Late gestational exposure to fenvalerate impacts ovarian reserve in neonatal mice via YTHDF2-mediated P-body assembly.

Fenvalerate (FEN), a type II pyrethroid pesticide, finds extensive application in agriculture, graziery and public spaces for pest control, resulting in severe environmental pollution. As an environmental endocrine disruptor with estrogen-like activity, exposure to FEN exhibited adverse effects on ovarian functions. Additionally, the presence of the metabolite of FEN in women's urine shows a positive association with the risk of primary ovarian insufficiency (POI). In mammals, the primordial follicle pool established during the early life serves as a reservoir for storing all available oocytes throughout the female reproductive life. The initial size of the primordial follicle pool and the rate of its depletion affect the occurrence of POI. Nevertheless, there is very limited research about the impact of FEN exposure on primordial folliculogenesis. In this study, pregnant mice were orally administrated with 0.2, 2.0 and 20.0 mg/kg FEN from 16.5 to 18.5 days post-coitus (dpc). Ovaries exposed to FEN exhibited the presence of large germ-cell cysts that persist on 1 days post-parturition (1 dpp), followed by a significant reduction in the total number of oocytes in pups on 5 dpp. Moreover, the levels of m6A-RNA and its associated proteins METTL3 and YTHDF2 were significantly increased in the ovaries exposed to FEN. The increased YTHDF2 promoted the assembly of the cytoplasmic processing bodies (P-body) in the oocytes, accompanied with altered expression of transcripts. Additionally, when YTHDF2 was knocked-down in fetal ovary cultures, the primordial folliculogenesis disrupted by FEN exposure was effectively restored. Further, the female offspring exposed to FEN displayed ovarian dysfunctions reminiscent of POI in early adulthood, characterized by decreases in ovarian coefficient and female hormone levels. Therefore, the present study revealed that exposure to FEN during late pregnancy disrupted primordial folliculogenesis by YTHDF2-mediated P-body assembly, causing enduring adverse effects on female fertility.

Cyfluthrin exposure during pregnancy causes neurotoxicity in offspring-Ca2+ overload via IP3R-GRP75-VDAC1 pathway.

Cyfluthrin (Cy) is a widely used pyrethroid insecticide. There is growing evidence that Cy can cause damage to the nervous, reproductive, and immune systems, but there is limited evidence on the potential effects of maternal Cy exposure on offspring. A model of maternal Cy exposure was used to assess its neurobehavioral effects on young-adult offspring. We found that gestational Cy exposure affected pregnancy outcomes and fetal development, and that offspring showed impairments in anxiety as well as learning and memory, accompanied by impairments in hippocampal synaptic ultrastructure and synaptic plasticity. In addition, the IP3R-GRP75-VDAC1 apoptogenic pathway was also upregulated, and in vitro models showed that inhibition of this pathway alleviated neuronal apoptosis as well as synaptic plasticity damage. In conclusion, maternal Cy exposure during pregnancy can cause neurobehavioral abnormalities and synaptic damage in offspring, which may be related to neuronal apoptosis induced by activation of the IP3R-GRP75-VDAC1 pathway in the hippocampus of offspring. Our findings provide clues to understand the neurotoxicity mechanism of maternal Cy exposure to offspring during pregnancy.

Bifenthrin induces changes in clinical poisoning symptoms, oxidative stress, DNA damage, histological characteristics, and transcriptome in Chinese giant salamander (Andrias davidianus) larvae.

