Assessing the negative impact of chlorantraniliprole, isoxaflutole, and simazine pesticides on phospholipid membrane models and tilapia gill tissues.

The indiscriminate and, very often, incorrect use of pesticides in Brazil, as well as in other countries, results in severe levels of environmental pollution and intoxication of human life. Herein, we studied plasma membrane models (monolayer and bilayer) of the phospholipid Dioleoyl-sn-glycerol-3-phosphocholine (DOPC) using Langmuir films, and large (LUVs) and giant (GUVs) unilamellar vesicles, to determine the effect of the pesticides chlorantraniliprole (CLTP), isoxaflutole (ISF), and simazine (SMZ), used in sugarcane. CLTP affects the lipid organization of the bioinspired models of DOPC π-A isotherms, while ISF and SMZ pesticides significantly affect the LUVs and GUVs. Furthermore, the in vivo study of the gill tissue in fish in the presence of pesticides (2.0 × 10-10 mol/L for CLTP, 8.3 × 10-9 mol/L for ISF, and SMZ at 9.9 × 10-9 mol/L) was performed using optical and fluorescence images. This investigation was motivated by the gill lipid membranes, which are vital for regulating transporter activity through transmembrane proteins, crucial for maintaining ionic balance in fish gills. In this way, the presence of phospholipids in gills offers a model for understanding their effects on fish health. Histological results show that exposure to CLTP, ISF, and SMZ may interfere with vital gill functions, leading to respiratory disorders and osmoregulation dysfunction. The results indicate that exposure to pesticides caused severe morphological alterations in fish, which could be correlated with their impact on the bioinspired membrane models. Moreover, the effect does not depend on the exposure period (24h and 96h), showing that animals exposed to pesticides for a short period suffer irreparable damage to gill tissue. In summary, we can conclude that the harm caused by pesticides, both in membrane models and in fish gills, occurs due to contamination of the aquatic system with pesticides. Therefore, water quality is vital for the preservation of ecosystems.

CF2-II Alternative Splicing Isoform Regulates the Expression of Xenobiotic Tolerance-Related Cytochrome P450 CYP6CY22 in Aphis gossypii Glover.

The expression of P450 genes is regulated by trans-regulatory factors or cis-regulatory elements and influences how endogenous or xenobiotic substances are metabolized in an organism's tissues. In this study, we showed that overexpression of the cytochrome P450 gene, CYP6CY22, led to resistance to cyantraniliprole in Aphis gossypii. The expression of CYP6CY22 increased in the midgut and remaining carcass of the CyR strain, and after repressing the expression of CYP6CY22, the mortality of cotton aphids increased 2.08-fold after exposure to cyantraniliprole. Drosophila ectopically expressing CYP6CY22 exhibited tolerance to cyantraniliprole and cross-tolerance to xanthotoxin, quercetin, 2-tridecanone, tannic acid, and nicotine. Moreover, transcription factor CF2-II (XM_027994540.2) is transcribed only as the splicing variant isoform CF2-II-AS, which was found to be 504 nucleotides shorter than CF2-II in A. gossypii. RNAi and yeast one-hybrid (Y1H) results indicated that CF2-II-AS positively regulates CYP6CY22 and binds to cis-acting element p (-851/-842) of CYP6CY22 to regulate its overexpression. The above results indicated that CYP6CY22 was regulated by the splicing isoform CF2-II-AS, which will help us further understand the mechanism of transcriptional adaption of cross-tolerance between synthetic insecticides and plant secondary metabolites mediated by P450s.

Unclassified glutathione-S-transferase AiGSTu1 confers chlorantraniliprole tolerance in Agrotis ipsilon.

