The environment of a large-scale vegetable production area can be exposed to antibiotic residues and antibiotic-resistant bacteria (ARB) via animal manure and irrigation with contaminated water, which can facilitate the dissemination of ARB. However, the occurrence of ARB in plantation areas and their dissemination in this environment remain largely unexplored. In total, 382 samples including those from vegetable (n = 106), soil (n = 87), well water (n = 24), river water (n = 20), river sediments (n = 20), farmer feces (n = 58) and farmer hands (n = 67) were collected in 2019 from a large-scale cultivation area in Shandong, China. Selective agar plates were used to screen for carbapenem-resistant Enterobacteriaceae (CRE) and whole-genome sequencing and Southern blotting were used to characterise isolates and mobile genetic elements carrying carbapenem resistance determinants. A total of nine NDM-5-producing isolates of Escherichia coli, Klebsiella pneumoniae, and Citrobacter spp. were identified from environmental sources and human feces, all of which were multidrug-resistant. Single nucleotide polymorphism analysis suggested clonal transmission of carbapenem-resistant Citrobacter sedlakii within greenhouse soils in the area. Eight of the isolates carried closely related or identical IncX3 plasmids carrying blaNDM₋₅, which were shown to be conjugative via filter mating experiments, indicating the highly transmissible nature of this genetic element. Isolates of E. coli and Citrobacter freundii were detected in the feces of local farm workers and contained similar IncX3 plasmids with blaNDM₋₅ environmental isolates, suggesting a potential risk of CRE transfer from the work environment to the farm workers. Thus, further research is required to investigate the potential health risks associated with environmental exposure to CRE in vegetable cultivation areas.

Within fossil- and solid-fuel dependent geographic locations, mechanisms of air pollution-induced asthma remains unknown. In particular, sources of greater genetic susceptibility to airborne carcinogen, namely, benzo[a]pyrene (B[a]P) has never been investigated beyond that of a few well known genes.To deepen our understanding on how the genotypic variations within the candidate genes contribute to the variability in the children's susceptibility to ambient B[a]P on doctor-diagnosed asthma.Clinically confirmed asthmatic versus healthy control children (aged, 7–15) were enrolled from historically polluted and rural background regions in Czech Republic. Contemporaneous ambient B[a]P concentration was obtained from the routine monitoring network. The sputum DNA was genotyped for 95 genes. B[a]P interaction with SNPs was studied by two-stage, semi-agnostic screening of 621 SNPs.The median B[a]P within the highly polluted urban center was 8-times higher than that in the background region (7.8 vs. 1.1 ng/m³) during the period of investigation. Within the baseline model, which considered B[a]P exposure-only, the second tertile range was associated with a significantly reduced odds (aOR = 0.28) of asthma (95% CI, 0.16 to 0.50) compared to those at the lowest range. However, the highest range of B[a]P was associated with 3.18-times greater odds of the outcome (95% CI, 1.77 to 5.71). Within the gene-environment interaction models, joint occurrence of a high B[a]P exposure range and having a high-risk genotype at CTLA4 gene (rs11571316) was associated with 9-times greater odds (95% CI, 4.56–18.36) of the asthma diagnosis. Similarly, rs11571319 at CTLA4 and a high B[a]P exposure range was associated with a 8-times greater odds (95% CI, 3.95–14.27) of asthma diagnosis. Furthermore, having TG + GG genotypes on rs1031509 near STAT4 was associated with 5-times (95% CI, 3.03–8.55) greater odds of asthma diagnosis at the highest B[a]P range, compared to the odds at the reference range. Also CYP2E1 AT + TT genotypes (rs2070673) was associated with 5-times (95% CI, 3.1–8.8) greater odds of asthma diagnosis at the highest B[a]P exposure.The children, who jointly experience a high B[a]P exposure (6.3–8.5 ng/m3) as well as susceptible genotypes in CTLA4 (rs11571316 and rs11571319), STAT4 (rs1031509), and CYP2E1 (rs2070673), respectively, are associated with a significantly greater odds of having doctor-diagnosed asthma, compared to those with neither risk factors.