Bifenthrin (BF) is a broad-spectrum insecticide that has gained widespread use due to its high effectiveness. However, there is limited research on the potential toxic effects of bifenthrin pollution on amphibians. This study aimed to investigate the 50 % lethal concentration (LC50) and safety concentration of Chinese giant salamanders (CGS) exposed to BF (at 0, 6.25,12.5,25 and 50 µg/L BF) for 96 h. Subsequently, CGS were exposed to BF (at 0, 0.04, and 4 µg/L BF) for one week to investigate its toxic effects. Clinical poisoning symptoms, liver pathology, oxidative stress factors, DNA damage, and transcriptome differences were observed and analyzed. The results indicate that exposure to BF at 4 µg/L significantly decreased the adenosine-triphosphate (ATP), superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) contents in the brain, liver, and kidney of CGS. Additionally, the study found that the malondialdehyde (MDA), reactive oxygen species (ROS), and 8-hydroxydeoxyguanosine (8-OHdG) contents were increased. The liver tissue exhibited significant inflammatory reactions and structural malformations. RNA-seq analysis of the liver showed that BF caused abnormal antioxidant indices of CGS. This affected molecular function genes such as catalytic activity, ATP-dependent activity, metabolic processes, signaling and immune system processes, behavior, and detoxification, which were significantly upregulated, resulting in the differential genes significantly enriched in the calcium signaling pathway, PPARα signaling pathway and NF-kB signaling pathway. The results suggest that BF induces the abnormal production of free radicals, which overwhelms the body's self-defense system, leading to varying degrees of oxidative stress. This can result in oxidative damage, DNA damage, abnormal lipid metabolism, autoimmune diseases, clinical poisoning symptoms, and tissue inflammation. This work provides a theoretical basis for the rational application of bifenthrin and environmental risk assessment, as well as scientific guidance for the conservation of amphibian populations.

Adverse effects of fenpropathrin on the intestine of common carp (Cyprinus carpio L.) and the mechanism involved.

Fenpropathrin (FEN), a pyrethroid pesticide, is frequently detected in natural water bodies, unavoidable pose adverse effects to aquatic organisms. However, the harmful effects and potential mechanisms of FEN on aquatic species are poorly understood. In this study, common carp were treatment with FEN at 0.45 and 1.35 µg/L for 14 d, and the toxic effects and underlying mechanisms of FEN on the intestine of carp were revealed. RNA-seq results showed that FEN exposure cause a wide range of transcriptional alterations in the intestine and the differentially expressed genes were mainly enrichment in the pathways related to immune and metabolism. Specifically, FEN exposure induced pathological damage and altered submicroscopic structure of the intestine, elevated the levels of Bacteroides fragilis enterotoxin, altered the contents of claudin-1, occludin, and zonula occluden-1 (ZO-1), and causing injury to the intestinal barrier. In addition, inflammation-related index TNF-α in the serum and IL-6 in the intestinal tissues were generally increased after FEN exposure. Moreover, FEN exposure promoted an increase in reactive oxygen species (ROS), altered the levels of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), upregulated the contents of malondialdehyde (MDA) in the intestines. The apoptosis-related parameter cytochrome c, caspase-9, and caspase-3 were significantly altered, indicating that inflammation reaction, oxidative stress, and apoptosis may be involved in the toxic mechanism of FEN on carp. Moreover, FEN treatment also altered the intestinal flora community significantly, which may affect the intestinal normal physiological function and thus affect the growth of fish. Overall, the present study help to clarify the intestinal reaction mechanisms after FEN treatment, and provide a basis for the risk assessment of FEN.

Understanding fenpropathrin-induced pulmonary toxicity: What apoptosis, inflammation, and pyreptosis reveal analyzing cross-links at the molecular, immunohistochemical, and immunofluorescent levels.

Fenpropathrin (FN), a pyrethroid has been linked to potential pulmonary toxic effects to humans via incident direct or indirect ingestion. Thus, we aimed to the investigate the underlying mechanisms of lung toxicity upon exposure to FN in the rat model, besides studying whether curcumin (CCM) and curcumin-loaded chitosan nanoformulation (CCM-Chs) can mitigate FN-induced lung damage. Six distinct groups, namely, control, CCM, CCM-Chs, FN, and CCM + FN, CCM-Chs + FN were assigned separately. The inflammatory, apoptotic, and oxidative stress states, histological, immunohistochemical, and immunofluorescence examination of different markers within the pulmonary tissue were applied. The results revealed that the FN-induced tissue damage might be caused by the oxidative stress induction and depressed antioxidant glutathione system in the lungs of rats. Furthermore, FN upregulated the expression of genes related to inflammation, and pyroptosis, and elevated the immunoreactivity of Caspase-3, tumor necrosis factor-α, vimentin, and 4-Hydroxynonenal in pulmonary tissues of FN-exposed rats compared to the control. CCM and CCM-Chs mitigated the FN-induced disturbances, while remarkably, CCM-Chs showed better potency than CCM in mitigating the FN-induced toxicity. In conclusion, this study shows the prominent preventive ability of CCM-Chs more than CCM in combatting the pulmonary toxicity induced by FN. This may be beneficial in developing therapeutic and preventive strategies against FN-induced pulmonary toxicity.

