From Water to Water: Insight into the Translocation of Pesticides from Plant Rhizosphere Solution to Leaf Guttation and the Associated Ecological Risks.

Plant guttation is an important source of water/nutrients for many beneficial insects, while the presence of pesticides in guttation has been considered as a new exposure route for nontarget insects. This study aimed to elucidate how 15 diverse pesticides are translocated from growth media to guttation by maize plants through a hydroponic experiment. All pesticides were effectively translocated from the growth solution to maize guttation and reached a steady state within 5 days. The strong positive correlation (R2 = 0.43-0.84) between the concentrations of pesticides in guttation and in xylem sap demonstrated that xylem sap was a major source of pesticides in guttation. The relationship between the bioaccumulation of pesticides in guttation (BCFguttation) and the chemical Kow was split into two distinct patterns: for pesticides with log Kow > 3, we identified a good negative linear correlation between log BCFguttation and log Kow (R2 = 0.71); however, for pesticides with log Kow < 3, all data fall close to a horizontal line of BCFguttation ≅ 1, indicating that hydrophilic pesticides can easily pass through the plants from rhizosphere solution to leaf guttation and reach saturation status. Besides, after feeding with pesticide-contaminated guttation, the mortality of honeybees was significantly impacted, even at very low levels (e.g., ∑600 µg/L with a mortality of 93%). Our results provide essential information for predicting the contamination of plant guttation with pesticides and associated ecological risks.

A sensitive fluoroimmunoassay for quantitative detection of imidacloprid based on quantum dot-streptavidin conjugate.

Imidacloprid (IMI), the most commonly used neonicotinoid, is widely present in both the environment and agro-products due to extensive and prolonged application, posing potential risks to ecological security and human health. This study introduced a sensitive and rapid fluorescence-linked immunosorbent assay, employing Quantum Dot-Streptavidin conjugate (QDs-SA-FLISA), for efficient monitoring of IMI residues in agro-products. Under optimized conditions, the QDs-SA-FLISA exhibited a half-maximal inhibition concentration (IC50) of 1.70 ng/mL and a limit of detection (LOD, IC20) of 0.5 ng/mL. Investigation into the sensitivity enhancement effect of the QDs-SA revealed that the sensitivity (IC50) of the QDs-SA-FLISA was 7.3 times higher than that of ELISA. The recoveries and relative standard deviation (RSD) ranged from 81.7 to 118.1 % and 0.5-9.4 %, respectively, for IMI in brown rice, tomato and pear. There was no significant difference in IMI residues obtained between QDs-SA-FLISA and UHPLC-MS/MS. Thus, the QDs-SA-FLISA represents a reliable approach for the quantitative determination of IMI in agro-products.

Residue levels, processing factors and risk assessment of pesticides in ginger from market to table.

Ginger is consumed as a spice and medicine globally. However, pesticide residues in ginger and their residue changes during processing remain poorly understood. Our results demonstrate that clothianidin, carbendazim and imidacloprid were the top detected pesticides in 152 ginger samples with detection rates of 17.11-27.63%, and these pesticides had higher average residues of 44.07-97.63 µg/kg. Although most samples contained low levels of pesticides, 66.45% of the samples were detected with pesticides, and 38.82% were contaminated with 2-5 pesticides. Peeling, washing, boiling and pickling removed different amounts of pesticides from ginger (processing factor range: 0.06-1.56, most <1). By contrast, pesticide residues were concentrated by stir-frying and drying (0.50-6.45, most >1). Pesticide residues were influenced by pesticide physico-chemical parameters involving molecular weight, melting point, degradation point and octanol-water partition coefficient by different ginger processing methods. Chronic and acute dietary risk assessments suggest that dietary exposure to pesticides from ginger consumption was within acceptable levels for the general population. This study sheds light on pesticide residues in ginger from market to processing and is of theoretical and practical value for ensuring ginger quality and safety.

