Arsenic (As) and cadmium (Cd), two major carcinogenic heavy metals, enters into human food chain by the consumption of rice or rice-based food products. Both As and Cd disturb plant-nutrient homeostasis and hence, reduces plant growth and crop productivity. In the present study, As/Cd modulated responses were studied in non-basmati (IR-64) and basmati (PB-1) rice varieties, at physiological, biochemical and transcriptional levels. At the seedling stage, PB-1 was found more sensitive than IR-64, in terms of root biomass; however, their shoot phenotype was comparable under As and Cd stress conditions. The ionomic data revealed significant nutrient deficiencies in As/Cd treated-roots. The principal component analysis identified NH₄⁺ as As-associated key macronutrient; while, NH₄⁺/NO₃⁻ and K⁺ was majorly associated with Cd mediated response, in both IR-64 and PB-1. Using a panel of 21 transporter gene expression, the extent of nutritional deficiency was ranked in the order of PB-1(As)<IR-64(As)<PB-1(Cd)<IR-64(Cd). A feed-forward model is proposed to explain nutrient deficiency induced de-regulation of gene expression, as observed under Cd-treated IR-64 plants, which was also validated at the level of sulphur metabolism related enzymes. Using urea supplementation, as nitrogen-fertilizer, significant mitigation was observed under As stress, as indicated by 1.018- and 0.794-fold increase in shoot biomass in IR-64 and PB-1, respectively compared to that of control. However, no significant amelioration was observed in response to supplementation of urea under Cd or potassium under As/Cd stress conditions. Thus, the study pinpointed the relative significance of various macronutrients in regulating As- and Cd-tolerance and will help in designing suitable strategies for mitigating As and/or Cd stress conditions.

The intestinal microbiota has a key role in human health via the interaction with the somatic and immune cells in the digestive tract environment. Food, through matrix effect, nutrient and non-nutrient molecules, is a key regulator of microbiota diversity. As a food contaminant, the pesticide chlorpyrifos (CPF) has an effect on the composition of the intestinal microbiota and induces perturbation of microbiota. Prebiotics (and notably inulin) are known for their ability to promote an equilibrium of the microbiota that favours saccharolytic bacteria. The SHIME® dynamic in vitro model of the human intestine was exposed to CPF and inulin concomitantly for 30 days, in order to assess variations in both the bacterial populations and their metabolites. Various analyses of the microbiota (notably temporal temperature gradient gel electrophoresis) revealed a protective effect of the prebiotic through inhibition of the enterobacterial (E. coli) population. Bifidobacteria were only temporarily inhibited at D15 and recovered at D30. Although other potentially beneficial populations (lactobacilli) were not greatly modified, their activity and that of the saccharolytic bacteria in general were highlighted by an increase in levels of short-chain fatty acids and more specifically butyrate. Given the known role of host-microbiota communication, CPF's impact on the body's homeostasis remains to be determined.

RNA N⁶-methyladenosine (m⁶A) modification regulates the cell stress response and homeostasis, but whether titanium dioxide nanoparticle (nTiO₂)-induced acute pulmonary injury is associated with the m⁶A epitranscriptome and the underlying mechanisms remain unclear. Here, the potential association between m⁶A modification and the bioeffects of several engineered nanoparticles (nTiO₂, nAg, nZnO, nFe₂O₃, and nCuO) were verified thorough in vitro experiments. nFe₂O₃, nZnO, and nTiO₂ exposure significantly increased the global m⁶A level in A549 cells. Our study further revealed that nTiO₂ can induce m⁶A-mediated acute pulmonary injury. Mechanistically, nTiO₂ exposure promoted methyltransferase-like 3 (METTL3)-mediated m⁶A signal activation and thus mediated the inflammatory response and IL-8 release through the degeneration of anti-Mullerian hormone (AMH) and Mucin5B (MUC5B) mRNAs in a YTH m⁶A RNA-binding protein 2 (YTHDF2)-dependent manner. Moreover, nTiO₂ exposure stabilized METTL3 protein by the lipid reactive oxygen species (ROS)-activated ERK1/2 pathway. The scavenging of ROS with ferrostatin-1 (Fer-1) alleviates the ERK1/2 activation, m⁶A upregulation, and the inflammatory response caused by nTiO₂ both in vitro and in vivo. In conclusion, our study demonstrates that m⁶A is a potential intervention target for alleviating the adverse effects of nTiO₂-induced acute pulmonary injury in vitro and in vivo, which has far-reaching implications for protecting human health and improving the sustainability of nanotechnology.

