Mycoremediation of the novel fungicide ametoctradin by different agricultural soils and accelerated degradation utilizing selected fungal strains.

Accelerating safety assessments for novel agrochemicals is imperative, advocating for in vitro setups to present pesticide biodegradation by soil microbiota before field studies. This approach enables metabolic profile generation in a controlled laboratory environment eliminating extrinsic factors. In the current study, ten different soil samples were utilized to check their capability to degrade Ametoctradin by their microbiota. Furthermore, five different fungal strains (Aspergillus niger, Aspergillus flavus, Aspergillus fumigatus, Lasiodiplodia theobromae, and Penicillium chrysogenum) were utilized to degrade Ametoctradin in aqueous media. A degradation pathway was established using the metabolic patterns created during the biodegradation of Ametoctradin. In contrast to 47% degradation (T1/2 of 34 days) when Ametoctradin was left in the soil samples, the fungal strain Aspergillus fumigatus demonstrated 71% degradation of parent Ametoctradin with a half-life (T1/2) of 16 days. In conclusion, soil rich in microorganisms effectively cleans Ametoctradin-contaminated areas while Fungi have also been shown to be an effective, affordable, and promising way to remove Ametoctradin from the environment.

Transgenerational effects of triazole fungicides on gene expression and egg compounds in non-exposed offspring: A case study using Red-Legged Partridges (Alectoris rufa).

Triazole fungicides are widely used to treat cereal seeds before sowing. Granivorous birds like the Red-legged Partridge (Alectoris rufa) have high exposure risk because they ingest treated seeds that remain on the field surface. As triazole fungicides can act as endocrine disruptors, affecting sterol synthesis and reproduction in birds several months after exposure, we hypothesized that these effects could also impact subsequent generations of exposed birds. To test this hypothesis, we exposed adult partridges (F0) to seeds treated at commercial doses with four different formulations containing triazoles as active ingredients (flutriafol, prothioconazole, tebuconazole, and a mixture of the latter two), simulating field exposure during late autumn sowing. During the subsequent reproductive season, two to four months after exposure, we examined compound allocation of steroid hormones, cholesterol, vitamins, and carotenoids in eggs laid by exposed birds (F1), as well as the expression of genes encoding enzymes involved in sterol biosynthesis in one-day-old chicks of this F1. One year later, F1 animals were paired again to investigate the expression of the same genes in the F2 chicks. We found changes in the expression of some genes for all treatments and both generations. Additionally, we observed an increase in estrone levels in eggs from partridges treated with flutriafol compared to controls, a decrease in tocopherol levels in partridges exposed to the mixture of tebuconazole and prothioconazole, and an increase in retinol levels in partridges exposed to prothioconazole. Despite sample size limitations, this study provides novel insights into the mechanisms of action of the previously observed effects of triazole fungicide-treated seeds on avian reproduction with evidence that the effects can persist beyond the exposure windows, affecting unexposed offspring of partridges fed with treated seeds. The results highlight the importance of considering long-term chronic effects when assessing pesticide risks to wild birds.

In vitro and in vivo investigation of a thyroid hormone system-specific interaction with triazoles.

Alterations in thyroid hormones (TH) and thyroid-stimulating hormone levels are frequently found following exposure to chemicals of concern. Dysregulation of TH levels can severely perturb physiological growth, metabolism, differentiation, homeostasis in the adult and developmental processes in utero. A frequently identified mode of action for this interaction is the induction of hepatic detoxification mechanisms (e.g. SULTs and UGTs), which lead to TH conjugation and elimination and therefore interfere with hormonal homeostasis, fulfilling the endocrine disruptors (EDs) definition. A short-term study in rats with dietary exposure to cyproconazole, epoxiconazole and prochloraz was conducted and hepatocyte hypertrophy, hepatic UGT activity and Phase 1/2 gene expression inductions were observed together with changes in TH levels and thyroid follicular hypertrophy and hyperplasia. To test for specific interaction with the thyroid hormone system, in vitro assays were conducted covering thyroidal I-uptake (NIS), TH transmembranal transport via MCT8 and thyroid peroxidase (TPO) function. Assays for iodothyronine deiodinases (DIO1-DIO3) and iodotyrosine deiodinase (DEHAL1) were included, and from the animal experiment, Dio1 and Dehal1 activities were measured in kidney and liver as relevant local indicators and endpoints. The fungicides did not affect any TH-specific KEs, in vitro and in vivo, thereby suggesting hepatic conjugation as the dominant MoA.

