Epigenetic regulation plays an important role in the evolution of species adaptations, yet little information is available on the epigenetic mechanisms underlying the adaptive evolution of bamboo‐eating in both giant pandas (Ailuropoda melanoleuca) and red pandas (Ailurus fulgens). To investigate the potential contribution of epigenetic to the adaptive evolution of bamboo‐eating in giant and red pandas, we performed hepatic comparative transcriptome and methylome analyses between bamboo‐eating pandas and carnivorous polar bears (Ursus maritimus). We found that genes involved in carbohydrate, lipid, amino acid, and protein metabolism showed significant differences in methylation and expression levels between the two panda species and polar bears. Clustering analysis of gene expression revealed that giant pandas did not form a sister group with the more closely related polar bears, suggesting that the expression pattern of genes in livers of giant pandas and red pandas have evolved convergently driven by their similar diets. Compared to polar bears, some key genes involved in carbohydrate metabolism and biological oxidation and cholesterol synthesis showed hypomethylation and higher expression in giant and red pandas, while genes involved in fat digestion and absorption, fatty acid metabolism, lysine degradation, resistance to lipid peroxidation and detoxification showed hypermethylation and low expression. Our study elucidates the special nutrient utilization mechanism of giant pandas and red pandas and provides some insights into the molecular mechanism of their adaptive evolution of bamboo feeding. This has important implications for the breeding and conservation of giant pandas and red pandas.

The hypoxic, cold, and high-ultraviolet radiation environments at high altitude pose severe challenges to mammalian immune and metabolic systems. However, little is known about how captive forest musk deer adapt to high-altitude environments and their seasonal variations. This study analyzed peripheral blood transcriptomes of 33 captive forest musk deer (Moschus berezovskii) at high altitude (~3900 m) and low altitude (~1450 m) during autumn-winter and spring-summer seasons. Results revealed comprehensive immune suppression in the high-altitude group during autumn-winter (downregulation of complement system CFB/C2/C3, interferon pathway genes including FLT3, with only natural killer (NK) cell PRKCQ upregulated), coupled with energy-conserving metabolic reprogramming (altered carbohydrate metabolism, inhibited lipid synthesis, fat mobilization, suppressed protein degradation). During spring-summer, neutrophil antimicrobial responses (SLPI/NCF1/ELANE) and humoral immunity (B cell differentiation genes PAX5/RUNX1; class-switch enzyme AICDA) partially recovered while cellular immunity (IL15/B2M) remained suppressed, accompanied by enhanced anabolic metabolism and adipocyte differentiation. Notably, NK cell-mediated cytotoxicity showed selective enhancement despite comprehensive immune suppression, representing an energy-efficient innate defense strategy. This study provides the first characterization of seasonal immune dynamics in a high-altitude cervid species. These findings reveal persistent immune constraints in high-altitude populations and provide theoretical foundations for disease prevention and health management in captive forest musk deer at high altitudes.

Specialized herbivores like giant pandas (Ailuropoda melanoleuca), red pandas (Ailurus fulgens), and bamboo rats, which primarily consume bamboo, are at risk of nutrient deficiencies, particularly vitamin B12 (VB12), potentially leading to cardiovascular diseases. This study explored the effects of VB12 supplementation on cardiovascular health in silver star bamboo rats (Rhizomys pruinosus). We first conducted a comprehensive genome annotation of R. pruinosus, laying the foundation for in-depth evolutionary studies. Comparative transcriptomic analysis revealed that genes related to cardiovascular disease (e.g., Sgcb, Adcy2, Itga1, Itgb8, Ifng, and Gpc1) were upregulated in the livers of R. pruinosus compared to carnivorous and omnivorous rodents, indicating a higher cardiovascular disease risk. After 60 days of VB12 supplementation, liver transcriptome analysis revealed significant improvements in cardiovascular health markers, including reduced cholesterol synthesis and enhanced fatty acid metabolism. Serum biochemical assays indicated that VB12 supplementation led to reduced homocysteine levels, decreased low-density lipoprotein (LDL)-to-high-density lipoprotein (HDL) ratios, and increased the apolipoprotein A-to-apolipoprotein B ratio. These findings suggest that VB12 may mitigate cardiovascular disease risk and could be considered in the dietary management of specialized bamboo-eating species. Our study provides valuable insights into disease prevention strategies for these species with similar dietary habits.