Comparative uptake, translocation and metabolism of phenamacril in crops under hydroponic and soil cultivation conditions.

Many studies investigate the plant uptake and metabolism of xenobiotics by hydroponic experiments, however, plants grown in different conditions (hydroponic vs. soil) may result in different behaviors. To explore the potential differences, a comparative study on the uptake, translocation and metabolism of the fungicide phenamacril in crops (wheat/rice) under hydroponic and soil cultivation conditions was conducted. During 7-14 days of exposure, the translocation factors (TFs) of phenamacril were greatly overestimated in hydroponic-wheat (3.6-5.2) than those in soil-wheat systems (1.1-2.0), with up to 3.3 times of difference between the two cultivation systems, implying it should be cautious to extrapolate the results obtained from hydroponic to field conditions. M-144 was formed in soil pore water (19.1-29.9 µg/L) in soil-wheat systems but not in the hydroponic solution in hydroponics; M-232 was only formed in wheat shoots (89.7-103.0 µg/kg) under soil cultivation conditions, however, it was detected in hydroponic solution (20.1-21.2 µg/L), wheat roots (146.8-166.0 µg/kg), and shoots (239.2-348.1 µg/kg) under hydroponic conditions. The root concentration factors (RCFs) and TFs of phenamacril in rice were up to 2.4 and 3.6 times higher than that in wheat for 28 days of the hydroponic exposure, respectively. These results highlighted that cultivation conditions and plant species could influence the fate of pesticides in crops, which should be considered to better assess the potential accumulation and transformation of pesticides in crops.

Gut microbiota-derived metabolites associate with circulating immune cell subsets in unexplained recurrent spontaneous abortion.

Currently, the precise causes of over 40 % of recurrent spontaneous abortion (RSA) cases cannot be identified, leading to the term "unexplained RSA" (URSA). Through an exploration of the gut microbiota, metabolites, and immune cell subsets in URSA, this study establishes a link between gut microbiota-derived metabolites and immune cells. The results indicate reduced diversity in the gut microbiota of URSA. Targeted metabolomic analyses reveal decreased levels of gut microbiota-derived deoxycholic acid (DCA), glycolithocholic acid (GLCA), acetate, propionate, and butyrate in URSA. Furthermore, elevated frequencies of Th1, Th17, and plasma B cells, along with decreased frequencies of Tregs and Bregs, are observed in the peripheral blood of URSA. The results demonstrate correlations between the levels of gut microbiota-derived bile acids and short-chain fatty acids and the frequencies of various immune cell subsets in circulation. Collectively, this study uncovers an association between gut microbiota-derived metabolites and circulating immune cell subsets in URSA.

Greenhouse cultivation enhances pesticide bioaccumulation in cowpeas following repeated spraying.

Understanding pesticide residue patterns in crops is important for ensuring human health. However, data on residue accumulation and distribution in cowpeas grown in the greenhouse and open field are lacking. Our results suggest that acetamiprid, chlorantraniliprole, cyromazine, and thiamethoxam residues in greenhouse cowpeas were 1.03-15.32 times higher than those in open field cowpeas. Moreover, repeated spraying contributed to the accumulation of pesticide residues in cowpeas. Clothianidin, a thiamethoxam metabolite, was detected at 1.04-86.00 µg/kg in cowpeas. Pesticide residues in old cowpeas were higher than those in tender cowpeas, and the lower half of the plants had higher pesticide residues than did the upper half. Moreover, pesticide residues differed between the upper and lower halves of the same cowpea pod. Chronic and acute dietary risk assessments indicated that the human health risk was within acceptable levels of cowpea consumption. Given their high residue levels and potential accumulation, pesticides in cowpeas should be continuously assessed.

Optimizing Analysis Methods: Rapid and Accurate Determination of Cuaminosulfate Residues with LC-MS/MS Based on Box-Behnken Design Study.

