The expansive field of drug discovery is continually seeking innovative approaches to identify and develop novel peptide-based therapeutics. With the advent of artificial intelligence (AI), there has been a transformative shift in the generation of new peptide drugs. AI offers a range of computational tools and algorithms that enables researchers to accelerate the therapeutic peptide pipeline. This review explores the current landscape of AI applications in peptide drug discovery, highlighting its potential, challenges, and ethical considerations. Additionally, it presents case studies and future prospectives that demonstrate the impact of AI on the generation of new peptide drugs.

Chill susceptible insects are thought to be injured through different mechanisms depending on the duration and severity of chilling. While chronic chilling causes “indirect” injury through disruption of metabolic and ion homeostasis, acute chilling is suspected to cause “direct” injury, in part through phase transitions of cell membrane lipids. Dietary supplementation of cholesterol can reduce acute chilling injury in Drosophila melanogaster , but the generality of this effect and the mechanisms underlying it remain unclear. To better understand how and why cholesterol has this effect, we assessed how a high cholesterol diet and thermal acclimation independently and interactively impact several measures of chill tolerance in both male and female flies. Cholesterol supplementation positively affected tolerance to acute chilling in warm-acclimated flies (as reported previously). Conversely, feeding on the high-cholesterol diet negatively affected tolerance to chronic chilling in both cold and warm acclimated flies, as well as tolerance to acute chilling in cold acclimated flies. Cholesterol had no effect on the ability of flies to remain active in the cold or recover movement after a cold stress. Our findings support the idea that dietary cholesterol reduces mechanical injury to membranes caused by direct chilling injury, and that acute and chronic chilling are associated with distinct mechanisms of injury. Feeding on a high-cholesterol diet may interfere with mechanisms involved in cold acclimation, leaving cholesterol augmented flies more susceptible to chilling injury under some conditions. Highlights: Cholesterol improves cold shock tolerance of warm-acclimated flies Cold acclimation and chronic cold instead lead to negative effects of cholesterol on chill tolerance Cholesterol did not affect the ability of flies to remain active in the cold Both sexes were similarly affected by a high cholesterol diet

Thermal tolerance limits are closely associated with insect distribution. Thermal injury sets limits to mobility or survival after removal from the stress, and these limits are frequently integrated into models describing or predicting climate suitability for species of interest. Cold stress severity, sex, and prior thermal acclimation status can all influence lower thermal limits. There is a growing understanding of chilling injuries initially manifest, but we poorly understand repair or further injury that may happen after rewarming. We exposed male and female Drosophila melanogaster to an acute or chronic cold stress before assessing their mobility over a 24 h period. Females progressively worsened under both conditions, but male mobility neither worsened nor improved. Female mobility declined slower in flies recovering at cooler temperatures, and cold acclimation significantly mitigated latent injury in females following the same degree of initial injury, regardless of recovery temperature. We conclude that latent chilling injury can be sex-specific, occurs independently from mechanisms driving tissue damage in the cold, is temperature-dependent, and is mitigated by prior thermal acclimation. We argue that latent chilling injury and the factors that influence it should be more carefully considered in estimating tolerance limits.