In this study, the molecular mechanisms involved in Ralstonia eutropha Q2-8-induced increased biomass and reduced cadmium (Cd) and arsenic (As) uptake in wheat plants (Triticum aestivum cv. Yangmai 16) were investigated in growth chambers. Strain Q2-8 significantly increased plant biomass (22–75%) without and with Cd (5 μM) + As (10 μM) stress and reduced plant above-ground tissue Cd (37%) and As (34%) contents compared to those in the controls. Strain Q2-8 significantly increased the proportions of Cd and As in wheat root cell walls. Under Cd and As stress, 109 root proteins were differentially expressed among which those involved in metabolisms, stress and defence, and energy were dominant in the presence of strain Q2-8. Furthermore, energy-, defence-, and cell wall biosynthesis-related proteins were found to be up-regulated. Notably, differentially expressed cell wall biosynthesis-related proteins in roots were only found in bacteria-inoculated plants under Cd and As stress. The results suggest that strain Q2-8 can alleviate Cd and As toxicity to wheat plant seedlings and reduce above-ground tissue Cd and As uptake by increasing the efficiency of root energy metabolism, defence, and cell wall biosynthesis under Cd and As stress.

Microplastics are widespread emerging contaminants that have been found globally in the marine and freshwater ecosystem, but there is limited knowledge regarding its impact on coral reef ecosystem and underpinning mechanism. In the present study, using Pocillopora damicornis as a model, we investigated cytological, physiological, and molecular responses of a scleractinian coral to acute microplastic exposure. No significant changes were observed in the density of symbiotic zooxanthellae during the entire period of microplastic exposure, while its chlorophyll content increased significantly at 12 h of microplastic exposure. We observed significant increases in the activities of antioxidant enzymes such as superoxide dismutase and catalase, significant decrease in the detoxifying enzyme glutathione S-transferase and the immune enzyme alkaline phosphatase, but no change in the other immune enzyme phenoloxidase during the whole experiment period. Transcriptomic analysis revealed 134 significantly up-regulated coral genes at 12 h after the exposure, enriched in 11 GO terms mostly related to stress response, zymogen granule, and JNK signal pathway. Meanwhile, 215 coral genes were significantly down-regulated at 12 h after exposure, enriched in 25 GO terms involved in sterol transport and EGF-ERK1/2 signal pathway. In contrast, only 12 zooxanthella genes exhibited significant up-regulation and 95 genes down-regulation at 12 h after the microplastic exposure; genes regulating synthesis and export of glucose and amino acids were not impacted. These results suggest that acute exposure of microplastics can activate the stress response of the scleractinian coral P. damicornis, and repress its detoxification and immune system through the JNK and ERK signal pathways. These demonstrate that microplastic exposure can compromise the anti-stress capacity and immune system of the scleractinian coral P. damicornis, despite the minimal impact on the abundance and major photosynthate translocation transporters of the symbiont in the short term.

Perfluorododecanoic acid (PFDoA), an artificial perfluorochemical, has been widely distributed in different ambient media and has been reported to have the potential to cause developmental neurotoxicity. However, the specific mechanism is largely unknown. In the current study, zebrafish embryos were treated with 0, 0.24, 1.2, and 6 mg/L PFDoA for 120 h. Exposure to PFDoA causes serious decreases in hatching delay, body length, as well as decreased locomotor speed in zebrafish larvae. Additionally, the acetylcholine (ACh) content as well as acetylcholinesterase (AChE) activity were determined to be significantly downregulated in PFDoA treatment groups. The level of dopamine was upregulated significantly after treating with 1.2 and 6 mg/L of PFDoA. Gene expressions related to the nervous system development were also analyzed, with the exception of the gene mesencephalic astrocyte-derived neurotrophic factor (manf), which is upregulated in the 6 mg/L treatment group. All other genes were significantly downregulated in larvae in the PFDoA group in different degrees. In general, the results demonstrated that PFDoA exposure could result in the disruption of the cholinergic system, dopaminergic signaling, and the central nervous system.

Propranolol (PRO), a human β-AR (β-adrenergic receptor) antagonist, is considered to result in specific effects in a non-target species, D. magna, based on our previous studies. The present study investigated the effects of β-AR agents, including an antagonist and agonist using pharmacologically relevant endpoints as well as a more holistic gene expression approach to reveal the impacts and potential mode of actions (MOAs) in the model non-target species. Results show that the responses in cardiac endpoints and gene expression in D. magna are partially similar but distinguishable from the observations in different organisms. No effect was observed on heart size growth in PRO and isoprenaline (ISO) exposure. The contraction capacity of the heart was decreased in ISO exposure, and the heart rate was decreased in PRO exposure. Time-series exposures showed different magnitudes of effect on heart rate and gene expression dependent on the type of chemical exposure. Significant enrichment of gene families involved in protein metabolism and biotransformation was observed within the differentially expressed genes, and we also observed differential expression in juvenile hormone-inducible proteins in ISO and PRO exposure, which is suspected of having endocrine disruption potential. Taken together, deviation between the effects of PRO and ISO in D. magna and other organisms suggests dissimilarity in MOAs or attributes of target bio-molecules between species. Additionally, PRO and ISO may act as endocrine disruptors based on the gene expression observation. Results in the present study confirm that it is challenging to predict ecological impact of active pharmaceutical ingredients (APIs) based on the available data acquired through human-focused studies. Furthermore, the present study provided unique data and a case study on the impact of APIs in a non-target organism.

