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Macrocyclic peptides containing a thiazole or thiazoline in the backbone are considered privileged structures in both natural compounds and drug discovery, owing to their enhanced bioactivity, stability, and permeability. Here, we present the biocompatible synthesis of macrocyclic peptides from N‐terminal cysteine and C‐terminal nitrile. While the N‐terminal cysteine is incorporated during solid‐phase peptide synthesis, the C‐terminal nitrile is introduced during cleavage with aminoacetonitrile, utilizing a cleavable benzotriazole linker. This method directly yields the fully functionalized linear peptide precursor. The biocompatible cyclization reaction occurs in buffer at physiological pH and room temperature. The resulting thiazoline heterocycle remains stable in buffer but hydrolyzes under acidic conditions. While such hydrolysis enables access to macrocyclic peptides with a complete amide backbone, mild oxidation of the thiazoline leads to the stable thiazole macrocyclic peptide. While conventional oxidation strategies involve metals, we developed a protocol simply relying on alkaline salt and air. Therefore, we offer a rapid and metal‐free pathway to macrocyclic thiazole peptides, featuring a biocompatible key cyclization step. [ABSTRACT FROM AUTHOR]

Type 2 innate lymphoid cells (ILC2) initiate early allergic inflammation in the lung, but the factors that promote subsequent resolution of type 2 inflammation and prevent prolonged ILC2 activation are not fully known. Here we show that SLAM-family receptors (SFR) play essential roles in this process. We demonstrate dynamic expression of several SFRs on ILC2s during papain-induced type 2 immunity in mice. SFR deficiency exacerbates ILC2-driven eosinophil infiltration in the lung, and results in a significant increase in IL-13 production by ILC2s exclusively in mediastinal lymph nodes (MLN), leading to increased dendritic cell (DC) and TH2 cell numbers. In MLNs, we observe more frequent interaction between ILC2s and bystander T cells, with T cell-expressed SFRs (especially SLAMF3 and SLAMF5) acting as self-ligands to suppress IL-13 production by ILC2s. Mechanistically, homotypic engagement of SFRs at the interface between ILC2s and T cells delivers inhibitory signaling primarily mediated by SHIP-1. This prevents activation of NF-κB, driven by IL-7 and IL-33, two major drivers of ILC2-mediated type 2 immunity. Thus, our study shows that an ILC2-DC-TH2 regulatory axis may promote the resolution of pulmonary type 2 immune responses, and highlights SLAMF3/SLAMF5 as potential therapeutic targets for ameliorating type 2 immunity. Type 2 innate lymphoid cells are instrumental to the early phases of pulmonary allergic inflammation, but the negative regulation that leads to their inhibition in the resolution phase is less known. Here authors show that SLAM-family receptors control Il-13 production and NF-κB activation in the mediastinal lymph nodes but not in the lung, eventually setting a limit to lung inflammation. [ABSTRACT FROM AUTHOR]

In China, the invasion of Spartina alterniflora is an important driver for the decrease of mangrove area and ecological service functions related to this habitat. In the past few decades, S. alterniflora clearing and mangrove restoration projects have mainly focused on the areas where it is already changed but ignored the potential distribution areas. This study suggested that implementation of mangrove protection prior to the areas with the threat of S. alterniflora invasion could greatly improve protection efficiency and save costs. Thus, using Maximum Entropy Modeling (MaxEnt), we estimated the potential spatial distribution of both mangroves and S. alterniflora in China, considering the current distribution data, topographical, sediments, sea surface temperature and bioclimatic variables. What's more, we identified and calculated the potential distributed areas in each province. We aimed to explore (i) the key factors determining the distribution of mangrove and Spartina alterniflora along the coastline and (ii) the hotspots of their competitive occurrence, including S. alterniflora invasion areas and mangroves degradation areas, in order to support mangrove conservation. The model showed that the distance to the coastline and the topography play important roles in the distribution of S. alterniflora, while mangroves were more sensitive to the range of the annual sea surface temperature. Our results furthermore confirm that S. alterniflora has a wider potential distribution area (~10,585 km2) than mangroves (~9124 km2) at the coastline of China; and predict the provinces Zhangzhou, Quanzhou, Zhanjiang, Beihai and Wenzhou as hotspots for the competition between mangroves and S. alterniflora. We propose that priority should be given to the protection or restoration of mangrove plants in those areas which are co-suitable for mangroves and S. alterniflora. In these areas, management measures should be conducted that hinder S. alterniflora invasions or clear existing S. alterniflora plants, firstly. This study provides guidance for the management of native species by preventing biological invasion. [ABSTRACT FROM AUTHOR]