This study aimed to examine whether and how third-hand smoke (THS) exposure would influence serum melatonin level. 1083 participants with or without exposure to THS were enrolled. Serum ROS, SOD, GSH-Px, and melatonin were measured by ELISA. Methylation microarrays detection and WGCNA were performed to identify hub methylated-sites. The methylation levels of hub-sites were validated in addtional samples. Moreover, mice were exposed to THS for 6 months mimicking exposure of human and the serum, liver, and pineal were collected. Oxidative stress-related indicators in serum, pineal, and liver were measured by ELISA. The expressions of mRNA and protein and methylation levels of hub-gene discovered in human data were further explored by RT-PCR, western-blot, and TBS. The results showed the participants exposed to THS had lower melatonin-level. 820 differentially methylated sites associated with THS were identified. And the hub-site located on the CYP1A2 promoter was identified, which mediated the association between THS and decreased melatonin-level. Decreased peak of serum melatonin, increased ROS and reduced SOD and GSH-Px in pineal and liver, and elevated CYP1A2 expression in liver was also found in the THS-exposed mice. Hypo-methylation of 7 CPG sites on the CYP1A2 promoter was identified, which accelerated the catabolism of melatonin. Overall, THS exposure is associated with abnormal melatonin catabolism through hypo-methylation of CYP1A2-promoter.

A new bacterium, Rhodococcus sp. S2-17, which could completely degrade an emerging organic pollutant, benzophenone-3 (BP-3), was isolated from contaminated sediment through an enrichment procedure, and its BP-3 catabolic pathway and genes were identified through metabolic intermediate and transcriptomic analyses and biochemical and genetic studies. Metabolic intermediate analysis suggested that strain S2-17 may degrade BP-3 using a catabolic pathway progressing via the intermediates BP-1, 2,4,5-trihydroxy-benzophenone, 3-hydroxy-4-benzoyl-2,4-hexadienedioic acid, 4-benzoyl-3-oxoadipic acid, 3-oxoadipic acid, and benzoic acid. A putative BP-3 catabolic gene cluster including cytochrome P450, flavin-dependent oxidoreductase, hydroxyquinol 1,2-dioxygenase, maleylacetate reductase, and α/β hydrolase genes was identified through genomic and transcriptomic analyses. Genes encoding the cytochrome P450 complex that demethylates BP-3 to BP-1 were functionally verified through protein expression, and the functions of the other genes were also verified through knockout mutant construction and intermediate analysis. This study suggested that strain S2-17 might have acquired the ability to catabolize BP-3 by recruiting the cytochrome P450 complex and α/β hydrolase, which hydrolyzes 4-benzoyl-3-oxoadipic acid to benzoic acid and 3-oxoadipic acid, genes, providing insights into the recruitment of genes of for the catabolism of emerging organic pollutants.

Developing a biotechnical system with rapid degradation of pesticide is critical for reducing environmental, food security and health risks. Here, we investigated a novel epigenetic mechanism responsible for the degradation of the pesticide atrazine (ATZ) in rice crops mediated by the key component CORONATINE INSENSITIVE 1a (OsCOI1a) in the jasmonate-signaling pathway. OsCOI1a protein was localized to the nucleus and strongly induced by ATZ exposure. Overexpression of OsCOI1a (OE) significantly conferred resistance to ATZ toxicity, leading to the improved growth and reduced ATZ accumulation (particularly in grains) in rice crops. HPLC/Q-TOF-MS/MS analysis revealed increased ATZ-degraded products in the OE plants, suggesting the occurrence of vigorous ATZ catabolism. Bisulfite-sequencing and chromatin immunoprecipitation assays showed that ATZ exposure drastically reduced DNA methylation at CpG context and histone H3K9me2 marks in the upstream of OsCOI1a. The causal relationships between the DNA demethylation (hypomethylatioin), OsCOI1a expression and subsequent detoxification and degradation of ATZ in rice and environment were well established by several lines of biological, genetic and chemical evidence. Our work uncovered a novel regulatory mechanism implicated in the defense linked to the epigenetic modification and jasmonate signaling pathway. It also provided a modus operandi that can be used for metabolic engineering of rice to minimize amounts of ATZ in the crop and environment.

