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Holometabolous insects stop feeding at the final larval instar stage and then undergo metamorphosis; however, the mechanism is unclear. In the present study, using the serious lepidopteran agricultural pest Helicoverpa armigera as a model, we revealed that 20-hydroxyecdysone (20E) binds to the dopamine receptor (DopEcR), a G protein-coupled receptor, to stop larval feeding and promote pupation. DopEcR was expressed in various tissues and its level increased during metamorphic molting under 20E regulation. The 20E titer was low during larval feeding stages and high during wandering stages. By contrast, the dopamine (DA) titer was high during larval feeding stages and low during the wandering stages. Injection of 20E or blocking dopamine receptors using the inhibitor flupentixol decreased larval food consumption and body weight. Knockdown of DopEcR repressed larval feeding, growth, and pupation. 20E, via DopEcR, promoted apoptosis; and DA, via DopEcR, induced cell proliferation. 20E opposed DA function by repressing DA-induced cell proliferation and AKT phosphorylation. 20E, via DopEcR, induced gene expression and a rapid increase in intracellular calcium ions and cAMP. 20E induced the interaction of DopEcR with G proteins αs and αq. 20E, via DopEcR, induced protein phosphorylation and binding of the EcRB1-USP1 transcription complex to the ecdysone response element. DopEcR could bind 20E inside the cell membrane or after being isolated from the cell membrane. Mutation of DopEcR decreased 20E binding levels and related cellular responses. 20E competed with DA to bind to DopEcR. The results of the present study suggested that 20E, via binding to DopEcR, arrests larval feeding and promotes pupation. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate whether polymorphisms of − 938C/A and Thr43Ala in the BCL-2 gene and G − 248A in the BAX gene are associated with the risk of developing non-Hodgkin lymphoma (NHL). We genotyped polymorphisms of − 938C/A and Thr43Ala in the BCL-2 gene and G-248A in the BAX gene among 424 patients with NHL and 446 controls. We found that the − 938AA genotype of the BCL2 gene was significantly associated with the risk of developing NHL ( p < 0.001) and this genotype was associated with advanced stage ( p = 0.01). Meanwhile, individuals having − 248AG + AA genotypes were significantly associated with an increased risk of NHL ( p = 0.01), and these genotypes were associated with larger tumor size ( p = 0.02). The present study demonstrated that the − 938AA genotype of the BCL-2 gene and − 248AG + AA genotype of the BAX gene may be susceptible genotypes for NHL. There appeared to be an impact of the BCL2 − 938AA genotype on advanced stage and − 248AG + AA genotypes on tumor size in NHL. [ABSTRACT FROM AUTHOR]