In view of the defects in the previous detection of cuaminosulfate, which only focused on the analysis of copper ions, there is currently no analysis method available to determine the actual state of cuaminosulfate as chelated or bound. In order to investigate the dissipation and terminal residues in soil and watermelon of cuaminosulfate for food safety and environmental risk, a highly effective technique was developed to detect cuaminosulfate residues in watermelon and soil, and field experiments were conducted in China. After single-factor experiments, residual cuaminosulfate in samples was extracted by pure water, purified using a liquid-liquid approach combined with a dispersive solid-phase extraction, and detected by liquid chromatography tandem mass spectrometry (LC-MS/MS). The Box-Behnken design (BBD) study was used to find the optimal solutions for the time of liquid-liquid purification, the amount of extraction solvent, and the amounts of cleanup sorbents for the analytical method. The average recovery of the method was in the range of 80.0% to 101.1%, the average relative standard deviation (RSD) was 5.3-9.9%, and the detection limit was lower than 0.05 mg/kg. The BBD study not only improved the extraction rate of the method, but also saved time and was operated easily. The final residues of cuaminosulfate in watermelon at different sampling intervals were all lower than 0.05 mg/kg under field conditions. The cuaminosulfate in soils dissipated following exponential kinetics, with half-life values in the range of 9.39 to 12.58 days, which varied by different locations. Based on the validated method, food safety residues and soil residues can be determined rapidly and accurately.

Pesticides in Greenhouse Airborne Particulate Matter: Occurrence, Distribution, Transformation Products, and Potential Human Exposure Risks.

Pesticides are frequently sprayed in greenhouses to ensure crop yields, where airborne particulate matter (PM) may serve as a carrier in depositing and transporting pesticides. However, little is known about the occurrence and fate of PM-borne pesticides in greenhouses. Herein, we examined the distribution, dissipation, and transformation of six commonly used pesticides (imidacloprid, acetamiprid, prochloraz, triadimefon, hexaconazole, and tebuconazole) in greenhouse PM (PM1, PM2.5, and PM10) after application as well as the associated human exposure risks via inhalation. During 35 days of experiment, the six pesticides were detected in all PM samples, and exhibited size- and time-dependent distribution characteristics, with the majority of them (>64.6%) accumulated in PM1. About 1.0-16.4% of initially measured pesticides in PM remained after 35 days, and a total of 12 major transformation products were elucidated, with six of them newly identified. The inhalation of PM could be an important route of human exposure to pesticides in the greenhouse, where the estimated average daily human inhalation dose (ADDinh) of the six individual pesticides was 2.1-1.2 × 104 pg/kg day-1 after application (1-35 days). Our findings highlight the occurrence of pesticides/transformation products in greenhouse PM, and their potential inhalation risks should be further concerned.

Glycolithocholic acid increases the frequency of circulating Tregs through constitutive androstane receptor to alleviate postmenopausal osteoporosis.

BACKGROUND AND PURPOSE: Gut microbiota and their metabolic activity are important regulators of host immunity. However, the role of gut microbiota and their metabolic activity-mediated osteoimmunity in postmenopausal osteoporosis (PMO) remains unknown. This study aimed to explore the role of gut microbiota and their metabolic activity in PMO. EXPERIMENTAL APPROACH: 16S rDNA sequencing was used for analyzing the gut microbiota diversity of patients with PMO and rat models, and a targeted metabolism study was performed for analyzing metabolite levels. Flow cytometry was used for analyzing the frequency of immune cells. Micro-CT was used for analyzing bone damage in rat models. Fecal microbiota transplantation was performed for exploring the therapeutic effect of the gut microbiota on PMO. CD4+ T cells were co-cultured with bone marrow mesenchymal stem cells for evaluating their molecular mechanisms. KEY RESULTS: Patients with PMO exhibited reduced gut microbiota diversity, and fecal glycolithocholic acid (GLCA) levels correlated with the degree of osteoporosis. GLCA levels in the gut were positively correlated with the frequency of circulating Tregs in ovariectomized rats. Restoration of the gut microbiota alleviated osteoporosis in ovariectomized rats. Circulating GLCA augmented CD4+ T cell differentiation into Tregs via constitutive androstane receptors. The increased frequency of Tregs further promoted the osteogenic differentiation of bone marrow mesenchymal stem cells to alleviate osteoporosis. CONCLUSION AND IMPLICATIONS: GLCA alleviated PMO by increasing the frequency of circulating Tregs, acting via the constitutive androstane receptor. This study reveals a new strategy for the treatment of PMO, with GLCA as a potential drug candidate.

