Environmental exposure to 4-nonylphenol (4-NP) is extensive, and studies related to human risk assessment must continue. Especially, prediction of toxicodynamics (TDs) related to reproductive toxicity in males is very important in risk-level assessment and management of 4-NP. This study aimed to develop a physiologically-based-toxicokinetic-toxicodynamic (PBTK-TD) model that added a TD prostate model to the previously reported 4-n-nonylphenol (4-n-NP) physiologically-based-pharmacokinetic (PBPK) model. Modeling was performed under the assumption of similar TKs between 4-n-NP and 4-NP because TK experiments on 4-NP, a random-mixture, are practically difficult. This study was very important to quantitatively predict the TKs and TDs of 4-NP by age at exposure using an advanced PBTK-TD model that reflected physiological-changes according to age. TD-modeling was performed based on the reported toxic effects of 4-NP on RWPE-1 cells, a human-prostate-epithelial-cell-line. Through a meta-analysis of reported human physiological data, body weight, tissue volume, and blood flow rate patterns according to age were mathematically modeled. These relationships were reflected in the PBTK-TD model for 4-NP so that the 4-NP TK and TD changes according to age and their differences could be confirmed. Differences in TK and TD parameters of 4-NP at various ages were not large, within 3.61-fold. Point-of-departure (POD) and reference-doses for each age estimated using the model varied as 426.37–795.24 and 42.64–79.52 μg/kg/day, but the differences (in POD or reference doses between ages) were not large, at less than 1.87-times. The PBTK-TD model simulation predicted that even a 100-fold 4-NP PODₘₐₙ dose would not have large toxicity to the prostate. With a focus on TDs, the predicted maximum possible exposure of 4-NP was as high as 6.06–23.60 mg/kg/day. Several toxicity-related values estimated by the dose-response curve were higher than those calculated, depending upon the PK or TK, which would be useful as a new exposure limit for prostate toxicity of 4-NP.

Nitrated and oxygenated polycyclic aromatic hydrocarbons (NPAHs and OPAHs) are receiving attention because of their high toxicity compared with parent PAHs. However, the experimental data of their physicochemical properties has been limited. This study proposed the gas chromatographic retention time (GC-RT) technique as an effective alternative one to determine octanol-air partition coefficients (KOA) and sub-cooled liquid vapor pressures (PL) for 11 NPAHs, 10 OPAHs, and 19 parent PAHs. The slopes and intercepts of the linear regressions between temperature versus KOA and PL were provided and can be used to estimate KOA and PL for the 40 targeted compounds at any temperature. The internal energies of phase transfer (ΔUOA) and enthalpies of vaporization (ΔHL) for all targeted compounds were also calculated using the GC-RT technique. High-molecular-weight compounds may release or absorb higher heat energy to transform between different phases. NPAHs and OPAHs had a non-ideal solution behavior with activity in octanol (γₒcₜ) in the range of 19–53 and 18–1,078, respectively, which is larger than the unity threshold. A comparison among four groups of PAH derivatives showed that a functional group (nitro-, oxygen-, chloro-, and bromo-) in PAH derivatives increased γₒcₜ for corresponding parent PAHs by tens (mono-group) to hundreds of times (di-group). This study suggests that the GC-RT method is applicable for indirectly measuring the physicochemical properties of various groups of organic compounds.

Benzene is a common environmental carcinogen that induces leukemia. Studies suggest that metabolic disorder has a relationship with the toxicity of benzene. Pyruvate kinase M2 (PKM2) is a key rate-limiting enzyme in glycolysis. However, the upstream and downstream regulatory mechanisms of PKM2 in benzene-induced hematotoxicity and the therapeutic effects of targeting PKM2 in vivo are unclear. This study aims to provide insights into the new mechanism of benzene-induced hematotoxicity and reveal the therapeutic significance of targeting PKM2. Herein, we demonstrated that PKM2-dependent glycolysis contributes to benzene-induced hematotoxicity by regulating inflammation reaction. Mechanistically, acetylated proteomics revealed that 1,4-benzoquinone (1,4-BQ) induced acetylation of PKM2 at position K66, and this modification contributed to the increase of PKM2 expression and can be inhibited by inhibition of acetyltransferase GCN5. Meanwhile, the elevated PKM2 was shown to prompt the activation of nuclear phosphorylated Stat3 (p-Stat3) and IL17A. Clinically, pharmacological inhibition of PKM2 alleviated the blood toxicity induced by benzene, which was mainly characterized by an increase in routine blood parameters and improvement of hematopoietic imbalance. Besides, elevated PKM2 is a promising biomarker in people occupationally exposed to benzene. Overall, we identified PKM2/p-Stat3/IL-17A axis participates in the hematotoxicity of benzene, and targeting PKM2 has certain therapeutic implications in hematologic diseases.

