The masking phenomenon of microplastics additives on oxidative stress responses in freshwater food chains.

The variability and intrinsic mechanisms of oxidative stress induced by microplastics at different trophic levels in freshwater food chains are not well understood. To comprehensively assess the oxidative stress induced by polystyrene microplastics (PS-MPs) in freshwater food chains, the present study first quantified the oxidative stress induced by PS-MPs in organisms at different trophic levels using factorial experimental design and molecular dynamics methods. Then focuses on analyzing the variability of these responses across different trophic levels using mathematical statistical analysis. Notably, higher trophic level organisms exhibit diminished responses under PS-MPs exposure. Furthermore, the coexistence of multiple additives was found to mask these responses, with antioxidant plastic additives significantly influencing oxidative stress responses. Mechanism analysis using computational chemistry simulation determines that protein structure and amino acid characteristics are key factors driving PS-MPs induced oxidative stress variation in freshwater organisms at different nutrient levels. Increased hydrophobic additives induce protein helicalization and amino acid residue aggregation. This study systematically reveals the variability of biological oxidative stress response under different nutrient levels, emphasizing the pivotal role of chemical additives. Overall, this study offers crucial insights into PS-MPs' impact on oxidative stress responses in freshwater ecosystems, informing future environmental risk assessment.

Exposure estimation and neurotoxicity inhibition of dioxins in sensitive populations near domestic waste incineration plant through adverse outcome pathway.

The neurotoxicity induced by dioxins has been recognized as a serious concern to sensitive population living near waste incineration plants. However, investigating the intracellular neurotoxicity of dioxin in humans and the corresponding mitigation strategies has been barely studied. Thus, a domestic waste incineration plant was selected in this study to characterize the neurotoxicity risks of sensitive populations by estimating the ratio of dioxin in human cells using membrane structure dynamics simulation; and constructing a complete dioxin neurotoxicity adverse outcome pathway considering the binding process of AhR/ARNT dimer protein and dioxin response element (DRE). Six dioxins with high neurotoxicity risk were identified. According to the composite neurotoxicity risk analysis, the highest composite neurotoxicity risk appeared when the six dioxins were jointly exposed. Dietary schemes were designed using 1/2 partial factor experimental design to mitigate the composite neurotoxicity risk of six dioxins and No. 16 was screened as the optimum combination which can effectively alleviate the composite neurotoxicity risk by 29.52%. Mechanism analysis shows that the interaction between AhR/ARNT dimer protein and DRE was inhibited under the optimal dietary scheme. This study provides theoretical feasibility and reference significance for assessing composite toxicity risks of pollutants and safety mitigation measures for toxic effects.

Identification and Mechanistic Analysis of Toxic Degradation Products in the Advanced Oxidation Pathways of Fluoroquinolone Antibiotics.

The degradation of fluoroquinolones (FQs) via advanced oxidation processes (AOPs) is a promising avenue, yet the complete mineralization of certain FQ molecules remains elusive, raising concerns about the formation of toxic by-products. This study delineates five primary AOP degradation pathways for 16 commercially available FQ molecules, inferred from existing literature. Density functional theory (DFT) was employed to calculate the bond dissociation energies within these pathways to elucidate the correlation between bond strength and molecular architecture. Subsequently, Comparative Molecular Similarity Index Analysis (CoMSIA) models were constructed for various degradation reactions, including piperazine ring cleavage, defluorination, hydroxylation, and piperazine ring hydroxylation. Three-dimensional contour maps generated from these models provide a deeper understanding of the interplay between FQ molecular structure and bond dissociation energy. Furthermore, toxicity predictions for 16 FQ molecules and their advanced oxidation intermediates, conducted using VEGA 1.2.3 software, indicate that degradation products from pathways P2 and P5 pose a heightened health risk relative to their parent compounds. Furthermore, the application of the Multwfn program to compute the Fukui function for FQ molecules discerns the disparity in degradation propensities, highlighting that N atoms with higher f0 values can augment the likelihood of piperazine ring cleavage. HOMO-LUMO distribution diagrams further confirm that methoxy substitution at the 1-position leads to a dilution of HOMOs on the piperazine ring and an increased energy gap for free radical reactions, diminishing the reactivity with hydroxyl radicals. This study elucidates the pivotal role of structural characteristics in FQ antibiotics for their degradation efficiency within AOPs and unveils the underlying mechanisms of bond dissociation energy disparities. The toxicity parameter predictions for FQ molecules and their intermediates offer unique perspectives and theoretical underpinnings for mitigating the use of high-risk FQs and for devising targeted degradation strategies to circumvent the generation of toxic intermediates in AOPs through molecular structure optimization.