Adsorption of acetochlor-contaminated water systems using novel P-doped biochar: Effects, application, and mechanism.

Given the serious threat of acetochlor (ACT) to the aquatic ecological environment, designing wastewater treatment-oriented adsorbents for the sustainable remediation of actual ACT-contaminated water is a promising yet challenging strategy. Herein, a novel P-doped biochar (PBC-800) with a high adsorption capacity (51.34 mg g-1) and a rapid reaction rate (47.35 mg g-1 h-1) for ACT was prepared through pyrolyzing of rice straw biomass pre-impregnated with potassium dihydrogen phosphate (KH2PO4). Additionally, P-doped biochars synthesized at different pyrolysis temperatures exhibited significant variations in ACT adsorption performance, which was mainly ascribed to the distinction between hydrophilicity and sp2 conjugate C (ID/IG = 0.84-1.08). The adsorption behavior of ACT on PBC-800 followed the Elovich kinetics and Freundlich adsorption isotherm models. Thermodynamic calculations indicated that the adsorption of ACT by PBC-800 was a spontaneously disordered decreasing exothermic process. Besides, PBC-800 exhibited a powerful anti-interference for ACT adsorption within complex water matrices, highlighting its potential for various of practical applications. Through characterization analysis and further experiments, it was proved that the excellent adsorption performance of PBC-800 on ACT was ascribed to a combination of physical and chemical adsorption mechanisms, including 57.5% pore filling, 23.4% hydrophobic interaction, 12.7% π-π interaction, and 6.4% hydrogen bonding. Moreover, PBC-800 exerted a prominent adhesion impact upon Gram-positive and negative bacteria at 3 h. This study offers a new idea for the utilization of agricultural residues and provides insights into the mechanism of ACT adsorption through its derived biochar.

Circ-Plod2 destabilizes Mpo mRNA by binding to IGF2BP2 to promote osteogenic differentiation of bone marrow mesenchymal stem cells.

Osteogenic differentiation, proliferation, and/or apoptosis of bone marrow mesenchymal stem cells (BMSCs) are involved in the progression of postmenopausal osteoporosis (PMO). However, circular RNA (circRNA)-mediated changes in the cellular function of BMSCs in PMO are still unclear. This study revealed the excellent ability of circ-Plod2 to promote osteogenic differentiation of BMSCs and its molecular mechanisms. In this study, ovariectomized (OVX) rats and control (Sham) rats were used to simulate PMO. Initially, we found that the expression of circ-Plod2 in OVX BMSCs is down-regulated and the expression of the Mpo gene is up-regulated by sequencing and verification. Further, we confirmed that circ-Plod2 is located in the cytoplasm and belongs to exon-type circRNA. Interestingly, circ-Plod2 promotes Mpo-dependent osteogenic differentiation of BMSCs without affecting proliferation, apoptosis, adipogenic differentiation, or chondrogenic differentiation of BMSCs. Mechanistically, we demonstrated that circ-Plod2 specifically binds IGF2BP2 to form an RNA-protein complex that destabilizes Mpo mRNA. Overexpression of circ-Plod2 in the bone marrow cavity effectively alleviated osteoporosis in OVX rats and inhibited the expression of MPO in BMSCs. Together, this study reveals that circ-Plod2 destabilizes Mpo mRNA by binding to IGF2BP2 to promote osteogenic differentiation of BMSCs to alleviate osteoporosis. The findings of this study may provide biomarkers for the diagnosis of PMO, and may also provide potential strategies for the clinical treatment of PMO.