Discovery of 1,2,3-triazole incorporated indole-piperazines as potent antitubercular agents: Design, synthesis, in vitro biological evaluation, molecular docking and ADME studies.

In this report, a library consisting of three sets of indole-piperazine derivatives was designed through the molecular hybridization approach. In total, fifty new hybrid compounds (T1-T50) were synthesized and screened for antitubercular activity against Mycobacterium tuberculosis H37Rv strain (ATCC-27294). Five (T36, T43, T44, T48 and T49) among fifty compounds exhibited significant inhibitory potency with the MIC of 1.6 µg/mL, which is twofold more potent than the standard first-line TB drug Pyrazinamide and equipotent with Isoniazid. N-1,2,3-triazolyl indole-piperazine derivatives displayed improved inhibition activity as compared to the simple and N-benzyl indole-piperazine derivatives. In addition, the observed activity profile of indole-piperazines was similar to standard anti-TB drugs (isoniazid and pyrazinamide) against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa strains, demonstrating the compounds' selectivity towards the Mycobacterium tuberculosis H37Rv strain. All the active anti-TB compounds are proved to be non-toxic (with IC50 > 300 µg/mL) as verified through the toxicity evaluation against VERO cell lines. Additionally, molecular docking studies against two target enzymes (Inh A and CYP121) were performed to validate the activity profile of indole-piperazine derivatives. Further, in silico-ADME prediction and pharmacokinetic parameters indicated that these compounds have good oral bioavailability.

Degradation of Triazole Fungicides by Plant Growth-Promoting Bacteria from Contaminated Agricultural Soil.

The widespread application of triazole fungicides (TFs) in agricultural practices can result in the considerable accumulation of active compound residues in the soil and a subsequent negative impact on the soil microbiota and crop health. In this study, we isolated three TF-degrading bacterial strains from contaminated agricultural soils and identified them as Klebsiella sp., Pseudomonas sp., and Citrobacter sp. based on analysis of morphological characteristics and 16S rRNA gene sequences. The strains used three common TFs, namely hexaconazole, difenoconazole, and propiconazole, as their only sources of carbon and energy for growth in a liquid mineral salt medium, with high concentrations (~ 500 mg/l) of each TF. In addition to the ability to degrade fungicides, the isolates also exhibited plant growth-promoting characteristics, such as nitrogen fixation, indole acetic acid production, phosphate dissolution, and cellulose degradation. The synergistic combination of three bacterial isolates significantly improved plant growth and development with an increased survival rate (57%), and achieved TF degradation ranging from 85.83 to 96.59% at a concentration of approximately 50 mg/kg of each TF within 45 days in the soil-plant system. Based on these findings, the three strains and their microbial consortium show promise for application in biofertilizers, to improve soil health and facilitate optimal plant growth.

Assessing the Toxicity of Benzotriazole Ultraviolet Stabilizers to Fishes: Insights into Aryl Hydrocarbon Receptor-Mediated Effects.

Benzotriazole ultraviolet stabilizers (BUVSs) are chemicals used to mitigate UV-induced damage to manufactured goods. Their presence in aquatic environments and biota raises concerns, as certain BUVSs activate the aryl hydrocarbon receptor (AhR), which is linked to adverse effects in fish. However, potencies of BUVSs as AhR agonists and species sensitivities to AhR activation are poorly understood. This study evaluated the toxicity of three BUVSs using embryotoxicity assays. Zebrafish (Danio rerio) embryos exposed to BUVSs by microinjection suffered dose-dependent increases in mortality, with LD50 values of 4772, 11 608, and 56 292 ng/g-egg for UV-P, UV-9, and UV-090, respectively. The potencies and species sensitivities to AhR2 activation by BUVSs were assessed using a luciferase reporter gene assay with COS-7 cells transfected with the AhR2 of zebrafish and eight other fishes. The rank order of potency for activation of the AhR2 from all nine species was UV-P > UV-9 > UV-090. However, AhR2s among species differed in sensitivities to activation by up to 100-fold. An approximate reversed rank order of species sensitivity was observed compared to the rank order of sensitivity to 2,3,7,8-tetrachlorodibenzo[p]dioxin, the prototypical AhR agonist. Despite this, a pre-existing quantitative adverse outcome pathway linking AhR activation to embryo lethality could predict embryotoxicities of BUVSs in zebrafish.

