Maternal exposure to air pollution has been associated with a higher birth defect (BD) risk. Previous studies suffer from inaccurate exposure assessment methods, confounding individual-level variations, and classical analytical modelling. This study aimed to examine the association between maternal exposure to criteria air pollutants and BD risk. A total of 553 cases and 10,214 controls were identified from private and public databases. Two subgroups were then formed: one for a matched case-control design, and another for Feature Selection (FS) analysis. Exposure assessment was based on the mean air pollutant-specific levels in the mother’s residential area during the specific BD gestational time window of risk (GTWR) and other time intervals. Multivariate regression models outcomes consistently showed a significant protective effect for folic acid intake and highlighted parental consanguinity as a strong BD risk factor. After adjusting for these putative risk factors and other covariates, results show that maternal exposure to PM₂.₅ during the first trimester is significantly associated with a higher overall BD risk (OR:1.05, 95%CI:1.01–1.09), and with a higher risk of genitourinary defects (GUD) (OR:1.06, 95%CI:1.01–1.11) and neural tube defects (NTD) (OR:1.10, 95%CI:1.03–1.17) during specific GTWRs. Maternal exposure to NO₂ during GTWR exhibited a significant protective effect for NTD (OR:0.94, 95%CI:0.90–0.99), while all other examined associations were not statistically significant. Additionally, maternal exposure to SO₂ during GTWR showed a significant association with a higher GUD risk (OR:1.17, 95%CI:1.08–1.26). When limiting selection to designated monitor coverage radiuses, PM₂.₅ maintained significance with BD risk and showed a significant gene-environment interaction for GUD (p = 0.018), while NO₂ protective effect expanded to other subtypes. On the other hand, FS analysis confirmed maternal exposure to PM₂.₅ and NO₂ as important features for GUD, CHD, and NTD. Our findings, set the basis for building a novel BD risk prediction model.

Evidence concerning effects of ambient air pollution on homocysteine (HCY) metabolism is scarce. We aimed to explore the associations between ambient particulate matter (PM) exposure and the HCY metabolism markers and to evaluate effect modifications by folate, vitamin B₁₂, and methylenetetrahyfrofolate reductase (MTHFR) C677T gene polymorphism. Between December 1, 2017 and January 5, 2018, we conducted a panel study in 88 young college students in Guangzhou, China, and received 5 rounds of health examinations. Real-time concentrations of PMs with aerodynamic diameter ≤2.5 (PM₂.₅), ≤1.0 (PM₁.₀), and ≤0.1 (PM₀.₁) were monitored, and the serum HCY metabolism markers (i.e., HCY, S-Adenosylhomocysteine [SAH], and S-Adenosylmethionine [SAM]) were repeatedly measured. We applied linear mixed effect models combined with a distributed lag model to evaluate the associations of PMs with the HCY metabolism markers. We also explored effect modifications of folate, vitamin B₁₂, and the MTHFR C677T polymorphism on the associations. We observed that higher concentrations of PM₂.₅ and PM₁.₀ were associated with higher serum levels of HCY, SAH, SAM, and SAM/SAH ratio (e.g., a 10 μg/m³ increase in PM₂.₅ during lag 0 day and lag 5 day was significantly associated with 1.3–19.4%, 1.3–28.2%, 6.2–64.4%, and 4.8–28.2% increase in HCY, SAH, SAM, and SAM/SAH ratio, respectively). In addition, we observed that the associations of PM₂.₅ with the HCY metabolism markers were stronger in participants with lower B vitamins levels. This study demonstrated that short-term exposure to PM₂.₅ and PM₁.₀ was deleteriously associated with the HCY metabolism markers, especially in people with lower B vitamins levels.

