Since the urbanization and industrialization are wildly spread in recent decades, the concentration of Zn in soil has increased in various regions. Although the interactions between P and Zn has long been recognized, the effect of high level of Zn on P uptake, translocation and distribution in rice and its molecular mechanism are not fully understood. In this study, we conducted both hydroponic culture and field trial with different combined applications of P and Zn to analyze the rice growth and yield, the uptake, translocation and distribution of P and Zn, as well as the P- and Zn-related gene expression levels. Our results showed that high level of Zn decreased the rice biomass and yield production, and inhibited the root-to-shoot translocation and distribution of P into new leaves by down-regulating P transporter genes OsPT2 and OsPT8 in shoot, which was controlled by OsPHR2-OsmiR399-OsPHO2 module. High Zn supply triggered P starvation signal in root, thereafter increased the activities of both root-endogenous and -secreted acid phosphatase to release more Pi, and induced the expression OsPT2 and OsPT8 to uptake more P for plant growth. On the other hand, high level of P significantly decreased the Zn concentrations in both root and shoot, and the root uptake ability of Zn through altering the expression levels of OsZIPs, which were further confirmed by the P high-accumulated mutant osnla1-2 and OsPHR2-OE transgenic plant. Taken together, we revealed the physiological and molecular mechanisms of P–Zn interactions, and proposed a working model of the cross-talk between P and Zn in rice plants. Our results also indicated that appropriate application of P fertilizer is an effective strategy to reduce rice uptake of excessive Zn when grown in Zn-contaminated soil.

While Cox17 functions importantly in copper metalation of cytochrome c oxidase and integral mitochondrial architecture in vertebrates, rare studies have been performed regarding the developmental and physiological characters of vertebrate cox17 mutants. In this study, normal-like developmental phenotype was observed in both cox17Δ6−/− and cox17Δ4−/− homozygous zebrafish mutants, while gene ontology term and pathway analysis of the differentially expressed genes in both mutants showed enrichment in oxidoreductase activity, ion transport, histone methylation, MICOS complex, Wnt signaling, etc. This implied the occurrence of damage to the integral function of Cox17 and change of transcriptomes in the two mutants. Further qRT-PCR and WISH assays revealed the down-regulated expression of Wnt signaling and reduced expression of swim bladder marker genes in the two mutants. Moreover, copper stimulation induced no obvious increase in reactive oxygen species (ROS) or in the expression of hemoglobin marker genes, but further reduced the expression of swim bladder marker genes in the mutants. The integral data in this study suggest that: (1) cox17 mutants cannot activate the response of oxidoreductase to copper stimulation; (2) copper depends on the integral function of Cox17 to induce developmental defects in hemoglobin rather than swim bladder and (3) Wnt signaling but not ROS might mediate copper-induced swim bladder developmental defects in fish.

Bisphenol A (BPA) is a harmful environmental contaminant acting as an endocrine disruptor in animals, but it also affects growth and development in plants. Here, we have elucidated the functional mechanism of root growth inhibition by BPA in Arabidopsis thaliana using mutants, reporter lines and a pharmacological approach. In response to 10 ppm BPA, fresh weight and main root length were reduced, while auxin levels increased. BPA inhibited root growth by reducing root cell length in the elongation zone by suppressing expansin expression and by decreasing the length of the meristem zone by repressing cell division. The inhibition of cell elongation and cell division was attributed to the enhanced accumulation/redistribution of auxin in the elongation zone and meristem zone in response to BPA. Correspondingly, the expressions of most auxin biosynthesis and transporter genes were enhanced in roots by BPA. Taken together, it is assumed that the endocrine disruptor BPA inhibits primary root growth by inhibiting cell elongation and division through auxin accumulation/redistribution in Arabidopsis. This study will contribute to understanding how BPA affects growth and development in plants.

Transcription factors including pregnane X receptor (Pxr) and nuclear factor-erythroid 2-related factor-2 (Nrf2) are important modulators of Adenosine triphosphate-binding cassette (ABC) transporters in mammalian cells. However, whether such modulation is conserved in zebrafish embryos remains largely unknown. In this manuscript, pxr- and nrf2-deficient models were constructed with CRISPR/Cas9 system, to evaluate the individual function of Pxr and Nrf2 in the regulation of ABC transporters and detoxification of heavy metal ions like Cd²⁺ and Ag⁺. As a result, both Cd²⁺ and Ag⁺ conferred extensive interactions with ABC transporters in wild type (WT) embryos: their accumulation and toxicity were affected by the activity of ABC transporters, and they significantly induced the mRNA expressions of ABC transporters. These induction effects were reduced by the mutation of pxr and nrf2, but elevations in the basal expression of ABC transporters compensated for the loss of their inducibility. This could be an explanation for remaining transporter function in both mutant models as well as the unaltered toxicity of metal ions in pxr-deficient embryos. However, mutation of nrf2 disrupted the production of glutathione (GSH), resulting in the enhanced toxicity of Cd²⁺/Ag⁺ in zebrafish embryos. In addition, elevated expressions of other transcription factors like aryl hydrocarbon receptor (ahr) 1b, peroxisome proliferator-activated receptor (ppar)-β, and nrf2 were found in pxr-deficient models without any treatment, while enhanced induction of ahr1b, ppar-β and pxr could only be seen in nrf2-deficient embryos after the treatment of metal ions, indicating different compensation phenomena for the absence of transcription factors. After all, pxr-deficient and nrf2-deficient zebrafish embryos are useful tools in the functional investigation of Pxr and Nrf2 in the early life stages of aquatic organisms. However, the compensatory mechanisms should be taken into consideration when interpreting the results and need in-depth investigations.

