Non-small cell lung cancer (NSCLC) remains a major cause of cancer-related mortality worldwide, emphasizing the need for novel therapeutic strategies. In this study, we demonstrate that homoyessotoxin (hYTXs), a marine-derived natural compound, exerts potent anti-NSCLC progression. Network pharmacology, molecular docking, molecular dynamics simulations, and SPR analysis confirmed a strong binding affinity between hYTXs and EGFR. Mechanistically, hYTXs disrupted EGFR trafficking by accelerating its endocytosis and enhancing its accumulation within lysosomes, thereby accelerating receptor degradation without altering EGFR mRNA levels. CHX chase and lysosomal inhibition assays further verified that hYTXs downregulated EGFR through post-translational regulation. This degradation led to suppression of downstream PI3K/AKT/ERK signaling, reduced phosphorylation of FOXO3a and p70S6K, and enhanced PTEN nuclear translocation. Functionally, hYTXs induced apoptosis, oxidative stress, S-phase arrest, mitochondrial dysfunction, and DNA damage in A549 cells, with comparable inhibitory potency in EGFR-mutant lines (PC9, H1975) but minimal cytotoxicity toward normal lung epithelial cells. In vivo, hYTXs significantly inhibited tumor growth and exhibited excellent safety based on serum biochemistry and lung histology. Collectively, hYTXs represents a promising next-generation EGFR-targeting compound that overcomes kinase-mutation-driven resistance by promoting receptor degradation rather than kinase inhibition.

The high productivity of coral reef ecosystems depends on homeostatic regulation and efficient cycling of nutrients—particularly carbon—mediated by symbiotic organisms. Although both zooxanthellae and microbes are essential for coral carbon metabolism, their responses to temperature stress remain poorly understood. This study compared carbon metabolic profiles of thermally susceptible Acropora pruinosa and resilient Porites lutea under heat (30°C), ambient seawater (24°C), and cold (16°C) temperature conditions using integrated physiological and omics analyses. In A. pruinosa, heat stress reduced pigmentation, zooxanthellae density, and photosynthetic efficiency, with even stronger impairments under cold stress. Both temperature extremes, but especially cold stress, reshaped microbial composition, diversity, network complexity, and influenced carbon-related functional genes. In contrast, P. lutea exhibited partial inhibition of zooxanthellae and microbial carbon metabolism under both temperature extremes, reflecting greater resilience. The findings also indicate that zooxanthellae play a dominant role in sustaining carbon balance under temperature stress—especially cold—supporting a model in which zooxanthellae act as regulators and microbes as adaptors in maintaining carbon metabolic homeostasis. Overall, this study demonstrates species-specific sensitivity of corals to temperature stress as well as distinct, heterogeneous effects of low and high temperatures on carbon metabolism and sequestration efficiency of coral-associated microorganisms.