Crotalaria juncea L. enhances the bioremediation of sulfentrazone-contaminated soil and promotes changes in the soil bacterial community.

Sulfentrazone (STZ) is an efficient tool for the pre- and post-emergence control of monocotyledonous and dicotyledonous weeds in fields of crops such as pineapple, coffee, sugarcane, citrus, eucalyptus, tobacco, and soybean. However, this herbicide persists in the soil, causing phytotoxicity in the subsequent crop. Therefore, it is important to use efficient strategies for the remediation of STZ-contaminated areas. The aim of this study was to evaluate the effects of Crotalaria juncea L. on the remediation of STZ-contaminated soil and on the microbial activity and bacterial community structure therein. The study was conducted in three stages: (i) cultivation of C. juncea in soil contaminated with 200, 400, and 800 g ha-1 STZ; (ii) determination of the soil microbial activity (basal respiration, microbial biomass carbon, and bacterial community structure); and (iii) cultivation of a bioindicator species and determination of the residual fraction of STZ. The soil microbial activity was impacted by the soil type and STZ dose. Soil previously cultivated with C. juncea (rhizospheric soil) displayed higher CO2 and lower qCO2 values than non-rhizospheric soil (no previous C. juncea cultivation). Increasing doses of STZ reduced the activity and lowered the diversity indices of the soil microorganisms. The bacterial community structure was segregated between the rhizospheric and non-rhizospheric soils. Regardless of soil type, the bioindicator of remediation (Pennisetum glaucum R.Br.) grew only at the STZ dose of 200 g ha-1, and the plant intoxication level was also lower in rhizospheric soil treated with this herbicide dose. All P. glaucum plants died in the soils treated with 400 and 800 g ha-1 STZ. Previous cultivation of C. juncea in soils contaminated with 200, 400, and 800 g ha-1 STZ reduced the residual fraction of the herbicide by 4.8%, 12.5%, and 17.4%, respectively, compared with that in the non-rhizospheric soils. In conclusion, previous cultivation with C. juncea promoted increases in the soil bacterial activity and diversity indices, mitigated the deleterious effects of STZ on the bioindicator crop, and reduced the residual fraction of the herbicide in the soil.

Sex-specific metabolic dysregulation in digestive glands of green mussels following exposure to triazophos.

As a ubiquitous environmental pollutant in China, triazophos (TP) is known to have neurotoxicity, oxidative stress, and reproductive toxicity to mussels. To investigate the molecular mechanisms of TP toxicity, metabolic changes in the digestive glands of Perna viridis in different sexes were examined after treated with 35 µg/L TP. Notably, 158 significant different metabolites (SDMs) were detected in TP-treated mussels and more than half of the SDMs were lipids and lipid-like molecules, which suggested that TP disturbed the lipid metabolism of P. viridis. In addition, metabolites associated with neurotoxicity and reproductive disturbance were also detected in female and male mussels. Moreover, a larger number of SDMs were found in male mussels (120 SDMs) than females (99 SDMs), and 60 common metabolites exhibited consistent variation tendency and similar magnitude in both sexes. The metabolic alternations in female and male mussels displayed similar protective mechanisms and also sex-specific responses, male mussels were more sensitive to TP exposure. This research provided new data about the molecular mechanisms of TP toxicity and the gender specific changes in mussels after treated by chemicals.

New insights into triazole fungicide-caused hematopoietic abnormality in zebrafish based on GRα screening developmental toxicity.

Triazole fungicides (TFs) are known to be common environmental contaminants that can be toxic to aquatic animals, but their developmental toxicity is not fully understood. To address this gap, we first used a glucocorticoid receptor α (GRα)-mediated dual luciferase reporter gene system to explore the possible development toxicity of ten TFs and found that flusilazole (FLU) exhibited stronger agonistic activity against GRα. Subsequent transcriptome sequencing showed that FLU exposure affected GRα activation and hematopoiesis associated with a variety of biological processes, including responses to corticosteroid release, embryonic hematopoiesis, erythroid differentiation, and the development of hematopoietic or lymphoid organs. Furthermore, based on in situ hybridization and staining techniques, we clarified that FLU decreased the expression of the primitive hematopoietic marker genes gata1 and pu.1. and caused the defects in the posterior blood island (PBI), thereby impacting intermediate hematopoietic processes. Also, FLU significantly reduced the expression of the crucial hematopoietic gene cmyb and disrupted the production of erythrocytes and bone marrow cells during definitive hematopoiesis. Consistently, we found that FLU induced lesions in the kidney, a hematopoietic organ, including the infiltration of inflammatory cells, tubular collapse, reduced tubular filtration area, and interstitial hydronephrosis. We also found that FLU increased aberrant red blood cells in the peripheral blood of zebrafish. These findings provide new insights into the developmental toxicity and ecotoxicological risk of TFs.

