N⁶-methyladenosine (m⁶A), the most abundant and reversible RNA modification, plays critical a role in tumorigenesis. However, whether m⁶A can regulate p53, a leading antitumor protein remains poorly understood. In this study, we explored the regulatory role of m⁶A on p53 activation using an arsenite-transformed keratinocyte model, the HaCaT-T cell line. We created the cell line by exposing human keratinocyte HaCaT cells to 1 μM arsenite for 5 months. We found that the cells exhibited an increased m⁶A level along with an aberrant expression of the methyltransferases, demethylase, and readers of m⁶A. Moreover, the cells exhibited decreased p53 activity and reduced p53 phosphorylation, acetylation, and transactivation with a high nucleus export rate of p53. Knockdown of the m⁶A methyltransferase, METTL3 significantly decreased m⁶A level, restoring p53 activation and inhibiting cellular transformation phenotypes in the arsenite-transformed cells. Further, using both a bioinformatics analysis and experimental approaches, we demonstrated that m⁶A downregulated the expression of the positive p53 regulator, PRDM2, through the YTHDF2-promoted decay of PRDM2 mRNAs. We showed that m⁶A upregulated the expression of the negative p53 regulator, YY1 and MDM2 through YTHDF1-stimulated translation of YY1 and MDM2 mRNA. Taken together, our study revealed the novel role of m⁶A in mediating arsenite-induced human keratinocyte transformation by suppressing p53 activation. This study further sheds light on the mechanisms of arsenic carcinogenesis via RNA epigenetics.

Potassium (K) fertilizer plays an important role in increasing crop yield, quality, and nitrogen use efficiency. However, little is known about its environmental impacts, such as its effects on emissions of the greenhouse gas nitrous oxide (N₂O). A nitrogen-15 (¹⁵N) tracer laboratory experiment was therefore performed in an acidic agricultural soil in the suburbs of Wuhan, central China, to determine the effects of K fertilizer on N₂O emissions and nitrification/denitrification product ratios under N fertilization. During 15-d incubation periods with a fixed initial N concentration (80 mg kg⁻¹), K application increased average N₂O emission rates significantly (1.6–10.8-fold) compared to the control treatment. N₂O emissions derived from nitrification and denitrification both increased in K-treated soil, and denitrification contributed more to the increase; its contribution ratio rose from 32% without K fertilizer to 53% with 300 mg kg⁻¹ of K applied. The increase in N₂O emissions under K fertilization is probably due to an increase in the activity of denitrifying microorganisms and acid-resistant nitrifying microorganisms caused by higher K⁺ concentrations and lower soil pH. Combined treatment with potassium chloride (KCl) and N fertilizer produced lower N₂O emissions than combined treatment with potassium sulfate (K₂SO₄) and N fertilizer during 15-d incubation periods. Our results imply that there are significant interaction effects between N fertilizers and K fertilizers on N₂O emissions. In particular, combining N fertilizers with fertilizers that reduce soil acidity or contain Cl or K ions may significantly affect agricultural N₂O emissions.

The use of pesticides has historically helped improve agricultural productivity, although their continued use may have unforeseen effects upon the natural environment when not applied appropriately. Metaldehyde is a commercial pesticide widely used to reduce crop losses resulting from terrestrial mollusc damage. However, following precipitation and runoff it frequently enters waterbodies with largely unknown consequences for aquatic fauna. This study represents one of the first attempts to examine its potential effects on aquatic macroinvertebrate communities at sites known to have experienced elevated metaldehyde concentrations alongside unaffected control sites. In addition, a series of laboratory exposures specifically examined the effects of metaldehyde on the survivorship of non-target aquatic mollusc species. When the entire aquatic macroinvertebrate community and aquatic mollusc community were considered, limited differences were observed between metaldehyde affected and control sites based on field data. Laboratory exposures highlighted that for the molluscs examined, gastropods (Bithynia tentaculata, Planorbis planorbis, Radix balthica and Potamopyrgus antipodarum) had a greater tolerance to metaldehyde than bivalves (Sphaerium corneum and Corbicula fluminea). However, the concentrations required to reduce survivorship of all species were much greater than those ever recorded historically under field conditions. The results suggest that the differences in the community composition recorded between sites exposed to elevated metaldehyde concentrations and control sites were probably due to nutrient loading (N and P from agricultural fertilizers) rather than metaldehyde. However, these results do not negate wider concerns regarding metaldehyde use, particularly issues caused when ingested by vertebrate wildlife, livestock or children and pets in domestic settings.