Simultaneous determination of 27 pesticides in corn and cow matrices by ultra-performance liquid chromatography-tandem mass spectrometry.

In this paper, we developed a sensitive UPLC-MS/MS method to determine pesticide residues in plant matrices (corn, fresh corn, fresh corn stover, old corn stover, and corn silage) and animal matrices (beef, fat, milk, milk fat, kidney, liver, and cow stomach) quantitatively. Twenty-seven pesticides were extracted with acetonitrile from all plant and animal matrices separately and purified with a mixture of primary secondary amine (PSA) and graphitized carbon black (GCB) or octadecylsilane (C18). The average recoveries of these compounds ranged from 60.7% to 118.2%, and the relative standard deviations were less than 20.0%. The limit of quantitation for all compounds was 0.01 mg kg-1 (for cyhalothrin and beta cypermethrin the LOQ was 0.02 mg kg-1). The establishment of multi-residue analysis methods for a variety of matrices can be used as a database for future method research. The results of this study are essential for calculating the transfer of pesticide residues from feed to animal products and for monitoring food safety, which will protect people's health and safety.

The fate of mycotoxins in oranges during storage and processing.

To evaluate the safety of orange consumption induced by mycotoxins, 'Newhall' navel oranges were artificially inoculated with P. expansum and A. tenuissima, followed by an evaluation of the distribution and migration patterns of corresponding mycotoxins (patulin [PAT], tentoxin [Ten], altenuene [ALT], alternariol monomethyl ether [AME], alternariol [AOH] and tenuazonic acid [TeA]) during orange storage and processing. The concentration of mycotoxins decreased as the increase of distance from the lesion, and mycotoxins could be detected throughout the orange when the lesion extended to 8 mm in diameter. AOH and AME pose the primary source of dietary risk with high concentrations and low thresholds of toxicological concern. Orange juice and pectin processing could remove 43.4-98.7% of mycotoxins, while tangerine peelprocessing might lead to significant enrichment of mycotoxins with the processing factors (PFs) of 2.8-3.5. The findings may offer scientific insights into mitigating the dietary risk of mycotoxin exposure from oranges and their derivatives.

Effects of Fungicides and Nontarget Pesticides on Accumulation of the Mycotoxin Deoxynivlenol in Wheat.

Deoxynivalenol (DON) is an important virulence factor of the Fusarium head blight of wheat and threatens the health of humans. The effect of fungicides on DON production after stressing wheat to produce H2O2 and the effect of nontarget pesticides on DON accumulation are largely unknown. Five pesticides were selected to explore the effect of pesticide-induced oxidative stress on DON production in vitro and in vivo. Epoxiconazole and hexaconazole significantly induced an increase in H2O2 in vitro, and H2O2 further stimulated the production of DON and the expression of the Tri5 gene. Imidacloprid, isoproturon, and mesosulfuron-methyl had no direct effect in vitro. All pesticides activated the activities of superoxide dismutase, catalase, and peroxidase in wheat and caused the excessive accumulation of H2O2. However, excessive H2O2 did not stimulate the accumulation of DON. Imidacloprid indirectly stimulated the production of DON in vivo, which may be due to its impact on the secondary metabolism of wheat. In brief, pesticide-induced H2O2 in vitro is an important factor in stimulating DON production, but the stressed physiological H2O2 in wheat is not sufficient to stimulate DON production. The bioaccumulation results indicated that imidacloprid and epoxiconazole increase the risk of DON contamination, especially under field spraying conditions.

Bioavailability evaluation of epoxiconazole and difenoconazole in rice and the influence of dissolved organic matter in reducing uptake and translocation.

