Unravelling nicotinic receptor and ligand features underlying neonicotinoid knockdown actions on the malaria vector mosquito Anopheles gambiae.

With the spread of resistance to long-established insecticides targeting Anopheles malaria vectors, understanding the actions of compounds newly identified for vector control is essential. With new commercial vector-control products containing neonicotinoids under development, we investigate the actions of 6 neonicotinoids (imidacloprid, thiacloprid, clothianidin, dinotefuran, nitenpyram and acetamiprid) on 13 Anopheles gambiae nicotinic acetylcholine receptor (nAChR) subtypes produced by expression of combinations of the Agα1, Agα2, Agα3, Agα8 and Agß1 subunits in Xenopus laevis oocytes, the Drosophila melanogaster orthologues of which we have previously shown to be important in neonicotinoid actions. The presence of the Agα2 subunit reduces neonicotinoid affinity for the mosquito nAChRs, whereas the Agα3 subunit increases it. Crystal structures of the acetylcholine binding protein (AChBP), an established surrogate for the ligand-binding domain, with dinotefuran bound, shows a unique target site interaction through hydrogen bond formation and CH-N interaction at the tetrahydrofuran ring. This is of interest as dinotefuran is also under trial as the toxic element in baited traps. Multiple regression analyses show a correlation between the efficacy of neonicotinoids for the Agα1/Agα2/Agα8/Agß1 nAChR, their hydrophobicity and their rate of knockdown of adult female An. gambiae, providing new insights into neonicotinoid features important for malaria vector control.

Changes in the proteome of Apis mellifera acutely exposed to sublethal dosage of glyphosate and imidacloprid.

Uncontrolled use of pesticides has caused a dramatic reduction in the number of pollinators, including bees. Studies on the effects of pesticides on bees have reported effects on both metabolic and neurological levels under chronic exposure. In this study, variations in the differential expression of head and thorax-abdomen proteins in Africanized A. mellifera bees treated acutely with sublethal doses of glyphosate and imidacloprid were studied using a proteomic approach. A total of 92 proteins were detected, 49 of which were differentially expressed compared to those in the control group (47 downregulated and 2 upregulated). Protein interaction networks with differential protein expression ratios suggested that acute exposure of A. mellifera to sublethal doses of glyphosate could cause head damage, which is mainly associated with behavior and metabolism. Simultaneously, imidacloprid can cause damage associated with metabolism as well as, neuronal damage, cellular stress, and impairment of the detoxification system. Regarding the thorax-abdomen fractions, glyphosate could lead to cytoskeleton reorganization and a reduction in defense mechanisms, whereas imidacloprid could affect the coordination and impairment of the oxidative stress response.

Acute toxicity of the fungicide captan to honey bees and mixed evidence for synergism with the insecticide thiamethoxam.

Honey bees are commonly co-exposed to pesticides during crop pollination, including the fungicide captan and neonicotinoid insecticide thiamethoxam. We assessed the impact of exposure to these two pesticides individually and in combination, at a range of field-realistic doses. In laboratory assays, mortality of larvae treated with captan was 80-90% greater than controls, dose-independent, and similar to mortality from the lowest dose of thiamethoxam. There was evidence of synergism (i.e., a non-additive response) from captan-thiamethoxam co-exposure at the highest dose of thiamethoxam, but not at lower doses. In the field, we exposed whole colonies to the lowest doses used in the laboratory. Exposure to captan and thiamethoxam individually and in combination resulted in minimal impacts on population growth or colony mortality, and there was no evidence of synergism or antagonism. These results suggest captan and thiamethoxam are each acutely toxic to immature honey bees, but whole colonies can potentially compensate for detrimental effects, at least at the low doses used in our field trial, or that methodological differences of the field experiment impacted results (e.g., dilution of treatments with natural pollen). If compensation occurred, further work is needed to assess how it occurred, potentially via increased queen egg laying, and whether short-term compensation leads to long-term costs. Further work is also needed for other crop pollinators that lack the social detoxification capabilities of honey bee colonies and may be less resilient to pesticides.

6-shogaol against 3-Nitropropionic acid-induced Huntington's disease in rodents: Based on molecular docking/targeting pro-inflammatory cytokines/NF-κB-BDNF-Nrf2 pathway.