The metabolic syndrome (MetS) is a group of diseases that tend to occur together, including diabetes, hypertension, central obesity, cardiovascular disease and hyperlipidemia. Exposure to persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) has been associated with increased risk of development of several of the components of the MetS. The goal of this study is to determine whether the associations with POPs are identical for each of the components and for the MetS. The subject population was 601 Native Americans (Akwesasne Mohawks) ages 18 to 84 who answered a questionnaire, were measured for height and weight and provided blood samples for clinical chemistries (serum lipids and fasting glucose) and analysis of 101 PCB congeners and three OCPs [dichlorodiphenyldichloroethylene (DDE), hexachlorobenzene (HCB) and mirex]. Associations between concentrations of total PCBs and pesticides, as well as various PCB congener groups with each of the different components of the MetS were determine so as to ask whether there were similar risk factors for all components of the MetS. After adjustment for other contaminants, diabetes and hypertension were strongly associated with lower chlorinated and mono-ortho PCBs, but not other PCB groups or pesticides. Obesity was most closely associated with highly chlorinated PCBs and was negatively associated with mirex. High serum lipids were most strongly associated with higher chlorinated PCBs and PCBs with multiple ortho-substituted chlorines, as well as total pesticides, DDE and HCB. Cardiovascular disease was not closely associated with levels of any of the measured POPs. While exposure to POPs is associated with increased risk of most of the various diseases comprising the MetS, the specific contaminants associated with risk of the component diseases are not the same.

The increasing production and applications of graphene oxide (GO, a novel carbon nanomaterial) have raised numerous environmental concerns regarding its ecological risks. Triphenyl phosphate (TPhP) disperses in water and poses an increasing hazard to the ecosystem and human health. It is critical to study the environmental responses and molecular mechanisms of GO and TPhP together to assess both chemicals; however, this information is lacking. The present work revealed that GO promoted the bioaccumulation of TPhP in zebrafish larvae by 5.0%–24.3%. The TPhP-induced growth inhibition of embryos (malformation, mortality, heartbeat, and spontaneous movement) at environmentally relevant concentrations was significantly amplified by GO, and these results were supported by the downregulated levels of genes and proteins associated with cytoskeletal construction and cartilage and eye development. TPhP induced negligible alterations in the genes or proteins involved in oxidative stress and apoptosis, but those related proteins were all upregulated by GO. GO and TPhP coexposure activated the mTOR signaling pathway and subsequently promoted apoptosis in zebrafish by potentiating the oxidative stress induced by TPhP, presenting synergistic toxicity. These findings highlight the potential risks and specific molecular mechanisms of combining emerging carbon nanomaterials with coexisting organic contaminants.

Soil organic matter (SOM) affects arsenic (As) and antimony (Sb) mobility in soils under waterlogged conditions by acting as an electron donor, by catalyzing redox–cycling through electron shuttling and by acting as a competing ligand. This study was set up to disentangle these different effects of SOM towards As and Sb sorption in anaerobic soils. Nine samples were taken at different depths in an agricultural soil profile to collect samples with a natural SOM gradient (<1–40 g soil organic carbon kg⁻¹). The samples were incubated either or not under waterlogged conditions in an anaerobic chamber for 63–70 days, and glucose (5 g C kg⁻¹) was either or not added to the anaerobic incubated samples as an electron donor that neither acts as an electron shuttle nor as a competing ligand. The solid-liquid distribution coefficients (KD) of As and Sb were measured at trace levels. The KD values of As decreased ∼2 orders of magnitude upon waterlogging the SOM rich topsoil, while no additional changes were observed when glucose was added. In contrast, smaller changes in the As KD values were found in the low SOM containing subsoil samples, unless glucose was added that mobilised As. The Sb KD values increased upon reducing conditions up to factor 20, but again only in the high SOM topsoil samples. Surprisingly, the Sb immobilisation during waterlogging only occurred in Sb amended soils whereas the geogenic Sb was mobilised upon reducing conditions, although total dissolved Sb concentrations remained low (<10 nM). The change in As and Sb sorption upon waterlogging was similar in the SOM rich topsoil as in the low SOM subsoil amended with glucose. This suggests that the SOM dependent changes in As and Sb mobility in response to soil waterlogging are primarily determined by the role of SOM as electron donor.

Gradual contamination of agricultural land with copper (Cu), due to the indiscriminate uses of fungicides and pesticides, and the discharge of industrial waste to the environment, poses a high threat for soil degradation and consequently food crop production. In this study, we combined morphological, physiological and biochemical assays to investigate the mechanisms underlying acetate-mediated Cu toxicity tolerance in lentil. Results demonstrated that high dose of Cu (3.0 mM CuSO₄. 5H₂O) reduced seedling growth and chlorophyll content, while augmenting Cu contents in both roots and shoots, and increasing oxidative damage in lentil plants through disruption of the antioxidant defense. Principle component analysis clearly indicated that Cu accumulation and increased oxidative damage were the key factors for Cu toxicity in lentil seedlings. However, acetate pretreatment reduced Cu accumulation in roots and shoots, increased proline content and improved the responses of antioxidant defense (e.g. increased catalase and glutathione-S-transferase activities, and improved action of glutathione-ascorbate metabolic pathway). As a result, excess Cu-induced oxidative damage was reduced, and seedling growth was improved under Cu stress conditions, indicating the role of acetate in alleviating Cu toxicity in lentil seedlings. Taken together, exogenous acetate application reduced Cu accumulation in lentil roots and shoots and mitigated oxidative damage by activating the antioxidant defense, which were the major determinants for alleviating Cu toxicity in lentil seedlings. Our findings provide mechanistic insights into the protective roles of acetate in mitigating Cu toxicity in lentil, and suggest that application of acetate could be a novel and economical strategy for the management of heavy metal toxicity and accumulation in crops.

