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The release of extracellular vesicles (EV) by pathogenic microbes is considered an alternative cell-to-cell transport of macromolecules transport mechanism. In Gram-negative bacteria, EVs may be formed by outer membrane budding, so-called outer membrane vesicles (OMVs). Previous studies have revealed E. coli constitutively release nano-sized OMVs, which can be potent activators of cellular functions without live bacteria. But the immunomodulatory activity of E. coli OMVs is still relatively poorly understood. Here we investigated the morphological characterization and composition of E.Coli OMVs, kinetics of internalization by Raw 264.7 macrophage cells, and their immunomodulatory activity on cells. By transmission electron microscopy and dynamic light scattering, E.Coli OMVs were identified as typical cup-shaped, bilayered membranous structures, mainly distributed between 72.5 and 212.5 nm. We also demonstrated by confocal fluorescence microscopy that exposure of Raw 264.7 cells to E.Coli OMVs resulted in internalization of these nanoparticles and decreased mitochondrial membrane potential. In addition, E. Coli OMVs treatment induced the production of ROS, iNOS, IL-1β, IL-6, IL-10 and up-regulation of CD86 and CD206. Taken together, our results indicated that E.Coli OMVs are immunobiologically active, can directly interact with macrophage and participate in immune responses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Five new meroterpenoids, clavipols A-B ( 1 - 2 ) with a 12-membered ether ring and clavilactones G-I ( 3 - 5 ) having a 10-membered carbocycle connected to a hydroquinone and an α,β-epoxy/unsaturated lactone, were obtained from the fruiting bodies of the basidiomycete Clitocybe clavipes . Their structures were determined by comprehensive analysis of their spectroscopic data, and the absolute configuration of 1 was established by quantum chemical calculations of electronic circular dichroism (ECD). All the isolated compounds ( 1 - 5 ) were tested for their cytotoxic activity against three human tumor cell lines (Hela, SGC-7901, and SHG-44) in vitro after treatment for 48 h. Compound 4 exhibited moderate cytotoxic activity against Hela and SGC-7901 tumor cell lines, with IC 50 values of 23.5 and 14.5 µM, respectively., Competing Interests: References