Manganese (Mn) is an essential trace element, but an excess or accumulation can be toxic. Until now, few studies have examined the effects of maternal Mn level on the risk of spontaneous preterm birth (SPB). The aims of this study were to examine the association between maternal Mn level and the risk of SPB at the early stage of pregnancy, and investigate whether this association was modified by single nucleotide polymorphisms (SNPs) in genes of superoxide dismutase (SOD) and catalase (CAT). We conducted a nested case-control study in three maternal and child health care hospitals in Shanxi province, China, from December 2009 to December 2013. From an overall cohort of 4229 women, 528 were included in our study, including 147 cases of SPB and 381 controls. Maternal blood samples were collected during 4–22 gestational weeks. The maternal serum concentrations of Mn was measured using inductively coupled plasma–mass spectrometry. We found the maternal Mn concentration in the case group (median: 1.55 ng/mL) was significantly higher than that in the control group (median: 1.27 ng/mL). Compared to the lowest level, the SPB risk was significantly increased to 1.44 (95%CI: 0.60–3.43), 2.42 (95%CI: 1.06–5.55) and 2.46 (95%CI: 1.08–5.62) respectively for the second, third and fourth quartiles in first trimester, but not significant in second trimester or overall. When exposure to a high Mn level, women who with AA (6.36, 95%CI: 1.57–25.71) and AG (3.04, 95%CI: 1.59–5.80) of rs2758352, with CC (2.34, 95%CI: 1.31–4.18) of rs699473, and with GG (2.26, 95%CI: 1.22–4.16) of rs769214 were more likely to develop a SPB, but not among women with other genotypes. In conclusion, high maternal serum Mn level is associated with the increased SPB risk in first trimester, and the association is modified by maternal SNPs of SOD2, SOD3 and CAT.

Our previous study showed heritable reproductive toxicity in the nematode Caenorhabditis elegans after multigenerational exposure to AgNO₃ and silver nanoparticles (Ag-NPs). The aim of this study was to determine whether such inheritable effects are correlated with induced germline mutations in C. elegans. Individual C. elegans lineages were exposed for 10 generations to equitoxic concentrations at EC₃₀ of AgNO₃, Ag-NPs, and sulfidized Ag-NPs (sAg-NPs), a predominant environmentally transformed product of pristine Ag-NPs. The mutations were detected via whole genome DNA sequencing approach by comparing F₀ and F₁₀ generations. An increase in the total number of variants, though not statistically significant, was observed for all Ag treatments and the variants were mainly contributed by single nucleotide polymorphisms (SNPs). This potentially contributed towards reproductive as well as growth toxicity shown previously after ten generations of exposure in every Ag treatment. However, despite Ag-NPs and AgNO₃ inducing stronger reproductive toxicity than sAg-NPs, exposure to sAg-NPs resulted in higher mutation accumulation with significant increase in the number of transversions. Thus our results suggest that other mechanisms of inheritance, such as epigenetics, may be at play in Ag-NP- and AgNO₃-induced multigenerational and transgenerational reproductive toxicity.

An association of influenza-like illness (ILI) with outdoor air pollution has been reported. However, the effect of indoor air pollution on ILI was rarely investigated. We aimed to determine an association of indoor air pollution from coal combustion (IAPCC) and lifestyle with ILI risk in housewives, and the modification effect of phase II metabolic enzyme genes. We recruited 403 housewives for a cross-sectional study in Shanxi Province, China, including 135 with ILI frequency (≥1 time per year in the past ten years) as the case group and 268 with ILI frequency (<1 times per year) as the control group. Information on their energy usage characteristics and lifestyle was collected by questionnaires, as well as the single nucleotide polymorphisms (SNPs) of epoxide hydrolase 1 (rs1051740 and rs2234922), N-acetyltransferase 2 (rs1041983), and glutathione S-transferase (rs1695). We used exposure index to indicate the level of IAPCC among housewives. Our results revealed that the exposure index was positively correlated with ILI frequency. A significant dose-response trend between the exposure index and ILI risk was found with or without adjusting for confounders. Cooking frequency in kitchen with coal as primary fuel and ventilation frequency in the living room or bedroom with a coal-fueled stove for heating during the heating season were two important risk factors to affect ILI frequency. Only rs1051740 was found to be associated with exposure index, whereas it didn’t have interaction effect with exposure index on ILI frequency. In conclusion, IAPCC and SNPs of rs1051740 were both associated with ILI frequency.