Assessing the toxicity posed by mixtures of unknown chemicals to aquatic organisms is challenging. In this study, water samples from six cross-sections along the Xitiaoxi River Basin (XRB) were monthly or bimonthly collected in 2014. The year-period physiochemical parameters as well as one-month-water sample based acute biotoxicity tests showed that the river water quality of the year was generally in a good status. High performance liquid chromatography (HPLC) screening based on one-month-water samples suggested that the organic pollutants might be non-to-moderately-polar chemicals in very low concentrations. One-month-water sample based RNA-seq was performed to measure the mRNA differential expression profile of zebrafish larvae to furtherly explore the potential bioeffect and the spatial water quality change of the river. Result indicated that the number of deferentially expressed genes (DEGs) tended to increase along the downstream direction of the river. Gene ontology (GO) enrichment analysis implied that the key pollutants might mainly be the function disruptors of biological processes. Principle components analysis (PCA) combining with transcripts and one-month-water sample based physiochemical parameters indicated that the pollution might be similar at TP, DP and CTB sites while pollution homology existed on some extent between YBQ and JW sites. Although the water quality of the river had a complex time-space alternation during the year, and the one-month-data based RNA-seq could not reflex the whole year-water quality of a watershed, the gene expression profile via RNA-seq provided an alternative way for assessing integrated biotoxicity of surface water, and it was relatively fit for early-warning of water quality of a watershed with unobservable acute toxicity. However, the identification of detail toxicants and the links between DEGs and pollution level as well as physiological-biochemical toxicity needed further investigation.

Waterborne microcystin-LR (MC-LR) has been reported to disrupt sex hormones, while its estrogenic potency remains controversial. We hypothesized that MC-LR could induce estrogenic effects via disrupting sex hormone synthesis, and verified this hypothesis by in vitro and in vivo assays. Effects of MC-LR (1, 10, 100, 500, 1000 and 5000 μg/L) on steroidogenesis were assessed in the H295R cells after 48 h. The contents of 17β-estradiol (E2) and testosterone (T) increased in a non-dose-dependent manner, which showed positive correlations with the expression of steroidogenic genes. In the in vivo assay, adult male zebrafish were exposed to 0.3, 1, 3, 10 and 30 μg/L MC-LR for 30 d. Similarly, E2 and T contents in the testis were increased, accompanied by extensive up-regulation of steroidogenic genes, especially cyp19a. Meanwhile, the percentage of spermatid in the testis declined. In the liver, the vtg1 gene was significantly up-regulated while both the transcriptional and protein levels of the estrogenic receptor (ER) declined. These results indicate that MC-LR induced non-dose-dependent estrogenic effects at environmental concentrations, which may result from steroidogenesis stimulation via a non-ER-mediated pathway. Our findings support a paradigm shift in the risk assessment of MC-LR from traditional toxicity to estrogenic risk, particularly at low concentrations, and emphasize the potential threat to the male reproductive capacity of wildlife in bloom areas.

To examine the mechanism of hexavalent chromium [Cr(VI)]-induced carcinogenesis, a cross-sectional study in workers with or without exposure to Cr(VI) as well as in vitro administration of Cr(VI) in 16HBE cells was conducted. We explored the associations between Cr(VI) exposure, methylation modification of DNA repair genes and their expression levels, and genetic damage. Results showed that hypermethylation of CpG sites were observed in both occupationally exposed workers and 16HBE cells administrated Cr(VI). DNA damage markers including 8-hydroxydeoxyguanosine (8-OHdG) and micronucleus frequency in Cr(VI)-exposed workers were significantly higher than the control group. Among workers, blood Cr concentration was positively correlaed with the methylation level of CpG sites in DNA repair genes including CpG6,7, CpG8, CpG9,10,11 of MGMT, CpG11 of HOGG1; CpG15,16,17, CpG19 of RAD51, and genetic damage markers including 8-OHdG and micronucleus frequency. Significant negative association between methylation levels of CpG sites in DNA repair genes and corresponding mRNA was also observed in 16HBE cells. This indicated that Cr(VI) exposure can down-regulate DNA repair gene expression by hypermethylation, which leads to enhanced genetic damage. The methylation level of these CpG sites of DNA repair genes can be potential epigenetic markers for Cr(VI)-induced DNA damage.