The coexistence of di (2-ethylhexyl) phthalate (DEHP), Cd, and Zn poses a serious challenge to soil ecosystems. This study aimed to evaluate the phytoremediation potential of rice assisted with a plant growth promoting rhizobacteria (PGPR) consortium for the remediation of DEHP, Cd, and Zn co-contaminated soil. The consortium consisted of four bacterial strains, all of which exhibited Cd–Zn resistance and DEHP degradability. The results showed that the rice assisted by the bacterial consortium dissipated 86.1% DEHP while removing 76.0% Cd²⁺ and 92.2% Zn²⁺ from soil within 30 d. The presence of the PGPR consortium promoted plant growth and improved soil enzymatic activity, which may have helped enhance the removal of DEHP and heavy metals from the soil. Moreover, the application of the consortium modified the bacterial community and increased the relative abundance of bacteria related to DEHP degradation (Sphingomonas, Xanthobacteraceae), heavy metal immobilization (Massilia), and soil nutrient cycling (Nitrospira, Vicinamibacterales), which promoted plant growth and the removal of DEHP and heavy metals from soil. Notably, the DEHP and heavy metal contents in rice decreased substantially during the phytoremediation process. Therefore, the PGPR consortium could be beneficial for enhancing the removal of DEHP and heavy metals from the soil, without inducing the accumulation of these pollutants in rice. In general, this study confirmed that the combined use of rice and the PGPR consortium could remedy DEHP and heavy metal co-contaminated soil economically and ecologically without simultaneously posing risks for rice consumption.

Understanding the metabolic defense and compensation to maintain homeostasis is crucial for assessing the potential health risk of organic pollutants in crops. Currently, limited understanding is available regarding the targeted metabolic pathways and response mechanism under contaminant stress. This study showed that ciprofloxacin (CIP) at the environmental concentrations (1, 5, 25, 50 mg/L) did not significantly inhibit growth or cause severe oxidative damage to rice (Oryza sativa L.). Instead, the increment in CIP concentration induced a series of sequential metabolic disorders, which were characterized predominantly by primary and secondary metabolic disturbances, including phenylpropanoid biosynthesis, the carbohydrate, lipid and amino acid metabolism. After CIP in vivo exceeded a certain threshold level (>0.29 mg/g dry weight), β-glucosidases (BGLUs) mediated the transition from the activation of the genes related to phenylpropanoid biosynthesis to the inhibition of the genes related to carbohydrate metabolism in rice. In particular, starch and sucrose metabolism showed the most profound perturbation stressed by environmental concentrations of CIP (5 mg/L) and other tested organic pollutants (10 μg/L of tricyclazole, thiamethoxam, polybrominated diphenyl ethers, and polychlorinated biphenyls). Besides, the key genes encoding endoglucanase and BGLU were significantly downregulated (|log₂FC| > 3.0) under 100 μg/L of other tested organic pollutants, supporting the transition from the activation of secondary defense metabolism to the disruption of primary energy metabolism. Thus, in addition to bioaccumulation, changes in BGLU activity and starch and sucrose metabolism can reflect the potential adverse effects of pollutants on rice. This study explained the stepwise metabolic and transcriptional responses of rice to organic pollutants, which provided a new reference for the comprehensive evaluation of their environmental risks.

Bisphenol A (BPA) is widely used by manufacturers and in consumer products. Its release in the environment may affect male reproductive function. In this study, we examined the effect of low dose (0.1 mg/kg BW), short term exposure during puberty (PD21-35) on adult rat male reproduction. The results indicated that such exposure reset growth hormone (GH) and follicular stimulating hormone (FSH) homeostasis and resulted in a significantly higher level of serum testosterone without affecting serum luteinizing hormone level. QPCR and Western blot results showed that BPA significantly up-regulated selective genes/proteins in the Leydig cell steroidogenic pathway, including steroidogenic acute regulatory protein, cytochrome P450 11A1, cytochrome P450 17A, and low-density lipoprotein receptor. RNA-Seq analysis of testicular RNAs showed that BPA significantly affected the gene profiles of multiple testicular interstitial populations without affecting germ cells. Also, GO- and KEGG-analysis suggested that IGF1-related PI3K/AKT signaling was activated, which was confirmed by the increased phosphorylation of IRS1, AKT1 and CREB. The results indicated that a low-dose, short-term BPA exposure during puberty affected the adult male rat pituitary (GH and FSH) and testis (testosterone) homeostasis.

The link between zinc exposure and glucose metabolism or the development of type 2 diabetes (T2D) is controversial, and underlying mechanisms are unclear. This study aimed to explore the associations of zinc exposure with glucose-insulin homeostasis traits and the long-term effects of zinc on the development of T2D, and further to estimate the potential roles of inflammation and oxidative damage in such relationships. We investigated 3890 urban adults from the Wuhan-Zhuhai cohort, and followed up every three years. Mixed linear model was applied to estimate dose-response associations between urinary zinc and glycemia traits [fasting plasma insulin (FPI), fasting plasma glucose (FPG), insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR), and β-cell dysfunction (homeostasis model assessment of β-cell function, HOMA-B)], as well as zinc and biomarkers for systemic inflammation (C-reactive protein) and oxidative damage (8-isoprostane and 8-hydroxy-2′-deoxyguanosine). Logistic regression model and Cox regression model were conducted to evaluate the relationships between urinary zinc and prevalence and incidence of T2D, respectively. We further performed mediation analysis to assess the roles of inflammation and oxidative damage biomarkers in above associations. At baseline, we observed significant dose-response relationships of elevated urinary zinc with increased FPI, FPG, HOMA-IR, and T2D prevalence and decreased HOMA-B, and such associations could be strengthened by increased C-reactive protein, 8-isoprostane, and 8-hydroxy-2′-deoxyguanosine. Elevated C-reactive protein significantly mediated 9.09% and 17.67% of the zinc-related FPG and HOMA-IR increments, respectively. In longitudinal analysis, a significantly positive association between urinary zinc and T2D incidence was observed among subjects with persistent high urinary zinc levels when compared with those with persistent low zinc levels. Our results suggested that high levels of zinc exposure adversely affected on glucose-insulin homeostasis and further contributed to increased risk of T2D cross-sectionally and longitudinally. Moreover, inflammatory response might play an important role in zinc-related glucose metabolic disorder.