A paradoxical impact of high rates of production and consumption of antibiotics is their widespread release in the environment. Consequently, low concentrations of antibiotics and their byproducts have been routinely identified from various environmental settings especially from aquatic environments. However, the impact of such low concentrations of antibiotics on the exposed host especially in early life remains poorly understood. We exposed zebrafish to two different environmental concentrations of oxytetracycline and sulfamethoxazole, from larval stage to adulthood (∼120 days) and characterized their impact on the taxonomic diversity, antibiotic resistance genes, and metabolic pathways of the gut microbiome using metagenomic shotgun sequencing and analysis. Long term exposure of environmental concentrations of oxytetracycline and sulfamethoxazole significantly impacted the taxonomic composition and metabolic pathways of zebrafish gut microbiome. The antibiotic exposed samples exhibited significant enrichment of multiple flavobacterial species, including Flavobacterium sp. F52, Flavobacterium johnsoniae and Flavobacterium sp. Fl, which are well known pathogenic bacteria. The relative abundance of antibiotic resistance genes, especially several tetratcycline and sulfonamide resistance genes were significantly higher in the exposed samples and showed a linear correlation with the antibiotic concentrations. Furthermore, several metabolic pathways, including folate biosynthesis, oxidative phosphorylation, and biotin metabolism pathways, showed significant enrichment in the antibiotic exposed samples. Collectively, our results suggest that early life exposure of the environmental concentrations of antibiotics can increase the abundance of unfavorable bacteria, antibiotic resistance genes and associated pathways in the gut microbiome of zebrafish.

We previously found that folic acid (FA) attenuated cardiac defects in zebrafish embryos exposed to extractable organic matter (EOM) from PM2.5, but the underlining mechanisms remain to be elucidated. Since DNA methylation is crucial to cardiac development, we hypothesized that EOM-induced aberrant DNA methylation changes could be diminished by FA supplementation. In this study, zebrafish embryos were exposed to EOM in the absence or presence of FA. Genomic-wide DNA methylation analysis identified both DNA hypo- and hyper-methylation changes in CCGG sites in zebrafish embryos exposed to EOM, which were attenuated by FA supplementation. We identified a total of 316 genes with extensive DNA methylation changes in EOM samples but little or no DNA methylation changes in EOM plus FA samples. The genes were involved in critical cellular processes and signaling pathways important for embryo development. In addition, the EOM-decreased SAM/SAH ratio was counteracted by FA supplementation. Furthermore, FA attenuated the EOM-induced changes in the expression of genes involved in the regulation of DNA methylation and in folate biosynthesis. In conclusion, our data suggest that FA supplementation protected zebrafish embryos from the cardiac developmental toxicity of PM2.5 by alleviating EOM-induced DNA methylation changes.

Thyroid hormones play a fundamental role in the regulation of metabolism of almost all mammalian tissue including the reproductive system. Hyperthyroidism in early life may cause delayed sexual maturation, although physical development is normal and skeletal growth may be accelerated. Hyperthyroidism after puberty influences reproductive functions and increases testosterone level. The aim of this work is to study the effect of induced hyperthyroidism by L-thyroxine sodium administration on the testis of rats and to evaluate the ameliorating role of different antioxidants as ascorbic acid and folic acid on the hyperthyroid state via the assessment of different biochemical markers, histopathological and immunochemical sections. DNA analysis of the D1 deiodinase was performed to determine genetic mutation due to hyperthyroidism. The results showed partially disrupted in the measured biochemical parameters and spermatogenesis in hyperthyroid rats. Post-administration of both folic and ascorbic acids together in hyperthyroid rats showed the best ameliorating effects on the thyroid hormones, testosterone, testicular GGT and ALP, and all oxidative stress markers. There is no genetic mutations that occurred in D1 deiodinase due to hyperthyroidism. These findings were indicated by the proliferating cell nuclear antigen (PCNA) studies of testes.