A drastic decrease in the suspended sediment of Dongting Lake (DTL) has been observed due to Three Gorges Dam (TGD) impoundment operation since 2003. However, the relationship between sediment loads and metal fluxes has not been studied. This study comprehensively analyzed the content characteristics of seven metal(loid)s (As, Cd, Cr, Cu, Hg, Pb, and Zn) in the surface sediment of DTL from 2000 to 2019. The period of 2005–2009 corresponded to a metal(loid) enrichment stage in the sediment of DTL. The metal(loid) cumulative input of DTL from 2000 to 2019 reached 153 × 10³ t, and the increasing rate was gradually diminished because of TGD operation, while the metal(loid) cumulative output reached 132 × 10³ t. Undergoing an input-output state transition, the metal(loid) cumulative deposition of DTL in 2019 was only 42% of its peak in 2007. Especially, the metal(loid) fluxes of DTL all became negative for the first time in 2006. It is worth noting that Cd in DTL has shifted to a net export during the study period. Finally, the assessment results of pollution, risk, and toxicity indicated that metal(loid) effects on sediment quality were weakening in recent years. This study confirmed that DTL has shifted from metal(loid) deposition to export, providing new information for future DTL management options.

The derivation of sediment quality guideline values (SQGVs) presents significant challenges. Arguably the most important challenge is to conduct toxicity tests using contaminated sediments with physico-chemistry that represents real-world scenarios. We used a novel metal spiking method for an experiment that ultimately aims to derive a uranium SQGV. Two pilot studies were conducted to inform the final spiking design, i.e. percolating a uranyl sulfate solution through natural wetland sediments. An initial pilot study that used extended mixing equilibration phases produced hardened sediments not representative of natural sediments. A subsequent percolation method produced sediment with similar texture to natural sediment and was used as the method for spiking the sediments. The range of total recoverable uranium (TR-U) concentrations achieved was 8–3200 mg/kg. This reflected the concentrations found in natural wetlands and water management ponds found on a uranium mine site and was above natural levels. Dilute-acid extractable uranium (AE-U) concentrations were >80% of total concentrations, indicating that much of the uranium in the spiked sediment was labile and potentially bioavailable. The portion of TR-U extractable as AE-U was similar at the start and end of the 4.5-month field-deployment. Porewater uranium (PW–U) analyses indicated that partition coefficients (Kd) were 2000–20,000 L/kg, and PW-U was greater in post- than pre-field-deployed samples when TR-U was ≤1500 mg/kg, indicating the binding became weaker during the field-deployment period. At higher spiked-U concentrations, the PW-U was lower post-field-deployment. Comparing the physico-chemical data of the spiked sediments with environmental monitoring data from sediments in the vicinity of a uranium mining operation indicated that they were representative of sediments contaminated by mining and that the U-spiked sediments had a clear U concentration gradient. This confirmed the suitability of the spiking procedure for preparing sediments that were suitable for deriving a SQGV for uranium.

Phytases are a group of digestive enzymes which are commonly used as feed enzymes. These enzymes are used exogenously in the feeds of monogastric animals thereby it improves the digestibility of phosphorous and thus reduces the negative impact of inorganic P excretion on the environment. Even though these enzymes are widely distributed in many life forms, microorganisms are the most preferred and potential source of phytase. Despite the extensive availability of the phytase-producing microbial consortia, only a few microorganisms have been known to be exploited at industrial level. The high costs of the enzyme along with the incapability to survive high temperatures followed by the poor storage stability are noted to be the bottleneck in the commercialization of enzymes. For this reason, besides the conventional fermentation approaches, the applicability of cloning, expression studies and genetic engineering has been implemented for the past few years to accomplish the abovesaid benefits. The site-directed mutagenesis as well as knocking out have also validated their prominent role in microbe-based phytase production with enhanced levels. The present review provides detailed information on recent insights on the modification of phytases through heterologous expression and protein engineering to make thermostable and protease-resistant phytases.

