Several studies have reported an association between residential surrounding particulate matter with an aerodynamic diameter ≤2.5 μm (PM₂.₅) and coronary heart disease (CHD). However, the underlying biological mechanism remains unclear. To fill this research gap, this study enrolled a residentially stable sample of 942 patients with CHD and 1723 controls. PM₂.₅ concentration was obtained from satellite-based annual global PM₂.₅ estimates for the period 1998–2019. MicroRNA microarray and pathway analysis of target genes was performed to elucidate the potential biological mechanism by which PM₂.₅ increases CHD risk. The results showed that individuals exposed to high PM₂.₅ concentrations had higher risks of CHD than those exposed to low PM₂.₅ concentrations (odds ratio = 1.22, 95% confidence interval: 1.00, 1.47 per 10 μg/m³ increase in PM₂.₅). Systolic blood pressure mediated 6.6% of the association between PM₂.₅ and CHD. PM₂.₅ and miR-4726-5p had an interaction effect on CHD development. Bioinformatic analysis demonstrated that miR-4726-5p may affect the occurrence of CHD by regulating the function of RhoA. Therefore, individuals in areas with high PM₂.₅ exposure and relative miR-4726-5p expression have a higher risk of CHD than their counterparts because of the interaction effect of PM₂.₅ and miR-4726-5p on blood pressure.

With the continued increase of global ammonia emission, the damage to human or animal caused by ammonia pollution has attracted wide attention. The noncoding RNAs have been reported to regulate a variety of biological processes under different environmental stimulation via ceRNA (competing endogenous RNA) networks. Autophagy is a hallmark of tissue damage from air pollution. However, the specific role of circular RNAs (circRNAs) in the injury of intestinal tissue caused by autophagy remains unclear. Here, we established 42-days old ammonia-exposed broiler models and observed that autophagy flux in broiler jejunum was activated under ammonia exposure. Meanwhile, a total of eight significantly dysregulated expressed circRNAs were obtained and a circRNAs-miRNAs-genes interaction networks were constructed by bioinformatics analysis. Furthermore, an axis named circRNA-IGLL1/miR-15a/RNF43 was predicted to participate in the excessive autophagy by targeting RNF43. The target relationship was proved by dual-luciferase reporter assay in vitro. Mechanistically, downregulated circRNA-IGLL1 could suppress the expression of RNF43 in ammonia-exposed jejunum and the Wnt/β-catenin pathway was activated. Inhibition of miR-15a reversed autophagy caused by downregulated circRNA-IGLL1. CircRNA-IGLL1 could competitively bind miR-15a to regulate RNF43 expression, thus modulating the occurrence of autophagy. Taken together, our results showed that circRNA-IGLL1/miR-15a/RNF43 axis is involved in ammonia-induced intestinal autophagy in broilers.

N⁶-methyladenosine (m⁶A), the most abundant and reversible RNA modification, plays critical a role in tumorigenesis. However, whether m⁶A can regulate p53, a leading antitumor protein remains poorly understood. In this study, we explored the regulatory role of m⁶A on p53 activation using an arsenite-transformed keratinocyte model, the HaCaT-T cell line. We created the cell line by exposing human keratinocyte HaCaT cells to 1 μM arsenite for 5 months. We found that the cells exhibited an increased m⁶A level along with an aberrant expression of the methyltransferases, demethylase, and readers of m⁶A. Moreover, the cells exhibited decreased p53 activity and reduced p53 phosphorylation, acetylation, and transactivation with a high nucleus export rate of p53. Knockdown of the m⁶A methyltransferase, METTL3 significantly decreased m⁶A level, restoring p53 activation and inhibiting cellular transformation phenotypes in the arsenite-transformed cells. Further, using both a bioinformatics analysis and experimental approaches, we demonstrated that m⁶A downregulated the expression of the positive p53 regulator, PRDM2, through the YTHDF2-promoted decay of PRDM2 mRNAs. We showed that m⁶A upregulated the expression of the negative p53 regulator, YY1 and MDM2 through YTHDF1-stimulated translation of YY1 and MDM2 mRNA. Taken together, our study revealed the novel role of m⁶A in mediating arsenite-induced human keratinocyte transformation by suppressing p53 activation. This study further sheds light on the mechanisms of arsenic carcinogenesis via RNA epigenetics.

