Cotton Genomics and Genetics 2025, Vol.16, No.6, 278-289 http://cropscipublisher.com/index.php/cgg 284 Meanwhile, the key enzymes involved in carbohydrate and amino acid metabolism experienced fluctuations. The activity changes of glyceraldehyde-3-phosphate dehydrogenase, sucrose synthase and enolase, in combination with the regulation of glutamine synthase and aspartate aminotransferase, jointly maintained the carbon flow balance and also provided raw materials for the synthesis of defensive compounds (Li et al., 2019b). The focus of metabolism has gradually shifted to the synthesis of phenylpropyl and flavonoids. Enzymes such as phenylalanine ammonia-lyase (PAL), caffeyl-coA O-methyltransferase (CCoAOMT), and chalketone synthase (CHS) are expressed in large quantities, which enables the rapid accumulation of lignin and antibacterial compounds. These secondary metabolites can thicken the cell wall and inhibit the spread of pathogens, marking the shift of cotton's metabolic strategy from "growth first" to "defense first", which is a typical feature of adaptive resistance. 5.3 Signaling and transcription regulators The response of cotton to the Trichoderma lucidum is not merely a structural "reinforcement", but rather a more complex dialogue at the signal level. Calcium signals are always the first to be activated. Calmodulin (CaM) and calcium-dependent protein kinase (CDPK) accumulate rapidly, triggering a series of early responses and opening the "switch" for subsequent defense genes. Subsequently, the mitogen-activated protein kinase (MAPK) cascade makes its appearance. This system amplifies immune signals like a megaphone, promoting the activation of defense-related transcription factors. 14-3-3 proteins play the role of coordinators in this process, regulating stress responses, controlling the activity of metabolic enzymes, and preventing excessive defense responses. At the transcriptional level, factors such as WRKY, MYB, NAC and bZIP play core roles. For instance, GhWRKY70 promotes resistance through the jasmonic acid (JA) pathway, while GhWRKY55 exerts inhibitory effects in regulating lignin and JA synthesis (Ma et al., 2024). The waxing and waning between them reflect the meticulous balance of cotton between defense and metabolism. Finally, it is necessary to mention the interactive regulation of hormones. Salicylic acid (SA), jasmonic acid (JA), and ethylene (ET) do not act independently. The interweaving of signals among them determines the direction and intensity of defense. Sometimes it activates allergic reactions (HR), and sometimes it leans towards systemic acquired resistance (SAR). How to switch between the two is precisely the key to maintaining a balance in disease resistance. 6 Comparative Proteomics: Susceptible vs. Resistant Cultivars 6.1 Defense protein profiles Among different cotton genotypes, the gap between disease resistance and susceptibility can often be discerted at the protein level. The results of comparative proteomics show that the accumulation rate and extent of defense proteins almost determine the ability of cotton to resist the Trichoderma lucidum. Resistant varieties such as CRI 12, Zhongzhi Cotton No. 2, and Hai7124 Island cotton can activate disease-related proteins (PR) earlier and more strongly than disease-susceptible materials like Ape Cotton No. 3 or Jimian No. 11. Among them, chitinase, β-1, 3-glucanase, and PR-10 proteins are the most prominent. These proteins can directly degrade the cell walls of fungi. Slow down its diffusion in the vascular bundles. Meanwhile, the antioxidant systems of resistant varieties are also more "alert". The expression levels of superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbic acid peroxidase (APX) are higher, which help eliminate excess reactive oxygen species (ROS) during infection and maintain the REDOX balance of cells. In addition, the upregulation of heat shock proteins (HSP70, HSP90) and glutathione S-transferase (GSTs) makes the entire protein network more stable and detoxifying. In susceptible varieties, the activation of the defense system is often delayed. Slow response of PR protein and low level of antioxidant enzymes result in uncontrolled oxidative stress and accelerated fungal reproduction (Zhu et al., 2021). Therefore, the key to the difference in resistance does not seem to lie merely in "whether to respond",
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