Effect of beta-cypermethrin on the reproductive capacity of female mice in advanced age.

The aim of the present study was to investigate whether exposure to pesticides beta-cypermethrin (ß-CYP) harms the reproductive capacity of advanced-age female mice. The results evidenced that peri-implantation ß-CYP exposure significantly reduced the number of fetuses per advanced-age female in the first litter, and the number and weight of implantation sites. The levels of decidualization markers were significantly reduced in ß-CYP-administered advanced-age mice. Lower expression of Pcna, Cdk6, Foxo1, Ki67, and p62 protein and mRNA was found in the decidua of ß-CYP-treated advanced-age mice. The levels of Bax, cleaved caspase-3, Lc3a/b, Atg, mTOR, and p-mTOR protein, and the ratio of p-mTOR/mTOR protein expression were clearly downregulated by peri-implantation ß-CYP exposure. These results indicated that peri-implantation ß-CYP exposure may elevate the decline in reproductive capacity of early pregnant mice in advanced age.

Fenpropathrin provoked kidney damage via controlling the NLRP3/Caspase-1/GSDMD-mediated pyroptosis: The palliative role of curcumin-loaded chitosan nanoparticles.

This study assessed the ability of formulated curcumin-loaded chitosan nanoparticles (CU-CS-NPs) to reduce the kidney damage resulting from fenpropathrin (FPN) in rats compared to curcumin (CU) in rats. Sixty male Sprague Dawley rats were separated into six groups and orally administered 1 mL/kg b.wt corn oil, 50 mg CU/kg b.wt, 50 mg CU-CS-NPs /kg b.wt., 15 mg FPN /kg b.wt, CU+ FPN or CU-CS-NPs + FPN for 60 days. Then, serum renal damage products were assessed. Total antioxidant capacity, reactive oxygen species, interleukin 1ß (IL-1ß), malondialdehyde, NF-κB P65, cleaved-Caspase-1, and Caspase-8 were estimated in kidney homogenates. The cleaved Caspase-3 and TNF-α immunoexpression and pyroptosis-related genes were determined in renal tissues. The results showed that CU-CS-NPS significantly repressed the FPN-induced increment in kidney damage products (urea, uric acid, and creatinine). Moreover, the FPN-associated hypo-proteinemia, renal oxidative stress and apoptotic reactions, and impaired renal histology were considerably repaired by CU and CU-CS-NPs. Additionally, compared to FPN-exposed rats, CU, and CU-CS-NPs-treated rats had considerably lower immunoexpression of cleaved Caspase-3 and TNF-α in renal tissue. The pyroptosis-related genes NLRP3, GSDMD, IL-18, Caspase-3, Caspase-1, IL-1ß, Caspase-8, TNF-α, and NF-κB dramatically upregulated by FPN exposure in the renal tissues. Yet, in CU and CU-CS-NPs-treated rats, the gene above expression deviations were corrected. Notably, CU-CS-NPs were superior to CU in preventing oxidative damage and inflammation and regulating pyroptosis in the renal tissues of the FPN-exposed group. The results of the present study conclusively showed the superior favorable effect of CU-CS-NPs in counteracting renal impairment linked to environmental pollutants.

Neurotoxicity of Pyrethroids in neurodegenerative diseases: From animals' models to humans' studies.