Prorocentrum lima is a dinoflagellate that forms hazardous blooms and produces okadaic acid (OA), leading to adverse environmental consequences associated with the declines of zooplankton populations. However, little is known about the toxic effects and molecular mechanisms of P. lima or OA on zooplankton. Here, their toxic effects were investigated using the brine shrimp Artemia salina. Acute exposure of A. salina to P. lima resulted in lethality at concentrations 100-fold lower than densities observed during blooms. The first comprehensive results from global transcriptomic and metabolomic analyses in A. salina showed up-regulated mRNA expression of antioxidant enzymes and reduced non-enzyme antioxidants, indicating general detoxification responses to oxidative stress after exposure to P. lima. The significantly up-regulated mRNA expression of proteasome, spliceosome, and ribosome, as well as the increased fatty acid oxidation and oxidative phosphorylation suggested the proteolysis of damaged proteins and induction of energy expenditure. Exposure to OA increased catabolism of chitin, which may further disrupt the molting and reproduction activities of A. salina. Our data shed new insights on the molecular responses and toxicity mechanisms of A. salina to P. lima or OA. The simple zooplankton model integrated with omic methods provides a sensitive assessment approach for studying hazardous algae.

Cytochrome P450 1a (Cyp1a) is an important enzyme for metabolism of organic pollutants. To understand its reaction to polycyclic aromatic hydrocarbons (PAHs), we knocked out this gene in a marine model fish, Javanese medaka, Oryzias javanicus, using the CRISPR/Cas 9 system. A homozygous mutant (KO) strain with a four-base deletion was established using an environmental DNA (eDNA)-based genotyping technique. Subsequently, KO, heterozygous mutant (HT), and wild-type (WT) fish were exposed to model pollutants, pyrene and phenanthrene, and survivorship and swimming behavior were analyzed. Compared to WT, KO fish were more sensitive to pyrene, suggesting that Cyp1a transforms pyrene into less toxic metabolites. Conversely, WT fish were sensitive to phenanthrene, suggesting that metabolites transformed by Cyp1a are more toxic than the original compound. HT fish showed intermediate results. Thus, comparative use of KO and WT fish can distinguish modes of pollutant toxicity, providing a deeper understanding of fish catabolism of environmental pollutants.

Although coral species exhibit differential susceptibility to stressors, little is known about the underlying molecular mechanisms. Here we compared scleractinian corals Montipora peltiformis and Platygyra carnosa collected during the 2017 El Niño heat wave. Zooxanthellae density and chlorophyll a content declined and increased substantially during and after heat stress event, respective. However, the magnitude of change was larger in M. peltiformis. Transcriptome analysis showed that heat-stressed corals corresponded to metabolic depression and catabolism of amino acids in both hosts which might promote their survival. However, only M. peltiformis has developed the bleached coral phenotype with corresponding strong stress- and immune-related responses in the host and symbiont, and strong suppression of photosynthesis-related genes in the symbiont. Overall, our study reveals differences among species in the homeostatic capacity to prevent the development of the bleached phenotype under environmental stressors, eventually determining their likelihood of survival in the warming ocean.