BACKGROUND: Huntington's disease (HD) is an extremely harmful autosomal inherited neurodegenerative disease. Motor dysfunction, mental disorder, and cognitive deficits are the characteristic features of this disease. The current study examined whether 6-shogaol has a protective effect against 3-Nitropropionic Acid (3-NPA)-induced HD in rats. METHODS: A total of thirty male Wistar rats received 6-shogaol (10 and 20 mg/kg, per oral) an hour before injection of 3-NPA (10 mg/kg i.p.) for 15 days. Behavioral tests were performed, including narrow beam walk, rotarod test, and grip strength test. Biochemical tests promoting oxidative stress were evaluated [superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT) and malondialdehyde (MDA)], including changes to neurotransmitters serotonin (5-HT), dopamine (DA), norepinephrine (NE), homovanillic acid (HVA), (3,4-dihydroxyphenylacetic acid (DOPAC), γ-aminobutyric acid (GABA), and 5-hydroxy indole acetic acid (5-HIAA), nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), interleukins-1ß (IL-1ß), IL-6, brain-derived neurotrophic factor (BDNF), and nuclear factor erythroid 2-related factor 2 (Nrf2). The 6-shogaol was docked to the active site of TNF-α (2AZ5), NF-κB (1SVC), BDNF) [1B8M], and Nrf2 [5FZN] proteins using AutoDock tools. RESULTS: The 6-shogaol group significantly improved behavioral activity over the 3-NPA-injected control rats. Moreover, 3-NPA-induced significantly altered neurotransmitters, biochemical and neuroinflammatory indices, which could efficiently be reversed by 6-shogaol. The 6-shogaol showed favorable negative binding energies at -9.271 (BDNF) kcal/mol. CONCLUSIONS: The present investigation demonstrated the neuroprotective effects of 6-shogaol in an experimental animal paradigm against 3-NPA-induced HD in rats. The suggested mechanism is supported by immunohistochemical analysis and western blots, although more research is necessary for definite confirmation.

Development of nitroalkene-based inhibitors to target STING-dependent inflammation.

Stimulator of Interferon Genes (STING) is essential for the inflammatory response to cytosolic DNA. Despite that aberrant activation of STING is linked to an increasing number of inflammatory diseases, the development of inhibitors has been challenging, with no compounds in the pipeline beyond the preclinical stage. We previously identified endogenous nitrated fatty acids as novel reversible STING inhibitors. With the aim of improving the specificity and efficacy of these compounds, we developed and tested a library of nitroalkene-based compounds for in vitro and in vivo STING inhibition. The structure-activity relationship study revealed a robustly improved electrophilicity and reduced degrees of freedom of nitroalkenes by conjugation with an aromatic moiety. The lead compounds CP-36 and CP-45, featuring a ß-nitrostyrene moiety, potently inhibited STING activity in vitro and relieved STING-dependent inflammation in vivo. This validates the potential for nitroalkene compounds as drug candidates for STING modulation to treat STING-driven inflammatory diseases, providing new robust leads for preclinical development.

Elucidating the Gas-Phase Behavior of Nitazene Analog Protomers Using Structures for Lossless Ion Manipulations Ion Mobility-Orbitrap Mass Spectrometry.