Non-target biotransformation enzymes as a target for triazole-zinc mixtures.

Triazoles inhibit lanosterol 14α-demethylase and block ergosterol biosynthesis in fungal pathogens. However, they also interact with other cytochrome P450 enzymes and influence non-target metabolic pathways. Disturbingly, triazoles may interact with essential elements. The interaction of penconazole (Pen), cyproconazole (Cyp) and tebuconazole (Teb) with Zn2+ results in the formation of deprotonated ligands in their complexes or in the creation of complexes with Cl- as a counterion or doubly charged complexes. Triazoles, as well as their equimolar cocktails with Zn2+ (10-6 mol/L), decreased the activities of the non-target enzymes CYP19A1 and CYP3A4. Pen most decreased CYP19A1 activity and was best bound to its active centre to block the catalytic cycle in computational analysis. For CYP3A4, Teb was found to be the most effective inhibitor by both, activity assay and interaction with the active centre. Teb/Cyp/Zn2+ and Teb/Pen/Cyp/Zn2+ cocktails also decreased the CYP19A1 activity, which was in correlation with the formation of numerous triazole-Zn2+ complexes.

Enantioselective Toxic Effects of Prothioconazole toward Scenedesmus obliquus.

Prothioconazole (PTC) is a broad-spectrum triazole fungicide with one asymmetric center and consists of two enantiomers, R-(-)-PTC and S-(+)-PTC. To address the concern of its environmental safety, the enantioselective toxic effects of PTC on Scendesmus obliquus (S. obliquus) were investigated. PTC racemates (Rac-PTC) and enantiomers exhibited dose-dependent acute toxicity effects against S. obliquus at a concentration from 1 to 10 mg·L-1. The 72 h-EC50 value of Rac-, R-(-)-, and S-(+)-PTC is 8.15, 16.53, and 7.85 mg·L-1, respectively. The growth ratios and photosynthetic pigment contents of the R-(-)-PTC treatment groups were higher than the Rac- and S-(+)-PTC treatment groups. Both catalase (CAT) activities and esterase activities were inhibited in the Rac- and S-(+)-PTC treatment groups at high concentrations of 5 and 10 mg·L-1, and the levels of malondialdehyde (MDA) were elevated, which exceeded the levels in algal cells for the R-(-)-PTC treatment groups. PTC could disrupt the cell morphology of S. obliquus and induce cell membrane damage, following the order of S-(+)-PTC ≈ Rac-PTC > R-(-)-PTC. The enantioselective toxic effects of PTC on S. obliquus provide essential information for its ecological risk assessment.

Tolerance of microorganisms to residual herbicides found in eucalyptus plantations.

Competition with weeds is one of the main factors that limit the development of forest species. Some herbicides used to control these plants have a residual effect on the soil. Bioremediation is an alternative to decontaminate these areas. The aim of this study was to evaluate the tolerance of Aspergillus niger, Penicillium pinophilum and Trichoderma sp. and its degrading potential on residual effect herbicides. The tolerance of Bacillus subtilis, Pseudomonas sp. and Azospirillum brasilense to herbicides was also evaluated. The herbicides used in this study were indaziflam, sulfentrazone, sulfentrazone + diuron, clomazone and glyphosate + s-metolachlor. The analysis of the tolerance and degradation potential of fungi was carried out in Czapek Dox medium and the growth was evaluated by determining the biomass. Bacterial tolerance analysis was performed in Luria Bertani medium and growth monitored by optical density. The data were applied to the Gompertz model to evaluate the behavior of bacteria. Bacterial growth parameters were not influenced by the presence of herbicides. All fungi were tolerant to the herbicides tested and there was an increase in the growth of Trichoderma sp. Thus, the analysis of the degrading potential was performed only for Trichoderma sp. in the presence of herbicides that potentiated its growth. In this analysis, there was no effect of herbicides on fungal growth; the fungus was unable to use the carbon present in the herbicide to enhance its growth; and there was no significant effect of nitrogen in the presence of the herbicide. It is concluded, therefore, that the tested residual herbicides do not interfere with the development of the evaluated microorganisms.