BACKGROUND: Chlorantraniliprole (CAP) is a diamide insecticide with high efficacy against many pest insects, including the black cutworm, Agrotis ipsilon. Agrotis ipsilon is a serious pest causing significant yield losses in crops. Glutathione-S-transferases (GSTs) belong to a family of metabolic enzymes that can detoxify a wide range of pesticides. However, little is known about the functions of GSTs in CAP tolerance in A. ipsilon. RESULTS: A cDNA sequence (designated AiGSTu1) encoding an unclassified GST was identified from A. ipsilon. AiGSTu1 is highly expressed during the 3rd -instar larval and the pupal stages. Most of the mRNA transcripts were found in larval Malpighian tubules. Exposure to CAP strongly enhanced AiGSTu1 expression, GST activity, hydrogen peroxide (H2 O2 ) and malondialdehyde levels in larvae. H2 O2 treatment upregulated the transcription level of AiGSTu1, suggesting that CAP-induced oxidative stress may activate AiGSTu1 expression. The activity of recombinant AiGSTu1 was inhibited by CAP in a dose-dependent manner. Metabolism assay results demonstrated that AiGSTu1 is capable of depleting CAP. Overexpression of AiGSTu1 enhanced the tolerance of Escherichia coli cells to H2 O2 and the oxidative stress inducer, cumene hydroperoxide. Silencing of AiGSTu1 by RNA interference increased the susceptibility of A. ipsilon larvae to CAP. CONCLUSION: The findings of this study provide valuable insights into the potential role of AiGSTu1 in CAP detoxification and will improve our understanding of CAP tolerance in A. ipsilon. © 2023 Society of Chemical Industry.

The biochemically defined super relaxed state of myosin-A paradox.

The biochemical SRX (super-relaxed) state of myosin has been defined as a low ATPase activity state. This state can conserve energy when the myosin is not recruited for muscle contraction. The SRX state has been correlated with a structurally defined ordered (versus disordered) state of muscle thick filaments. The two states may be linked via a common interacting head motif (IHM) where the two heads of heavy meromyosin (HMM), or myosin, fold back onto each other and form additional contacts with S2 and the thick filament. Experimental observations of the SRX, IHM, and the ordered form of thick filaments, however, do not always agree, and result in a series of unresolved paradoxes. To address these paradoxes, we have reexamined the biochemical measurements of the SRX state for porcine cardiac HMM. In our hands, the commonly employed mantATP displacement assay was unable to quantify the population of the SRX state with all data fitting very well by a single exponential. We further show that mavacamten inhibits the basal ATPases of both porcine ventricle HMM and S1 (Ki, 0.32 and 1.76 µM respectively) while dATP activates HMM cooperatively without any evidence of an SRX state. A combination of our experimental observations and theories suggests that the displacement of mantATP in purified proteins is not a reliable assay to quantify the SRX population. This means that while the structurally defined IHM and ordered thick filaments clearly exist, great care must be employed when using the mantATP displacement assay.

Methionine can reduce the sublethal risk of Chlorantraniliprole to honeybees (Apis mellifera L.): Based on metabolomics analysis.

Bees, essential for pollination in agriculture and global economic growth. However, the great wax moth (Galleria mellonella, GWM), a Lepidopteran insect, poses a substantial threat to bee colonies, contributing to a global decline in bee populations. Chlorantraniliprole (CH) is one of the primary insecticide used to control GWM due to its efficacy and low toxicity to bees. To improve beekeeping safety and reduce the risk of GWM developing resistance to prolonged use of CH, we investigated the potential of combining methionine (MET) which has been found to have insecticidal activity against certain Lepidoptera pests, with chlorantraniliprole for use in the apiculture industry. This study assessed the combined effects of MET and CH on GWM and honeybees by employing the maximum concentration of MET (1 %, w/w), previously reported as safe for honeybees, and the practical concentration of CH (1 mg/kg) for GWM control. The results revealed limited acute lethal toxicity of MET to GWM and honeybees, whereas the combined chronic exposure of MET and CH (MIX) led to significant synergistic lethal effects on GWM mortality. Nevertheless, the protective effect of MET on honeybees exposed to CH was significant under chronic exposure. Potential mechanisms underlying the synergistic actions of MET and CH may stem from MET-induced protection of the "Cysteine and methionine" and the "Glycine, serine, and threonine" metabolism pathways. Furthermore, immune stress mitigation was also observed in honeybee immune-related gene transcripts treated by the combination of MET and CH under both acute and chronic exposure. The effects of MET on CH activity in GWM and honeybees are likely due to metabolic regulation. This study suggests the potential of developing MET as a promising biopesticide or protective agent in the future.

Therapeutic Effects of Long-Term Administration of Tranilast in an Animal Model for the Treatment of Fibroids.

