Finally, inhibition of autophagy in the cell lines by specific inhibitors or RNAi assays resulted in delayed cell death triggered by Cry toxins, suggesting that the increased autophagy activity observed after toxin intoxication may contribute to cell death.Insecticide resistance is an ongoing challenge in agriculture and disease vector control. Here, we demonstrate a novel strategy to attenuate resistance. We used genomics tools to target fundamental energy-associated pathways and identified a potential "Achilles' heel" for resistance, a resistance-associated protein that, upon inhibition, results in a substantial loss in the resistance phenotype. Specifically, we compared the gene expression profiles and structural variations of the insulin/insulin-like growth factor signaling (IIS) pathway genes in DDT-susceptible (91-C) and -resistant (91-R) Drosophila melanogaster (Drosophila) strains. A total of eight and seven IIS transcripts were up- and down-regulated, respectively, in 91-R compared to 91-C. A total of 114 nonsynonymous mutations were observed between 91-C and 91-R, of which 51.8% were fixed. Among the differentially expressed transcripts, phosphoenolpyruvate carboxykinase (PEPCK), down-regulated in 91-R, encoded the greatest number of amino acid changes, prompting us to perform PEPCK inhibitor-pesticide exposure bioassays. The inhibitor of PEPCK, hydrazine sulfate, resulted in a 161- to 218-fold decrease in the DDT resistance phenotype (91-R) and more than a 4- to 5-fold increase in susceptibility in 91-C. A second target protein, Glycogen synthase kinase 3β (GSK3β-PO), had one amino acid difference between 91-C and 91-R, and the corresponding transcript was also down-regulated in 91-R. A GSK3β-PO inhibitor, lithium chloride, likewise reduced the resistance but to a lesser extent than did hydrazine sulfate for PEPCK. We demonstrate the potential role of IIS genes in DDT resistance and the potential discovery of an "Achilles' heel" against pesticide resistance in this pathway.Due to the extensive use of chemical insecticides, the field populations of Rhopalosiphum padi, a serious wheat pest worldwide, have developed resistance to insecticides. Therefore, deep understanding of the mechanisms of the aphid's physiological response to insecticides would be of importance for the management of insecticide resistance in pests. Takeout belongs to a protein superfamily found exclusively in insects. Previous research showed that the takeout gene had various functions in insect physiology and behavior. However, few studies have explored the functions of takeout in insect insecticide susceptibility. The susceptibility of R. padi to imidacloprid and beta-cypermethrin was tested. Thirteen takeout-like genes were identified based on the genome database of R. padi. The number of exons was variable in these takeout-like genes, and nine highly conserved amino acids (two Cysteine, two Proline, four Glycine and one Aspartic acid) were identified. Expression levels of takeout-like-2, takeout-like-3, takeout-like-5, takeout-like-8, takeout-like-10 and takeout-like-11 were significantly increased after imidacloprid treatment; seven genes (takeout-like-1, takeout-like-2, takeout-like-5, takeout-like-6, takeout-like-7, takeout-like-8 and takeout-like-11) tended to be upregulated after beta-cypermethrin treatment. RNA interference results showed that the mortalities of R. padi injected with dsTOL-2, dsTOL-5, dsTOL-8, dsTOL-10 and dsTOL-11 were significantly increased after exposure to imidacloprid in comparison with control (injection of dsGFP). Under two sublethal concentrations of beta-cypermethrin, the silencing of takeout-like-2, takeout-like-5 and takeout-like-11 significantly increased the mortalities of R. padi. These results provide evidence for the involvement of takeout-like genes in insecticide susceptibility of R. padi, which improves our understanding the determinant of insecticide susceptibility.Insect antennae play a fundamental role in perceiving and recognizing a broad spectrum of conventional semiochemicals and host plant-derived odors. As such, genes that are tightly associated with the antennae are thought to have olfactory-related roles related to signal transduction mechanisms. Several mechanisms suggest that enzymatic inactivation could contribute to the signal termination process, such as odorant-degrading enzymes (ODEs). To date, a few ODEs have been identified and characterized in detail in insect herbivores, but little is known about aldehyde oxidases (AOXs); moreover, direct in vivo experimental evidence is needed. AOXs are a major family of metabolic enzymes that oxidize a variety of aromatic aldehydes, and they may also play a significant role in detoxification and degradation of environmental chemical cues. Here, we report on the identification and characterization of a novel cDNA encoding the putative odorant-degrading enzyme, PxylAOX3, from the antennae of the diamondback moth, (DBM), Plutella xylostella (L.) (Lepidoptera Plutellidae). The purified recombinant protein showed a wide-range of substrate zymography oxidizing both sex pheromone compounds as well as plant-derived aldehydes with distinct activities. Our data suggest PxylAOX3 might be involved in the degradation of many structurally diverse aldehyde odorants. Furthermore, PxylAOX3 could participate in olfactory neuron protection by inactivation of redundant odorants and xenobiotic detoxification, making it a potential target for pesticide development as well.Dermanyssus gallinae poses a significant threat to poultry production, and the resistance to pyrethroids has been identified worldwide. Periodic monitoring of acaricide resistance in D. gallinae is very important for its control, and molecular mechanism associated with beta-cypermethrin resistance in D. gallinae is not fully clear. Results showed, four field isolates of CBP-1, CBP-2, CBP-5 and CBY-1 from China remained either susceptible or with decreased susceptibility (resistance ratio less then 5.0) to phoxim, amitraz, propoxur and carbaryl. Four field isolates of CBP-1, CBP-3, CBY-2 and CBH-1 had developed high or extremely high level of resistance (resistance ratio ≥ 40.0) to beta-cypermethrin or permethrin. Detoxification enzyme activity of GSTs was significantly higher in beta-cypermethrin resistant (RS) than susceptible strain (SS), indicating that GSTs are probably involved in beta-cypermethrin resistance in D. INS018-055 gallinae. The recombinant GSTs (rGST-1, 2, 3) showed a pronounced activity toward the conjugates of 1-chloro-2, 4 dinitrobenzene (CDNB) and glutathione (GSH), with rGST-1 presenting the highest enzymatic activity.