Background: Preparations derived from Periplaneta americana, such as Kangfuxin Liquid, have been used in China for wound and ulcer management, yet their active constituents remain incompletely characterized. Recombinant P. americana thymosin isoforms (Pa-THYs) have been reported to accelerate wound closure in nondiabetic mice. Their effects and associated transcriptional responses in diabetic wounds remain unclear. Methods: Three Pa-THYs (THY1–3) were topically applied to full-thickness excisional wounds in ob/ob diabetic mice, with thymosin β4 (Tβ4) and PBS used as positive and negative controls. Wound healing was assessed by planimetry, hematoxylin and eosin (H&E) staining, Masson trichrome staining, and CD31 immunohistochemistry. RNA sequencing of wound tissues on days 3 and 8 post-injury was performed, followed by differential gene expression analysis, Gene Ontology and pathway enrichment analysis, protein–protein interaction network construction, marker gene-based cell-type-associated expression scoring, and preranked GSEA. Results: On day 8, mean wound-closure percentages ranged from 95% to 97% across the THY1, THY2, THY3, and Tβ4 groups compared to 81% in the PBS group. At this time point, treated wounds showed more complete epithelial coverage. The CD31-positive area fraction was higher in all active-treatment groups, whereas the collagen volume fraction was higher in the THY2 and THY3 groups than in the PBS group. Among the Pa-THY groups, THY2 showed the largest day-3 DEG set, whereas THY1 and THY3 showed prominent epithelial-differentiation signatures at the later time point. THY3 showed the largest day-8 DEG set and the greatest pairwise DEG overlap with Tβ4. As a complementary threshold-independent analysis, GSEA identified coordinated early metabolic responses, broadly distributed interferon-associated enrichment, and late keratinization enrichment in THY1, THY3, and Tβ4. Conclusions: Topical THY1, THY2, and THY3 improved day-8 wound closure in male ob/ob mice, with accompanying changes in epithelial coverage, CD31-positive area fractions, and collagen staining. The transcriptomic findings indicate shared pathway-level responses together with time- and isoform-associated differences. These results support a further preclinical evaluation of Pa-THYs.

Age-related changes throughout the lifespan are known to influence gut microbiota composition, microbial functional potential, and host-associated metabolic processes. Understanding these age-related variations is important for elucidating their potential physiological implications at different life stages. However, information regarding the gut microbiome and metabolomic characteristics of super-geriatric captive giant pandas (Ailuropoda melanoleuca) remains limited. In this study, fecal samples were collected from adult and super-geriatric captive giant pandas and analyzed using metagenomic sequencing combined with untargeted metabolomics. The gut microbiota of super-geriatric individuals exhibited a marked decrease in Bacillota and an enrichment of Pseudomonadota compared with adult individuals. Functional profiling revealed age-associated shifts in microbial metabolic potential, with a transition from biosynthesis-dominated pathways toward pathways related to substrate degradation and energy utilization. Metabolomic analyses further revealed pronounced metabolic alterations in super-geriatric giant pandas, including elevated levels of unsaturated fatty acids and changes in bile acid–related metabolites. Alterations in gut microbiota composition, particularly the relative enrichment of Pseudomonadota-associated taxa, were associated with inflammation-related metabolic features. Collectively, these findings indicate coordinated changes in gut microbial composition and metabolic profiles during aging. Overall, this study characterizes age-associated alterations in gut microbiota structure and fecal metabolic signatures in super-geriatric captive giant pandas, providing a scientific basis for future studies on microbiota–metabolism interactions and for improving nutritional management and health monitoring strategies in aged individuals of this endangered species.