Tranilast (N-3, 4-dimethoxycinnamoyl anthranilic acid) is an orally administered drug with antiallergic properties and approved in Japan and the Republic of Korea for the treatment of asthma and hypertrophic scars. Previous in vitro studies indicated that tranilast reduced fibroid growth through its inhibitory effects on cell proliferation and induction of apoptosis. The objective of this study was to determine the efficacy of tranilast for treatment of human-derived fibroids in a mouse model. SCID mice (ovariectomized, supplemented with estrogen and progesterone) were implanted with fibroid explants and treated for two months with tranilast (50 m/kg/daily) or the vehicle. After sacrifice, xenografts were excised and analyzed. Tranilast was well tolerated without adverse side effects. There was a 37% reduction in tumor weight along with a significant decrease in staining for Ki67, CCND1, and E2F1; a significant increase in nuclear staining for cleaved caspase 3; and reduced staining for TGF-ß3 and Masson's trichrome in the tranilast treated mice. There was a significant inhibition of mRNA and protein expression of fibronectin, COL3A1, CCND1, E2F1, and TGF-ß3 in the xenografts from the tranilast-treated mice. These promising therapeutic effects of tranilast warrant additional animal studies and human clinical trials to evaluate its efficacy for treatment of fibroids.

The ryanodine receptor mutation I4728M confers moderate-level resistance to diamide insecticides in Spodoptera litura.

BACKGROUND: The common cutworm, Spodoptera litura (Fabricius), is one of the most widespread and destructive polyphagous pests in tropical and subtropical Asia. S. litura has evolved resistance to different insecticides, including diamide insecticides. Here, we identified a ryanodine receptor (RyR) mutation (I4728M) associated with target site resistance to diamides in a field-collected population of S. litura. The contribution of this mutation to diamide resistance was investigated through establishing a near-isogenic resistant strain of S. litura. RESULTS: The ND21 population of S. litura, collected from Ningde, Fujian province of China in 2021, exhibited 130.6-fold resistance to chlorantraniliprole compared to the susceptible NJ-S strain. S. litura RyR mutation I4728M, corresponding to Plutella xylostella RyR I4790M, was identified in the ND21 population. SlRyR I4728M mutation of ND21 was introgressed into a susceptible background strain (NJ-S) with marker-assisted backcrossing. The introgressed strain named ND21-R, which was homozygous for the mutant 4728M allele, shared about 94% of the genetic background with the NJ-S strain. ND21-R strain showed moderate levels of resistance to two anthranilic diamides (19.1-fold to chlorantraniliprole, 19.7-fold to cyantraniliprole) and the phthalic diamide flubendiamide (23.4-fold). Genetic analysis showed that chlorantraniliprole resistance was autosomal, incompletely recessive and tightly linked with SlRyR I4728M mutation in the introgressed ND21-R strain of S. litura. CONCLUSION: Identification of the I4728M mutation and its contribution to diamide resistance in S. litura will help develop allelic discrimination assays for resistance monitoring and guide resistance management practices for diamides in S. litura. © 2023 Society of Chemical Industry.

In Silico Investigation of Selected Pesticides and Their Determination in Agricultural Products Using QuEChERS Methodology and HPLC-DAD.

In this study, we considered some pesticides as active substances within formulations for the protection of plant-based food in the Republic of Serbia in silico, because these pesticides have not often been investigated in this way previously, and in an analytical way, because there are not very many available fast, cheap, and easy methods for their determination in real agricultural samples. Seven pesticides were detected in selected agricultural products (tomatoes, cucumbers, peppers, and grapes) using the QuEChERS methodology and HPLC-DAD. Standard curves for the investigated pesticides (chlorantraniliprole, methomyl, metalaxyl, thiacloprid, acetamiprid, emamectin benzoate, and cymoxanil) show good linearity, with R2 values from 0.9785 to 0.9996. The HPLC-DAD method is fast, and these pesticides can be determined in real spiked samples in less than 15 min. We further characterized the pesticides we found in food based on physicochemical properties and molecular descriptors to predict the absorption, distribution, metabolism, elimination, and toxicity (ADMET) of the compounds. We summarized the data supporting their effects on humans using various computational tools to determine their potential adverse effects. The results of our prediction study show that all of the selected pesticides considered in this study have good oral bioavailability, and those with high toxicity, therefore, could be harmful to human health. Chlorantraniliprole was shown in a molecular docking study as a good starting point for a new Alzheimer's disease drug candidate.

Synthesis, Solid State Structure, and Cytotoxic Activity of a Complex Dimer of Yttrium with Anthranilic Acid against Cancer Cells.