The gut microbiota is important for maintaining homeostasis of the host. Gut microbes represent the initial site for toxicant processing following dietary exposures to environmental contaminants. The diet is the primary route of exposure to polychlorinated biphenyls (PCBs), which are absorbed via the gut, and subsequently interfere with neurodevelopment and behavior. Developmental exposures to PCBs have been linked to increased risk of neurodevelopmental disorders (NDD), including autism spectrum disorder (ASD), which are also associated with a high prevalence of gastrointestinal (GI) distress and intestinal dysbiosis. We hypothesized that developmental PCB exposure impacts colonization of the gut microbiota, resulting in GI pathophysiology, in a genetically susceptible host. Mouse dams expressing two heritable human mutations (double mutants [DM]) that result in abnormal Ca²⁺ dynamics and produce behavioral deficits (gain of function mutation in the ryanodine receptor 1 [T4826I-RYR1] and a human CGG repeat expansion [170–200 CGG repeats] in the fragile X mental retardation gene 1 [FMR1 premutation]). DM and congenic wild type (WT) controls were exposed to PCBs (0–6 mg/kg/d) in the diet starting 2 weeks before gestation and continuing through postnatal day 21 (P21). Intestinal physiology (Ussing chambers), inflammation (qPCR) and gut microbiome (16S sequencing) studies were performed in offspring mice (P28–P30). Developmental exposure to PCBs in the maternal diet caused significant mucosal barrier defects in ileum and colon (increased secretory state and tight junction permeability) of juvenile DM mice. Furthermore, PCB exposure increased the intestinal inflammatory profile (Il6, Il1β, and Il22), and resulted in dysbiosis of the gut microbiota, including altered β-diversity, in juvenile DM mice developmentally exposed to 1 mg/kg/d PCBs when compared to WT controls. Collectively, these findings demonstrate a novel interaction between PCB exposure and the gut microbiota in a genetically susceptible host that provide novel insight into environmental risk factors for neurodevelopmental disorders.

The knowledge of gene-chemical interaction can be used to derive toxicological mechanism of chemical pollutants, therefore, it might be useful to discriminate chemicals with different mechanisms. In this study, three narcotic chemicals (4-chlorophenol (4-CP), 3, 4-dichloroaniline (DCA) and 2, 2, 2-trichloroethanol (TCE)) and three specific acting chemicals (triclosan (TCS), clarithromycin (CLARY), sulfamethoxazole (SMX)) were assessed by Escherichia coli (E. coli) genome-wide knockout screening. 66, 97, 88, 144, 198 and 180 initial robust hits were identified by exposure to 4-CP, DCA, TCE, TCS, CLARY and SMX with two replicates at the concentration of IC50, respectively. The average fold change values of responsive mutants to the three narcotic chemicals were smaller than the three specific acting chemicals. The common gene ontology (GO) term of biological process enriched by the three narcotic chemicals was “response to external stimulus” (GO: 0009605). Other GO terms like “lipopolysaccharide biosynthetic process” (induced by 4-CP) and “purine nucleotide biosynthetic process” (induced by DCA) were also influenced by the narcotic chemicals. The toxic target of three known specific acting chemicals could be validated by GSEA of responsive genes. Four genes (flhC, fliN, fliH and flhD) might serve as potential biomarkers to distinguish narcotic chemicals and specific acting chemicals. The E. coli functional genomic approach presented here has shown great potential not only for the molecular mechanistic screening of chemicals, rather it can discriminate chemicals based on their mode-of-action.

2,2′,4,4′-Tetrabromodiphenyl ether (BDE-47), a representative congener of polybrominated diphenyl ethers in the environment, is known to have reproductive toxicity. However, the underlying mechanisms remain to be clarified, especially in in vivo systems. In the present study, we employed Caenorhabditis elegans to study the effects of BDE-47 on reproduction. Our results showed that BDE-47 impaired worm fecundity and induced germ cell apoptosis. To elucidate the mechanisms, DNA damage and oxidative stress induction were investigated by determining the numbers of foci formation in transgenic worms expressing HUS-1::GFP and the levels of reactive oxygen species, respectively. We found that BDE-47 induced oxidative stress but not DNA damage, and treatment with the antioxidant, N-acetyl-L-cysteine, completely abrogated BDE-47-induced germ cell apoptosis. In addition, the apoptosis was blocked in mutants carrying mek-1, sek-1 or abl-1 loss-of-function alleles, but not in the p53/cep-1 deficient worms, suggesting that the mitogen-activated protein kinase (MAPK) signaling cascade was essential for BDE-47-induced germ cell apoptosis and p53/cep-1 was not required. Moreover, the apoptosis in the strains deficient for DNA damage response was not suppressed under BDE-47 treatment. Overall, we demonstrated that BDE-47 could induce oxidative stress and subsequent germ cell apoptosis in Caenorhabditis elegans through a MAPK-mediated p53-independent pathway.

