the fatigue life of DD6 under TMF loading. (c) 2021 Elsevier B.V. All rights reserved