2-Benzylbenzimidazoles, or "nitazenes", are a class of novel synthetic opioids (NSOs) that are increasingly being detected alongside fentanyl analogs and other opioids in drug overdose cases. Nitazenes can be 20× more potent than fentanyl but are not routinely tested for during postmortem or clinical toxicology drug screens; thus, their prevalence in drug overdose cases may be under-reported. Traditional analytical workflows utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS) often require additional confirmation with authentic reference standards to identify a novel nitazene. However, additional analytical measurements with ion mobility spectrometry (IMS) may provide a path toward reference-free identification, which would greatly accelerate NSO identification rates in toxicology laboratories. Presented here are the first IMS and collision cross section (CCS) measurements on a set of fourteen nitazene analogs using a structures for lossless ion manipulations (SLIM)-orbitrap MS. All nitazenes exhibited two high intensity baseline-separated IMS distributions, which fentanyls and other drug and druglike compounds also exhibit. Incorporating water into the electrospray ionization (ESI) solution caused the intensities of the higher mobility IMS distributions to increase and the intensities of the lower mobility IMS distributions to decrease. Nitazenes lacking a nitro group at the R1 position exhibited the greatest shifts in signal intensities due to water. Furthermore, IMS-MS/MS experiments showed that the higher mobility IMS distributions of all nitazenes possessing a triethylamine group produced fragment ions with m/z 72, 100, and other low intensity fragments while the lower mobility IMS distributions only produced fragment ions with m/z 72 and 100. The IMS, solvent, and fragmentation studies provide experimental evidence that nitazenes potentially exhibit three gas-phase protomers. The cyclic IMS capability of SLIM was also employed to partially resolve four sets of structurally similar nitazene isomers (e.g., protonitazene/isotonitazene, butonitazene/isobutonitazene/secbutonitazene), showcasing the potential of using high-resolution IMS separations in MS-based workflows for reference-free identification of emerging nitazenes and other NSOs.

Oleic acid reduces oxidative stress in rat brain induced by some anticancer drugs.

Oleic acid (OA) is a monounsaturated compound with many health-benefitting properties such as obesity prevention, increased insulin sensitivity, antihypertensive and immune-boosting properties, etc. The aim of this study was to analyze the effect of oleic acid (OA) and some anticancer drugs against oxidative damage induced by nitropropionic acid (NPA) in rat brain. Six groups of Wistar rats were treated as follows: Group 1, (control); group 2, OA; group 3, NPA + OA; group 4, cyclophosphamide (CPP) + OA; group 5, daunorubicin (DRB) + OA; and group 6, dexrazoxane (DXZ) + OA. All compounds were administered intraperitoneally route, every 24 h for 5 days. Their brains were extracted to measure lipoperoxidation (TBARS), H2O2, Ca+2, Mg+2 ATPase activity, glutathione (GSH) and dopamine. Glucose, hemoglobin and triglycerides were measured in blood. In cortex GSH increased in all groups, except in group 2, the group 4 showed the highest increase of this biomarker. TBARS decrease, and dopamine increase in all regions of groups 4, 5 and 6. H2O2 increased only in cerebellum/medulla oblongata of group 5 and 6. ATPase expression decreased in striatum of group 4. Glucose increased in group 6, and hemoglobin increased in groups 4 and 5. These results suggest that the increase of dopamine and the antioxidant effect of oleic acid administration during treatment with oncologic agents could result in less brain injury.

Biological Activity of Complexes Involving Nitro-Containing Ligands and Crystallographic-Theoretical Description of 3,5-DNB Complexes.

Drug resistance in infectious diseases developed by bacteria and fungi is an important issue since it is necessary to further develop novel compounds with biological activity that counteract this problem. In addition, new pharmaceutical compounds with lower secondary effects to treat cancer are needed. Coordination compounds appear to be accessible and promising alternatives aiming to overcome these problems. In this review, we summarize the recent literature on coordination compounds based on nitrobenzoic acid (NBA) as a ligand, its derivatives, and other nitro-containing ligands, which are widely employed owing to their versatility. Additionally, an analysis of crystallographic data is presented, unraveling the coordination preferences and the most effective crystallization methods to grow crystals of good quality. This underscores the significance of elucidating crystalline structures and utilizing computational calculations to deepen the comprehension of the electronic properties of coordination complexes.

Temporal and spatial trends of imidacloprid-related hazards in France.

Neonicotinoids are the top-selling insecticides worldwide. Because of their method of use, mainly to coat seeds, neonicotinoids have been found to widely contaminate the environment. Their high toxicity has been shown to be a major concern in terms of impact on biodiversity, and the use of these insecticides has been associated with population declines of species in different countries. Despite the widespread recognition of the risk of neonicotinoids to biodiversity, their temporal and spatial use remains poorly known in many countries. Yet this information is essential to address the potential impacts of these pesticides on biodiversity and to inform measures to establish protected areas or biodiversity restoration. The present study relied a large publicly available dataset to characterise the temporal and spatial use in France of imidacloprid, the most widely used neonicotinoid worldwide, as well as analysed water contamination surveys between 2005 and 2022 to assess the contamination of the environment. The results show that imidacloprid was the main neonicotinoid used in France over the study period. This use was spatially structured, with higher use in northern and western France, particularly related to cereal and beet crops area. The water contamination survey indicated that imidacloprid has widely contaminated the environment and consequently increased the risk to biodiversity, especially in counties crossed by the Loire, Seine and Vilaine rivers. This risk increased between 2005 and 2018 due to the higher use of imidacloprid and decreased sharply after 2018 due to its ban, although it was reauthorized by derogation for sugar beet in 2021. This study is the first assessment of imidacloprid pressure on biodiversity in France and shows the spatial and temporal correlation between agricultural practices and the freshwater contamination level. These results will help to identify priority areas for mitigation and restoration measures.

