NOD-like receptor family, pyrin domain containing 3 (NLRP3) contributes to inflammation, pyroptosis, and mucin production in human airway epithelium on rhinovirus infection.

BACKGROUND: The airway epithelium maintains mucosal homeostasis and effectively responds to pathogens. The roles of the epithelial NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome in human rhinovirus (hRV) infection and its effects mediating epithelial functional changes remain poorly understood. OBJECTIVE: We investigated the mechanisms and cellular functions mediated by the epithelial NLRP3 inflammasome on hRV infection. METHODS: Using models of primary human nasal epithelial progenitor cells and differentiated human nasal epithelial cells (hNECs) infected by hRV, we functionally examined key factors for NLRP3 inflammasome activation, cell death, and mucus production. Furthermore, NLRP3 and IL-1ß in human epithelium from nasal mucosal inflammation induced by hRV were evaluated. RESULTS: The inflammasome-mediated IL-1ß secretion and pyroptosis in human nasal epithelial progenitor cells and hNECs on hRV infection were dependent on the DDX33/DDX58-NLRP3-caspase-1-GSDMD axis. In differentiated hNECs hRV could also promote major airway epithelial mucin (MUC5AC) production through this axis. Our results further confirmed that the NLRP3 inflammasome signaling pathway was responsible for suppressing hRV replication in airway epithelium. Finally, hRV infection in chronically inflamed nasal mucosa was associated with epithelial mucus hyperproduction, whereas NLRP3 and IL-1ß expression levels were significantly increased in hRV-infected epithelium with goblet cell hyperplasia compared with normal epithelium without viral infection. CONCLUSION: The current study showed that the NLRP3 inflammasome signaling axis could functionally mediate hRV-induced inflammation, pyroptosis, and mucus production in airway epithelium, which might be an essential mechanism associated with hRV-induced airway remodeling.

Serum metabolomic analysis reveals key metabolites in drug treatment of central precocious puberty in female children.

Precocious puberty (PP) is a common condition among children. According to the pathogenesis and clinical manifestations, PP can be divided into central precocious puberty (CPP, gonadotropin dependent), peripheral precocious puberty (PPP, gonadotropin independent), and incomplete precocious puberty (IPP). Identification of the variations in key metabolites involved in CPP and their underlying biological mechanisms has increased the understanding of the pathological processes of this condition. However, little is known about the role of metabolite variations in the drug treatment of CPP. Moreover, it remains unclear whether the understanding of the crucial metabolites and pathways can help predict disease progression after pharmacological therapy of CPP. In this study, systematic metabolomic analysis was used to examine three groups, namely, healthy control (group N, 30 healthy female children), CPP (group S, 31 female children with CPP), and treatment (group R, 29 female children) groups. A total of 14 pathways (the top two pathways were aminoacyl-tRNA biosynthesis and phenylalanine, tyrosine, and tryptophan biosynthesis) were significantly enriched in children with CPP. In addition, two short peptides (His-Arg-Lys-Glu and Lys-Met-His) were found to play a significant role in CPP. Various metabolites associated with different pathways including amino acids, PE [19:1(9Z)0:0], tumonoic acid I, palmitic amide, and linoleic acid-biotin were investigated in the serum of children in all groups. A total of 45 metabolites were found to interact with a chemical drug [a gonadotropin-releasing hormone (GnRH) analog] and a traditional Chinese medicinal formula (DBYW). This study helps to understand metabolic variations in CPP after drug therapy, and further investigation may help develop individualized treatment approaches for CPP in clinical practice.

[Study on chemical constituents of the root of Liriope platyphylla].

OBJECTIVE: To study the constituents from the root of Liriope platypgylla. METHODS: Six chemical constituents were isolated from the chloroform fraction and n-BuOH fraction from EtOH extract of Liriope platyphylla. RESULTS: Their structures were elucidated as beta-sitosterol-3-O-beta-D-glucopyranosile(I), palmic acid (II), ruscogenin (III), LP-C(IV), LP-D(V), 25 (S) -ruscogenin 1-O-beta-D-xylopyranoside-3-O-alpha-L-rhamnopyranoside (VI), respectively. CONCLUSION: All these compounds are isolated from this plant for the first time.

Climate regulates the functional traits - aboveground biomass relationships at a community-level in forests: A global meta-analysis.

The relationships between plant functional traits and aboveground biomass (AGB) stock have been explored across forest biomes. Yet, meta-analyses synthesizing our understanding regarding the influences of climate and soil on the functional traits - AGB relationships at a community-level in global forests are still unavailable. Here, we evaluated the latitudinal gradient in the functional traits -AGB relationships in forests, including functional trait diversity (FTD) - AGB (FTD-AGB), community-weighted mean (CWM) of conservative traits (CWMCT-AGB), CWM of acquisitive traits (CWMAT-AGB), and CWM of plant maximum height or diameter (FunDom-AGB), and then answer the question whether climate and soil conditions modulate the functional traits - AGB relationships in global forests. To do so, we selected those studies which reported the relationships of FTD and CWM with AGB stock (i.e. in Mg ha-1) rather with AGB productivity or growth (i.e. Mg ha-1 yr-1) at a community-level (i.e. forest plot). By using piecewise structural equation meta-modeling, we found that: (1) functional traits - AGB relationships at a community-level were driven by mean annual temperature (MAT), aridity and soil fertility. (2) Higher MAT and low aridity promoted FTD-AGB relationships but the opposite trend was true for CWMCT-AGB, whereas higher MAT promoted CWMAT-AGB and FunDom-AGB at high aridity levels. (3) The FunDom-AGB relationship increased with increasing the number of forest plots but other relationships declined. (4) The negligible or negative FTD-AGB relationships but the positive AGB-FunDom relationships were conspicuous across global forests, indicating the mass ratio effect in terms of functional dominance. Our meta-analysis suggests that functional dominance and conservative species' strategy in relation to favorable abiotic conditions should be promoted to increase AGB stock under global environmental changes.

Perfluoroalkyl substance pollutants activate the innate immune system through the AIM2 inflammasome.

Perfluoroalkyl substances (PFAS) are widely used in various manufacturing processes. Accumulation of these chemicals has adverse effects on human health, including inflammation in multiple organs, yet how PFAS are sensed by host cells, and how tissue inflammation eventually incurs, is still unclear. Here, we show that the double-stranded DNA receptor AIM2 is able to recognize perfluorooctane sulfonate (PFOS), a common form of PFAS, to trigger IL-1ß secretion and pyroptosis. Mechanistically, PFOS activates the AIM2 inflammasome in a process involving mitochondrial DNA release through the Ca2+-PKC-NF-κB/JNK-BAX/BAK axis. Accordingly, Aim2-/- mice have reduced PFOS-induced inflammation, as well as tissue damage in the lungs, livers, and kidneys in both their basic condition and in an asthmatic exacerbation model. Our results thus suggest a function of AIM2 in PFOS-mediated tissue inflammation, and identify AIM2 as a major pattern recognition receptor in response to the environmental organic pollutants.