This paper presents the synthesis and isolation of a new binuclear complex of yttrium with anthranilic acid (HA). The complex [Y2(HA)6(H2O)4] Cl6.2C2H5OH (C1) was obtained as single crystals that its X-ray analysis revealed its triclinic P-1 space group in addition to anti-prismatic geometry around each of the yttrium ions. In the complex, the anthranilic acid ligands are bidentate, zwitter ionic and neutral, and the yttrium ions' charge is only compensated by six chloride ions. The cytotoxicity of this complex against human breast cancer MDA-MB-231 cells, prostate cancer PC-3 cells, and bladder cancer T-24 cells was evaluated. This yttrium complex displayed more cytotoxic activity against the bladder cancer cells with an IC50 value of 307.7 µg/ml (223 µM). On the other hand, the activities of complex C1 against the MDA-MB-231 and PC-3 cells were less significant respectively with IC50 values of 1097 µg/ml (796 µM) and 921 µg/ml (669 µM).

Anticancer, Antimicrobial, and Antioxidant Activities of Organodiselenide-Tethered Methyl Anthranilates.

Novel methyl anthranilate-based organodiselenide hybrids were synthesized, and their chemical structures were confirmed by state-of-the-art spectroscopic techniques. Their antimicrobial properties were assessed against Staphylococcus aureus, Escherichia coli, and Candida albicans microbial strains. Moreover, the antitumor potential was estimated against liver and breast carcinomas, as well as primary fibroblast cell lines. The Staphylococcus aureus and Candida albicans strains were more sensitive than Escherichia coli toward the OSe compounds. Interestingly, methyl 2-amino-5-(methylselanyl) benzoate (14) showed similar antifungal activity to the standard drug clotrimazole (IA% = 100%) and manifested promising antibacterial activity against E. coli (IA% = 91.3%) and S. aureus (IA% = 90.5%). Furthermore, the minimum inhibitory concentration experiments confirmed the antimicrobial activity of the OSe 14, which in turn was comparable to clotrimazole and ampicillin drugs. Interestingly, the anticancer properties were more pronounced in the HepG2 cells. The OSe 14 was the most cytotoxic (IC50 = 3.57 ± 0.1 µM), even more than the Adriamycin drug (IC50 = 4.50 ± 0.2 µM), and with therapeutic index (TI) 17 proposing its potential selectivity and safety. Additionally, OSe compounds 14 and dimethyl 5,5'-diselanediylbis(2-aminobenzoate) (5) exhibited promising antioxidants in the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) in vitro assays with 96%, 92%, 91%, and 86% radical scavenging activities compared to 95% by vitamin C in the DPPH and ABTS assays, respectively. These results point to promising antimicrobial, anticancer, and antioxidant activities of OSe 14 and 5 and warrant further studies.

Polymeric micelles effectively reprogram the tumor microenvironment to potentiate nano-immunotherapy in mouse breast cancer models.

Nano-immunotherapy improves breast cancer outcomes but not all patients respond and none are cured. To improve efficacy, research focuses on drugs that reprogram cancer-associated fibroblasts (CAFs) to improve therapeutic delivery and immunostimulation. These drugs, however, have a narrow therapeutic window and cause adverse effects. Developing strategies that increase CAF-reprogramming while limiting adverse effects is urgent. Here, taking advantage of the CAF-reprogramming capabilities of tranilast, we developed tranilast-loaded micelles. Strikingly, a 100-fold reduced dose of tranilast-micelles induces superior reprogramming compared to free drug owing to enhanced intratumoral accumulation and cancer-associated fibroblast uptake. Combination of tranilast-micelles and epirubicin-micelles or Doxil with immunotherapy increases T-cell infiltration, resulting in cures and immunological memory in mice bearing immunotherapy-resistant breast cancer. Furthermore, shear wave elastography (SWE) is able to monitor reduced tumor stiffness caused by tranilast-micelles and predict response to nano-immunotherapy. Micellar encapsulation is a promising strategy for TME-reprogramming and SWE is a potential biomarker of response.

Antiviral Compounds Screening Targeting HBx Protein of the Hepatitis B Virus.

