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.

Understanding of aquaporins (AQPs) facilitating the transport of water and many other small solutes including metalloids like silicon (Si) and arsenic (As) is important to develop stress tolerant cultivars. In the present study, 40 AQPs were identified in the genome of pigeonpea (Cajanus cajan), a pulse crop widely grown in semi-arid region and areas known to affected with heavy metals like As. Conserved domains, variation at NPA motifs, aromatic/arginine (ar/R) selectivity filters, and pore morphology defined here will be crucial in predicting solute specificity of pigeonpea AQPs. The study identified CcNIP2-1 as an AQP predicted to transporter Si (beneficial element) as well as As (hazardous element). Further Si quantification in different tissues showed about 1.66% Si in leaves which confirmed the predictions. Furthermore, scanning electron microscopy showed a higher level of Si accumulation in trichomes on the leaf surface. A significant alleviation in level of As, Sb and Ge stress was also observed when these heavy metals were supplemented with Si. Estimation of relative water content, H₂O₂, lipid peroxidation, proline, total chlorophyll content and other physiological parameters suggested Si derived stress tolerance. Extensive transcriptome profiling under different developmental stages from germination to senescence was performed to understand the tissue-specific regulation of different AQPs. For instance, high expression of TIP3s was observed only in reproductive tissues. Co-expression network developed using transcriptome data from 30 different conditions and tissues, showed interdependency of AQPs. Expression profiling of pigeonpea performed using real time PCR showed differential expression of AQPs after Si supplementation. The information generated about the phylogeny, distribution, molecular evolution, solute specificity, and gene expression dynamics in article will be helpful to better understand the AQP transport system in pigeonpea and other legumes.

The intensification of anomalous events of seawater warming and the co-occurrence with local anthropogenic stressors are threatening coastal marine habitats, including seagrasses, which form extensive underwater meadows. Eutrophication highly affects coastal environments, potentially summing up to the widespread effects of global climate changes. In the present study, we investigated for the first time in seagrasses, the transcriptional response of different plant organs (i.e., leaf and shoot apical meristem, SAM) of the Mediterranean seagrass Posidonia oceanica growing in environments with a different history of nutrient enrichment. To this end, a mesocosm experiment exposing plants to single (nutrient enrichment or temperature increase) and multiple stressors (nutrient enrichment plus temperature increase), was performed. Results revealed a differential transcriptome regulation of plants under single and multiple stressors, showing an organ-specific sensitivity depending on plants' origin. While leaf tissues were more responsive to nutrient stress, SAM revealed a higher sensitivity to temperature treatments, especially in plants already impacted in their native environment. The exposure to stress conditions induced the modulation of different biological processes. Plants living in an oligotrophic environment were more responsive to nutrients compared to plants from a eutrophic environment. Evidences that epigenetic mechanisms were involved in the regulation of transcriptional reprogramming were also observed in both plants’ organs. These results represent a further step in the comprehension of seagrass response to abiotic stressors pointing out the importance of local pressures in a global warming scenario.

Perfluorooctanesulfonic acid (PFOS) is a persistent anthropogenic chemical that can affect the thyroid hormone system in humans and animals. In adults, thyroid hormones (THs) are regulated by the hypothalamic-pituitary-thyroid (HPT) axis, but also by organs such as the liver and potentially the gut microbiota. PFOS and other xenobiotics can therefore disrupt the TH system at various locations and through different mechanisms. To start addressing this, we exposed adult male rats to 3 mg PFOS/kg/day for 7 days and analysed effects on multiple organs and pathways simultaneously by transcriptomics. This included four primary organs involved in TH regulation, namely hypothalamus, pituitary, thyroid, and liver. To investigate a potential role of the gut microbiota in thyroid hormone regulation, two additional groups of animals were dosed with the antibiotic vancomycin (8 mg/kg/day), either with or without PFOS. PFOS exposure decreased thyroxine (T4) and triiodothyronine (T3) without affecting thyroid stimulating hormone (TSH), resembling a state of hypothyroxinemia. PFOS exposure resulted in 50 differentially expressed genes (DEGs) in the hypothalamus, 68 DEGs in the pituitary, 71 DEGs in the thyroid, and 181 DEGs in the liver. A concomitant compromised gut microbiota did not significantly change effects of PFOS exposure. Organ-specific DEGs did not align with TH regulating genes; however, genes associated with vesicle transport and neuronal signaling were affected in the hypothalamus, and phase I and phase II metabolism in the liver. This suggests that a decrease in systemic TH levels may activate the expression of factors altering trafficking, metabolism and excretion of TH. At the transcriptional level, little evidence suggests that the pituitary or thyroid gland is involved in PFOS-induced TH system disruption.

