Ambient air pollutants are well-known risk factors for childhood asthma and asthma exacerbation. It is unknown whether different air pollutants individually or jointly affect pathophysiological mechanisms of asthma. In this study, we aim to integrate transcriptome and untargeted metabolome to identify dysregulated genetic and metabolic pathways that are associated with exposures to a mixture of ambient and traffic-related air pollutants among adults with asthma history. In this cross-sectional study, 102 young adults with childhood asthma history were enrolled from southern California in 2012. Whole blood transcriptome was measured with 20,869 expression signatures, and serum untargeted metabolomics including 937 metabolites were analyzed by Metabolon, Inc. Participants’ exposures to regional air pollutants (NO₂, O₃, PM₁₀, PM₂.₅) and near-roadway air pollutants averaged at one month and one year before study visit were estimated based on residential addresses. xMWAS network analysis and joint-pathway analysis were performed to identify subnetworks and genetic and metabolic pathways that were associated with exposure to air pollutants adjusted for socio-characteristic covariates. Network analysis found that exposures to air pollutants mixture were connected to 357 gene markers and 92 metabolites. One-year and one-month averaged PM₂.₅ and NO₂ were associated with several amino acids related to serine, glycine, and beta-alanine metabolism. Lower serum levels of carnosine and aspartate, which are involved in the beta-alanine metabolic pathway, as well as choline were also associated with worse asthma control (p < 0.05). One-year and one-month averaged PM₁₀ and one-month averaged O₃ were associated with higher gene expression levels of HSPA5, LGMN, CTSL and HLA-DPB1, which are involved in antigen processing and presentation. These results indicate that exposures to various air pollutants are associated with altered genetic and metabolic pathways that affect anti-oxidative capacity and immune response and can potentially contribute to asthma-related pathophysiology.

Exposure to tobacco smoke during pregnancy has been associated with a series of adverse reproductive outcomes; however, the underlying molecular mechanisms are not well-established. We conducted an untargeted metabolome-wide association study to identify the metabolic perturbations and molecular mechanisms underlying the association between cotinine, a widely used biomarker of tobacco exposure, and adverse birth outcomes. We collected early and late pregnancy urine samples for cotinine measurement and serum samples for high-resolution metabolomics (HRM) profiling from 105 pregnant women from the Atlanta African American Maternal-Child cohort (2014–2016). Maternal metabolome perturbations mediating prenatal tobacco smoke exposure and adverse birth outcomes were assessed by an untargeted HRM workflow using generalized linear models, followed by pathway enrichment analysis and chemical annotation, with a meet-in-the-middle approach. The median maternal urinary cotinine concentrations were 5.93 μg/g creatinine and 3.69 μg/g creatinine in early and late pregnancy, respectively. In total, 16,481 and 13,043 metabolic features were identified in serum samples at each visit from positive and negative electrospray ionization modes, respectively. Twelve metabolic pathways were found to be associated with both cotinine concentrations and adverse birth outcomes during early and late pregnancy, including tryptophan, histidine, urea cycle, arginine, and proline metabolism. We confirmed 47 metabolites associated with cotinine levels, preterm birth, and shorter gestational age, including glutamate, serine, choline, and taurine, which are closely involved in endogenous inflammation, vascular reactivity, and lipid peroxidation processes. The metabolic perturbations associated with cotinine levels were related to inflammation, oxidative stress, placental vascularization, and insulin action, which could contribute to shorter gestations. The findings will support the further understanding of potential internal responses in association with tobacco smoke exposures, especially among African American women who are disproportionately exposed to high tobacco smoke and experience higher rates of adverse birth outcomes.