The aim of this study was to assess the bioavailability of epoxiconazole (EPO) and difenoconazole (DIF) in rice plants by evaluating their uptake, translocation, and accumulation. The results showed that the concentration of DIF in the roots was approximately three times higher than EPO, and both accumulated mainly in the roots. In addition, EPO continued to be transported from stems to leaves, causing a rise in its concentration in leaves. Contrastingly, only a minimal amount of DIF was transported to the leaves. This phenomenon is mainly governed by their differing octanol-water partition coefficient. The effects of dissolved organic carbon (DOC) on the accumulation of EPO and DIF in the roots were similar to those of the freely dissolved concentration measured by OECAMs. The concentrations of EPO and DIF in the roots and OECAMs consistently decreased with increasing DOC levels. Furthermore, a significant linear relationship was observed between the EPO and DIF concentrations in root and OECAMs. We also confirmed the accuracy and usefulness of the OECAMs method in predicting the bioavailability of EPO and DIF in rice roots. Therefore, OECAMs show good potential for use as a passive sampler to evaluate the bioavailability of EPO and DIF.

Bioavailability assessment of difenoconazole to earthworms (Eisenia fetida) in soil by oleic acid-embedded cellulose acetate membrane.

Passive sampling technology is widely used to evaluate the bioavailability of pollutants. However, relatively few studies have used passive sampling membranes (PSMs) to evaluate the environmental risks of pollutants in soil, particularly pesticides. Here, the bioavailability of difenoconazole to earthworms (Eisenia fetida) was evaluated using an oleic acid-embedded cellulose acetate membrane (OECAM) for the first time. Difenoconazole reached 94 % equilibrium (T94%) within 1 d in OECAM. For soil pore water, the freely dissolved concentration (Cfree) of difenoconazole was determined using OECAM (R2 = 0.969). In the soil system, a strong linear correlation between the difenoconazole concentration in OECAM and earthworms was observed (R2 = 0.913). The bioavailability of difenoconazole was affected by the soil type and biochar content. The higher the content of soil organic matter and biochar, the lower the concentration of difenoconazole in earthworms, OECAM, and soil pore water. The concentrations of difenoconazole in pore water, earthworms, and OECAM decreased by 65.3, 42.0, and 41.6 %, respectively, when 0.5 % biochar was added. Difenoconazole mainly enters OECAM and earthworms through passive diffusion with similar uptake pathways. Therefore, the bioavailability of difenoconazole to earthworms in different soils can be evaluated using the OECAM.

Rational understanding of chiral fungicide penthiopyrad stereoselectivity: Bioactivity, aquatic toxicity and cytotoxicity.

Penthiopyrad is a novel chiral succinate dehydrogenase inhibitor (SDHI) fungicide with two enantiomers. However, enantioselective information on the biological activity, nontarget organisms and human health risk of penthiopyrad is not comprehensive, which may cause inaccurate risk assessment. In this study, the enantioselective bioactivity to three kinds of phytopathogens (Rhizoctonia solani, Botrytis cinerea and Sclerotinia sclerotiorum) was first disclosed, and the antifungal activity of S-(+)-penthiopyrad was higher than that of R-(-)-penthiopyrad by 12-37 times. Moreover, its enantioselective toxicity to Raphidocelis subcapitata and Daphnia magna was also clarified, and the order of toxicity was S-(+)-penthiopyrad > rac-penthiopyrad >R-(-)-penthiopyrad, with 1.8- and 5.3-fold differences between the two enantiomers. Furthermore, the enantioselectivity of penthiopyrad on HepG2 cytotoxicity was studied. The data showed that the cytotoxicity of S-(+)-penthiopyrad was 1.8 times higher than that of R-(-)-penthiopyrad, and S-(+)-penthiopyrad had a stronger impact on cell proliferation, oxidative stress and lipid peroxidation. In summary, due to the enantioselectivity of the activity and toxicity of the chiral pesticide, the efficacy and risk evaluation of penthiopyrad should be considered at the enantiomer level.

Insight into the Long-Lasting Control Efficacy of Neonicotinoid Imidacloprid against Wheat Aphids during the Entire Growth Period.