Cropland contamination by toxic trace metal (loid)s (TTMs) has attracted increasing attention due to the serious consequential threat to crop quality and human health. Mitigation of plant TTM stress by silica amendment has been proposed recently. However, the relationship between the siliceous structure of phytoliths and TTMs in plants, and the environmental implications of phytolith-occluded trace metal (loid)s (PhytTMs) remain unclear. This study assessed the accumulation of five metal (loid)s, including lead (Pb), zinc (Zn), cadmium (Cd), copper (Cu) and arsenic (As), in the organic tissues and phytoliths of wheat grown in a mixed-TTM contaminated soil under both lightly and heavily contaminated conditions. The results show that the concentrations of plant TTMs and PhytTMs were significantly (p < 0.05) positively correlated, and higher in heavily contaminated wheats than those in lightly contaminated ones. The bio-enrichment factors between phytoliths and organic tissues were higher for As (1.83), Pb (0.27) and Zn (0.30) than for Cd (0.03) and Cu (0.14), implying that As, Pb and Zn were more readily co-precipitated with silicon (Si) in phytolith structures than Cd and Cu. Network analysis of the relationship between soil and plant elements with PhytTMs showed that severe contamination could impact the homeostasis of elements in plants by altering the translocation of TTMs between soils, plants, and phytoliths. The accumulation of TTMs in phytoliths was affected by the capacity of Si deposition in tissues and chelation of TTMs with silica, which could impact the role of PhytTMs in global biogeochemical TTM cycles.

Maintaining thyroid homeostasis during pregnancy is vital for fetal development. The few studies that have investigated associations between metal exposure and gestational thyroid function have yielded mixed findings. To evaluate the association of exposure to a mixture of toxic metals with thyroid parameters in 824 pregnant women from the Rhea birth cohort in Crete, Greece. Concentrations of three toxic metals [cadmium (Cd), antimony (Sb), lead (Pb)] and iodine were measured in urine using inductively coupled plasma mass spectrometry and thyroid hormones [Thyroid Stimulating Hormone (TSH), free thyroxine (fT4), and free triiodothyronine (fT3)] were measured in serum in early pregnancy. Associations of individual metals with thyroid parameters were assessed using adjusted regression models, while associations of the metal mixture with thyroid parameters were assessed using Bayesian Kernel Machine Regression (BKMR).Women with high (3rd tertile) concentrations of urinary Cd, Sb and Pb, respectively, had 13.3 % (95%CI: 2.0 %, 23.2 %), 12.5 % (95%CI: 1.8 %, 22.0 %) and 16.0 % (95%CI: 5.7 %, 25.2 %) lower TSH compared to women with low concentrations (2nd and 1st tertile). In addition, women with high urinary Cd had 2.2 % (95%CI: 0.0 %, 4.4 %) higher fT4 and 4.0 % (95%CI: −0.1 %, 8.1 %) higher fT3 levels, and women with high urinary Pb had 4 % (95%CI: 0.2 %, 8.0 %) higher fT3 levels compared to women with low exposure. The negative association of Cd with TSH persisted only when iodine sufficiency was unfavorable. BKMR attested that simultaneous exposure to toxic metals was associated with decreased TSH and increased fT3 and revealed a potential synergistic interaction of Cd and Pb in association with TSH. The present results suggest that exposure to toxic metals even at low levels can alter gestational thyroid homeostasis.

Chronic toxicity of copper (Cu) at sublethal levels is associated with ionoregulatory disturbance and oxidative stress. These factors were considered in a toxicokinetic-toxicodynamic model in the present study. The ionoregulatory disturbance was evaluated by the activity of the Na⁺/K⁺-ATPase enzyme (NKA), while oxidative stress was presented by lipid peroxidation (LPO) and glutathione-S-transferase (GST) activity. NKA activity was related to the binding of Cu²⁺ and Na ⁺ to NKA. LPO and GST activity were linked with the simulated concentration of unbound Cu. The model was calibrated using previously reported data and empirical data generated when zebra mussels were exposed to Cu. The model clearly demonstrated that Cu might inhibit NKA activity by reducing the number of functional pump sites and the limited Cu-bound NKA turnover rate. An ordinary differential equation was used to describe the relationship between the simulated concentration of unbound Cu and LPO/GST activity. Although this method could not explain the fluctuations in these biomarkers during the experiment, the measurements were within the confidence interval of estimations. Model simulation consistently shows non-significant differences in LPO and GST activity at two exposure levels, similar to the empirical observation.