A functional cure of hepatitis B virus (HBV) infection or HB antigen loss is rarely achieved by nucleos(t)ide analogs which target viral polymerase. HBx protein is a regulatory protein associated with HBV replication. We thought to identify antiviral compounds targeting HBx protein by analyzing HBx binding activity. Recombinant GST-tagged HBx protein was applied on an FDA-approved drug library chip including 1018 compounds to determine binding affinity by surface plasmon resonance imaging (SPRi) using a PlexArray HT system. GST protein alone was used for control experiments. Candidate compounds were tested for anti-HBV activity as well as cell viability using HepG2.2.15.7 cells and HBV-infected human hepatocytes. Of the 1018 compounds screened, 24 compounds showed binding to HBx protein. Of the top 6 compounds with high affinity to HBx protein, tranilast was found to inhibit HBV replication without affecting cell viability using HepG2.2.15.7 cells. Tranilast also inhibited HBV infection using cultured human hepatocytes. Tranilast reduced HB antigen level dose-dependently. Overall, theSPRi screening assay identified novel drug candidates targeting HBx protein. Tranilast and its related compounds warrant further investigation for the treatment of HBV infection.

Application of insecticides by soil drenching before seedling transplanting combined with anti-insect nets to control tobacco whitefly in tomato greenhouses.

Application of chemical pesticides is currently the main effective method to control tobacco whitefly (Bemisa tabaci) in tomato in China. The B. tabaci control efficacy of three systemic insecticides (thiamethoxam, sulfoxaflor and cyantraniliprole) by pre-transplant soil drenching with anti-insect nets throughout the tomato growth period was evaluated in two tomato greenhouses in the suburbs of Beijing, China, in 2018 and 2019. In two greenhouse trials, thiamethoxam 25% water dispersible granules (WDG) at a field rate of 21 g a.i./hm2, sulfoxaflor 22% aqueous suspension (AS) at 18 g a.i./hm2 or cyantraniliprole 10% oil-based suspension concentrate (OD) at 18 g a.i./hm2 applied via soil drenching before seedling transplanting in combination with white anti-insect nets (50 mesh) all effectively controlled the damage to B. tabaci and resulted in a low density of adults and eggs during the entire growing season, which was significantly lower than application of thiamethoxam, sulfoxaflor or cyantraniliprole via soil drenching before seedling transplanting without anti-insect net treatments or anti-insect nets alone (P < 0.05). All of the above treatments provided significantly better results than the untreated control (P < 0.05). All chemically treated tomato fruits had acceptable insecticide residuals that were lower than the corresponding maximum residue limits. The results suggest that application of thiamethoxam 25% WDG at a field rate of 21 g a.i./hm2, sulfoxaflor 22% AS at 18 g a.i./hm2 or cyantraniliprole 10% OD at 18 g a.i./hm2 by pre-transplant soil drenching combined with anti-insect nets could be recommended to control B. tabaci throughout the tomato growth period as part of integrated pest management programs in China.

Pharmacological and In Silico Analysis of Oat Avenanthramides as EGFR Inhibitors: Effects on EGF-Induced Lung Cancer Cell Growth and Migration.

Avena sativa L. is a wholegrain cereal and an important edible crop. Oats possesses high nutritional and health promoting values and contains high levels of bioactive compounds, including a group of phenolic amides, named avenanthramides (Avns), exerting antioxidant, anti-inflammatory, and anticancer activities. Epidermal growth factor receptor (EGFR) represents one of the most known oncogenes and it is frequently up-regulated or mutated in human cancers. The oncogenic effects of EGFR include enhanced cell growth, angiogenesis, and metastasis, and down-regulation or inhibition of EGFR signaling has therapeutic benefit. Front-line EGFR tyrosine kinase inhibitor therapy is the standard therapy for patients with EGFR-mutated lung cancer. However, the clinical effects of EGFR inhibition may be lost after a few months of treatment due to the onset of resistance. Here, we showed the anticancer activity of Avns, focusing on EGFR activation and signaling pathway. Lung cancer cellular models have been used to evaluate the activity of Avns on tumor growth, migration, EMT, and anoikis induced by EGF. In addition, docking and molecular dynamics simulations showed that the Avns bind with high affinity to a region in the vicinity of αC-helix and the DGF motif of EGFR, jeopardizing the target biological function. Altogether, our results reveal a new pharmacological activity of Avns as EGFR tyrosine kinase inhibitors.

High frequency of ryanodine receptor and cytochrome P450 CYP9A186 mutations in insecticide-resistant field populations of Spodoptera exigua from China.