Developmental defects and potential mechanisms in F1 generation of parents exposed to difenoconazole at different life stages of zebrafish (Danio rerio).

As a typical triazole fungicide, difenoconazole is extensively used to control plant diseases; however, its residue in environmental waters poses a risk to aquatic organisms. In this study, we investigated the acute toxicity of different life stages and sub-lethal toxicity in embryonic yolk sac stage of difenoconazole to zebrafish, and the developmental toxicity in F1 generation of parents exposed to difenoconazole at different life stages of zebrafish. Furthermore, we used transcriptomics to explore the potential mechanisms of difenoconazole on the F1 larvae of parents exposed to the chemical at the embryonic stage. The results of this study showed that developmental defects were observed in the F1 embryo/larvae of parents exposed to 3, 30, and 300 µg/L of difenoconazole at different (embryo, larval, juvenile, and adult) life stages, and exposure to difenoconazole at the embryonic stage caused more severe developmental toxicity than those at other life stages. Developmental defects (malformation, inhibition of heartbeat and body length) were observed in the F1 embryos and larvae of parents exposed to difenoconazole at the embryonic stage. In addition, the total cholesterol and triglyceride contents were significantly reduced in the F1 larvae, and RNA-seq analysis revealed significant alterations in the expression of nine genes (msmo1, hsd17b7, sc5d, tm7sf2, ebp, cyp2r1, lss, cyp51, and cyp27b1) in the steroid synthesis pathway. This is suggested that F1 larvae of parents exposed to difenoconazole at the embryonic stage show abnormalities in the steroid biosynthetic pathway. These results reveal the differences in toxicity of difenoconazole to zebrafish at different life stages, improve studies on difenoconazole toxicity to zebrafish, and provide a new perspective for assessing the risk of contaminants to aquatic organisms.

Triazole fungicides induce adipogenesis and repress osteoblastogenesis in zebrafish.

Triazoles are a major group of azole fungicides commonly used in agriculture, and veterinary and human medicine. Maternal exposure to certain triazole antifungal medication causes congenital malformations, including skeletal malformations. We hypothesized that triazoles used as pesticides in agriculture also pose a risk of causing skeletal malformations in developing embryos. In this study, teratogenic effects of three commonly used triazoles, cyproconazole, paclobutrazol, and triadimenol, were investigated in zebrafish, Danio rerio. Exposure to the triazole fungicides caused bone and cartilage malformations in developing zebrafish larvae. Data from whole-embryo transcriptomics with cyproconazole suggested that exposure to this compound induces adipogenesis while repressing skeletal development. Confirming this finding, the expression of selected bone and cartilage marker genes were significantly downregulated with triazoles exposure as determined by quantitative PCR. The expression of selected adipogenic genes was upregulated by the triazoles. Furthermore, exposure to each of the three triazoles induced adipogenesis and lipid droplet formation in vitro in 3T3-L1 pre-adipocyte cells. In vivo in zebrafish larvae, cyproconazole exposure caused lipid accumulation. These results suggest that exposure to triazoles promotes adipogenesis at the expense of skeletal development, and thus they expand the chemical group of bona fide bone to fat switchers.

Enantioselectivity effects of energy metabolism in honeybees (Apis mellifera) by triticonazole.

The heavy use of agrochemicals is considered a major factor contributing to the decline in wild honeybee populations. Development of low-toxicity enantiomers of chiral fungicides is the key to reducing the potential threats to honeybees. In this study, we evaluated the enantioselective toxic effects of triticonazole (TRZ) on honeybees and its molecular mechanisms. The results showed that after long-term exposure to TRZ, the content of thoracic ATP decreased significantly, by 41 % in R-TRZ treatments and by 46 % in S-TRZ treatments. Furthermore, the transcriptomic results indicated that S-TRZ and R-TRZ significantly altered the expression of 584 genes and 332 genes, respectively. Pathway analysis indicated that R- and S-TRZ could affect different genes expressed in GO terms and metabolic pathways, especially the transport GO terms (GO: 0006810) and pathways of alanine, aspartate and glutamate metabolism, drug metabolism - cytochrome P450, and pentose phosphate. Additionally, S-TRZ had a more pronounced effect on honeybee energy metabolism, disrupting a greater number of genes involved in the TCA cycle and glycolysis/glycogenesis, exerting a stronger effect on energy metabolic pathways, including nitrogen metabolism, sulfur metabolism, and oxidative phosphorylation. In summary, we recommend reducing the proportion of S-TRZ in racemate to minimize the threat to the survival of honeybees and protect the diversity of economic insects.