Maleic anhydride-functionalized cellulose nanocrystal-stabilized high internal phase Pickering emulsion for pesticide delivery.

The salt-responsiveness of Pickering emulsions has significantly influenced their applications due to the large amount of salt on the surface of plant leaves. The present study provided a maleic anhydride-functionalized cellulose nanocrystal-stabilized high internal phase Pickering emulsion (MACNCs-HIPPEs) that was stable to high-concentration salt and used for pesticide delivery. The stability of MACNCs-HIPPEs was investigated by adjusting the oil-phase volume fraction (φ), the MACNCs concentration, NaCl dosages, and the rheological properties. The high internal phase Pickering emulsion was obtained at φ of 0.8 and MACNCs concentration of 2wt% and showed excellent salt stability (NaCl, 1200 mM) and significant storage stability (60 days). The sustained release of imidacloprid (IMI) from imidacloprid-loaded MACNCs-HIPPEs (IMI@MACNCs-HIPPEs) showed a positive correlation to the temperature (15°C, 25°C, 35°C), indicating clear thermo-responsiveness of the prepared pesticide formulation. The test of spread and retention of IMI@MACNCs-HIPPEs on the leaf surface showed a significant advantage compared with the commercial IMI water dispersible granules (CG). All the advantages mentioned above showed the excellent potential of the MACNCs-HIPPEs in delivering lipophilic pesticides.

Impact of imidacloprid exposure on gestational hyperglycemia: A multi-omics analysis.

Imidacloprid (IMI), a commonly utilized neonicotinoid insecticide, has been identified to adversely impact glucose homeostasis. Pregnant women are believed to be more sensitive to toxins than non-pregnant women, and the impact of IMI exposure on gestational hyperglycemia remain unclear. To explore the impact, pregnant mice fed a high-fat diet were exposed to different doses (0.06, 0.6, 6 mg/kg bw/day) of IMI by gavage. Glucose homeostasis-related parameters were measured. The glucose homeostasis influenced by IMI treatment was explored through integrating gut microbiota, metabolomic and transcriptomic analysis. Results showed that IMI-H (6 mg/kg bw/day) exposure notably restricted gestational weight gain and perturbed glucose homeostasis characterized by reduced glucose tolerance and insulin sensitivity, alongside elevated levels of fasting blood glucose and insulin. Multi-omics analysis revealed that IMI-H exposure induced significant changes in the richness and composition of the gut microbiome. The metabolite profiles of serum samples and cecal contents, and transcriptome of liver and ileum were all affected by IMI-H treatment. The altered gut microbiota, metabolites and genes exhibited significant correlations with glucose homeostasis-related parameters. These differential metabolites and genes were implicated in various metabolic pathways including bile secretion, glucagon signaling pathway, lipid metabolism, fatty acid metabolism. Significant correlations were observed between the altered gut microbiota and caecum metabolome as well as liver transcriptome. For example, the abundance of Oscillibacter was strongly correlated with gut microflora-related metabolites (Icosenoic acid, Lysosulfatide, and fluticasone) and liver differential genes (Grin3b, Lifr, and Spta1). Together, IMI exposure resulted in significant changes in microbial composition, along with alterations in certain metabolites and genes associated with metabolic process, which may promote gestational hyperglycemia.

Thermal adaptation affects the temperature-dependent toxicity of the insecticide imidacloprid to soil invertebrates.

