Sarcopenic obesity (SO), a geriatric syndrome characterized by the coexistence of progressive skeletal muscle atrophy and excessive adipose tissue accumulation, represents a growing public health challenge associated with aging populations. While multifactorial pathogenesis involves chronic inflammation, hormonal changes, and mitochondrial dysfunction, sedentary lifestyles and aging remain primary modifiable and non-modifiable risk factors, respectively. Mechanistically, exercise exerts dual therapeutic effects: (1) hypertrophy of type II muscle fibers through IGF-1/Akt/mTORC1 signaling activation, and (2) enhanced lipid β-oxidation via AMPK/PGC1α axis stimulation, thereby mitigating both sarcopenia and adiposity. The autophagy-lysosome system, a conserved cellular quality-control mechanism, orchestrates organelle turnover and nutrient recycling through three distinct pathways: macroautophagic, chaperone-mediated autophagy, and mitophagy. In SO, impaired proteolytic and lipolytic processes converge to induce autophagic flux blockade, manifested by accumulated p62/SQSTM1 and reduced LC3-II/LC3-I ratio. Targeting the AMPK/mTOR signaling nexus, which senses cellular energy status, emerges as a strategic intervention. Exercise-mediated ATP depletion activates AMPK while suppressing mTORC1, thereby synchronously inducing autophagy initiation (ULK1 phosphorylation) and lysosomal biogenesis (TFEB nuclear translocation). This metabolic reprogramming ultimately restores proteostasis and lipid homeostasis in myocytes and adipocytes.

Porcine epidemic diarrhea virus (PEDV), a member of the Alpha-coronavirus genus in the Coronaviridae family, induces acute diarrhea, vomiting, and dehydration in neonatal piglets. This study aimed to investigate the genetic dependencies of PEDV and identify potential therapeutic targets by using a single-guide RNA (sgRNA) lentiviral library to screen host factors required for PEDV infection. Protein kinase C θ (PKCθ), a calcium-independent member of the PKC family localized in the cell membrane, was found to be a crucial host factor in PEDV infection. The investigation of PEDV infection was limited in Vero and porcine epithelial cell-jejunum 2 (IPEC-J2) due to defective interferon production in Vero and the poor replication of PEDV in IPEC-J2. Therefore, identifying suitable cells for PEDV investigation is crucial. The findings of this study reveal that human embryonic kidney (HEK) 293T and L929 cells, but not Vero and IPEC-J2 cells, were suitable for investigating PEDV infection. PKCθ played a significant role in endocytosis and the replication of PEDV, and PEDV regulated the expression and phosphorylation of PKCθ. Apoptosis was found to be involved in PEDV replication, as the virus activated the PKCθ-B-cell lymphoma 2 (BCL-2) ovarian killer (BOK) axis in HEK293T and L929 cells to increase viral endocytosis and replication via mitochondrial apoptosis. This study demonstrated the suitability of HEK293T and L929 cells for investigating PEDV infection and identified PKCθ as a host factor essential for PEDV infection. These findings provide valuable insights for the development of strategies and drug targets for PEDV infection.

Exercise is widely recognized as a critical determinant of health, yet its effects can diverge substantially depending on intensity, duration, and individual characteristics. This review synthesizes current knowledge on the mechanisms underlying exercise-induced stress responses, outlining a sequential cascade from biomechanical signal perception, through organelle and metabolic regulation, to systemic integration via hormonal, myokine, and immune pathways. We highlight the concept of a bidirectional threshold theory, which proposes that moderate exercise promotes adaptation and health benefits, while excessive exercise may trigger maladaptive responses and pathological outcomes. At the same time, we note that significant inter-individual variability in exercise responses raises important questions regarding the generalizability of this framework. By integrating evidence across molecular, cellular, and systemic levels, this review provides a holistic perspective on the dual effects of exercise, underscores the need for improved biomarkers to monitor adaptive vs. maladaptive responses, and identifies research gaps that must be addressed to translate these mechanisms into personalized exercise strategies.

Background: Alcohol-associated liver disease (ALD) involves ethanol-related metabolic injury, inflammation, gut–liver dysfunction, and progressive loss of skeletal muscle and functional reserve. Exercise could influence several of these pathways, but ALD-specific evidence remains limited. We therefore evaluated exercise as an adjunct, not a substitute for established care, across the ALD spectrum. Methods: We conducted a structured narrative review of PubMed/MEDLINE, Google Scholar, and publisher records updated through 20 August 2026. Evidence was classified as direct human ALD/MetALD evidence, direct preclinical alcohol-injury evidence, indirect clinical evidence from MASLD or mixed-etiology cirrhosis, or mechanistic evidence from broader exercise biology. Results: Direct human evidence is predominantly observational. Leisure-time physical activity is associated with lower liver mortality across drinking patterns and with lower odds of at-risk advanced fibrosis in MetALD/ALD. These associations do not establish the efficacy of structured exercise training. Preclinical alcohol-injury models support redox- and Nrf2-mediated hepatoprotection, whereas proposed effects on AMPK-SIRT1-PGC-1α signaling, mitochondrial quality, gut microbial metabolites, myokines, and ammonia handling remain largely extrapolated. Metabolomic studies identify disturbances in redox balance, lipid intermediates, acylcarnitines, bile acids, and amino acid and tryptophan metabolism. These alterations provide candidate endpoints for future trials. Myostatin and decorin are associated with ALD severity, but their responsiveness to exercise is unknown. We therefore propose a stage-specific research and practice framework with explicit safety considerations. Conclusions: Exercise is a promising but unproven multisystem adjunct for ALD. It should complement abstinence support, alcohol use disorder care, nutrition, and standard medical management. ALD-specific trials should integrate metabolomics, liver outcomes, functional measures, sex, alcohol exposure, disease stage, and adverse events.