No abstract

Hermansky-Pudlak syndrome (HPS) comprises a group of inherited disorders caused by mutations that alter the function of lysosome-related organelles. Pulmonary fibrosis is the major cause of morbidity and mortality in HPS-1 and HPS-4 patients. However, the mechanisms that underlie the exaggerated injury and fibroproliferative repair responses in HPS have not been adequately defined. In particular, although Galectin-3 (Gal-3) is dysregulated in HPS, its roles in the pathogenesis of HPS have not been adequately defined. In addition, although chitinase 3-like 1 (CHI3L1) and its receptors play major roles in the injury and repair responses in HPS, the ability of Gal-3 to interact with or alter the function of these moieties has not been evaluated. In this article, we demonstrate that Gal-3 accumulates in exaggerated quantities in bronchoalveolar lavage fluids, and traffics abnormally and accumulates intracellularly in lung fibroblasts and macrophages from bleomycin-treated pale ear, HPS-1-deficient mice. We also demonstrate that Gal-3 drives epithelial apoptosis when in the extracellular space, and stimulates cell proliferation and myofibroblast differentiation when accumulated in fibroblasts and M2-like differentiation when accumulated in macrophages. Biophysical and signaling evaluations also demonstrated that Gal-3 physically interacts with IL-13Rα2 and CHI3L1, and competes with TMEM219 for IL-13Rα2 binding. By doing so, Gal-3 diminishes the antiapoptotic effects of and the antiapoptotic signaling induced by CHI3L1 in epithelial cells while augmenting macrophage Wnt/β-catenin signaling. Thus, Gal-3 contributes to the exaggerated injury and fibroproliferative repair responses in HPS by altering the antiapoptotic and fibroproliferative effects of CHI3L1 and its receptor complex in a tissue compartment-specific manner.

Electrolytic ammonia synthesis from nitrogen at ambient conditions is appearing as a promising alternative to the Haber-Bosch process which is consuming high energy and emitting CO 2 . Here, a typical MOF material, HKUST-1 (CuÀ BTC, BTC = benzene-1,3,5-tricarboxylate), was selected as an electrocatalyst for the reaction of converting N 2 to NH 3 under ambient conditions. At À 0.75 V vs. reversible hydrogen electrode, it achieves excellent catalytic performance in the electrochemical synthesis of ammonia with high NH 3 yield (46.63 μg h À 1 mg À 1 cat. or 4.66 μg h À 1 cm À 2 ) and good Faraday efficiency (2.45%). It is indicated that the good performance of the HKUST-1 catalyst may originate from the formation of Cu(I). In addition, the catalyst also has good selectivity for N 2 to NH 3 . NH 3 plays an important role in the manufacture of inorganic fertilizers, pharmaceuticals, and explosives. [1] Although the atmosphere contains about 78% of nitrogen gas, most organisms must utilize diverse methods to convert free nitrogen from the air into nitrogen-containing compounds before digesting and absorbing because of the inertness of nitrogen itself, which is known as "nitrogen fixation". [2][3][4] Compared with the traditional high energy-intensive Haber-Bosch method, electrochemical NH 3 synthesis can be operated at normal temperature and pressure with the advantages of simple equipments and without releasing a large amount of CO 2 . [5] However, the slow kinetics of N 2 adsorption and the strong N � N bond energy lead to a low efficiency of the NH 3 yields. Hence, stable and efficient electrocatalysts are needed to run the N 2 reduction reaction (NRR) at ambient conditions. Although noble metal materials exhibit high catalytic activity in the electrochemical synthesis of NH 3 , [6][7][8][9] the defects of high cost and low storage are the biggest obstacles for large scale usage. Therefore, substantial efforts have been devoted to nonprecious metal electrocatalysts which are abundant in earth as an extremely promising alternative for the electrochemical synthesis of NH 3 . [10][11][12][13][14][15][16][17][18] Metal-organic frameworks (MOFs) have ultra-high specific surface area, unsaturated metal sites, extended frame structure, and adjustable functions. [19] Based on these unique characteristics, MOFs have been used widely in the field of hydrogen storage, [20,21] gas adsorption and separation, [22][23][24][25][26] light, [27] electricity, [28,29] and magnetic. [30] HKUST-1 (CuÀ BTC, BTC = benzene-1,3,5-tricarboxylate) with Cu(II) nodes coordinated by negatively charged BTC linkers exhibits a octahedral cages structure with large cavities, and unsaturated Cu sites act as strong adsorption part of various molecules or water vapor. [31][32][33][34] During the electrochemical reduction, Cu(II) can be transformed into to Cu 2 O/Cu(0) induced by the potential, which increases the electro-conductivity and is likely to be the catalytically active species. [35,36] Inspired by this, we studied the N 2 to NH 3 catalytic acti...

Introduction. Evidence has linked exogenous and endogenous sex hormones with the human microbiome. Hypothesis/Gap statement. The longitudinal effects of oral contraceptives (OC) on the human gut microbiome have not previously been studied. Aim. We sought to examine the longitudinal impact of OC use on the taxonomic composition and metabolic functions of the gut microbiota and endogenous sex steroid hormones after initiation of OC use. Methodology. We recruited ten healthy women who provided blood and stool samples prior to OC use, 1 month and 6 months after starting OC. We measured serum levels of sex hormones, including estradiol, progesterone, sex hormone-binding globulin (SHBG), and total testosterone. Shotgun metagenomic sequencing was performed on DNA extracted from faecal samples. Species and metabolic pathway abundances were determined using MetaPhlAn2 and HUMAnN2. Multivariate association with linear models was used to identify microbial species and metabolic pathways associated with OC use and endogenous levels of sex hormones. Results. The percentage variance of the microbial community explained by individual factors ranged from 9.9 % for age to 2.7 % for time since initiation of OC use. We observed no changes in the diversity or composition of the gut microbiome following OC initiation. However, the relative abundance of the biosynthesis pathways of peptidoglycan, amino acids (lysine, threonine, methionine, and tryptophan), and the NAD salvage pathway increased after OC initiation. In addition, serum levels of estradiol and SHBG were positively associated with Eubacterium ramulus, a flavonoid-degrading bacterium. Similarly, microbes involving biosynthesis of l-lysine, l-threonine, and l-methionine were significantly associated with lower estradiol, SHBG, and higher levels of total testosterone. Conclusion. Our study provides the first piece of evidence supporting the association between exogenous and endogenous sex hormones and gut microbiome composition and function.