Fine particulate matter 2.5 (PM2.5) exposure leads to the progress of pulmonary disease. It has been reported that N6-methyladenosine (m6A) modification was involved in various biological processes and diseases. However, the critical role of m6A modification in pulmonary disease during PM2.5 exposure remains elusive. Here, we revealed that lung inflammation and mucus production caused by PM2.5 were associated with m6A modification. Both in vivo and in vitro assays demonstrated that PM2.5 exposure elevated the total level of m6A modification as well as the methyltransferase like 3 (METTL3) expression. Integration analysis of m6A RNA immunoprecipitation-seq (meRIP-seq) and RNA-seq discovered that METTL3 up-regulated the expression level and the m6A modification of Interleukin 24 (IL24). Importantly, we explored that the stability of IL24 mRNA was enhanced due to the increased m6A modification. Moreover, the data from qRT-PCR showed that PM2.5 also increased YTH N6-Methyladenosine RNA Binding Protein 1 (YTHDF1) expression, and the up-regulated YTHDF1 augmented IL24 mRNA translation efficiency. Down-regulation of Mettl3 reduced Il24 expression and ameliorated the pulmonary inflammation and mucus secretion in mice exposed to PM2.5. Taken together, our finding provided a comprehensive insight for revealing the significant role of m6A regulators in the lung injury via METTL3/YTHDF1-coupled epitranscriptomal regulation of IL24.

Amyl salicylate (AS) is a fragrance massively used as a personal care product and following the discharged in wastewaters may end up in the aquatic environment representing a potential threat for the ecosystem and living organisms. AS was recently detected in water of the Venice Lagoon, a vulnerable area continuously subjected to the income of anthropogenic chemicals. The lagoon is a relevant area for mollusc farming, including the Mediterranean mussels (Mytilus galloprovincialis) having an important economic and ecological role. Despite high levels of AS occurred in water of the Lagoon of Venice, no studies investigated the possible consequences of AS exposures on species inhabiting this ecosystem to date. For the first time, we applied a multidisciplinary approach to investigate the potential effects of the fragrance AS on Mediterranean mussels. To reach such a goal, bioaccumulation, cellular, biochemical, and molecular analyses (RNA-seq and microbiota characterization) were measured in mussels treated for 7 and 14 days with different AS Venice lagoon environmental levels (0.1 and 0.5 μg L⁻¹). Despite chemical investigations suggested low AS bioaccumulation capability, cellular and molecular analyses highlighted the disruption of several key cellular processes after the prolonged exposures to the high AS concentration. Among them, potential immunotoxicity and changes in transcriptional regulation of pathways involved in energy metabolism, stress response, apoptosis and cell death regulations have been observed. Conversely, exposure to the low AS concentration demonstrated weak transcriptional changes and transient increased representation of opportunistic pathogens, as Arcobacter genus and Vibrio aestuarianus. Summarizing, this study provides the first overview on the effects of AS on one of the most widely farmed mollusk species.

Fomesafen (FSA) is widely used in soybean fields for weed control. However, the persisting characteristics of FSA in the agricultural soil or water may become a hidden danger causing environmental pollution and phytotoxicity to succession crops. In this study, the growth and physiological responses of rice to FSA were investigated. It was found that the growth of rice seedlings was obviously inhibited by FSA exposure especially at over 0.1 mg L⁻¹. To gain an insight into the molecular mechanisms for the potential ecotoxicology, four libraries of rice roots and shoots exposed to FSA were created and subjected to the global RNA-sequencing (RNA-Seq) combined with HRLC-Q-TOF-MS/MS analytical technologies to comprehensively characterize the biochemical processes and catalytic reactions involved in FSA metabolism in rice. Compared with those without FSA, 499 and 450 up-regulated genes in roots and shoots with FSA were detected. Many of them were closely correlated with the tolerance to environmental stress, detoxification of xenobiotics and molecular metabolism process including cytochrome P450, glutathione S-transferases and acetyltransferase. A total of eight metabolites and fourteen conjugates in the reactive pathways of hydrolysis, substitution, reduction, methylation, glycosylation, acetylation, and malonylation were characterized by HRLC-Q-TOF-MS/MS. The relationship between the metabolized derivatives of FSA and enhanced expression the corresponding enzymatic regulators was established. This study will help understand the mechanisms and pathways of FSA metabolism and inspire the further research on FSA degradation in the paddy crops and environmental or health risks.