The Deception Island, located in Maritime Antarctica, is a volcanic island with geothermal activity and one of the most visited by tourists. However, the extent of the anthropogenic impact remains largely unknown and the factors shaping the resistance/tolerance mechanisms in the microbiomes from Whalers Bay ecosystems have never been investigated. In this context, this study aimed to reveal the resistome profiles of Whalers Bay sediments and correlate them with environmental factors. Samples were collected at four sites during the summer 2014/2015 along a transect of 27.5 m in the Whalers Bay sediments. DNA isolated from sediment samples was sequenced using the Illumina HiSeq platform. Bioinformatic analyses allowed the assembly of contigs and scaffolds, prediction of ORFs, and taxonomic and functional annotation using NCBI RefSeq database and KEGG orthology, respectively. Microorganisms belonging to the genera Psychrobacter, Flavobacterium and Polaromonas were shown to dominate all sites, representing 60% of taxonomic annotation. Arsenic (As), copper (Cu) and iron (Fe) were the most abundant metal resistance/tolerance types found in the microbiomes. Beta-lactam was the most common class related to antibiotics resistance/tolerance, corroborating with previous environmental resistome studies. The acridine class was the most abundant amongst the biocide resistance/tolerances, related to antiseptic compounds. Results gathered in this study reveal a repertoire of resistance/tolerance classes to antibiotics and biocides unusually found in Antarctica. However, given the volcanic nature (heavy metals-rich region) of Deception Island soils, this putative impact must be viewed with caution.

A comparative study was conducted to (1) assess the potential of raw sewage used for urban agriculture to disseminate bacterial resistance in two cities of different size in Cameroon (Central Africa) and (2) compare the outcome with data obtained in Burkina Faso (West Africa). In each city, raw sewage samples were sampled from open-air canals in three neighbourhoods. After DNA extraction, the microbial population structure and function, presence of pathogens, antibiotic resistance genes and Enterobacteriaceae plasmids replicons were analysed using whole genome shotgun sequencing and bioinformatics. Forty-three pathogen-specific virulenc e factor genes were detected in the sewage. Eighteen different incompatibility groups of Enterobacteriaceae plasmid replicon types (ColE, A/C, B/O/K/Z, FIA, FIB, FIC, FII, H, I, N, P, Q, R, T, U, W, X, and Y) implicated in the spread of drug-resistance genes were present in the sewage samples. One hundred thirty-six antibiotic resistance genes commonly associated with MDR plasmid carriage were identified in both cities. Enterobacteriaceae plasmid replicons and ARGs found in Burkina Faso wastewaters were also present in Cameroon waters. The abundance of Enterobacteriaceae, plasmid replicons and antibiotic resistance genes was greater in Yaounde, the city with the greater population.In conclusion, the clinically relevant environmental resistome found in raw sewage used for urban agriculture is common in West and Central Africa. The size of the city impacts on the abundance of drug-resistant genes in the raw sewage while ESBL gene abundance is related to the prevalence of Enterobacteriaceae along with plasmid Enterobacteriaceae abundance associated to faecal pollution.

The earthworm Lumbricus rubellus (Hoffmeister, 1843) is a terrestrial pollution sentinel. Enzyme activity and transcription of phase II detoxification superfamily glutathione transferases (GST) is known to respond in earthworms after soil toxin exposure, suggesting GST as a candidate molecular-based pollution biomarker. This study combined sub-proteomics, bioinformatics and biochemical assay to characterise the L. rubellus GST complement as pre-requisite to initialise assessment of the applicability of GST as a biomarker. L. rubellus possesses a range of GSTs related to known classes, with evidence of tissue-specific synthesis. Two affinity-purified GSTs dominating GST protein synthesis (Sigma and Pi class) were cloned, expressed and characterised for enzyme activity with various substrates. Electrospray ionisation mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS) following SDS-PAGE were superior in retaining subunit stability relative to two-dimensional gel electrophoresis (2-DE). This study provides greater understanding of Phase II detoxification GST superfamily status of an important environmental pollution sentinel organism. This study currently provides the most comprehensive view of the Phase II detoxification enzyme superfamily of glutathione transferases within the important environmental pollution sentinel earthworm Lumbricus rubellus.