The beet armyworm, Spodoptera exigua is a global agricultural pest that is polyphagous, highly dispersive, and often difficult to control due to resistance to many insecticides. Previous studies showed that a target site mutation in the S. exigua ryanodine receptor (SeRyR) corresponding to I4743M contributes approximately 20-fold resistance to chlorantraniliprole, whereas a mutation in the cytochrome P450 enzyme CYP9A186 corresponding to F116V confers 200-fold to emamectin benzoate through enhanced metabolic detoxification. Here, high frequencies of mutations were found among six China S. exigua field populations collected from 2016 to 2019 resulting in SeRyR I4743M and CYP9A186 F116V substitutions, with some populations having high levels of resistance to chlorantraniliprole and emamectin benzoate, respectively. Whereas we found a significant correlation between emamectin benzoate resistance level and the allele frequency of CYP9A186 F116V, no significant correlation was found between chlorantraniliprole resistance level and SeRyR I4743M allele frequency in the six field populations. These results suggest that CYP9A186 F116V is a major resistance mechanism for emamectin benzoate in the tested field populations, whereas it is likely that resistance mechanisms other than SeRyR I4743M are responsible for resistance to chlorantraniliprole in the six China field populations. Because of the growing resistance to these two insecticides by S. exigua in China, the use of insecticidal compounds with different modes of action and/or other integrated pest management strategies are needed to further delay the evolution of insecticide resistance and effectively manage S. exigua in China.

A multi-target directed ligands strategy for the treatment of Alzheimer's disease: Dimethyl fumarate plus Tranilast modified Dithiocarbate as AChE inhibitor and Nrf2 activator.

Alzheimer's disease (AD) possessed intricate pathogenesis. Currently, multi-targeted drugs were considered to have the potential to against AD by simultaneously triggering molecules in functionally complementary pathways. Hence, a series of molecules based on the pharmacophoric features of Dimethyl fumarate, Tranilast, and Dithiocarbate were designed and synthesized. These compounds showed significant AChE inhibitory activity in vitro. Among them, compound 4c2 displayed the mighty inhibitory activity to hAChE (IC50 = 0.053 µM) and held the ability to cross the BBB. Kinetic study and molecular docking pointed out that 4c2 bound well into the active sites of hAChE, forming steady and sturdy interactions with key residues in hAChE. Additionally, 4c2 as an Nrf2 activator could promote the nuclear translocation of Nrf2 protein and induce the expressions of Nrf2-dependent enzymes HO-1, NQO1, and GPX4. Moreover, 4c2 rescued BV-2 cells from H2O2-induced injury and inhibited ROS accumulation. For the anti-neuroinflammatory potential of 4c2, we observed that 4c2 could lower the levels of pro-inflammatory cytokines (NO, IL-6 and TNF-α) and suppressed the expressions of iNOS and COX-2. In particular, 4c2 was well tolerated in mice (2500 mg/kg, p.o.) and efficaciously recovered the memory impairment in a Scopolamine-induced mouse model. Overall, these results highlighted that 4c2 was a promising multi-targeted agent for treating AD.

Acute toxicity of Zanthoxylum bungeanum against two stored product insects and synergistic interactions between two major compounds limonene and linalool.

In order to find and develop new botanical pesticides against storage pests, components of the essential oil (EO) from Zanthoxylum bungeanum were identified by GC-MS and their insecticidal activity against the stored product pests were studied. The EO was obtained by steam distillation. Results showed that EO was rich in limonene (23.67), linalool (21.76) and linalyl anthranilate (10.87). In contact assays, linalool exhibited strongest toxicity to red flour beetle adult (LD50 = 17.06 µg/adult) and larvae (LD50 = 16.42 µg/larvae), and linalool was the most active one against the Lasioderma serricorne (LD50 = 15.36 µg/larvae). Then limonene and linalool showed different levels of fumigant activities against the two insect species. Synergism effect existed in the proportion of contact assays against Tribolium castaneum adults, and additive was observed in the proportion of 7:1 against T. castaneum larvae. This work provides important information for the development and utilization of Z. bungeanum and suggests that the EO of Z. bungeanum has the potential to serve as bio-insecticides for controlling pest damage in stored products.

The inhibition of intestinal glucose absorption by oat-derived avenanthramides.