In this study, the accumulation and toxicity effect of 1–7 μM of Hg was determined during 24–72 h on two strains of Chlamydomonas reinhardtii, CC-125 and CC-503 as a cell wall-deficient mutant, by monitoring the growth rate and the maximum quantum yield of Photosystem II. In addition, the level of extracytoplasmic polyphosphates (polyP related to the cell wall) was determined to understand the polyP physiological role in Hg-treated algal cells. The results showed that the polyP level was higher in the strain CC-125 compared to CC-503. When algal cells were exposed to 1 and 3 μM of Hg, the accumulation of Hg was correlated with the degradation of polyP for both strains. These results suggested that the degradation of polyP participated in the sequestration of Hg. In fact, this mechanism might explain at 72 h the recovery of the polyP level, the efficiency of maximum PSII quantum yield, the low inhibition of growth rate, and the low accumulated Hg in algal biomass. Under the effect of 5 and 7 μM of Hg, the degradation of polyP was complete and could not be recovered, which was caused by a high accumulation and toxicity of Hg already at 24 h. Our results demonstrated that the change of polyP level was correlated with the accumulation and effect of Hg on algal cells during 24–72 h, which can be used as a biomarker of Hg toxicity. Therefore, this study suggested that extracytoplasmic polyP in C. reinhardtii contributed to the cellular tolerance for Hg.

The recently recognized adverse environmental and toxic effects of neonicotinoid insecticides (NNIs) on non-target organisms are alarming. A comprehensive design, screening, and regulatory system was developed to generate NNI derivatives and mutant receptors with selective-ecotoxicological effects to overcome such adverse effects. For ligand design, taking ACE-09 derivative as an example, the toxicity on non-target animals (aboveground: bees; underground: earthworms), plant absorption, and soil absorption decreased by 4.80% and 13.7%, 10.0%, and 121%, while the toxicity on target animals (aboveground: aphids; underground: B. odoriphagas), plant metabolism, and soil degradation increased by 70.2% and 51.7%, 5.08%, and 8.28%. For receptor modification, the ability of mutants to absorb ACE-09 derivative decreased by 31.0%, while the ability of mutants to metabolize ACE-09 derivative increased by 28.0% in scenario 2 (mainly plant selectivity); the ability of mutants to degrade ACE-09 derivative increased by 11.6% in scenario 3 (mainly soil selectivity). The above results indicated that the selective-ecotoxicological effects of ligand design and receptor modification were both improved. Additionally, the combined effects of the ACE-09 derivative on plant absorption and metabolic mutants improved by 31.1% and 31.4% in scenario 2, respectively, while the effect on microbial degradation mutant improved by 14.9%, indicating that there was a synergistic effect between ligand design and receptor modification. Finally, based on the interaction between the ACE-09 derivative and mutants, the optimal environmental factors that improved the selectivity of their ecotoxicological effects were determined. For example, alternate application of nitrogen and phosphorus fertilizers effectively reduced the oxidative damage to plants caused by NNI residues. The novel ligand-receptor joint modification method, combined with the regulation of environmental factors under multiple scenarios, can biochemically address the ecotoxicological concern and highlight the harmful effects of pesticides on the environment and non-target organisms.

Ethylene regulates plant root growth and resistance to environment stress. However, the role and mechanism of ethylene signaling in response to Cd stress in rice remains unclear. Here, we revealed that ethylene signaling plays a positive role in the resistance of rice to Cd toxicity. Blocking the ethylene signal facilitated root elongation under normal conditions, but resulted in severe oxidative damage and inhibition of root growth under Cd stress. Conversely, ethylene signal enhancement by EIN2 overexpression caused root bending, similar to the response of roots to Cd stress, and displayed higher Cd tolerance than the wildtype (WT) plants. Comparative transcriptome analysis indicated EIN2-mediated upregulation of genes involved in flavonoid biosynthesis and peroxidase activity under Cd stress. The synthesis of phenolic acids and flavonoids were positively regulated by ethylene. Thus, the ein2 (ethylene insensitive 2) mutants displayed lower ROS scavenging capacity than the WT. Moreover, a significant increase in Cd accumulation and relatively increased apoplastic flow were observed in the root apex of the ein2 mutant compared with the WT plants. Overall, EIN2-mediated Cd resistance in rice is mediated by the upregulation of flavonoid biosynthesis and peroxidase activity to induce ROS scavenging, and apoplastic transport barrier formation reduces Cd uptake.