Neurodegenerative diseases are associated with diverse symptoms, both motor and mental. Genetic and environmental factors can trigger neurodegenerative diseases. Chemicals as pesticides are constantly used in agriculture and also domestically. In this regard, pyrethroids (PY), are a class of insecticides in which its main mechanism of action is through disruption of voltage-dependent sodium channels function in insects. However, in mammals, they can also induce oxidative stress and enzyme dysfunction. This review investigates the association between PY and neurodegenerative diseases as Alzheimer's, Huntington's, Parkinson's, Amyotrophic Lateral Sclerosis, and Autism in animal models and humans. Published works using specific and non-specific models for these diseases were selected. We showed a tendency toward the development and/or aggravating of these neurodegenerative diseases following exposure to PYs. In animal models, the biochemical mechanisms of the diseases and their interaction with the insecticides are more deeply investigated. Nonetheless, only a few studies considered the specific model for each type of disease to analyze the impacts of the exposure. The choice of a specific model during the research is an important step and our review highlights the knowledge gaps of PYs effects using these models reinforcing the importance of them during the design of the experiments.

Cypermethrin induces Sertoli cell apoptosis through endoplasmic reticulum-mitochondrial coupling involving IP3R1-GRP75-VDAC1.

A widely used type II pyrethroid pesticide cypermethrin (CYP) is one of endocrine disrupting chemicals (EDCs) with anti-androgenic activity to induce male reproductive toxicology. However, the mechanisms have not been fully elucidated. This study was to explore the effects of CYP on apoptosis of mouse Sertoli cells (TM4) and the roles of endoplasmic reticulum (ER)-mitochondria coupling involving 1,4,5-trisphosphate receptor type1-glucose-regulated protein 75-voltage-dependent anion channel 1 (IP3R1-GRP75-VDAC1). TM4 were cultured with different concentrations of CYP. Flow cytometry, calcium (Ca2+) fluorescent probe, transmission electron microscopy and confocal microscopy, and western blot were to examine apoptosis of TM4, mitochondrial Ca2+, ER-mitochondria coupling, and expressions of related proteins. CYP was found to increase apoptotic rates of TM4 significantly. CYP was shown to significantly increase expressions of cleaved caspase-3, cleaved poly ADP-ribose polymerase (PARP). Concentration of mitochondrial Ca2+ was increased by CYP treatment significantly. CYP significantly enhanced ER-mitochondria coupling. CYP was shown to increase expressions of IP3R, Grp75 and VDAC1 significantly. We suggest that CYP induces apoptosis in TM4 cells by facilitating mitochondrial Ca2+ overload regulated by ER-mitochondria coupling involving IP3R1-GRP75-VDAC1. This study identifies a novel mechanism of CYP-induced apoptosis in Sertoli cells.

Modulation in growth, oxidative stress, photosynthesis, and morphology reveals higher toxicity of alpha-cypermethrin than chlorpyrifos towards a non-target green alga at high doses.

Considering the frequent detection of pesticides in the aquatic environment, the ecotoxicological effects of Chlorpyrifos (CHP), an organophosphate, and alpha-cypermethrin (ACM), a pyrethroid, on freshwater microalgae were compared for the first time in this study. High concentrations of both CHP and ACM significantly suppressed the growth of test microalga Graesiella emersonii (p < 0.05). The 96-h EC50 of CHP and ACM were 54.42 mg L-1 and 29.40 mg L-1, respectively. Sub-inhibitory doses of both pesticides increased ROS formation in a concentration-dependent manner, which was accompanied by changes in antioxidant enzymes activities, lipid peroxidation, and variations in photosynthetic pigment concentration. Furthermore, both pesticides influenced photosystem II performance, oxygen-evolving complex efficiency and, intracellular ATP levels. Scanning electron microscopy analysis revealed that high concentrations of both CHP and ACM caused considerable morphological changes in the microalga. In comparison, CHP was more toxic than ACM at low concentrations, whereas ACM was more toxic at high concentrations.

Using an internal body residue approach to assess acute pesticide toxicity in juvenile Chinook salmon (Oncorhynchus tshawytscha).