Phthalates are widely used as binders and plasticizers in industrial and consumer products but show diverse toxicity. We investigated the level of human exposure to phthalates in Beijing, one of the most densely populated cities in the world. In this study, 12 metabolites of phthalates were measured in 70 spot urine samples collected from Beijing residents from August 2017 to April 2018 using ultra high-performance liquid chromatography tandem mass spectrometry. We found that metabolites of phthalates were ubiquitous in all urine samples. Total concentrations of phthalate metabolites ranged from 39.6 to 1931 ng mL⁻¹, with median concentrations were in decreasing order of children (371 ng mL⁻¹)> younger adults (332 ng mL⁻¹)> older adults (276 ng mL⁻¹). Mono-n-butyl phthalate (MnBP) was the predominant compound, and occurred at concentrations greater than those reported for people in other countries. The mean values of estimated daily intakes (EDIs) of ∑phthalate were 35.2, 10.3 and 10.9 ng (kg-bm)⁻¹ d⁻¹ for children, younger adults and older adults, respectively. EDIs of di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP) and di-(2-ethylhexyl) phthalate (DEHP) exceeded reference values suggested by the US Environmental Protection Agency and the European Food Safety Authority. When concentrations were normalized to volume or creatinine-adjusted, hazard quotients (HQs) for 40 of 70 participants exhibited larger HQs >1 for individual phthalates, which was indicative of potential for adverse effects. Thus, exposure to phthalates might be a critical factor contributing to adverse health effects in Beijing residents. To the best of our knowledge, this is the first study to establish a pre-baseline level of urinary phthalate metabolites among residents in Beijing.

Bioremediation has gained global prominence as an effective method for treating hydrocarbon-contaminated drill mud waste (HCDW). However, the problem of low nutrient content, bioavailability and microbial presence remain largely unresolved. In this study, the synergistic effects of compost, cow bile and bacterial culture on the degradation rate of HCDW was investigated. A homogenized HCDW sample (80 kg) obtained from 25 different drill mud tanks was divided into 20 portions (4 kg each) and each adjusted to 1.4% nitrogen content + 20 ml cow bile (i.e., basic treatment). Pure cultures of Brevibacterium casei (Bc) and Bacillus zhangzhouensi (Bz) and their mixture (BcBz) were subsequently added to 12 of the amended HCDW (basic) to undergo a 6-week incubation. A portion of the unamended HCDW (2 kg) was used as control. Initial pH, electrical conductivity and surface tension values of the HCDW were 8.83, 2.34 mS/cm and 36.5 mN/m, respectively. Corresponding values for total petroleum hydrocarbon (TPH), total nitrogen and total plate count bacteria were 165 g/kg, 0.04% and 4.4 × 10² cfu/ml. The treatments led to a substantial reduction in TPH (p < 0.05) while the control had no significant effect (p > 0.05). TPH reduction after the experimental period occurred in the order: basic + BcBz (99.7%) > basic + Bz (99.5%) > basic + Bc (99.2%) > basic (95.2%) > control (0.06%). Multiple regression analysis revealed significant effect of total plate count, pH, CN ratio and electrical conductivity (R² = 0.87, p = 0.05) on the degradation of TPH in the HCDW. The study demonstrates strong interactive effects of compost, cow bile and bacteria culture on the remediation of HCDW, which can be applied to boost the efficiency of the bioremediation technique.

The aim of this study was to examine the effects of arbuscular mycorrhizal (AM) fungi, biochar (BC) addition and phosphorus (P) fertilizer applications on the mycorrhizal response, biomass and elemental uptake of Trifolium repens in cadmium (Cd)-polluted soils. The results showed that mycorrhizal colonization were significantly decreased by 100 mg P kg⁻¹ fertilizer input. Moreover, AM fungi, BC addition and P fertilizer significantly increased shoot biomass accumulation at all treatments. In the absence of BC, the nitrogen (N), potassium (K), calcium (Ca) and magnesium (Mg) contents in the shoots were not affected by AM fungi after P fertilizer application, but the P content in the shoots significantly increased in response to AM fungi. In the absence of BC, both AM fungi and P fertilizer significantly reduced the Cd concentrations in the plant tissues as well as the soil diethylenetriaminepentaacetic acid (DTPA)-Cd concentration. These results indicated that the translocation factors (TFs) were influenced only by BC addition and that the roots could accumulate greater amounts of Cd than the shoots. On the basis of the hygienic standard for feed in China, the shoot Cd concentration in white clover was below the maximum permitted Cd concentration (1 μg g⁻¹) across all treatments. Therefore, it is suggested that no negative mycorrhizal-white clover symbiotic relationships were observed and T. repens could be a suitable forage species for planting in soils with low concentrations of Cd contamination when BC and P fertilizer are applied.