Understanding the mechanism of long-lasting control efficacy of pesticides is important for developing sustainable high-efficacy pesticides, decreasing pesticide-use frequency and environmental input. This study investigates the long-term control mechanism of imidacloprid against wheat aphids under seed treatment. The concentrations of imidacloprid and its metabolites were 2.2-69.6 times lower than their individual LC50 after 238 days of treatment, and the control efficacy was still higher than 94.6%. The mixed bioactivity tests demonstrated that the insecticidal activity of the mixture of imidacloprid and its bioactive metabolites was approximately 1.5-189.7 times greater than that of a single compound against wheat aphids. The concentrations of imidacloprid, 5-hydroxy imidacloprid, and imidacloprid olefin in top flag leaves were 0.022, 0.084, and 0.034 mg/kg, respectively, during the aphid flourishing period, which were higher than the LC50 of the mixture (0.011 mg/kg), therefore providing long-lasting control efficacy. The study provides a first insight into the synergistic effects between a pesticide and its bioactive metabolites in ensuring long-term control performance.

Toxicity assessment of a novel biopesticide guvermectin and identification of its transformation products in soils.

Guvermectin is a novel biopesticide often used as seed soaking to promote the rice yield. However, its biotoxicity and degradation behavior in soils were still not disclosed, which posed a knowledge gap to guide its rational application. Therefore, the degradation behaviors of guvermectin in four typical soils under aerobic and anaerobic conditions were investigated in the laboratory. The results showed that guvermectin was degraded fast with DT50 ranging from 0.95 to 10.10 d, and the degradation rate was higher in aerobic condition than that in anaerobic condition. Eight transformation products were screened using UPLC-QTOF/MS. The acute toxicities tests of guvermectin to Coturnix coturnix japonica and Apis mellifera were measured by biological laboratory experiments, and the acute and chronic toxicities of transformation products to Danio rerio, Daphnia magna Straus and Green algae were predicted by ECOSAR software. The results showed that guvermectin has low toxic to quail and honeybee (LD50 2000 mg a.i./kg body weight, LD50 Ëƒ 100 µg a.i./bee), and its transformation products were also low toxic class to Danio rerio, Daphnia magna Straus and Green algae (LC50/EC50 > 100 mg a.i./L). However, the nucleoside-like metabolites may pose a potential risk due to their similarity to genetic material, which should be concerned. The findings provided important environmental risk assessment data for the rational use of guvermectin.

The role of miRNA-26a-5p and target gene socs1a in flutolanil induced hepatotoxicity of zebrafish at environmental relevant levels.

Flutolanil has been detected worldwide in aquatic environment and fish, which has become an undeniable stressor on ecosystem and human health. Flutolanil has been reported to be toxic to aquatic organisms. However, the pathophysiological and molecular mechanism behind the detrimental effects remains obscure. Here we reported hepatotoxicity induced by flutolanil in HepG2 cells and zebrafish, as revealed by toxicokinetic, HE staining, miRNAs-mRNAs sequencing, molecular dynamic simulations and dual luciferase reporter assays. Collectively, our results indicated that flutolanil could be absorbed by and accumulated in the liver of zebrafish, causing hepatic vacuolar degeneration, steatosis and nuclear condensation and abnormal liver function, where its exposure at environmental levels disrupted the expressions of miRNA-26a-5p and its target gene socs1a by mediating JAK-STAT signaling pathway, which was partially responsible for hepatotoxicity, correlated with oxidative stress, cell apoptosis, inflammation, cell cycle disorder and mitochondrial dysfunction. These findings suggest that miRNA-26a-5p/socs1a can serve as potential biomarkers of hepatotoxicity in zebrafish following exposure to flutolanil. This uncovered route will provide a new tool for the risk assessment of flutolanil and a guide to proper use of flutolanil and environmental remedy, and open up a new horizon for liver disease assessment.