Biodegradation of insensitive munition (IM) formulations: IMX-101 and IMX-104 using aerobic granule technology.

A laboratory-scale aerobic granular sludge (AGS) sequencing batch bioreactor (SBR) was initiated in this study for the biodegradation of hazardous insensitive munition (IM) formulation constituents; 2,4-dinitroanisole (DNAN), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), 1-nitroguanidine (NQ), and 3-nitro-1,2,4-triazol-5-one (NTO). Efficient (bio)transformation of the influent DNAN and NTO was achieved throughout reactor operation with removal efficiencies greater than 95%. An average removal efficiency of 38.4 ± 17.5% was recorded for RDX. NQ was only slightly removed (3.96 ± 4.15%) until alkalinity was provided in the influent media, which subsequently increased the NQ removal efficiency up to an average of 65.8 ± 24.4%. Batch experiments demonstrated a competitive advantage for aerobic granular biofilms over flocculated biomass for the (bio)transformation DNAN, RDX, NTO, and NQ, as aerobic granules were capable of reductively (bio)transforming each IM compound under bulk aerobic conditions while flocculated biomass could not, thus demonstrating the contribution of inner oxygen-free zones within aerobic granules. A variety of catalytic enzymes were identified in the extracellular polymeric matrix of the AGS biomass. 16 S rDNA amplicon sequencing found Proteobacteria (27.2-81.2%) to be the most abundant phyla, with many genera associated with nutrient removal as well as genera previously described in relation to the biodegradation of explosives or related compounds.

Exposure to high-performance benzotriazole ultraviolet stabilizers: Advance in toxicological effects, environmental behaviors and remediation mechanism using in-silica methods.

Benzotriazole ultraviolet stabilizers (BUVSs), as light stabilizers, have attracted widespread attention because of their easy migration in the environment and their acute toxicity and biological toxicity effects, such as immunotoxicity and hepatotoxicity. Accordingly, the treatment and remediation mechanisms of high-performance, environmentally friendly, and low human health risk BUVS substitutes were analyzed. Firstly, the weights and the comprehensive effect (CE) values of migration and toxicity of BUVSs were determined by Topsis assisted by the coefficient of variation (CV) method. From this, a three-dimensional quantitative structure activity relationship (3D-QSAR) model based on the CE values of the 13 BUVSs was constructed. Secondly, EPI software was used to predict the functionality and environmental friendliness of BUVS substitutes, and a partial least squares regression machine learning (ML-PLSR) model was used to analyze the mechanism. Then, ADMET (absorption, distribution, metabolism, excretion, toxicity), TOPKAT, and exposure dose models were used to evaluate the ecological and human health risks of BUVSs and their substitutes. Finally, the key charge information affecting the UV-326 substitutes was deduced by time dependent density functional theory (TDDFT). Using UV-326 as an example, 15 UV-326 substitutes with reduced CE values were designed (reductions of 2.61%-23.18%). Compared with ML-PLSR models of acute toxicity, immunotoxicity, and hepatotoxicity, it was found that the decrease of DM and Qyy values and the increase of Qzz value could further decrease the toxicity of the UV-326 substitutes. Ecological and human health risk assessment showed that the exposure risks of the six UV-326 substitutes were within acceptable limits. TDDFT showed that the change of electron distribution and electron excitation type were the key factors affecting the performance of the UV-326 substitutes, and a charge transfer excitation type was more conducive to obtaining high-performance, environmentally friendly UV-326 substitutes. This study aims to alleviate the toxic damage to the ecological environment and human health caused by BUVS exposure.

Maternal exposure to chiral triazole fungicide tebuconazole induces enantioselective thyroid disruption in zebrafish offspring.