Avenanthramides are phenolic compounds unique to oats and may contribute to health-promoting properties associated with oat consumption. This study used Xenopus laevis oocytes expressing the glucose transporters, glucose transporter 2 (GLUT2) or sodium-glucose transport protein 1 (SGLT1) and human Caco-2 cells models to investigate the effect of oat avenanthramides on human intestinal glucose transporters. The presence of avenanthramide reduced the glucose uptake in a dose-dependent manner in Caco-2 cells. Glucose uptake in oocytes expressing either GLUT2 or SGLT1 was nullified by oat avenanthramide. There was no significant difference between the inhibition potencies of avenanthramides C and B. Thus, our results suggest that avenanthramides may contribute to the antidiabetic properties of oats. PRACTICAL APPLICATIONS: The present research focus on the antidiabetic properties of avenanthramides, which are unique phenolic compounds found in oats. Inhibiting the activities of the glucose transport proteins expressed in the small intestine is a known strategy to improve the control of postprandial glucose level. We therefore examined the inhibitory effects of avenanthramides on two glucose transporters, glucose transporter 2 and sodium-glucose transport protein 1, predominantly found in the small intestine using the human small intestinal cell model Caco-2 cell line and by heterologously expressing these two transporters in the Xenopus laevis oocytes. Based on our results, we have confirmed for the first time that the glucose uptake is indeed inhibited by the presence of avenanthramides, suggesting the possibility of incorporating avenanthramides in foods to enhance postprandial glucose response, and ultimately improve the management of diabetes. Therefore, future research could consider utilizing this evidence in the development of diabetic-friendly functional foods or nutraceuticals containing avenanthramides.

The Mechanism of Chlorantraniliprole Resistance and Detoxification in Trichogramma chilonis (Hymenoptera: Trichogrammatidae).

Parasitic Trichogramma chilonis Ishii, an egg parasitoid of Grapholita molesta, is a critical agent for biological control of insect pests in crop plants. However, the efficiency of T. chilonis is influenced by its resistance to the common pesticide chlorantraniliprole. To elucidate the chlorantraniliprole detoxification mechanism, differentially expressed genes (DEGs) related to chlorantraniliprole resistance were studied at different developmental stages of the wasp. Individuals of T. chilonis were grouped and treated with chlorantraniliprole at different developmental stages. Untreated wasps were used as controls. Transcriptomic analysis identified the DEGs associated with chlorantraniliprole resistance and detoxification in T. chilonis. A total of 1,483 DEGs were associated with chlorantraniliprole resistance at all developmental stages. DEGs that correlated with chlorantraniliprole sensitivity of T. chilonis at different developmental stages were distinct and had various functions. The newly identified DEGs are involved in cytochrome P450- and glutathione metabolism-related pathways, which were predicted to contribute to chlorantraniliprole detoxification. Chlorantraniliprole detoxification by T. chilonis was associated with cytochrome P450- and glutathione-related pathways. Our findings may be useful for balancing chemical and biological control practices aimed to optimize agricultural production.

Toxicological and transcriptomic effects in Mythimna separata (Lepidoptera: Noctuidae) exposed to chlorantraniliprole and functional characterization of glutathione S-transferases.

BACKGROUND: Chlorantraniliprole (CAP) is an efficient anthranilic diamide insecticide against economically important pests such as the oriental armyworm, Mythimna separata (Lepidoptera: Noctuidae). Resistance to CAP may develop due to enhanced enzymatic detoxification. The glutathione S-transferase (GST) superfamily in M. separata has not been systematically characterized. The aim of this study was therefore to explore the effects of lethal and sublethal doses of CAP on M. separata larvae, screen differentially expressed genes (DEGs) responding to CAP exposure, identify and characterize the GST superfamily, and analyze the metabolism of CAP by recombinant GSTs. RESULTS: The toxicity bioassay showed that CAP was active against M. separata third-instar larvae. LC50 was 17.615, 3.127, and 1.336 mg/L after 24, 48, and 72 h, respectively. Poisoned larvae showed contracted somites and disrupted midgut. Total GST activity in larvae was significantly elevated 24 h after CAP exposure. RNA-sequencing generated 43 055 unigenes with an average length of 1010 bp, and 567 up-regulated and 692 down-regulated DEGs responding to CAP treatment were screened. Thirty-five GST genes were identified from unigenes, including 31 cytosolic, three microsomal, and one unclassified. The expression profile of GST genes was analyzed using samples from different developmental stages, adult tissues, and CAP treatments. Metabolic assays indicated that CAP was depleted by recombinant MseGSTe2 and MseGSTs6. CONCLUSIONS: This study provides insight into the toxicological and transcriptomic effects in M. separata larvae exposed to CAP. The identification and functional characterization of the GST superfamily will improve our understanding of CAP detoxification by GSTs. © 2022 Society of Chemical Industry.