Effect of ozone sterilization on controlling leaf mildew and gray mold tomato disease in a glasshouse and its influence on other growth parameters.

BACKGROUND: In order to explore the effect of ozone sterilization treatment on tomato disease control and increase fruit setting rate, this study took 906 pink fruit tomato as test material, used a small ozone generator to carry out ozone treatment single-factor test, and then selected orthogonal table to guide the ozone treatment combination. The effects of different ozone treatment concentration, ozone treatment duration and ozone treatment times on the growth, disease and fruit setting rate of potted tomato were analyzed. RESULTS: Different ozone treatment had effects on leaf mildew, gray mold and fruit setting rate of tomato. The influence degree of three factors on leaf mildew, gray mold and fruit setting rate was from large to small, a > b > c, a > c > b, b > a > c. A quadratic regression model was established with the control effect of tomato leaf mildew, gray mold and fruit setting rate as response values, and the optimal parameter combination was determined: The ozone treatment concentration was 0.0465 g kg-1, the ozone treatment time was 30 min, and the ozone treatment times were twice a week. In this case, the control efficiency of tomato leaf mildew was 95.02%, the control effect of gray mold was 99.49%, and the fruit setting rate was 76.5%. The test parameters were accurate and reliable. CONCLUSION: The ozone sterilization method proposed in this article is safe and green, and can provide theoretical support for the recovery and reconstruction of tomato disease in a glasshouse. © 2024 Society of Chemical Industry.

Amide herbicides: Analysis of their environmental fate, combined plant-microorganism soil remediation scheme, and risk prevention and control strategies for sensitive populations.

In this study, we predicted the environmental fate of amide herbicides (AHs) using the EQC (EQuilibrium Criterion) model. We found that the soil phase is the main reservoir of AHs in the environment. Second, a toxicokinetic prediction indicated that butachlor have a low human health risk, while the alachlor, acetochlor, metolachlor, napropamide, and propanil are all uncertain. To address the environmental and human-health-related threats posed by AHs, 27 new proteins/enzymes that easily absorb, degrade, and mineralize AHs were designed. Compared with the target protein/enzyme, the comprehensive evaluation value of the new proteins/enzymes increased significantly: the absorption protein increased by 20.29-113.49%; the degradation enzyme increased by 151.26-425.22%; and the mineralization enzyme increased by 23.70-52.16%. Further experiments revealed that the remediating effect of 13 new proteins/enzymes could be significantly enhanced to facilitate their applicability under real environmental conditions. The hydrophobic interactions, van der Waals forces, and polar solvation are the key factors influencing plant-microorganism remediation. Finally, the simulations revealed that appropriate consumption of kiwifruit or simultaneous consumption of ginseng, carrot, and spinach, and avoiding the simultaneous consumption of maize and carrot/spinach are the most effective means reduce the risk of exhibiting AH-linked toxicity.

Multi-process regulation of novel brominated flame retardants: Environmentally friendly substitute design, screening and environmental risk regulation.

Novel brominated flame retardants (NBFRs), one of the most widely used synthetic flame-retardant materials, have been considered as a new group of pollutants that potentially affect human health. To overcome the adverse effects of NBFRs, a systematic approach for molecular design, screening, and performance evaluation was developed to generate environmentally friendly NBFR derivatives with unaltered functionality. In the present study, the features of NBFRs (long-distance migration, biotoxicity, bioenrichment, and environmental persistence) were determined and characterized by the multifactor comprehensive characterization method with equal weight addition, and the similarity index analysis (CoMSIA) model was constructed. Based on the three-dimensional equipotential diagram of the target molecule 2-ethylhexyl tetrabromobenzoic acid (TBB), 23 TBB derivatives were designed. Of these, 22 derivatives with decreased environmental impact and unaltered functional properties (i.e., flame retardancy and stability) were selected using 3D-QSAR models and density functional theory methods. The health risks of these derivatives to humans were assessed by toxicokinetic analysis; the results narrowed down the number of candidates to three (Derivative-7, Derivative-10, and Derivative-15). The environmental impact of these candidates was further evaluated and regulated in the real-world environment by using molecular dynamics simulation assisted by the Taguchi experimental design method. The relationship between the binding effects and the nonbonding interaction resultant force (TBB derivatives-receptor proteins) was also studied, and it was found that the larger the modulus of the binding force, the stronger the binding ability of the two. This finding indicated that the environmental impact of the designed NBFR derivatives was decreased. The present study aimed to provide a new idea and method for designing NBFR substitutes and to provide theoretical support for restraining the potential environmental risks of NBFRs.

