Bt Research 2025, Vol.16, No.6, 259-268 http://microbescipublisher.com/index.php/bt 261 2.3 Insecticidal mechanism of Bt crops and their target pest species How exactly do we control pests on Bt crops? It's not that toxins should be killed immediately upon contact with insects; instead, they must be consumed first. After insect larvae ingest Cry or Vip proteins, these toxins will travel to their midgut, bind to the receptors there, form holes, and eventually the gut will rupture and the cells will dissolve, preventing the insects from surviving. This set of processes sounds simple, but in fact, it's quite complicated behind the scenes. Toxins must first be activated in an alkaline environment, then find specific receptors like cadherin, followed by oligomerization, insertion into cell membranes, and finally damage the intestinal barrier, causing sepsis (Figure 1) (Xiao and Wu, 2019). The key point is that these toxins are not universally applicable. Their effects are related to the type of insect, the structure of the midgut, and even the stage of development. At present, Bt crops mainly target pests of Lepidoptera and Coleoptera, such as cotton bollworm, fall armyworm, certain beetles, etc. Some toxins also have an effect on hemiptera (Arsov et al., 2023; Cao et al., 2025). However, it is not without problems. Some pests have developed resistance, possibly due to receptor mutations or the blocking of the activation process. This requires the design of toxin combinations with multiple different mechanisms in order to delay the development of resistance and maintain the protective effect on crops. This is also one of the key points in the current Bt crop design. Figure 1 Models of the evolution of pink bollworm (PBW) Bt resistance. In the United States, the effective implementation of high-dose/refuge strategies when growing single-Bt cotton (i.e. a line with one Bt toxin) has maintained PBW populations with few Bt-resistant genes (Adopted from Xiao and Wu, 2019) 3 Comparative Analysis of Global Regulatory Systems for Bt Crops 3.1 The U.S. tri-agency system: EPA, FDA, and USDA The United States does not rely on a single agency to act alone in regulating Bt crops, but rather on the "separate cooperation" of the EPA, FDA and USDA. The EPA mainly focuses on the environment and pest resistance, the FDA is concerned with food safety, and the USDA looks at plant health, such as whether Bt crops have the potential to become "ecological troubles". Such a division of labor sounds clear, but in fact, it is not always smooth to coordinate. Fortunately, this regulatory framework in the United States places a strong emphasis on
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