The purpose of this study was to explore the interventional effects of folic acid on the heart damage caused by lead acetate exposure. Twenty-four 60-day-old male Sprague–Dawley (SD) rats were randomly divided into 4 groups with 6 rats in each group. The control group (C group) was normal rats; the lead exposure group (L group) rats drank 0.2% lead acetate solution freely for 14 days. The rats in the intervention group (T group) were given 0.2% lead acetate solution for 14 days, respectively, and 0.4 mg/kg BW folic acid solution was given to the rats by gavage on the 7th day of lead administration. The rats in the folic acid group (group E) were given 0.4 mg/kg BW folic acid solution by gavage. To weigh rat body weight and heart weight, calculate heart index, and observe the expression level of nuclear factor erythroid 2-related factor 2(Nrf2), heme oxygenase 1(HO-1), glucose-regulated protein 78/binding immunoglobulin protein (GRP78), and C/EBP-homologous protein (CHOP) by immunofluorescence method. The results showed that compared with group C, serum lead levels in group L and T were significantly increased (P < 0.05); superoxide dismutase (SOD), glutathione (GSH), and glutathione peroxidase (GSH-PX) levels in group L were significantly decreased (P < 0.05), and malondialdehyde (MDA) content was significantly higher increased (P < 0.05), and the GSH-PX content in group T were significantly increased in group L (P < 0.05), and the MDA content in group T was significantly lower than that in group L (P < 0.05). Compared with group C, the expression of Nrf2, HO-1, GRP78, and CHOP in group L increased significantly, and the difference was statistically significant (P < 0.05). Compared with the L group, the expression of Nrf2, HO-1, GRP78, and CHOP in the T group was reduced. Therefore, folic acid has a certain protective effect on the oxidative damage of lead-exposed rat heart tissue. Lead exposure will increase ROS, NO, MDA, and other oxidizing substances and reduce the level of GSH, SOD, CAT, GPx, and other antioxidant factors, which will lead to cardiac hypertrophy, cardiac index increase, oxidative stress, Nrf2, and HO-1. The expression of stress-related proteins such as GRP78 and CHOP also increased, leading to cardiomyocyte apoptosis. After a folic acid intervention, these changes can be significantly reversed.

Methotrexate is an antineoplastic folate analog of high environmental concern, due to its low biodegradability and toxicological properties. This study focused on its photodegradation under two irradiation conditions, aiming to be representative of environment (300–450 nm) and drinking water treatment (254 nm). The photodegradation experiments were conducted at two pH, to vary the methotrexate ionization state and to produce a large variety of transformation products (TPs). The degradation kinetics determined through LC-UV monitoring were contrasted according to pH and irradiation wavelength. However, the quantum yields were independent of ionization state at 254 nm and the changes in kinetics at higher wavelengths were attributed to a change in the degradation mechanism. The TPs formed during the reactions were identified by UHPLC-MS/MS, using both the positive and negative modes. Among the eleven proposed structures, five were described as methotrexate TPs for the first time. The TPs result from N-demethylation, glutamic acid oxidation, and C–N cleavage, all of them leading to further degraded photoproducts presenting modified or lost glutamic acid part. This was made possible thanks to the negative mode, which allowed the exploration of the glutamic acid moiety modifications. Cytotoxicity assessment on A549 cancer cells demonstrated that all photoproducts formed at pH 7 were less toxic than the parent compound.

Chlorella vulgaris and Bacillus licheniformis consortium was added to synthetic wastewater with exogenous vitamin B₁₂. In the presence of 100 ng/L vitamin B₁₂, removal efficiencies of TN, NH₃-N, PO₄³—P, and COD were 80.1%, 76.8%, 87.9%, and 76.7%, respectively. The functional groups on the cell surface of the consortium, including -NH, -CH₃, C=O, C=C, and P-O-C, increased with 100 ng/L vitamin B₁₂. These functional groups improved the biological adsorption of the consortium; however, higher concentrations of vitamin B₁₂ resulted in an occlusion of the functional groups. Furthermore, there were 5 significantly enriched protein pathways, namely carbon fixation in photosynthetic organisms; amino acid metabolic pathways; the pathway of one carbon pool by folate; nitrogen metabolism; and photosynthesis. Most proteins in these pathways were upregulated, which enhanced carbon fixation and photosynthesis in the algal cells. Simultaneously, B₁₂ promoted significant upregulation of proteins associated with the quorum-sensing pathway, which promoted the interaction between algae and bacteria.

