Choline acetyltransferase (Tcchat) is essential for metamorphosis, reproduction, and susceptibility to insecticide in Tribolium castaneum. However, the mechanisms through which Tcchat contributes to these biological processes remain poorly understood. Here we report the findings of RNA sequencing‐based transcriptome profiling of T. castaneum following RNA interference against Tcchat. In all, 173 differentially expressed genes were identified: 120 upregulated genes and 53 downregulated genes. Gene Ontology analysis classified the genes into 30 functional groups. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the genes were distributed over 22 different pathways. Silencing Tcchat reduced the activity of endopeptidase and inhibited regulation of protein decomposition in the beetles. Hence, knockdown of Tcchat inhibited the synthesis of chitinase and serine protease, which disturbed embryonic development in T. castaneum, thus affecting its development and reproduction. RNA interference of Tcchat also suppressed the synthesis of cytochrome P450 in the extracellular region and adversely affected normal functioning of the lysosomal pathway, which might have hindered the insects' ability to recognize, phagocytose, and degrade exogenous toxic substances, resulting in increased mortality. Furthermore, knockdown of Tcchat increased the susceptibility of larvae to carbamate and organophosphate insecticides, which supports the notion that Tcchat is indeed involved in susceptibility to insecticide in T. castaneum. Finally, Tcchat knockdown adults showed progressively reduced locomotor activity. These results provide novel insights into biological processes affected by Tcchat and provide a potential theoretical basis for the biological control of T. castaneum.

Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae) is one of the most destructive pests of stored products. Although there have been studies on the potential use of essential oils from plants in the Artemisia genus as insecticides, no comprehensive bioactivity data are available on the efficacy of Artemisia vulgaris L. (Asterales: Asteraceae) essential oil and its chemical constituents on stored-product pests. Therefore, in this study, the bioactivity of A. vulgaris essential oil and its chemical constituents, eugenol and terpinen-4-ol, against T. castaneum were determined by contact, fumigant, and repellent bioassays. Analysis of contact and fumigant bioassays showed that A. vulgaris essential oil, eugenol, and terpinen-4-ol have contact and fumigant toxicities against T. castaneum, of which terpinen-4-ol has a strong killing effect on larvae and adults, suggesting that terpinen-4-ol may be the main active component of A. vulgaris essential oil in contact and fumigant effects. Additionally, A. vulgaris essential oil and eugenol have higher repellent activity against T. castaneum larvae and adults, whereas the repellent activity of terpinen-4-ol is low, indicating that the main component of A. vulgaris essential oil in repellence may be eugenol. These results further provide relevant theoretical basis for the development of plant essential oil pesticides.

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Somatic mutations occurring on key enzymes are extensively studied and targeted therapies are developed with clinical promises. However, context-dependent enzyme function through distinct substrates complicated targeting a given enzyme. Here, we develop an algorithm to elucidate a new class of somatic mutations occurring on enzyme-recognizing motifs that cancer may hijack to facilitate tumorigenesis. We validate BUD13-R156C and -R230Q mutations evading RSK3-mediated phosphorylation with enhanced oncogenicity in promoting colon cancer growth. Further mechanistic studies reveal BUD13 as an endogenous Fbw7 inhibitor that stabilizes Fbw7 oncogenic substrates, while cancerous BUD13-R156C or -R230Q interferes with Fbw7Cul1 complex formation. We also find this BUD13 regulation plays a critical role in responding to mTOR inhibition, which can be used to guide therapy selections. We hope our studies reveal the landscape of enzyme-recognizing motif mutations with a publicly available resource and provide novel insights for somatic mutations cancer hijacks to promote tumorigenesis with the potential for patient stratification and cancer treatment.