Dinotefuran is a third-generation neonicotinoid pesticide and is increasingly used in agricultural production, which has adverse effects on nontarget organisms. However, the research on the impact of dinotefuran on nontarget organisms is still limited. Here the toxic effects of dinotefuran on an important economic species and a model lepidopteran insect, Bombyx mori, were investigated. Exposure to different doses of dinotefuran caused physiological disorders or death. Cytochrome P450, glutathione S-transferase, carboxylesterase, and UDP glycosyl-transferase activities were induced in the fat body at early stages after dinotefuran exposure. By contrast, only glutathione S-transferase activity was increased in the midgut. To overcome the lack of sensitivity of the biological assays at the individual organism level, RNA sequencing was performed to measure differential expressions of mRNA from silkworm larvae after dinotefuran exposure. Differential gene expression profiling revealed that various detoxification enzyme genes were significantly increased after dinotefuran exposure, which was consistent with the upregulation of the detoxifying enzyme. The global transcriptional pattern showed that the physiological responses induced by dinotefuran toxicity involved multiple cellular processes, including energy metabolism, oxidative stress, detoxification, and other fundamental physiological processes. Many metabolism processes, such as carbon metabolism, fatty acid biosynthesis, pyruvate metabolism, and the citrate cycle, were partially repressed in the midgut or fat body. Furthermore, dinotefuran significantly activated the MAPK/CREB, CncC/Keap1, PI3K/Akt, and Toll/IMD pathways. The links between physiological, biochemical toxicity and comparative transcriptomic analysis facilitated the systematic understanding of the integrated biological toxicity of dinotefuran. This study provides a holistic view of the toxicity and detoxification metabolism of dinotefuran in silkworm and other organisms.

Exposure of females to fine particulate matter ≤2.5 μm in diameter (PM2.5) prior to pregnancy could produce adverse impact on fertility and enhances susceptibility of the offspring to a variety of diseases. In the current study, female C57BL/6 mice (6 weeks of age) were exposed to either concentrated PM2.5 or filtered air (average PM2.5 concentration: 115.60 ± 7.77 vs. 14.07 ± 0.38 μg/m⁻³) using a whole-body exposure device for 12 weeks. Briefly, PM2.5 exposure decreased anti-Müllerian hormone level (613.40 ± 17.36 vs 759.30 ± 21.90 pg mL⁻¹, P＜0.01) and increased reactive oxygen species (ROS) level (45.39 ± 0.82 vs 24.20 ± 0.85 arbitrary unit in fluorescence assay, P＜0.01) in oocytes. The exposure increased oocyte degeneration rate (21.5% vs 5.1%, respectively (P＜0.01) and decreased the 2-cell formation rate (71.9% vs 86.0%, P < 0.01). Transcriptome profiling using RNA sequencing showed wide spectrum of abnormal expression of genes, particularly those involved in regulating the mitochondrial respiratory complex in oocytes and metabolic processes in blastocysts. The exposure decreased litter size (6 ± 0.37 vs 7 ± 0.26, P＜0.05) and weight (1.18 ± 0.02 vs 1.27 ± 0.02 g, P＜0.01). In summary, PM2.5 exposure decreased female fertility, possibly through increased ROS production in oocytes and metabolic disturbances in developing embryos. The cause-effect relationship, however, requires further investigation.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a well-known immunotoxic environmental pollutant. However, most immunotoxicology studies of TCDD were based on the animal models and the inner mechanisms have just focused on a few genes/proteins. In this study, the immune functions of THP-1-derived macrophages was measured with in-vitro bioassays after 24-h exposure of TCDD including environmentally relevant concentrations. RNA-seq and Weighted Gene Co-expression Network Analysis were used to characterize the immunotoxicity molecular mechanisms. Our study is the first report on the TCDD-induced effects of cell adhesion, morphology, and multiple cytokines/chemokines production on THP-1 macrophages. After TCDD treatment, we observed an inhibited cell adherence, probably attributed to the suppressed mRNA levels of adhesion molecules ICAM-1, VCAM-1 and CD11b, and a decrease in cell pseudopodia and expression of F-actin. The inflammatory cytokines TNF-α, IL-10 and other 8 cytokines/chemokines regulating granulocytes/T cells and angiogenesis were disrupted by TCDD. Alternative splicing event was found to be a sensitive target for TCDD. Using WGCNA, we identified 10 hub genes (TNF, SRC, FGF2, PTGS2, CDH2, GNG11, BDNF, WNT5A, CXCR5 and RUNX2) highly relevant to these observed phenotypes, suggesting AhR less important in the effects TCDD have on THP-1 macrophages than in other cells. Our findings broaden the understanding of TCDD immunotoxicity on macrophages and provide new potential targets for clarifying the molecular mechanisms.