The use of internal body residues has the potential to improve toxicological assessments of hydrophobic pesticides. The acute toxicity of three classes of pesticides were assessed in juvenile Chinook salmon using internal body residues. Chinook salmon were exposed to two current-use pesticides bifenthrin and fipronil, and 4,4'- dichlorodiphenyldichloroethylene (DDE), which is a degradation product of the legacy pesticide dichlorodiphenyltrichloroethane (DDT). After 96-h of aqueous exposure to each pesticide, the pesticide content in whole-body Chinook salmon homogenates was measured using gas chromatography/mass spectrometry with methane negative chemical ionization. The wet-weight (ww) normalized lethal residue at 50% mortality (LR50) was lowest for bifenthrin (0.654 nmol/g ww), followed by fipronil (7.17 nmol/g ww) and the sum of fipronil and its sulfone, sulfide, and desulfinyl degradation products (8.72 nmol/g ww). No lethality was observed for DDE, even at the highest body residue (>116 nmol/g ww). LR50 estimates were also normalized to dry weight and lipid content and compared to field-caught fish to assess risk. The use of a risk quotient approach indicated that bifenthrin imparts the highest risk of acute toxicity in juvenile Chinook salmon among the three pesticides tested. In comparison to external dose metrics, the use of internal body residues has the potential to improve risk assessment by providing a more direct link between pesticide concentration at the receptor site and toxicological effects.

Metabolomic analysis of the serum and urine of rats exposed to diazinon, dimethoate, and cypermethrin alone or in combination.

BACKGROUND: Multiple pesticides are often used in combination for plant protection and public health. Therefore, it is important to analyze the physiological changes induced by multiple pesticides exposure. The objective of this study was to investigate the combined toxicity of the widely-used organophosphorus and pyrethroid pesticides diazinon, dimethoate, and cypermethrin. METHODS: Male Wistar rats were administrated by gavage once daily with the three pesticides individual or in combination for consecutive 28 days. The metabolic components of serum and urine samples were detected by using 1H nuclear magnetic resonance (NMR)-based metabolomics method. Histopathological examination of liver and kidneys and serum biochemical determination were also carried out. RESULTS: The results showed that after the 28-day subacute exposure, serum glutamic transaminase and albumin were significantly increased and blood urea nitrogen was significantly decreased in the rats exposed to the mixture of the pesticides compared with the control rats, suggesting that the co-exposure impaired liver and kidney function. Metabolomics analysis indicated that the indicators 14 metabolites were statistically significant altered in the rats after the exposure of the pesticides. The increase in 3-hydroxybutyric acid in urine or decrease of lactate and N-acetyl-L-cysteine in serum could be a potentially sensitive biomarker of the subchronic combined effects of the three insecticides. The reduction level of 2-oxoglutarate and creatinine in urine may be indicative of dysfunction of liver and kidneys. CONCLUSION: In summary, the exposure of rats to pesticides diazinon, dimethoate, and cypermethrin could cause disorder of lipid and amino acid metabolism, induction of oxidative stress, and dysfunction of liver and kidneys, which contributes to the understanding of combined toxic effects of the pesticides revealed by using the metabolomics analysis of the urine and serum profiles.

The crosstalk between Toll and AMPK signaling pathways mediates growth inhibition of Eriocheir sinensis under deltamethrin stress.

Hepatopancreatic necrosis disease (HPND) broke out in 2015 in the Eriocheir sinensis aquaculture region of Xinghua, Jiangsu Province; however, the specific cause of HPND remains unclear. A correlation was found between HPND outbreak and the use of deltamethrin by farmers. In this study, E. sinensis specimens developed the clinical symptoms of HPND after 93 days of deltamethrin stress. The growth of E. sinensis with HPND was inhibited. Adenosine monophosphate-activated protein kinase (AMPK) is a central regulator of energy homeostasis, and its expression was up-regulated in the intestine of E. sinensis with HPND. Growth inhibitory genes (EsCabut, Es4E-BP, and EsCG6770) were also up-regulated in the intestine of E. sinensis with HPND. The expression levels of EsCabut, Es4E-BP, and EsCG6770 decreased after EsAMPK knockdown. Therefore, AMPK mediated the growth inhibition of E. sinensis with HPND. Further analysis indicated the presence of a crosstalk between the Toll and AMPK signaling pathways in E. sinensis with HPND. Multiple genes in the Toll signaling pathway were upregulated in E. sinensis under 93 days of deltamethrin stress. EsAMPK and its regulated growth inhibition genes were down-regulated after the knockdown of genes in the Toll pathway. In summary, the crosstalk between the Toll and AMPK signaling pathways mediates the growth inhibition of E. sinensis under deltamethrin stress.