The Pearl River Estuary (PRE) is the largest estuary in southern China and under high metal stress. In the present study, we employed an integrated method of transcriptomics and proteomics to investigate the ecotoxicological effects of trace metals on the Hong Kong oyster Crassostrea hongkongensis. Three oyster populations with distinct spatial distributions of metals were sampled, including the Control (Station QA, the lowest metal levels), the High Cd (Station JZ, the highest Cd), and the High Zn–Cu–Cr–Ni (Station LFS, with the highest levels of zinc, copper, chromium, and nickel). Dominant metals in oysters were differentiated by principal component analysis (PCA), and theirgene and protein profiles were studied using RNA-seq and iTRAQ techniques. Of the 2250 proteins identified at both protein and RNA levels, 70 proteins exhibited differential expressions in response to metal stress in oysters from the two contaminated stations. There were 8 proteins altered at both stations, with the potential effects on mitochondria and endoplasmic reticulum by Ag. The genotoxicity, including impaired DNA replication and transcription, was specifically observed in the High Cd oysters with the dominating influence of Cd. The structural components (cytoskeleton and chromosome-associated proteins) were impaired by the over-accumulated Cu, Zn, Cr, and Ni at Station LFS. However, enhanced tRNA biogenesis and exosome activity might help the oysters to alleviate the toxicities resulting from their exposure to these metals. Our study provided comprehensive information on the molecular changes in oysters at both protein and RNA levels in responding to multi-levels of trace metal stress.

Triclocarban (TCC), an antibacterial agent widely used in personal care products, can affect embryonic development. However, the specific molecular mechanism of TCC-induced embryonic developmental damage remains unclear. In this study, TCC exposure was found to increase the expression of tmbim4 gene in zebrafish embryos. The tmbim4 mutant embryos are more susceptible to TCC exposure than wild-type (WT) embryos, with tmbim4 overexpression reducing TCC-induced embryonic death in the former. Exposure of tmbim4 mutant larvae to 400 μg/L TCC substantially increased apoptosis in the hindbrain and eyes. RNA-sequencing of WT and tmbim4 mutant larvae indicated that knockout of the tmbim4 gene in zebrafish affects the autophagy pathway. Abnormalities in autophagy can increase apoptosis and TCC exposure caused abnormal accumulation of autophagosomes in the hindbrain of tmbim4 mutant zebrafish embryos. Pretreatment of TCC-exposed tmbim4 mutant zebrafish embryos with autophagosome formation inhibitors, substantially reduced the mortality of embryos and apoptosis levels. These results indicate that defects in the tmbim4 gene can reduce zebrafish embryo resistance to TCC. Additionally, apoptosis induced by abnormal accumulation of autophagosomes is involved in this process.

Nitrate is a major pollutant component in ambient PM₂.₅. It is known that chronic exposure to PM₂.₅ NO₃⁻ damages respiratory functions. We aim to explore the underlying toxicological mechanism at single cell resolution.We systematically conducted exposure experiments on forty C57BL/6 mice, assessed respiratory functions, and profiled lung transcriptome. . Afterward, we estimated the cell type compositions from RNA-seq data using deconvolution analysis. The genes and pathways associated with respiratory function and dysregulated by to PM₂.₅ NO₃⁻ exposure were characterized at bulk-tissue and single-cell resolution.PM₂.₅ NO₃⁻ exposure did not significantly modify the cell type composition in lung, but profoundly altered the gene expression within each cell type. At ambient concentration (22 μg/m³), exposure significantly (FDR<10%) altered 95 genes’ expression. Among the genes associated with respiratory functions, a large fraction (74.6–91.7%) were significantly perturbed by PM₂.₅ NO₃⁻ exposure. For example, among the 764 genes associated with peak expiratory flow (PEF), 608 (79.6%) were affected by exposure (p = 1.92e-345). Pathways known to play role in lung disease pathogenesis, including circadian rhythms, sphingolipid metabolism, immune response and lysosome, were found significantly associated with respiratory functions and disrupted by PM₂.₅ NO₃⁻ exposure.This study extended our knowledge of PM₂.₅ NO₃⁻ exposure’s effect to the levels of lung gene expression, pathways, lung cell type composition and cell specific transcriptome. At single cell resolution, we provided insights in toxicological mechanism of PM₂.₅ NO₃⁻ exposure and subsequent pulmonary disease risks.

Polychlorinated biphenyls (PCBs) in the air are predominantly the less chlorinated congeners. Non-dioxin-like (NDL) low-chlorinated PCBs are more neurotoxic, and cause neurodevelopmental and neurobehavioral alterations in humans. However, the underlying mechanisms for this neurodevelopmental toxicity remain unknown. In the present study, Wistar rats were treated by gavage with PCB52 (1 mg/kg body weight) or corn oil from gestational day 7 to postnatal day 21. Both the body lengths and weights of the suckling rats at birth were significantly decreased by PCB52 treatment, suggesting developmental toxicity. Although no obvious histopathological changes were observed in the brain, using RNA-sequencing, 208 differentially expressed genes (DEGs) were identified in the striatum of PCB52-treated male offspring, while just 13 DEGs were identified in female offspring, suggesting sex-specific effects. Furthermore, using Gene Ontology enrichment analysis, neurodevelopmental processes, neurobehavioral alterations, and neurotransmission changes were enriched from the 208 DEGs in male offspring. Similarly, using Kyoto Encyclopedia of Genes and Genomes enrichment analysis, neuroactive ligand receptor interactions and multiple synapse pathways were enriched in male offspring, implying dysfunction of the neurotransmission system. Reductions in the protein expressions of these ligand receptors were also identified in the striatum, cerebral cortex, and hippocampus using western blotting methods. Taken together, our findings indicate that PCB52 exposure during gestation and lactation results in the abnormal expression of neurotransmission ligand-receptors in male offspring with a sex bias, and that this may contribute to neurodevelopmental toxicity.