Reduced bacterial resistance antibiotics with improved microbiota tolerance in human intestinal: Molecular design and mechanism analysis.

Antibiotic selectivity and bacterial resistance are critical global public health issues. We constructed a multi-class machine learning model to study antibiotic effects on human intestinal microbiota abundance and identified key features. Binding energies of ß-lactam antibiotics with Escherichia coli PBP3 mutant protein were calculated, and a 2D-QSAR model for bacterial resistance was established. Sensitivity analysis identified key features affecting bacterial resistance. By coupling key features from the machine learning model and 2D-QSAR model, we designed ten flucloxacillin (FLU) substitutes that improved intestinal microbiota tolerance and reduced antibiotic bacterial resistance. Concurrently, the substitutes exhibited superior degradability in soil, aquatic environments, and under photolytic conditions, coupled with a reduced environmental toxicity compared to the FLU. Evaluations under combined medication revealed significant improvements in functionality and bacterial resistance for 80% of FLU substitutes, with 50% showing more than a twofold increase. Mechanistic analysis demonstrated enhanced binding to target proteins and increased biodegradability for FLU substitutes due to more concentrated surface charges. Reduced solvent hindrance and increased cell membrane permeability of FLU substitutes, mainly due to enhanced interactions with phospholipid bilayers, contributed to their functional selectivity. This study aims to address poor antibiotic selectivity and strong bacterial resistance, providing guidance for designing antibiotic substitutes.

Microplastics in cultivated soil environment: Construction of toxicity grading evaluation system, development of priority control checklist, and toxicity mechanism analysis.

The present study aimed to comprehensively evaluate the toxicological effects of microplastics (MPs) on cultivated soil quality. Based on improved G1 evaluation method, we first constructed a grading evaluation system comprising of the indicators of toxicological effects of cultivated soil quality under MPs exposure, while focusing on types of MPs that had significant/non-significant toxicity effects. Furthermore, we verified reliability of screening results of significance-links at each level, using several data processing methods. Then, using natural breakpoint classification method, a priority control checklist of toxicological effects of 18 types of MPs on cultivated soil was developed to determine the types of MPs having significant toxicity risks and cultivated soil quality links significantly affected by the toxicity of MPs exposure. Finally, quantum-mechanics/molecular-mechanics (QM/MM) methods were used to carry out the differential toxicity mechanism analysis. The results showed that MPs with higher non-polar surface area may lead to stronger toxicity effect to the cultivated soil quality. Notably, the MPs that have abundant binding sites enhance the binding affinity, and less polar MPs bind more strongly to the non-polar amino acids of target receptors. Our study provides a new theoretical perspective for multi-dimensional analysis toxicological effects of different MPs exposure on cultivated soil quality.

Screening eco-friendliness tire antioxidants alternatives: functional 2,2,4-trimethyl-1,2-dihydroquinoline derivatives design and toxicity evaluation.

Antioxidants which are indispensable functional additives used in rubber tires, are released into aquatic habitats from tire wear particles (TWP), collected in water bodies, and threaten the aquatic ecosystem. This study aimed to design eco-friendly derivatives of 2,2,4-trimethyl-1,2-dihydroquinoline (TMQ) with increased antioxidant activity to use as tire antioxidants. Initially, seventy highly efficient derivatives of TMQ were designed by hydroxylation modifications at multiple sites. The antioxidant activity of hydroxyl derivatives was characterized based on DFT method and compared with TMQ. Twenty derivatives showing a significant (greater than 9%) increase in antioxidant activity compared to TMQ were selected for the next stage. The toxicity risk of these twenty TMQ derivatives was assessed using various toxicokinetic methods. Finally, six TMQ derivatives with significantly lower toxicity risk compared to that of TMQ were evaluated for potential developmental toxicity. They were characterized using molecular docking and molecular dynamics techniques to assess the developmental toxicity risk in silver salmon by absorption of their ROO·, HO·, O2·- and O3 derivatives. TMQ-6 and TMQ-48 showed the lowest toxicity among all TMQ derivatives by a rather large margin. The study throws light on the path of future endeavors to develop highly efficient and greener tire antioxidants.

Mechanism analysis and improved molecular modification: Design of high efficiency and environmentally friendly triazole fungicide substitutes.