Pesticides could induce long-term impacts on aquatic ecosystem via transgenerational toxicity. However, for many chiral pesticides, the potential enantioselectivity of transgenerational toxicity has yet to be fully understood. In this study, we used zebrafish as models to evaluate the maternal transfer risk of tebuconazole (TEB), which is a chiral triazole fungicide currently used worldwide and has been frequently detected in surface waters. After 28-day food exposure (20 and 400 ng/g) to the two enantiomers of TEB (S- and R-TEB) in adult female zebrafish (F0), increased malformation rate and decreased swimming speed were found in F1 larvae, with R-TEB showing higher impacts than S-enantiomer. Additionally, enantioselective effects on the secretion of thyroid hormones (THs) and expression of TH-related key genes along the hypothalamic-pituitary-thyroid (HPT) axis were found in both F0 and F1 after maternal exposure. Both the two enantiomers significantly disrupted the triiodothyronine (T3) and thyroxine (T4) contents in F0 with different degrees, whereas in F1, significant effects were only found in R-TEB groups with decreasing of both T3 and T4 contents. Most of the HPT axis related genes in F0 were upregulated by TEB and more sensitive to R-TEB than to S-TEB. In contrast, most of the genes in F1 were downregulated by both R- and S-TEB, especially the genes that are primarily responsible for thyroid development and growth (Nkx2-1), TH synthesis (NIS and TSHꞵ) and metabolism (Deio1). Findings from this study highlight the key role of enantioselectivity in the ecological risk assessment of chiral pesticides through maternal transfer.

Crosstalk of oxidative stress, inflammation, apoptosis, and autophagy under reactive oxygen stress involved in difenoconazole-induced kidney damage in carp.

Difenoconazole is a commonly used triazole fungicide in agricultural production. Because of its slow degradation and easy accumulation in the environment, it seriously endangers both animal health and the ecological environment. Therefore, it is hoped that the effects on carp kidneys can be studied by simulating difenoconazole residues in the environment. The experiment was designed with two doses (0.488 mg/L, 1.953 mg/L) as exposure concentrations of difenoconazole for 4 d. Histopathological results showed that difenoconazole could cause severe damage to the kidney structure and extensive inflammatory cell infiltration in carp. Elevated levels of Creatinine, and BUN suggested the development of kidney damage. The DHE fluorescence probe's result suggested that difenoconazole might cause reactive oxygen species (ROS) to accumulate in the kidney of carp. Difenoconazole was found to increase MDA levels while decreasing the activities of CAT, SOD, and GSH-PX, according to biochemical indicators. In addition, difenoconazole could up-regulate the transcription levels of inflammatory factors tnf-α, il-6, il-1ß, and inos. At the same time, it inhibited the transcription level of il-10 and tgf-ß1. The TUNEL test clearly showed that difenoconazole induced apoptosis in the kidney and vastly raised the transcript levels of apoptosis-related genes p53, caspase9, caspase3, and bax while inhibiting the expression of Bcl-2, fas, capsase8. Additionally, TEM imaging showed that clearly autophagic lysosomes and autophagosomes were formed. Elevated levels of LC3II protein expression, increased transcript levels of the autophagy-related gene atg5 as well as decreased transcript levels of p62 represented the generation of autophagy. In conclusion, the study illustrated that oxidative stress, inflammation, apoptosis, and autophagy all played roles in difenoconazole-induced kidney injury in carp, which was closely linked to ROS production. This work provides a valuable reference for studying the toxicity of difenoconazole to aquatic organisms.

Triadimenol promotes the production of reactive oxygen species and apoptosis with cardiotoxicity and developmental abnormalities in zebrafish.

Various types of fungicides, especially triazole fungicides, are used to prevent fungal diseases on farmlands. However, the developmental toxicity of one of the triazole fungicides, triadimenol, remains unclear. Therefore, we used the zebrafish animal model, a representative toxicological model, to investigate it. Triadimenol induced morphological alterations in the eyes and body length along with yolk sac and heart edema. It also stimulated the production of reactive oxygen species and expression of inflammation-related genes and caused apoptosis in the anterior regions of zebrafish, especially in the heart. The phosphorylation levels of Akt, ERK, JNK, and p38 proteins involved in the PI3K and MAPK pathways, which are important for the development process, were also reduced by triadimenol. These changes led to malformation of the heart and vascular structures, as observed in the flk1:eGFP transgenic zebrafish models and a reduction in the heart rate. In addition, the expression of genes associated with cardiac and vascular development was also reduced. Therefore, we elucidated the mechanisms associated with triadimenol toxicity that leads to various abnormalities and developmental toxicity in zebrafish.