Although the exposure to traffic-related air pollution (TRAP) has emerged as one of main problem worldwide to inhabitants’ health in urban centers, its impact on metabolic responses during exercise is poorly understood. The aim of study was to characterize the profile of non-target serum metabolomics during prolonged exercise performed under TRAP conditions. Ten healthy men completed two 90 min constant-load cycling trials under conditions of either TRAP or filtered air. Experimental trials were performed in a chamber located on an avenue with a high volume of vehicle traffic. Blood samples were taken at 30 min, 60 min, and 90 min of exercise. Based on Nuclear Magnetic Resonance metabolomics, the non-target analysis was used to assess the metabolic profile. Twelve, 16 and 18 metabolites were identified as discriminants. These were: at 30 min of exercise, the coefficient of determination (R²) 0.98, the predictive relevance, (Q²) 0.12, and the area under the curve (AUC) 0.91. After 60 min of exercise: (R²: 0.99, Q²: 0.09, AUC: 0.94); and at 90 min of exercise (R²: 0.91, Q²: <0.01, AUC: 0.89), respectively. The discriminant metabolites were then considered for the target analysis, which demonstrated that the metabolic pathways of glycine and serine metabolism (p = 0.03) had been altered under TRAP conditions at 30 min of exercise; arginine and proline metabolism (p = 0.04) at 60 min of exercise; and glycolysis (p = 0.05) at 90 min of exercise. The present results suggest that exposure to TRAP during prolonged exercise leads to a significant change in metabolomics, characterized by a transitional pattern and lastly, impairs the glucose metabolism.

Microcystins are cyanotoxins produced by many species of cyanobacteria. They are specific inhibitors of serine/threonine protein phosphatases and are phytotoxic to agricultural plants. This study used a formal meta-analysis to estimate the phytotoxicity and bioconcentration rates of agricultural plants exposed to microcystins, and the human health risk from consuming microcystin-contaminated plants. Among the 35 agricultural plants investigated, microcystins were most phytotoxic to durum wheat, corn, white mustard and garden cress. Leafy vegetables such as dill, parsley and cabbage could bioconcentrate ∼3 times more microcystins in their edible parts than other agricultural plants. Although the human health risk from ingesting microcystins could be greater for leafy vegetables than other agricultural plants, further work is needed to confirm bioconcentration of microcystins in realistic water-soil-plant environments. Still, we should avoid growing leafy vegetables, durum wheat and corn on agricultural land that is irrigated with microcystins-contaminated water and be attentive to the risk of microcystins contamination in the agricultural food supply.

Bisphenol A (BPA) is a classical chemical contaminant in food, and the mode of action (MOA) of BPA remains unclear, constraining the progress of risk assessment. This study aims to assess the potential MOAs of BPA regarding reproductive/developmental toxicity, neurological toxicity, and proliferative effects on the mammary gland and the prostate potentially related to carcinogenesis by using the Comparative Toxicogenomics Database (CTD)-based bioinformatics analysis and the quantitative weight of evidence (QWOE) approach on the basis of the principles of Toxicity Testing in the 21st Century. The CTD-based bioinformatics analysis results showed that estrogen receptor 1, estrogen receptor 2, mitogen-activated protein kinase (MAPK) 1, MAPK3, BCL2 apoptosis regulator, caspase 3, BAX, androgen receptor, and AKT serine/threonine kinase 1 could be the common target genes, and the apoptotic process, cell proliferation, testosterone biosynthetic process, and estrogen biosynthetic process might be the shared phenotypes for different target organs. In addition, the KEGG pathways of the BPA-induced action might involve the estrogen signaling pathway and pathways in cancer. After the QWOE evaluation, two potential estrogen receptor-related MOAs of BPA-induced testis dysfunction and learning-memory deficit were proposed. However, the confidence and the human relevance of the two MOAs were moderate, prompting studies to improve the MOA-based risk assessment of BPA.

Metal pollution in Laizhou Bay along the Bohai Sea in China has been posing a risk on fishery species and hence may affect seafood quality. In this work, shrimps Fenneropenaeus chinensis were sampled from three sites, namely, a reference (site 6334) and two metal-polluted (sites 6262 and 7262) sites, located in Laizhou Bay. The metal concentrations in shrimp muscle tissues were tested using the ICP-MS technique. The Cr and Cu concentrations were the highest in the shrimp samples from site 7262, exceeding the national seafood safety standard Ⅱ, and the As concentration was much higher than the national seafood safety standard Ⅲ. NMR-based metabolomics indicated that metal pollution induced oxidative and immune stresses, damaged the muscular structure, and disrupted energy metabolism in shrimps at sites 6262 and 7262, in particular disturbed osmotic regulation in shrimps at site 7262. Glycine and serine could serve as biomarkers for Cd in F. chinensis.

