Sepsis is a life-threatening condition caused by an immune response triggered by infection, and highly elevated cytokine/chemokine levels in the blood play crucial roles in the progression of sepsis. Serum exosomes are nanovesicles that have multiple biological functions, playing roles in antigen presentation, intercellular signal communication, inflammatory response and immune surveillance. However, the biological functions and related molecular bases remain to be elucidated. In this study, we investigated the profiles of cytokines/chemokines harbored in the exosomes of septic mice and explored the mechanisms of immunomodulation on T cells treated with exosomes harvested from septic mice. Blood cytokines/chemokines existed in both the soluble form and in the insoluble exosomal form; the profiles of the cytokines/chemokines in these two forms displayed different dynamics in the blood of mice challenged with LPS. Exosomes from septic mice induced the differentiation of Th1/Th2 cells, which was blocked by specific antibodies targeting IL-12 and IL-4. In addition, these exosomes significantly augmented the proliferation and migration of T lymphocytes. Furthermore, preadministration of exosomes by intravenous injection restrained the inflammatory response, attenuated lung and liver tissue damage, and prolonged the survival of cecal ligation and puncture (CLP) mice. Our results indicate that exosomes enriched with cytokines/chemokines play critical roles in T cell differentiation, proliferation and chemotaxis during the sepsis process and have a protective effect on cecal ligation and puncture (CLP) mice. Thus, these findings not only strengthen our understanding of the role of sepsis via exosomes but also provide potential targets for therapeutic applications.

It is necessary to explore new molecules for the improvement of precise diagnosis and antitumor therapies in lung cancer. LncRNAs (long non-coding RNAs) play an important role in the regulation of cancer cell malignant behavior and tumor development. In this work, we found that a newly discovered lncRNA, lncRNA PGM5P4-AS1, was lower expressed in lung cancer tissues than adjacent tissues. Then, the lncRNA PGM5P4-AS1 was overexpressed or knocked-down in different lung cancer cells, and its effects on the malignant phenotypes were measured by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay, cell cycle assay, wound healing assay, and transwell assay. The results showed that the overexpression of PGM5P4-AS1 inhibited lung cancer cell proliferation, migration, and invasion activities, while these abilities were prominently promoted by the interference of PGM5P4-AS1. Further, the growth of lung cancer tumors in nude mice was also inhibited by PGM5P4-AS1 overexpression. In mechanism, PGM5P4-AS1 has the binding site of miR-1275 and could positively regulate the expression of LZTS3 via sponging miR-1275. In conclusion, PGM5P4-AS1 could be a potential precise diagnosis and therapeutic target biomarker of lung cancer.

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Myeloid-related protein 8/14 (MRP8/14) participates in various inflammatory responses, however, its effect on macrophage efferocytosis remains unclear. Here, we demonstrate that MRP8/14 significantly inhibits the efferocytosis of apoptotic thymocytes by mouse bone marrow-derived macrophages (BMDMs), which later proves to be associated with the receptor for advanced glycation end products (RAGE) or for reducing the expression of growth arrest-specific protein 6 and milk fat globule epidermal growth factor 8, independent of RAGE. Furthermore, MRP8/14 promotes polarization of BMDMs from the M 2to M 1-like phenotype by upregulating expression of M 1-related surface receptor proteins and signature M 1-marker genes and by downregulating signature M 2-marker gene expression, which depends on Toll-like receptor 4 and p38 mitogen-activated protein kinase/nuclear factor κB pathways. Thus, we report a significant inhibitory effect of MRP8/14 on macrophage efferocytosis and MRP8/14-mediated phenotypic polarization, which may be helpful in developing novel therapeutic strategies leading to inflammation resolution. K E Y W O R D S efferocytosis, myeloid-related protein, polarization, receptor of advanced glycation end products, Toll-like receptor 4 1 | INTRODUCTION Efferocytosis refers to the engulfment and removal of apoptotic cells from inflammatory sites by macrophages, which is beneficial for resolving inflammation (Headland & Norling, 2015; Henson, 2017). During apoptosis, cellular phosphatidylserine (PtdSer) is flipped to the outer side of the membrane, allowing recognition and binding by macrophages either through PtdSer receptors such as receptors of advanced glycation end products (RAGE) or the assistance of bridging molecules such as growth arrest-specific protein 6 (Gas6) and milk fat globule epidermal growth factor 8 (MFG-E8; Greenlee-Wacker, 2016; Ravichandran, 2010). Gas6 links PtdSer to the protooncogene Mer tyrosine kinase (MerTK) on macrophages, and MFG-E8 bridges externalized PtdSer and α v β 3 integrin (Elliott, Koster, & Murphy, 2017; Gilroy & De Maeyer, 2015). In addition, efferocytosis can be triggered by various inflammatory mediators, such as lipopolysaccharide (LPS; Feng et al., 2011) and high-mobility group box 1

In this paper, the role of surface reactions in the explosion limits of hydrogen−oxygen mixtures was investigated, which was found to substantially affect the limits. Specifically, we compared situations with and without surface reactions by considering various sticking coefficients, with the temperature exponents of the radicals varying simultaneously and individually, site density of surface and no surface reactions, dilutions of four gases, equivalence ratio of H 2 and O 2 , reactor size (sphere radii), and residence time. The specific roles of these factors were identified, demonstrating that the existence of surface reactions can substantially modify the explosion limits and that the simulation can accurately predict the experimental data from both the closed vessel and flow reactor by accounting for the surface reactions.