The gut microbiome is sensitive to diet and environmental exposures and is involved in the regulation of host metabolism. Additionally, gut inflammation is an independent risk factor for the development of metabolic diseases, specifically atherosclerosis and diabetes. Exposures to dioxin-like pollutants occur primarily via ingestion of contaminated foods and are linked to increased risk of developing cardiometabolic diseases. We aimed to elucidate the detrimental impacts of dioxin-like pollutant exposure on gut microbiota and host gut health and metabolism in a mouse model of cardiometabolic disease. We utilized 16S rRNA sequencing, metabolomics, and regression modeling to examine the impact of PCB 126 on the microbiome and host metabolism and gut health. 16S rRNA sequencing showed that gut microbiota populations shifted at the phylum and genus levels in ways that mimic observations seen in chronic inflammatory diseases. PCB 126 reduced cecum alpha diversity (0.60 fold change; p = 0.001) and significantly increased the Firmicutes to Bacteroidetes ratio (1.63 fold change; p = 0.044). Toxicant exposed mice exhibited quantifiable concentrations of PCB 126 in the colon, upregulation of Cyp1a1 gene expression, and increased markers of intestinal inflammation. Also, a significant correlation between circulating Glucagon-like peptide-1 (GLP-1) and Bifidobacterium was evident and dependent on toxicant exposure. PCB 126 exposure disrupted the gut microbiota and host metabolism and increased intestinal and systemic inflammation. These data imply that the deleterious effects of dioxin-like pollutants may be initiated in the gut, and the modulation of gut microbiota may be a sensitive marker of pollutant exposures.

The aryl hydrocarbon receptor (AhR) plays an important role in mediating dioxins toxicity. Currently, genes of P450 families are major research interests in studies on AhR-mediated gene alterations caused by dioxins. Genes related to other metabolic pathways or processes may be also responsive to dioxin exposures. Amino acid transporter B0AT1 (encoded by SLC6A19) plays a decisive role in neutral amino acid transport which is present in kidney, intestine and liver. However, effects of dioxins on its expression are still unknown. In the present study, we focused on the effects of dioxin and dioxin-like compounds on SLC6A19 expression in HepG2 cells. We identified SLC6A19 as a novel putative target gene of AhR activation in HepG2 cells. 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) increased the expression of SLC6A19 in time- and concentration-dependent manners. Using AhR antagonist CH223191 and/or siRNA assays, we demonstrated that certain AhR agonists upregulated SLC6A19 expression via AhR, including TCDD, 1,2,3,7,8-pentachlorodibenzo-p-dioxin (1,2,3,7,8-PeCDD), 2,3,4,7,8- pentachlorodibenzofuran (2,3,4,7,8-PeCDF) and PCB126. In addition, the expression of B0AT1 was also significantly induced by TCDD in HepG2 cells. Our study suggested that dioxins might affect the transcription and translation of SLC6A19 in HepG2 cells, which might be a novel putative gene to assess dioxins' toxicity in amino acid transport and metabolism in liver.

Adverse effect studies of gasoline exhaust are scarce, even though gasoline direct injection (GDI) vehicles can emit a high number of particles.The aim of this study was to conduct an in vitro hazard assessment of different GDI exhausts using two different cell culture models mimicking the human airway. In addition to gasoline particle filters (GPF), the effects of two lubrication oils with low and high ash content were assessed, since it is known that oils are important contributors to exhaust emissions.Complete exhausts from two gasoline driven cars (GDI1 and GDI2) were applied for 6 h (acute exposure) to a multi-cellular human lung model (16HBE14o-cell line, macrophages, and dendritic cells) and a primary human airway model (MucilAir™). GDI1 vehicle was driven unfiltered and filtered with an uncoated and a coated GPF. GDI2 vehicle was driven under four settings with different fuels: normal unleaded gasoline, 2% high and low ash oil in gasoline, and 2% high ash oil in gasoline with a GPF. GDI1 unfiltered was also used for a repeated exposure (3 times 6 h) to assess possible adverse effects.After 6 h exposure, no genes or proteins for oxidative stress or pro-inflammation were upregulated compared to the filtered air control in both cell systems, neither in GDI1 with GPFs nor in GDI2 with the different fuels. However, the repeated exposure led to a significant increase in HMOX1 and TNFa gene expression in the multi-cellular model, showing the responsiveness of the system towards gasoline engine exhaust upon prolonged exposure.The reduction of particles by GPFs is significant and no adverse effects were observed in vitro during a short-term exposure. On the other hand, more data comparing different lubrication oils and their possible adverse effects are needed. Future experiments also should, as shown here, focus on repeated exposures.