The contribution of geographical distance was similar for both microbial groups. © 2020 The Authors. Environmental Microbiology published by Society for Applied Microbiology and John Wiley & Sons Ltd.Atropisomers possessing multiple stereogenic axes are intriguing molecules with huge uncovered potential. As compared with molecules with multiple stereogenic centers for which countless methods exist for their stereocontrolled synthesis, only few approaches have been developed for the enantioselective synthesis of this peculiar class of atropisomers. This is due to the still under developed field of axial chirality control and also the often-low configurational stability of the stereogenic bond, rendering systems with more than one chiral axis even more difficult to assemble with high enantiocontrol. Besides these difficulties, innovative methods have emerged in recent years, opening unforeseen possibilities on future developments in the synthesis of this original class of atropisomeric compounds. This review will cover the history of the development in this field, based on a classification of the multi-axis systems according to the distance between the stereogenic axes and the strategy used to build them [aryl-aryl cross-coupling, (2+2+2) cycloaddition, dynamic kinetic resolution, central-to-axial chirality conversion, trapping chiral vinylidene-quinone methides and a very recent miscellaneous cycloisomerization strategy]. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Mast cells are immune sentinels and a driving force in both normal and pathological contexts of inflammation, with a prominent role in allergic hypersensitivities. Crosslinking of FcεRI by allergen-bound IgE Abs leads to mast cell degranulation, resulting in an early-phase response and release of newly synthesized pro-inflammatory mediators in the late-phase. The MAPK and NF-κB pathways are established as critical intracellular mechanisms directing mast cell-induced inflammation. Rosemary extract (RE) has been shown to modulate the MAPK and NF-κB pathways in other cellular contexts in vitro and in vivo. However, the effect of RE on mast cell activation has not been explored, and thus we aim to evaluate the potential of RE in modulating mast cell activation and FcεRI/c-kit signaling, potentially via these key pathways. Primary murine mast cells were sensitized with anti-TNP IgE and stimulated with cognate allergen (TNP-BSA) under stem cell factor (SCF) potentiation while treated with 0-25 µg/ml RE. RE treatment inhibited phosphorylation of p38 and JNK MAPKs while also impairing NF-кB transcription factor activity. Gene expression and mediator secretion analysis showed that RE treatment decreased IL-6, TNF, IL-13, CCL1, and CCL3, but major component polyphenols do not contribute to these effects. Importantly, RE treatment significantly inhibited early phase mast cell degranulation (down to 15% of control), with carnosic acid and carnosol contributing. These findings indicate that RE is capable of modulating mast cell functional outcomes and that further investigation of the underlying mechanisms and its potential therapeutic properties in allergic inflammatory conditions is warranted. ©2020 Society for Leukocyte Biology.Periodontal ligament stem cells (PDLSCs) from beagle dogs had the characteristics of multi-directional differentiation and had great application potential in tissue engineering and cell regenerative medicine. In this study, we analysed the odontogenesis and neuronal differentiation characteristics of PDLSCs in vitro. Results showed that the calcined tooth powder (CTP) and silver nanoparticles (AgNPs) additives could induce the PDLSCs into odontogenesis differentiation; besides, the immunofluorescence staining identified that the high dosage calcined tooth powder (400 μg/mL) significantly facilitated the odontogenesis associated with BMP4 expression. While the nutritional factor (L-glutamine, NGF (nerve growth factor), bFGF (basic fibroblast growth factor), IGF-1 (insulin-like growth factor-1) and EGF (epidermal growth factor)) additives were prior to induce the PDLSCs into neuronal differentiation. Simultaneously, PDLSCs had high proliferation ability with the different supplemented additives. Importantly, the Western blot results also proved the BMP4 and SMAD1 proteins were highly expressed in the induced odontoblast, while the SOX1, NCAM1, GFAP and VEGFA proteins were all obviously expressed in the induced neurons. Hence, PDLSCs had characteristics of both odontogenesis and neuronal differentiation. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.Most approved cancer immunotherapies lack T-regulatory (Treg) or tumor specificity. TNF receptor 2 (TNFR2) antibody antagonism is emerging as an attractive immunotherapy due to its tumor microenvironment (TME) specificity. Here we show that the human TNFR2 receptor is overexpressed on both human tumor cells and on human tumor-residing Tregs, but negligibly expressed on beneficial T effectors (Teffs). Further, we found widespread, if variable, TNFR2 expression on 788 human tumor cell lines from diverse cancer tissues. These findings provided strong rationale for developing a targeted immunotherapy using a TNFR2 antibody antagonist. We designed a novel, human-directed TNFR2 antibody antagonist and tested it for function using three cell-based TME assays. The antagonist showed TME specificity by killing of TNFR2-expressing tumor cells and Tregs, but sparing Teffs, which proliferated. However, the antagonist shuffled between five isoforms, only one of which showed the desirable function.  https://www.selleckchem.com/products/idf-11774.html  We designed and tested several new chimeric human versions of the antagonist, finding that the IgG2 isotype functioned better than the IgG1 isotype. To further improve function, we introduced targeted mutations to its amino acid sequence to stabilize the natural variability of the IgG2 isotype's hinge. Altogether, our findings suggest that optimal TNFR2 antagonists are of the human IgG2 isotype, have hinge stabilization, and have wide separation of antibody arms to bind to newly synthesized TNFR2 on rapidly growing tumor cells. Antagonistic antibodies with these characteristics, when bound to TNFR2, can form a nonsignaling cell surface dimer that functions with high TME specificity. ©2020 Society for Leukocyte Biology.