Neonicotinoid insecticides have posed a great threat to non-target organisms, yet the mechanisms underlying their toxicity are not well characterized. Major modes of action (MoAs) of imidacloprid were analyzed in an aquatic insect Chironomus dilutus. Lethal and sublethal outcomes were assessed in the midges after 96-h exposure to imidacloprid. Global transcriptomic profiles were determined using de novo RNA-sequencing to more holistically identify toxicity pathways. Transcriptional 10% biological potency values derived from ranked KEGG pathways and GO terms were 0.02 (0.01–0.08) (mean (95% confidence interval) and 0.05 (0.04–0.06) μg L⁻¹, respectively, which were more sensitive than those from phenotypic traits (10% lethal concentration: 0.44 (0.23–0.79) μg L⁻¹; 10% burrowing behavior concentration: 0.30 (0.22–0.43) μg L⁻¹). Major MoAs of imidacloprid in aquatic species were identified as follows: the activation of nicotinic acetylcholine receptors (nAChRs) induced by imidacloprid impaired organisms’ nerve system through calcium ion homeostasis imbalance and mitochondrial dysfunction, which posed oxidative stress and DNA damage and eventually caused death of organisms. The current investigation highlighted that imidacloprid affected C. dilutus at environmentally relevant concentrations, and elucidated toxicity pathways derived from gene alteration to individual outcomes, calling for more attention to toxicity of neonicotinoids to aquatic organisms.

Zeolite-supported nanoscale zero-valent iron (Z-NZVI) has great potential for metal(loid) removal, but its encapsulation mechanisms and ecological risks in real soil systems are not completely clear. We conducted long-term incubation experiments to gain new insights into the interactions between metal(loid)s (Cd, Pb, As) and Z-NZVI in naturally contaminated farmland soils, as well as the alteration of indigenous bacterial communities during soil remediation. With the pH-adjusting and adsorption capacities, 30 g kg⁻¹ Z-NZVI amendment significantly decreased the available metal(loid) concentrations by 10.2–96.8% and transformed them into strongly-bound fractions in acidic and alkaline soils after 180 d. An innovative magnetic separation of Z-NZVI from soils followed by XRD and XPS characterizations revealed that B-type ternary complexation, heterogeneous coprecipitation, and/or concurrent redox reactions of metal(loid)s, especially the formation of Cd₃(AsO₄)₂, PbFe₂(AsO₄)₂(OH)₂, and As⁰, occurred only under specific soil conditions. Sequencing of 16S rDNA using Illumina MiSeq platform indicated that temporary shifts in iron-resistant/sensitive, pH-sensitive, denitrifying, and metal-resistant bacteria after Z-NZVI addition were ultimately eliminated because soil characteristics drove the re-establishment of indigenous bacterial community. Meanwhile, Z-NZVI recovered the basic activities of bacterial DNA replication and denitrification functions in soils. These results confirm that Z-NZVI is promising for the long-term remediation of metal(loid)s contaminated farmland soil without significant ecotoxicity.

Biofumigation is an effective, non-chemical method to control soil-borne pests and diseases and to maximize crop yield. We studied the responses of soil bacterial and fungal communities, the soil’s nutritional state and strawberry yield, when the soil was biofumigated each year for five consecutive years using fresh chicken manure (BioFum). BioFum significantly increased the soil’s NH4+-N, NO3−-N, available P and K and organic matter. Fusarium spp. and Phytophthora spp. which are known to cause plant disease, were significantly decreased after BioFum. In addition, Biofum increased the soil’s temperature, enhanced chlorophyll levels in the leaves of strawberry plants, and the soluble sugar and ascorbic acid content in strawberry fruit. We used high-throughput gene sequencing to monitor changes in the soil’s bacterial and fungal communities. Although BioFum significantly decreased the diversity of these communities, it increased the relative abundance of some biological control agents in the phylum Actinobacteria and the genera Pseudomonas, Bacillus and Chaetomium. An increase in these biological control agents would reduce the incidence of soil-borne pathogens and plant disease. Although strawberry marketable yield using BioFum was higher in the first three years, the decline in the final two years could be due to the accumulation of P and K which may have delayed flowering and fruiting. Methods to overcome yield losses using BioFum need to be developed in the future. Our research, however, showed that BioFum enhanced soil fertility, reduced the presence of soil pathogens, increased the relative abundance of beneficial bacteria and fungi and improved strawberry quality. Unlike chemical soil treatments that can cause pest and disease resistance when used continuously over many years, our multi-year research program on BioFum showed that this treatment provided significant benefits to the soil, plant and strawberry fruit.