Multigenerational, Indirect Exposure to Pyrethroids Demonstrates Potential Compensatory Response and Reduced Toxicity at Higher Salinity in Estuarine Fish.

Estuarine environments are critical to fish species and serve as nurseries for developing embryos and larvae. They also undergo daily fluctuations in salinity and act as filters for pollutants. Additionally, global climate change (GCC) is altering salinity regimes within estuarine systems through changes in precipitation and sea level rise. GCC is also likely to lead to an increased use of insecticides to prevent pests from damaging agricultural crops as their habitats and mating seasons change from increased temperatures. This underscores the importance of understanding how insecticide toxicity to fish changes under different salinity conditions. In this study, larval Inland Silversides (Menidia beryllina) were exposed to bifenthrin (1.1 ng/L), cyfluthrin (0.9 ng/L), or cyhalothrin (0.7 ng/L) at either 6 or 10 practical salinity units (PSU) for 96 h during hatching, with a subset assessed for end points relevant to neurotoxicity and endocrine disruption by testing behavior, gene expression of a select suite of genes, reproduction, and growth. At both salinities, directly exposed F0 larvae were hypoactive relative to the F0 controls; however, the indirectly exposed F1 larvae were hyperactive relative to the F1 control. This could be evidence of a compensatory response to environmentally relevant concentrations of pyrethroids in fish. Effects on development, gene expression, and growth were also observed. Overall, exposure to pyrethroids at 10 PSU resulted in fewer behavioral and endocrine disruptive effects relative to those observed in organisms at 6 PSU.

Exposure to organophosphate, pyrethroid, and neonicotinoid insecticides and dyslexia: Association with oxidative stress.

Organophosphates (OPPs), pyrethroids (PYRs), and neonicotinoids (NNIs) are three major classes of insecticides used worldwide. They might compromise child neurodevelopment. However, few studies have explored the association between exposure to them and dyslexia. The present study aimed to investigate the association between dyslexia and exposure to the three classes of insecticides, as well as explore the potential role of oxidative stress in the association. A total of 355 dyslexic children and 390 controls were included in this study. The exposure biomarkers were determined by liquid chromatography-tandem mass spectrometry. Specifically, the exposure biomarkers included three typical metabolites of OPPs, three of PYRs, and nine of NNIs. Additionally, three typical oxidative stress biomarkers, namely, 8-hydroxy-2'-deoxyguanosine (8-OHdG) for DNA damage, 8-hydroxyguanosine (8-OHG) for RNA damage, and 4-hydroxy-2-nonenal-mercapturic acid (HNEMA) for lipid peroxidation were measured. The detection frequencies of the urinary biomarkers ranged from 83.9% to 100%. Among the target metabolites of the insecticides, a significant association was observed between urinary 3,5,6-trichloro-2-pyridinol (TCPy, the metabolite of chlorpyrifos, an OPP insecticide) and dyslexia. After adjusting for potential confounding variables, children in the highest quartile of TCPy levels had an increased odds of dyslexia (odds ratio [OR], 1.68; 95% confidence interval [CI]: 1.03, 2.75] in comparison to those in the lowest quartile. Among the three oxidative stress biomarkers, urinary HNEMA concentration showed a significant relationship with dyslexia. Children in the highest quartile of HNEMA levels demonstrated an increased dyslexic odds in comparison to those in the lowest quartile after multiple adjustments (OR, 1.64; 95% CI: 1.01, 2.65). Mediation analysis indicated a significant effect of HNEMA in the association between urinary TCPy and dyslexia, with an estimate of 17.2% (P < 0.01). In conclusion, this study suggested the association between urinary TCPy and dyslexia. The association could be attributed to lipid peroxidation partially.