Terrestrial ectotherms are vulnerable to climate change since their biological rates depend on the ambient temperature. As temperature may interact with toxicant exposure, climate change may cause unpredictable responses to toxic stress. A population's thermal adaptation will impact its response to temperature change, but also to interactive effects from temperature and toxicants, but these effects are still not fully understood. Here, we assessed the combined effects of exposure to the insecticide imidacloprid across the temperatures 10-25 °C of two populations of the Collembola Hypogastrura viatica (Tullberg, 1872), by determining their responses in multiple life history traits. The con-specific populations differ considerably in thermal adaptations; one (arctic) is a temperature generalist, while the other (temperate) is a warm-adapted specialist. For both populations, the sub-lethal concentrations of imidacloprid became lethal with increasing temperature. Although the thermal maximum is higher for the warm-adapted population, the reduction in survival was stronger. Growth was reduced by imidacloprid in a temperature-dependent manner, but only at the adult life stage. The decrease in adult body size combined with the absence of an effect on the age at first reproduction suggests a selection on the timing of maturation. Egg production was reduced by imidacloprid in both populations, but the negative effect was only dependent on temperature in the warm-adapted population, with no effect at 10 °C, and decreases of 41 % at 15 °C, and 74 % at 20 °C. For several key traits, the population best adapted to utilize high temperatures was also the most sensitive to toxic stress at higher temperatures. It could be that by allocating more energy to faster growth, development, and reproduction at higher temperatures, the population had less energy for maintenance, making it more sensitive to toxic stress. Our findings demonstrate the need to take into account a population's thermal adaptation when assessing the interactive effects between temperature and other stressors.

Enantioselective toxicity of the neonicotinoid dinotefuran on honeybee (Apis mellifera) larvae.

The threat of neonicotinoids to insect pollinators, particularly honeybees (Apis mellifera), is a global concern, but the risk of chiral neonicotinoids to insect larvae remains poorly understood. In the current study, we evaluated the acute and chronic toxicity of dinotefuran enantiomers to honeybee larvae in vitro and explored the mechanism of toxicity. The results showed that the acute median lethal dose (LD50) of S-dinotefuran to honeybee larvae was 30.0 µg/larva after oral exposure for 72 h, which was more toxic than rac-dinotefuran (92.7 µg/larva) and R-dinotefuran (183.6 µg/larva). Although the acute toxicity of the three forms of dinotefuran to larvae was lower than that to adults, chronic exposure significantly reduced larval survival, larval weight, and weight of newly emerged adults. Analysis of gene expression and hormone titer indicated that dinotefuran affects larval growth and development by interfering with nutrient digestion and absorption and the molting system. Analysis of hemolymph metabolome further revealed that disturbances in the neuroactive ligand-receptor interaction pathway and energy metabolism are the key mechanisms of dinotefuran toxicity to bee larvae. In addition, melatonin and vitellogenin are used by larvae to cope with dinotefuran-induced oxidative stress. Our results contribute to a comprehensive understanding of dinotefuran damage to bees and provide new insights into the mechanism of enantioselective toxicity of insecticides to insect larvae.

High-throughput screening unveils nitazoxanide as a potent PRRSV inhibitor by targeting NMRAL1.

Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) poses a major threat to the global swine industry, yet effective prevention and control measures remain elusive. This study unveils Nitazoxanide (NTZ) as a potent inhibitor of PRRSV both in vitro and in vivo. Through High-Throughput Screening techniques, 16 potential anti-PRRSV compounds are identified from a library comprising FDA-approved and pharmacopeial drugs. We show that NTZ displays strong efficacy in reducing PRRSV proliferation and transmission in a swine model, alleviating viremia and lung damage. Additionally, Tizoxanide (TIZ), the primary metabolite of NTZ, has been identified as a facilitator of NMRAL1 dimerization. This finding potentially sheds light on the underlying mechanism contributing to TIZ's role in augmenting the sensitivity of the IFN-ß pathway. These results indicate the promising potential of NTZ as a repurposed therapeutic agent for Porcine Reproductive and Respiratory Syndrome (PRRS). Additionally, they provide valuable insights into the antiviral mechanisms underlying NTZ's effectiveness.

Effects of imidacloprid combined with validamycin on the population fitness and symbiotic of Nilaparvata lugens (Hemiptera: Delphacidae).