The adverse effects of triazole fungicides (TFs) on the soil and the environmental damage caused by their residues have attracted the attention of the international community. To effectively prevent and control the above problems, this paper designed 72 substitutes of TFs with significantly better molecular functionality (>40%) using Paclobutrazol (PBZ) as the template molecule. Then, the comprehensive scores for environmental effects calculated after normalization by "extreme value method-entropy weight method-weighted average method" was the dependent variable, the structural parameters of TFs molecules was the independent variable (PBZ-214 was the template molecule) to construct the 3D-QSAR model of integrated environmental effects of TFs with high degradability, low bioenrichment, low endocrine disruption effects, and low hepatotoxicity and designed 46 substitutes of TFs with significantly better comprehensive environmental effects (>20%). After confirming the above effects of TFs and assessing human health risk and the universality of biodegradation and endocrine disruption, we screened PBZ-319-175 as the eco-friendly substitute of TF, which had high efficiency (improved functionality) and better environmental effects than those of the target molecule by 51.63% and 36.09%, respectively. Finally, the results of the molecular docking analysis showed that non-bonding interactions (hydrogen bonding, electrostatic, or polar force) predominantly affected the association between PBZ-319-175 and its biodegradable protein, and the hydrophobic effect of the amino acids distributed around PBZ-319-175 played a significant role. Additionally, we determined the microbial degradation path of PBZ-319-175 and found that the steric hindrance of the substituent group after molecular modification promoted its biodegradability. In this study, we enhanced molecular functionality twice and also reduce the major damage of TFs to the environment by performing iterative modifications. This paper provided theoretical support for the development and application of high-performance, eco-friendly substitutes of TFs.

Innovative screening for functional improved aromatic amine derivatives: Toxicokinetics, free radical oxidation pathway and carcinogenic adverse outcome pathway.

Aromatic amines, one of the most widely used low-cost antioxidants in rubbers, have been regarded as pollutants with human health concerns. To overcome this problem, this study developed a systematic molecular design, screening, and performance evaluation method to design functionally improved, environmentally friendly and synthesizable aromatic amine alternatives for the first time. Nine of 33 designed aromatic amine derivatives have improved antioxidant property (lower bond dissociation energy of N-H), and their environmental and bladder carcinogenicity impacts were evaluated through toxicokinetic model and molecular dynamics simulation. The environmental fate of the designed AAs-11-8, AAs-11-16, and AAs-12-2 after antioxidation (i.e., peroxyl radicals (ROO·), hydroxyl radicals (HO·), superoxide anion radicals (O2·-) and ozonation reaction) was also analyzed. Results showed that the by-products of AAs-11-8 and AAs-12-2 have less toxicity after antioxidation. In addition, human bladder carcinogenicity of the screened alternatives was also evaluated through adverse outcome pathway. The carcinogenic mechanisms were analyzed and verified through amino acid residue distribution characteristics, 3D-QSAR and 2D-QSAR models. AAs-12-2, with high antioxidation property, low environmental impacts and carcinogenicity, was screened as the optimum alternative for 3,5-Dimethylbenzenamine. This study provided theoretical support for designing environmentally friendly and functionally improved aromatic amine alternatives from toxicity evaluation and mechanism analysis.

Potential thyroid hormone disorder risks of tire antioxidants to aquatic food chain organisms after absorbing free radicals in marine and freshwater environments.

Tire antioxidants are essential functional chemical additives in tire rubber production. Because of the characteristic easy precipitation in the water environment, the environmental pollution problem caused by tire antioxidants is concerning. To reveal the mechanism by which tire antioxidants reduce common oxidative factors (free radicals) in the environment and to control the potential biological thyroid hormone disorder risk of tire antioxidant derivatives, eight commonly used antioxidants in tire production were selected for analysis. Firstly, the ability of tire antioxidants to reduce three different free radicals was quantitatively characterized based on Gaussian calculation method and inferring the radical reduction mechanism of tire antioxidants. Moreover, using the PaDEL-Descriptor software and random forest algorithm found that the N-octanol/water partition coefficient, a structure descriptor of tire antioxidant molecules, significantly correlated with their reducing ability. Second, molecular docking and molecular dynamics methods were used to assess the thyroid hormone disorder risk to aquatic organisms of eight antioxidants after reducing three free radicals. And this is the first study to construct an assessment score list of potential thyroid hormone disorder risk of the derivatives of tire antioxidants after reducing free radicals to marine and freshwater aquatic organisms based on the risk entropy method. Through the screening of this list, it was found that the derivative of the antioxidant 2,2,4-trimethyl-1,2-dihydroquinoline oxidized by free radicals had the highest risk of thyroid hormone disorder. In addition, the top organism in the aquatic food chain was the most affected. This study also revealed that van der Waals interactions and hydrogen bonding were the main influencing factors of thyroid hormone disorder risk to aquatic organisms of the derivatives of tire antioxidants that reduce free radicals based on amino acid residue analysis. Overall, the results provide theoretical support for the selection of antioxidants and the avoidance and control of environmental risks in the tire rubber production process.