Downregulation of Ambra1 by altered DNA methylation exacerbates dopaminergic neuron damage in a fenpropathrin-induced Parkinson-like mouse model.

Fenpropathrin (Fen), a volatile pyrethroid insecticide, is used widely for agricultural applications and has been reported to increase the risk of Parkinson's disease (PD). However, the molecular basis, underlying mechanisms, and pathophysiology of Fen-exposed Parkinsonism remain unknown. Recent studies have revealed epigenetic mechanisms underlying PD-related pathway regulation, including DNA methylation. Epigenetic mechanisms are potential targets for therapeutic intervention in neurodegenerative diseases. After whole-genome bisulfite sequencing (WGBS) of midbrain tissues from a Fen-exposed PD-like mouse model, we performed an association analysis of DNA methylation and gene expression. Then we successfully screened for the DNA methylation differential gene Ambra1, which is closely related to PD. The hypermethylation-low expression Ambra1 gene aggravated DA neuron damage in vitro and in vivo through the Ambra1/Parkin/LC3B-mediated mitophagy pathway. We administered 5-aza-2'-deoxycytidine (5-Aza-dC) to upregulate Ambra1 expression, thereby reducing Ambra1-mediated mitophagy and protecting DA neurons against Fen-induced damage. In conclusion, these findings elucidate the potential function of Ambra1 under the regulation of DNA methylation, suggesting that the inhibition of DNA methylation may alleviate Fen-exposed neuron damage.

Biomarker responses and lethal dietary doses of tau-fluvalinate and coumaphos in honey bees: Implications for chronic acaricide toxicity.

Evidence suggests that acaricide residues, such as tau-fluvalinate and coumaphos, are very prevalent in honey bee colonies worldwide. However, the endpoints and effects of chronic oral exposure to these compounds remain poorly understood. In this study, we calculated LC50 and LDD50 endpoints for coumaphos and tau-fluvalinate, and then evaluated in vivo and in vitro effects on honey bees using different biomarkers. The LDD50 values for coumaphos were 0.539, and for tau-fluvalinate, they were 12.742 in the spring trial and 8.844 in the autumn trial. Chronic exposure to tau-fluvalinate and coumaphos resulted in significant changes in key biomarkers, indicating potential neurotoxicity, xenobiotic biotransformation, and oxidative stress. The Integrated Biomarker Response was stronger for coumaphos than for tau-fluvalinate, supporting their relative lethality. This study highlights the chronic toxicity of these acaricides and presents the first LDD50 values for tau-fluvalinate and coumaphos in honey bees, providing insights into the risks faced by colonies.

JH degradation pathway participates in hormonal regulation of larval development of Bombyx mori following λ-cyhalothrin exposure.

λ-Cyhalothrin (λ-cyh), a widely utilized pyrethroid insecticide, poses serious threats to non-target organisms due to its persistence nature in the environment. Exposure to low concentrations of λ-cyh has been observed to result in prolonged larval development in Bombyx mori, leading to substantial financial losses in sericulture. The present study was undertaken to elucidate the underlying mechanisms for prolonged development caused by λ-cyh (LC10) exposure. The results showed that the JH Ⅲ titer was significantly increased at 24 h of λ-cyh exposure, and the JH interacting genes Methoprene-tolerant 2, Steroid Receptor Co-activator, Krüppel-homolog 1, and JH binding proteins were also up-regulated. Although the target of rapamycin (Tor) genes were induced by λ-cyh, the biosynthesis of JH in the corpora allata was not promoted. Notably, 13 JH degradation genes were found to be significantly down-regulated in the midgut of B. mori. The mRNA levels and enzyme activity assays indicated that λ-cyh had inhibitory effects on JH esterase, JH epoxide hydrolase, and JH diol kinase (JHDK). Furthermore, the suppression of JHDK (KWMTBOMO01580) was further confirmed by both western blot and immunohistochemistry. This study has offered a comprehensive perspective on the mechanisms underlying the prolonged development caused by insecticides, and our results also hold significant implications for the safe production of sericulture.