Rivers can be sinks for potential toxic elements (PTEs) inputted in their systems by both natural and anthropic processes. Many indices have been proposed to assess the contamination degree of sediments and the environmental conditions of surficial water bodies. Above all, enrichment factor (EF) is the most used tool, but also it is the most debated for its limitations. The need for a reference element and for a background/baseline composition makes the EF method dependent on the researcher's expertise, implying that its repeatability may not be granted. Starting from the awareness that geochemical processes, bringing to compositional changes in the environmental matrices, involve multiple elements rather than individual variables, we developed a modified EF (mEF) based on the use of elemental associations. Different multivariate statistical methods (i.e. Robust Principal Component Analysis and Fuzzy Clustering), in a compositional data analysis (CoDA) perspective, were used to set all the terms of the mEF. The mEF was applied to 101 sediment samples collected from a 2 m-long core, covering a sedimentation period of about 150 years (1850–2007), located in the lower Changjiang River (China). The method resulted effective in recognizing most of the signals proceeding from the main natural and anthropogenic events which affected the lower river basin in the considered timespan. The largest geochemical variations recorded fit well the flooding events occurred; besides, the effects produced on the system by the recent socio-economic development (following the end of the civil war in 1949 and the beginning of economic reforms in 1978) and the start-up of the Three Gorges Dam (the world's largest power station since 2012) were also intercepted. The proposed method represents a step forward to enhance the effectiveness of the EF in discriminating geochemical anomalies that may be significant to assess the human historical impact on the environment.

Silver nanoparticles (AgNPs) are increasingly released into the aquatic environments because of their extensive use in consumer products and industrial applications. Some researchers have explored the toxicity of AgNPs to nitrogen (N) and carbon (C) cycles, but little is known about the role of aquatic plants in regulating the impact of AgNPs on these biogeochemical processes and related microorganisms. Here, two 90-day pot experiments were conducted to determine the effect of AgNPs on denitrification rates and greenhouse gas emissions in riparian wetland soils, with or without emergent plants (Typha minima Funck). As a comparison, the toxicity of equal concentration of AgNO₃ was also determined. The results showed that AgNPs released a great quantity of free Ag⁺, most of which was accumulated in soils, while little (less than 2%) was absorbed by plant shoots and roots. Both AgNPs and AgNO₃ could increase the soil redox potential and affect the growth and nutrient (N and phosphorus) uptake of plants. In soils with plants, there was no significant difference in denitrification rates and emissions of N₂O and CH₄ between control and AgNPs or AgNO₃ treatments at all tested concentrations (0.5, 1 and 10 mg kg⁻¹). However, low levels of AgNPs (0.5 mg kg⁻¹) significantly enhanced CO₂ emission throughout the experiment. Interestingly, in the absence of plants, a high dosage (10 mg kg⁻¹) of AgNPs generally inhibited soil denitrification and stimulated the emissions of CO₂, CH₄ and N₂O in the short-term. Meanwhile, the abundance of key denitrifying genes (nirS and nirK) was significantly increased by exposure to 10 mg kg⁻¹ AgNPs or AgNO₃. Our results suggest that emergent plants can alleviate the short-term negative effects of AgNPs on N and C cycling processes in wetland soils through different pathways.

Silver nanoparticles (AgNPs) of both biologically and chemically origins trigger various physiological and metabolic processes through interaction with plant cells, exerting positive, negative and inconsequential effects. However, their impacts on plant systems must be critically investigated to guarantee their safe application in food chain. In this study, the effects of chemically synthesized (synthetic) AgNPs (sAgNPs) and biologically synthesized (biogenic) AgNPs (bAgNPs) on physiological and biochemical features of Eschscholzia californica Cham were evaluated at different concentrations (0, 10, 25, 50 and 100 mg L⁻¹). Plants exposed to bAgNPs (at 10 and 25 mg L⁻¹) and sAgNPs (at 10 mg L⁻¹) displayed relatively uniform deposition of AgNPs on leaf surface, however, the higher concentration (100 mg L⁻¹) was accompanied by aggregation of AgNPs, resulting in anatomical and physiological disorders. Foliar application of both AgNPs at lower concentrations resulted in significant (P < 0.01) improve in the content of photosynthetic pigments (chlorophylls a, b, a+b, and carotenoids) and total phenolics over the control in a dose-related manner. Leaf relative water content decreased steadily with increasing both sAgNPs and bAgNPs concentrations-with sAgNPs being more inhibitive. Both types of AgNPs at 100 mg L⁻¹ significantly (P < 0.05) increased electrolyte leakage index, level of lipid peroxidation product (malondialdehyde), and leaf soluble sugar content when compared to controls. No significant difference was found on cell membrane stability index among the plants exposed to bAgNPs and sAgNPs at the lowest concentration over the control. Californidine content was significantly (P < 0.01, by 45.1%) increased upon all the bAgNPs treatments (with a peak at 25 mg L⁻¹) relative to control. The obtained extracts from plants treated with bAgNPs at lower concentrations revealed a significant induction of antioxidant capacity (based on DPPH˙ free radical scavenging and ferrous ions-chelating activities) with lower IC₅₀ values compared to the other treatments. Conclusively, bAgNPs at lower concentrations are potent elicitors of pharmaceutically active compounds biosynthesis, which enhance physiological efficiency of E. californica, but at higher concentrations bAgNPs are equally toxic as sAgNPs.

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.