Efficient and synergistic degradation of fluoroquinolones by bacteria and microalgae: Design of environmentally friendly substitutes, risk regulation and mechanism analysis.

Fluoroquinolones (FQs) are widely used as antimicrobial agents, and their nonbiodegradable in sewage has become an increasingly concerning. High-biochemical substitutes of FQs were designed with bacteria and microalgae as driving forces of biodegradation, and this is the first study on efficient synergistic degradation of FQs by multiple microorganisms. Among 143 designed FQ substitutes, only one was screened with high biodegradability (increased by 120.51 %), improved functional properties (genotoxicity: 13.66 %), less environmental impacts (bio-accumulation: -44.81 %), less human health and ecological risk (hepatotoxicity: -106.21 %). The complex functional protein with the synergistic degradation effect of bacteria and microalgae was constructed, which proved their synergistic degradation and realized the effect of "1 + 1 > 2″. The best risk regulation scheme determined using molecular dynamics simulation proved the degradation ability of complex functional protein and found the CIP-129 was easy to be degraded in real environment compared with CIP, and the degradation rate increased by 70.42 %. The synthesis path of CIP-129 and CIP were inferred and calculated, and the results showed the Gibbs free energies of three CIP-129 synthetic paths (40.64 a.u.; 40.61 a.u.; 40.65 a.u.) were close to the energy required for the CIP (39.43 a.u.), indicating there was no significant difference in the energy consumption of CIP-129 in laboratory synthesis.

Direct Z-Scheme Heterojunction Catalysts Constructed by Graphitic-C3N4 and Photosensitive Metal-Organic Cages for Efficient Photocatalytic Hydrogen Evolution.

The demand for improving the activity, durability, and recyclability of metal-organic cages (MOCs) that work as photocatalytic molecular devices in a homogeneous system has promoted research to combine them with other solid materials. An M2L4 type photosensitive metal-organic cage MOC-Q2 with light-harvesting ligands and catalytic Pd2+ centers has been synthesized and further heterogenized with graphitic carbon nitride to prepare a robust direct Z-scheme heterojunction photocatalyst for visible-light-driven hydrogen generation. The optimized g-C3N4/MOC-Q2 (0.7 wt%) sample exhibits a high H2 evolution activity of 6423 µmol g-1 h-1 in 5 h, and a total turnover number of 39,695 after 10 h, significantly superior to the bare MOC-Q2 used in the homogeneous solution and the comparison sample Pd/g-C3N4/L-4. The enhanced performances of g-C3N4/MOC-Q2 can be ascribed to its direct Z-scheme heterostructure, which effectively improves the charge separation and transfer efficiency. This work presents a rational approach of designing a binary photocatalytic system through combing micromolecular MOCs with heterogeneous semiconductors for water splitting.

Molecular design of high-efficacy and high drug safety Fluoroquinolones suitable for a variety of aerobic biodegradation bacteria.

The present study attempted to improve the biodegradation removal rate of Fluoroquinolones (FQs) in sewage treatment plants. The similarity index analysis (CoMSIA) model for combined biodegradability was constructed, and 33 kinds of molecular derivatives of FQs suitable for a variety of aerobic biodegradation microorganisms were designed. Further, derivative-20 and derivative-28, with high drug efficiency, drug safety, and environmental friendliness were selected through pharmacokinetics (ADMET), toxicokinetics (TOPKAT), FQs functional characteristics, and environmental friendliness evaluations. Compared with the target molecules, the combined biodegradability of the above two FQ-derivative molecules were increased by 193.57 % and 205.07 %, respectively, while their environment-friendly characteristics were improved to a certain degree. Through molecular docking and molecular dynamic simulation analysis, it showed that van der Waals force (decreased by 2.73 %-61.74 %) was the main factor influencing the binding ability of the modified FQ molecules to the receptor proteins. In addition, the relationship among the non-bonding interaction resultant force, the binding effect of the FQ-derivative molecules, and the receptor protein-related amino acid residues were studied for the first time. It was observed that the higher the value of the non-bonding interaction resultant force, the better was the binding effect, which demonstrating the significantly improved biodegradability of the designed FQ-derivative molecules.