Heat shock protein A2 (HSPA2) is a testis-specific molecular chaperone of the 70 kDa heat shock protein (HSP70) family and reported to play a key role in spermatogenesis as well as in the remodelling of the sperm surface during capacitation. It is established that mice lacking HSPA2 gene are infertile and spermatozoa that fail to interact with the zona pellucida of the oocyte consistently lack HSPA2 protein expression. However, its role in post fertilization events is not fully understood. Owing to the importance of HSPA2 in male reproduction, the present study is undertaken to reveal the association between genetic mutation and phenotypic variation in recurrent pregnancy loss (RPL) patients through an in silico prediction analysis. In this study, we used different computational tools and servers such as SIFT, PolyPhen2, PROVEAN, nsSNPAnalyzer, and SNPs & GO to analyse the functional consequences of the nsSNPs in human HSPA2 gene. The most damaging amino acid variants generated were subjected to I-Mutant 2.0 and ConSurf. Post-translational modifications such as phosphorylation mediated by these deleterious nsSNPs were analysed using NetPhos 2.0, and gene-gene interaction study was conducted using GeneMANIA. Finally, in-depth studies of the nsSNPs were studied through Project HOPE. The findings of the study revealed 18 nsSNPs to be deleterious using a combinatorial bioinformatic approach. Further functional analysis suggests that screening of nsSNP variants of HSPA2 that tend to be conserved and has potential to undergo phosphorylation at critical positions (rs764410231, rs200951589, rs756852956) may be useful for predicting outcome in altered reproductive outcome. The physicochemical alterations and its impact on the structural and functional conformity were determined by Project HOPE. Gene-gene interaction depicts its close association with antioxidant enzyme (SOD1) strongly supporting an inefficient oxidative scavenging regulatory mechanism in the spermatozoa of RPL patients as reported earlier. The present study has thus identified high-risk deleterious nsSNPs of HSPA2 gene and would be beneficial in the diagnosis and prognosis of the paternal effects in RPL patients.

Our study evaluated 163 individuals, being 74 soybean farmers, occupationally exposed to pesticides, and 89 individuals from Goias municipalities, Central Brazil, with similar conditions to the exposed group, comprising the control group. Of the 74 soybean farmers, 43 exposed directly to pesticides and 31 exposed indirectly. The exposed group consisted of individuals aged 19 to 63 years, 21 women and 53 men, and the control group had ages ranging from 18 to 64 years, being 36 women and 53 men. 18.9% of the exposed group were poisoned by pesticides, and the most common symptoms were headache and gastrointestinal problems. The genotype frequencies of the rs2031920 (T>C) polymorphism in the CYP2E1 gene present significant differences between the exposed and control groups (p = 0.02), showing that 24.3% of the exposed group were heterozygotes against 6.7% in the control group. For the OGG1 gene, two SNPs, rs1052133 (G>C) and rs293795 (T>C), were evaluated and the genotype frequencies were not statistically different between the exposed and control groups. The DNA damage was distinct (p < 0.05) in the three analyzed comet parameters (tail length, Olive tail moment, %DNA) between groups. However, there was no influence of age and alcohol consumption between the groups associated with the polymorphisms in the CYP2E1 and OGG1 genes and DNA damage. We also did not find altered hematological and biochemical parameters in the exposed group. Thus, this pioneering study at Goias State carried out an overview of the health of soybean farmers. We evaluated classic laboratory exams, associated with exposure markers (comet assay) and susceptibility markers (genetic polymorphisms), emphasizing the need to expand the Brazilian health assessment protocol. We found, in soybean farmers, increased DNA damage and a higher number of heterozygotes in CYP2E1 gene, compared with the control group, despite the lack of association with age, educational level, smoking, drinking habits, and genetic polymorphisms.