Using a high-efficiency insecticide in combination with fungicides that have different mechanisms of action is a conventional method in the current management of brown planthopper (BPH) resistance. In this study, we investigate the separate and combined effects of the low-toxicity fungicide validamycin and the non-cross-resistant insecticide imidacloprid on the fitness and symbiosis of BPH. These research results indicate that when the proportion of active ingredients in validamycin is combined with imidacloprid at a ratio of 1:30, the toxicity ratio and co-toxicity coefficient are 1.34 and 691.73, respectively, suggesting that the combination has a synergistic effect on the control of BPH. The number of yeast-like symbiotic (YLS) and dominant symbiotic (Noda) in the imidacloprid + validamycin groups were significantly lower than the other three treatment groups (validamycin, imidacloprid, and water). The results of the study on population fitness show that the lifespan of the BPH population in validamycin, imidacloprid, and imidacloprid + validamycin was shortened. Notably, the BPH populations in the imidacloprid + validamycin groups were significantly lower than other groups in terms of average generation cycle, intrinsic growth rate, net reproduction rate, finite rate of increase, and fitness. The Real-time quantitative PCR showed that validamycin and imidacloprid + validamycin can significantly inhibit the expression of the farnesyl diphosphate farnesyl transferase gene (EC2.5.1.21) and uricase gene (EC1.7.3.3), with imidacloprid + validamycin demonstrating the most pronounced inhibitory effect. Our research results can provide insights and approaches for delaying resistance and integrated management of BPH.

Various functions of detoxification enzymes against insecticides in Nilaparvata lugens selected by toxicity assays and RNAi methods.

The brown planthopper (BPH), Nilaparvata lugens is a devastating agricultural pest of rice, and they have developed resistance to many pesticides. In this study, we assessed the response of BPH nymphs to nitenpyram, imidacloprid, and etofenprox using contact and dietary bioassays, and investigated the underlying functional diversities of BPH glutathione-S-transferase (GST), carboxylesterase (CarE) and cytochrome P450 monooxygenase (P450) against these insecticides. Both contact and ingestion toxicity of nitenpyram to BPH were significantly higher than either imidacloprid or etofenprox. Under the LC50 concentration of each insecticide, they triggered a distinct response for GST, CarE, and P450 activities, and each insecticide induced at least one detoxification enzyme activity. These insecticides almost inhibited the expression of all tested GST, CarE, and P450 genes in contact bioassays but induced the transcriptional levels of these genes in dietary bioassays. Silencing of NlGSTD2 expression had the greatest effect on BPH sensitivity to nitenpyram in contact test and imidacloprid in dietary test. The sensitivities of BPH to insecticide increased the most in the contact test was etofenprox after silencing of NlCE, while the dietary test was nitenpyram. Knockdown of NlCYP408A1 resulted in BPH sensitivities to insecticide increasing the most in the contact test was nitenpyram, while the dietary test was imidacloprid. Taken together, these findings reveal that NlGSTD2, NlCE, and NlCYP408A1 play an indispensable role in the detoxification of the contact and ingestion toxicities of different types of insecticides to BPH, which is of great significance for the development of new strategies for the sucking pest control.

Protective effect of melatonin on imidacloprid-induced pyroptosis and ferroptosis by mediating peptidoglycan in the gut of the common carp (Cyprinus carpio).

Imidacloprid (IMI) is a contaminant widespread in surface water, causing serious intestinal damage in the common carp. Melatonin (MT), an endogenous indoleamine hormone, plays a crucial role in mitigating pesticide-induced toxicity. Our previous research has demonstrated that MT effectively reduces the production of intestinal microbial-derived signal peptidoglycan (PGN) induced by IMI, thereby alleviating intestinal tight junction injuries in the common carp. In this study, we performed a transcriptomic analysis to explore the effect of MT on the IMI exposure-induced gut damage of the common carp. The results elucidated that the ferroptosis, mitogen-activated protein kinases (MAPKs), and nucleotide oligomerization domain (NOD)-like signaling pathways were significantly associated with IMI exposure and MT treatment. Meanwhile, the exposure to IMI resulted in the formation of pyroptotic bodies and distinct morphological features of ferroptosis, both mitigated with the addition of MT. Immunofluorescence double staining demonstrated that MT abolished the elevated expression of NOD-like receptor thermal protein domain associated protein 3 (NLRP3) and Gasdermin D (GSDMD) induced by IMI, as well as reduced expression of ferritin heavy chains (FTH) and glutathione peroxidase 4 (GPX4) in gut tissues. Subsequently, we found that the exposure to IMI or PGN enhanced the expression of toll-like receptors (TLR) 2 (a direct recognition receptor of PGN) triggering the P38MAPK signaling pathway, thereby aggravating the process of pyroptosis and ferroptosis of cell models. The addition of MT or SB203580 (a P38MAPK inhibitor) significantly reduced pyroptotic cells, and also decreased iron accumulation. Consequently, these results indicate that MT alleviates IMI-induced pyroptosis and ferroptosis in the gut of the common carp through the PGN/TLR2/P38MAPK pathway.