Heavy metal accumulation in crop grains due to hazardous metal contamination is considered a great concern. However, phytobeneficial fungi are reported to have important abilities for the biosafety of crops grown in contaminated soil. Therefore, the current study was undertaken to explore the mutualistic association of plant growth-promoting endophytic fungi in reducing heavy metal concentration in the seeds of soybean plants subsequently grown in contaminated soil, without comprising seed quality and biochemical profile. The results revealed that endophytic Paecilomyces formosus LHL10 and Penicillium funiculosum LHL06 synergistically produced higher amounts of GAs and IAA in a co-cultured medium. Moreover, the co-inoculation of LHL06 and LHL10 to soybean plants grown under multi-metal toxic conditions significantly mitigated the adverse effects of heavy metal toxicity and increased the seed production (number of pods per plants, number of seeds per pod, and 100 seed weight) of soybean plants grown under control and multi-metal toxic conditions. Moreover, the levels of carbohydrates (glucose, sucrose, and fructose), minerals (iron, calcium, magnesium, and potassium), amino acids (serine, glutamic acids, glycine, methionine, lysine, arginine, and proline), and antioxidants (superoxide dismutase, catalase, and peroxidase) were significantly enhanced in sole and co-inoculated plants under control and stress conditions. Whereas organic acids (citric acid, tartaric acid, malic acid, and succinic acid), lipid peroxidation (MDA) products, multi-metal accumulation (nickel, cadmium, copper, lead, chromium, and aluminum), and stress-responsive endogenous abscisic acid levels were significantly decreased in seeds of soybean plants grown under control and multi-metal toxic conditions upon LHL06 and LHL10 sole and co-inoculation. The current results suggested the positive biochemical regulation in seeds for improving the nutritional status and making it safe for human consumption.

This study investigated the metabolic response of E. coli after exposure to TiO₂ and ZnO NPs under solar simulated irradiation. A total of 14 altered metabolites involved in two metabolic pathways were recognized using multivariate analysis. Polyamine, putrescine was elevated in ZnO-treated group, as an adaptation to oxidative stress in cells, whereas it was significantly reduced in TiO₂-treated group. Glycine levels also were elevated in both the treatment groups, showing cellular protection in cells after exposure. In addition, glycine, serine, and threonine metabolism and arginine and proline metabolism were altered in ZnO and TiO₂-treated groups respectively.

Bioconversion of recalcitrant keratinous biomass is one of the greatest ways to utilize products of feather hydrolysis and recycle them into bionetwork. Present study revealed 87% degradation of poultry feathers within 48 h in a constructed bioreactor using Chryseobacterium sp. RBT. The resulting feather hydrolysate (FH) was rich in soluble protein (3.56 ± 0.18 mg/ml), amino acids (3.83 ± 0.20 mg/ml), and macro and micro nutrients like N (8.0302%), P (0.3876%), K (0.5532%), Cu (0.0684%), Mg (0.8078%), Mn (0.2001%), Ca (0.4832%), Zn (0.0442%), and Fe (0.0330%). HPTLC analysis of FH revealed presence of tryptophan, cysteine, methionine, phenylalanine, glycine, valine, tyrosine, lysine, leucine, and serine as the primary amino acids. Field studies were conducted to apply FH as the bioenhancer to commercially important crops like brinjal and chilli through root drenching (20%, v/v). FH showed positive impact on the growth and development of plants along with early flowering and improved crop yield. In addition, nutritional quality of brinjal and chilli in terms of protein, amino acids, reducing sugars, phenolics, flavonoids, and antioxidant was elevated. Therefore, promotion and utility of by-products generated in feather degradation would be an effective strategy focusing on sustainable agricultural practices and problems associated with the waste management.