For the first time (N = 6291), a study was undertaken to estimate associations between the concentratio ns of red blood cell folate (RBCF) and concentration of six perfluoroalkyl acids (PFAAs), namely, perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorohexane sulfonic acid (PFHxS), perfluorodecanoic acid (PFDA), perfluorononanoic acid (PFNA), and perfluoroundecanoic acid (PFUnDA) for US adults aged ≥20 years by fitting regression models for the data from National Health and Nutrition Examination Survey for 2007–2014. In almost consistent fashion, increasing concentrations of PFAAs were associated with decreasing concentrations of RBCF. For the total population, for a 10% increase in the concentrations of PFOA, PFOS, PFDA, PFHxS, PFNA, and PFUnDA, percent decreases in RBCF concentrations were found to be 0.33%, 0.66%, 0.83%, 0.16%, 0.89%, and 0.43%, respectively. RBCF concentrations of PFAAs were found to be 1104, 1042, 100, and 936 nmol/L across the four quartiles of PFOS; 112, 1068, 1009, and 948 nmol/L across the four quartiles of PFDA; 1125, 1054, 1005, and 967 nmol/L across the four quartiles of PFNA; and 1099, 1094, 989, and 952 nmol/L across the four quartiles of PFUnDA. Perfluorinated carboxylic acids with carbon chain length > 8 decreased concentrations of RBCF to a greater degree than those carbon chain length ≤ 8. Perfluorinated chemicals with a sulfonic group with carbon chain length > 6 decreased concentrations of RBCF to a greater degree than those carbon chain length ≤ 6. The degree to which concentrations of RBCF decrease varied by age, gender, and race/ethnicity. Non-Hispanic blacks as compared to non-Hispanic whites and Hispanics had the lowest decreases in RBCF concentrations. Mechanisms responsible for negative associations between RBCF and PFAA concentrations are not known and will need to be researched further.

In this paper, folic acid–coated graphene oxide nanocomposite (FA-GO) is used as an adsorbent for the treatment of heavy metals including cadmium (Cd²⁺) and copper (Cu²⁺) ions. As such, graphene oxide (GO) is modified by folic acid (FA) to synthesize FA-GO nanocomposite and characterized by the atomic force microscopy (AFM), Fourier transform-infrared (FT-IR) spectrophotometry, scanning electron microscopy (SEM), and C/H/N elemental analyses. Also, computational intelligence tests are used to study the mechanism of the interaction of FA molecules with GO. Based on the results, FA molecules formed a strong π-π stacking, chemical, and hydrogen bond interactions with functional groups of GO. Main parameters including pH of the sample solution, amounts of adsorbent, and contact time are studied and optimized by the Response Surface Methodology Based on Central Composite Design (RSM-CCD). In this study, the equilibrium of adsorption is appraised by two (Langmuir and Freundlich and Temkin and D-R models) and three parameter (Sips, Toth, and Khan models) isotherms. Based on the two parameter evaluations, Langmuir and Freundlich models have high accuracy according to the R² coefficient (more than 0.9) in experimental curve fittings of each pollutant adsorption. But, multilayer adsorption of each contaminant onto the FA-GO adsorbent (Freundlich equation) is demonstrated by three parameter isotherm analysis. Also, isotherm calculations express maximum computational adsorption capacities of 103.1 and 116.3 mg g⁻¹ for Cd²⁺ and Cu²⁺ ions, correspondingly. Kinetic models are scrutinized and the outcomes depict the adsorption of both Cd²⁺ and Cu²⁺ followed by the pseudo-second-order equation. Meanwhile, the results of the geometric model illustrate that the variation of adsorption and desorption rates do not have any interfering during the adsorption process. Finally, thermodynamic studies show that the adsorption of Cu²⁺ and Cd²⁺ onto the FA-GO nanocomposite is an endothermic and spontaneous process.