microRNA-3037 targeting CYP6CY2 confers imidacloprid resistance to Sitobion miscanthi (Takahashi).

The wheat aphid Sitobion miscanthi is a dominant and destructive pest in agricultural production. Insecticides are the main substances used for effective control of wheat aphids. However, their extensive application has caused severe resistance of wheat aphids to some insecticides; therefore, exploring resistance mechanisms is essential for wheat aphid management. In the present study, CYP6CY2, a new P450 gene, was isolated and overexpressed in the imidacloprid-resistant strain (SM-R) compared to the imidacloprid-susceptible strain (SM-S). The increased sensitivity of S. miscanthi to imidacloprid after knockdown of CYP6CY2 indicates that it could be associated with imidacloprid resistance. Subsequently, the posttranscriptional regulation of CYP6CY2 in the 3' UTR by miR-3037 was confirmed, and CYP6CY2 participated in imidacloprid resistance. This finding is critical for determining the role of P450 in relation to the resistance of S. miscanthi to imidacloprid. It is of great significance to understand this regulatory mechanism of P450 expression in the resistance of S. miscanthi to neonicotinoids.

Microbiota of pest insect Nezara viridula mediate detoxification and plant defense repression.

The Southern green shield bug, Nezara viridula, is an invasive piercing and sucking pest insect that feeds on crop plants and poses a threat to global food production. Given that insects are known to live in a close relationship with microorganisms, our study provides insights into the community composition and function of the N. viridula-associated microbiota and its effect on host-plant interactions. We discovered that N. viridula hosts both vertically and horizontally transmitted microbiota throughout different developmental stages and their salivary glands harbor a thriving microbial community that is transmitted to the plant while feeding. The N. viridula microbiota was shown to aid its host with the detoxification of a plant metabolite, namely 3-nitropropionic acid, and repression of host plant defenses. Our results demonstrate that the N. viridula-associated microbiota plays an important role in interactions between insects and plants and could therefore be considered a valuable target for the development of sustainable pest control strategies.

UDP-Glycosyltransferases UGT350C3 and UGT344L7 Confer Tolerance to Neonicotinoids in Field Populations of Aphis gossypii.

The cotton aphid, Aphis gossypii, is a polyphagous pest that stunts host plant growth via direct feeding or transmitting plant virus. Due to the long-term application of insecticides, A. gossypii has developed different levels of resistance to numerous insecticides. We found that five field populations had evolved multiple resistances to neonicotinoids. To explore the resistance mechanism mediated by uridine diphosphate glycosyltransferases (UGTs), two upregulated UGT genes in these five strains, UGT350C3 and UGT344L7, were selected for functional analysis of their roles in neonicotinoid detoxification. Transgenic Drosophila bioassay results indicated that compared with the control lines, the UGT350C3 and UGT344L7 overexpression lines were more tolerant to thiamethoxam, imidacloprid, and dinotefuran. Knockdown of UGT350C3 and UGT344L7 significantly increased A. gossypii sensitivity to thiamethoxam, imidacloprid, and dinotefuran. Molecular docking analysis demonstrated that these neonicotinoids could bind to the active pockets of UGT350C3 and UGT344L7. This study provides functional evidence of neonicotinoid detoxification mediated by UGTs and will facilitate further work to identify strategies for preventing the development of neonicotinoid resistance in insects.