The surface modifications of nanoparticles (NPs), are well-recognized parameters that affect the toxicity, while there has no study on toxicity of Al₂O₃ NPs with different surface modification. Therefore, for the first time, this study pays attention to evaluating the toxicity and potential mechanism of pristine Al₂O₃ NPs (p-Al₂O₃), hydrophilic (w-Al₂O₃) and lipophilic (o-Al₂O₃) modifications of Al₂O₃ NPs both in vitro and in vivo. Applied concentrations of 10, 20, 40, 80,100 and 200 μg/mL for 24 h exposure on Caenorhabditis elegans (C. elegans), while 100 μg/mL of Al₂O₃ NPs significantly decreased the survival rate. Using multiple toxicological endpoints, we found that o-Al₂O₃ NPs (100 μg/mL) could induce more severe toxicity than p-Al₂O₃ and w-Al₂O₃ NPs. After uptake by C. elegans, o-Al₂O₃ NPs increased the intestinal permeability, easily swallow and further destroy the intestinal membrane cells. Besides, cytotoxicity evaluation revealed that o-Al₂O₃ NPs (100 μg/mL) are more toxic than p-Al₂O₃ and w-Al₂O₃. Once inside the cell, o-Al₂O₃ NPs could attack mitochondria and induce the over-production of reactive oxygen species (ROS), which destroy the intracellular redox balance and lead to apoptosis. Furthermore, the transcriptome sequencing and RT-qPCR data also demonstrated that the toxicity of o-Al₂O₃ NPs is highly related to the damage of cell membrane and the imbalance of intracellular redox. Generally, our study has offered a comprehensive sight to the adverse effects of different surface modifications of Al₂O₃ NPs on environmental organisms and the possible underlying mechanisms.

The enantioselective toxic effect and environmental behavior of chiral pesticides have attracted increasing research attention. In this study, the enantioselective toxicity and residues of hexaconazole (HEX) in earthworms (Eisenia fetida) were investigated. In the present study, significant enantioselective degradation characteristics were observed in artificial soil with the R-enantiomer preferentially degrading (p < 0.05); however, no significant enantioselective bioaccumulation was observed in the earthworms (p > 0.05). The acute toxicity of S-(+)-HEX was higher than that of R-(−)-HEX in earthworms, with 48-h LC₅₀ values of 8.62 and 22.35 μg/cm², respectively. At 25 mg/kg, enantiospecific induction of oxidative stress was observed in earthworms; moreover, S-(+)-HEX had a greater influence on the contents of malonaldehyde, cytochrome P450, and 8-hydroxy-2-deoxyguanosine than R-(−)-HEX. These results were consistent with those of the enrichment analysis of differentially expressed genes. The transcriptome sequencing results showed that S-(+)-HEX had a more significant influence on steroid biosynthesis, arachidonic acid metabolism, and cell cycle processes than R-(−)-HEX, leading to abnormal biological function activities. These results indicate that S-(+)-HEX may pose a higher risk to soil organisms than R-(−)-HEX. This study suggests that the environmental risk of chiral pesticides to nontarget organisms should be assessed at the enantiomeric level.

N⁶-methyladenosine (m6A) modification, the most prevalent form of RNA methylation, modulates gene expression post-transcriptionally. Di-(2-ethylhexyl) phthalate (DEHP) is a common environmental endocrine disrupting chemical that induces testicular injury due to the inhibition of the demethylase fat mass and obesity-associated protein (FTO) and increases the m6A modification. How FTO-mediated m6A modification in testicular Leydig cell injury induced by DEHP remains unclear. Here, the TM3 Leydig cell line was treated with mono-(2-ethylhexyl) phthalate (MEHP), the main metabolite of DEHP in the body, as well as FB23-2, an inhibitor of FTO. Decreased levels of testosterone in the culture supernatant, significantly increased apoptosis, and a remarkable upregulation of global m6A modification were found in both TM3 cells treated with MEHP and FB23-2. Transcriptome sequencing showed that both treatments significantly induced apoptosis-associated gene expression. Methylated RNA immunoprecipitation sequencing showed that the Leydig cell injury induced by upregulated m6A modification could be associated with multiple physiological disorders, including histone acetylation, reactive oxygen species biosynthesis, MAPK signaling pathway, hormone secretion regulation, autophagy regulation, and male gonadal development. Overall, the inhibition of FTO-mediated up-regulation of m6A could be involved in MEHP-induced Leydig cell apoptosis.