Arsenic (As) toxicity and the effects of nitric oxide (NO), supplied as sodium nitroprusside (SNP), were analyzed in Pistia stratiotes. The plants, which were grown in nutrient solution at pH 6.5, were exposed to four treatments for 24 h: control; SNP (0.1 mg L-1); As (1.5 mg L-1); and As + SNP (1.5 and 0.1 mg L-1). As accumulated primarily in the roots, indicating the low translocation factor of P. stratiotes. The As accumulation triggered a series of changes with increasing production of reactive oxygen intermediates and damage to cell membranes. The application of SNP was able to mitigate the harmful effects of As. This attenuation was probably due to the action of the SNP as an antioxidant, reducing the superoxide anion concentration, and as a signaling agent. Acting as a signal transducer, SNP increased the activity of enzymatic antioxidants (POX, CAT, and APX) in the leaves and stimulated the entire phytochelatins biosynthetic pathway in the roots (increased sulfate uptake and synthesis of amino acids, non-proteinthiols, and phytochelatins). The As also stimulated the phytochelatins biosynthesis, but this effect was limited, probably because plants exposed only to pollutant showed small increments in the sulfate uptake. Thus, NO also may be involved in gene regulation of sulfate carriers. © 2013 Springer Science+Business Media Dordrecht.

Human β-defensin (HBD), a member of the antimicrobial peptides, is essential for respiratory epithelial cells’ microbial defense, and is affected by cigarette smoking (CS). Its expression is upregulated by stimulation from microbes or inflammation. Genetic polymorphisms in the HBD-1 gene have been implicated in the development of various smoking-related diseases, including chronic obstructive pulmonary disease and asthma. Thus, we sought to analyze possible associations between HBD-1 single-nucleotide polymorphism (SNP) in HBD-1 gene and CS in ethnic Saudi Arabian subjects. Variants rs1047031 (C/T), rs1799946 (C/T), rs2738047 (C/T), and rs11362 (C/T) were investigated by genotyping 575 blood specimens from males and females, smokers/non-smokers: 288/287. The CT and CT+TT genotypes of rs1799946 presented an ~5-fold increased correlation with CS among the female smokers, compared with the female controls (OR = 5.473, P = 0.02003; and OR = 5.211, P = 0.02028, respectively), an observation similar to rs11362 SNP in female smokers, but with protective effects in TT genotype, compared with the CC reference allele (OR = 0.143, P = 0.04368). In shisha smokers, the heterozygous CT and the CT/TT genotype of rs2738047 polymorphism showed the same results with ~3-fold increased correlation with CS (OR = 2.788; P = 0.03448), compared with the cigarette smokers category. No significant association was shown in genotypic distributions and allelic frequencies of rs1047031. Further investigations, including large study samples, are required to investigate the effects of shisha on human beta-defensin expression and protein levels.

The development of congenital heart disease (CHD) is a complicated process and affected by multiple environmental factors, as genetic factors, and the interactions among those factors. Previous studies have shown that intrauterine hypoxic environment exposure is a risk factor of CHD, but the genetic factors involved in the process are not clear. In this study, given that tetralogy of Fallot (TOF) is a CHD with hypoxemia as its primary pathophysiological manifestation, an in silico analysis was performed to reveal the relationship between potential target genes (miR-124) with the energy metabolism in non-syndromic TOF patients’ cardiomyocyte. Furthermore, the study investigated the correlation between the primary miR-124 (rs531564) polymorphism and CHD susceptibility in 432 sporadic patients and 450 controls from two different altitude provinces (city) in China. Our study indicated that the minor C allele of rs531564 correlated with reduced risk of CHD in the low altitude city. Besides, the C allele has elevated frequency in the high-altitude group. Therefore, our findings suggest that the minor C allele of rs531564 SNP may be involved in the reduction of the risk of CHD in a way that interacts with the intrauterine hypoxic environmental factors.