Systemic toxicity, particularly, developmental defects of humidifier disinfectant chemicals that have caused lung injuries in Korean children, remains to be elucidated. This study evaluated the mechanisms of the adverse effects of 5-chloro-2-methyl-4-isothiazoline-3-one/2methyl-4-isothiazolin-3-one (CMIT/MIT), one of the main biocides of the Korean tragedy, and identify the most susceptible developmental stage when exposed in early life. To this end, the study was designed to analyze several endpoints (morphology, heart rate, behavior, global DNA methylation, gene expressions of DNA methyl-transferases (dnmts) and protein profiling) in exposed zebrafish (Danio rerio) embryos at various developmental stages. The results showed that CMIT/MIT exposure causes bent tail, pericardial edema, altered heart rates, global DNA hypermethylation and significant alterations in the locomotion behavior. Consistent with the morphological and physiological endpoints, proteomics profiling with bioinformatics analysis suggested that the suppression of cardiac muscle contractions and energy metabolism (oxidative phosphorylation) were possible pivotal underlying mechanisms of the CMIT/MIT mediated adverse effects. Briefly, multi-level endpoint analysis indicated the most susceptible window of exposure to be ≤ 6 hpf followed by ≤ 48 hpf for CMIT/MIT. These results could potentially be translated to a risk assessment of the developmental exposure effects to the humidifier disinfectants.

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.

It is known that Di (2-ethylhexyl) phthalate (DEHP) may impact mammalian reproduction and that in females one target of the drug’s action is follicle assembly. Here we revisited the phthalate’s action on the ovary and from bioinformatics analyses of the transcriptome performed on newborn mouse ovaries exposed in vitro to DEHP, up-regulation of PDE3A, as one of the most important alterations caused by DEHP on early folliculogenesis, was identified. We obtained some evidence suggesting that the decrease of cAMP level in oocytes and the parallel decrease of PKA expression, consequent on the PDE3A increase, were a major cause of the reduction of follicle assembly in the DEHP-exposed ovaries. In fact, Pde3a RNAi on cultured ovaries reducing cAMP and PKA decrease counteracted the primordial follicle assembly impairment caused by the compound. Moreover, RNAi normalized the level of Kit, Nobox, Figla mRNA and GDF9, BMP15, CX37, γH2AX proteins in oocytes, and KitL transcripts in granulosa cells as well as their proliferation rate altered by DEHP exposure. Taken together, these results identify PDE3A as a new critical target of the deleterious effects of DEHP on early oogenesis in mammals and highlight cAMP-dependent pathways as major regulators of oocyte and granulosa cell activities crucial for follicle assembly. Moreover, we suggest that the level of intracellular cAMP in the oocytes may be an important determinant for their capability to repair DNA lesions caused by DNA damaging compounds including DEHP.

The immune organs, like thymus, are one of the targets of hydrogen sulfide (H₂S). Previously we reported that H₂S induced the differential expression of mRNAs that implicating apoptosis in thymus, however, the roles of noncoding RNAs (ncRNAs) in H₂S-induced thymus injury are still unknown. Pollution gases could alter the expression of ncRNAs, which have been shown to play important roles in many physiological and pathophysiological processes, including immune activity. This study revealed that H₂S exposure induced 9 differentially expressed circRNAs and 15 differentially expressed miRNAs in chicken thymus. Furthermore, the circRNA - miRNA - mRNA network was constructed. We discovered that circR-PTPN23 - miR-15a - E2F3 was involved in the cell cycle and apoptosis. Further, an in vitro H₂S exposure model was established using HD11 cell line and demonstrated that H₂S suppressed cell proliferation and induced apoptosis. Moreover, ciR-PTPN23 and E2F3 were downregulated, but miR-15a was upregulated in both the thymus and HD11 cell line after H₂S exposure. Bioinformatics analysis revealed that ciR-PTPN23 directly bound to miR-15a and that E2F3 was the target gene of miR-15a. Knocking down ciR-PTPN23 suppressed HD11 proliferation and caused G1 arrest and apoptosis, however, this phenomenon could be partially reversed by ciR-PTPN23 overexpression or miR-15a silencing. In summary, the ciR-PTPN23 - miR-15a - E2F3 axis was involved in H₂S-induced cell proliferation suppression and apoptosis.