The effects of three relevant organic pollutants: chlorpyrifos (CPF), a widely used insecticide, triphenyl phosphate (TPHP), employed as flame retardant and as plastic additive, and bisphenol A (BPA), used primarily as plastic additive, on sea urchin (Paracentrotus lividus) larvae, were investigated. Experiments consisted of exposing sea urchin fertilized eggs throughout their development to the 4-arm pluteus larval stage. The antioxidant enzymes glutathione reductase (GR) and catalase (CAT), the phase II detoxification enzyme glutathione S-transferase (GST), and the neurotransmitter catabolism enzyme acetylcholinesterase (AChE) were assessed in combination with responses at the individual level (larval growth). CPF was the most toxic compound with 10 and 50% effective concentrations (EC₁₀ and EC₅₀) values of 60 and 279 μg/l (0.17 and 0.80 μM), followed by TPHP with EC₁₀ and EC₅₀ values of 224 and 1213 μg/l (0.68 and 3.7 μM), and by BPA with EC₁₀ and EC₅₀ values of 885 and 1549 μg/l (3.9 and 6.8 μM). The toxicity of the three compounds was attributed to oxidative stress, to the modulation of the AChE response, and/or to the reduction of the detoxification efficacy. Increasing trends in CAT activity were observed for BPA and, to a lower extent, for CPF. GR activity showed a bell-shaped response in larvae exposed to CPF, whereas BPA caused an increasing trend in GR. GST also displayed a bell-shaped response to CPF exposure and a decreasing trend was observed for TPHP. An inhibition pattern in AChE activity was observed at increasing BPA concentrations. A potential role of the GST in the metabolism of CPF was proposed, but not for TPHP or BPA, and a significant increase of AChE activity associated with oxidative stress was observed in TPHP-exposed larvae. Among the biochemical responses, the GR activity was found to be a reliable biomarker of exposure for sea urchin early-life stages, providing a first sign of damage. These results show that the integration of responses at the biochemical level with fitness-related responses (e.g., growth) may help to improve knowledge about the impact of toxic substances on marine ecosystems.

Long-term exposure to particular matter (PM), especially fine PM (< 2.5 μm in the aerodynamic diameter, PM₂.₅), is associated with increased risk of cardiovascular disorders. This study aimed to evaluate the association between long-term exposure to PM₂.₅/PM₁₀ and the metabolic change in the plasma. Specifically, using metabolomics, we sought to identify the biomarkers for the vulnerable subgroup to PM₂.₅ exposure. A total of 78 college student volunteers were recruited into this prospective cohort study. All participants received 8 rounds of physical examinations at twice quarterly. Air purifiers were placed in 40 of 78 participants’ dormitories for 14 days. Before and after intervention, physical examinations were performed and the peripheral blood was collected. Plasma metabolomics was determined by ultra-performance liquid chromatography-mass spectrometry. During the follow-up, the average concentrations of PM₂.₅ and PM₁₀ were 53 μg/m³ and 93 μg/m³, respectively. Totally, 42 and 120 differential metabolic features were detected for PM₁₀ and PM₂.₅ exposure, respectively. In total, 25 differential metabolites were identified for PM₂.₅ exposure, most of which were phospholipids. No distinctive metabolites were found for PM₁₀ exposure. A total of 6 differential metabolites (lysoPC (P-20:0), lysoPC (P-18:1(9z)), lysoPC (20:1), lysoPC (O-16:0), choline, and found 1,3-diphenylprop-2-en-1-one) were characterized and confirmed for sensitive individuals. Importantly, we found LysoPC (P-20:0) and LysoPC (P-18:1(9z)) changed significantly before and after air purifier intervention. Our results indicated that the phospholipid catabolism was involved in long-term PM₂.₅ exposure. LysoPC (P-20:0) and LysoPC (P-18:1(9z)) may be the biomarkers of PM₂.₅ exposure.

Nylon powders are a type of microplastic (MP) used in personal care products such as cosmetics and sunscreens. To determine the effects of nylon polymers on freshwater microalgae, we investigated the effects of two types of micrometer-sized nylon polymers, i.e., powdered nylon 6 (Ny6-P) and nylon 12 (Ny12), and four other micrometer-sized MPs, i.e., low-density polyethylene, polyethylene terephthalate, polystyrene, and ultra-high-molecular-weight polyethylene, on the microalga Raphidocelis subcapitata. The results showed that Ny6-P inhibited R. subcapitata growth more than the other MPs; R. subcapitata growth was inhibited by 54.2% with 6.25 mg/L Ny6-P compared with the control. Ny6-P in the culture media adhered to R. subcapitata cells electrostatically, which may have disrupted growth and photosynthetic activity. Metabolomic analysis revealed that many metabolites related to the amino acid catabolic pathway and γ-glutamyl cycle were induced, which might trigger responses to avoid starvation and oxidative stress. Our study provides important information on the effects of Ny6-P on algae in freshwater environments.