Ferroptosis, a distinct form of programmed cell death characterized by iron-dependent lipid peroxidation, has emerged as a critical factor in the pathogenesis of various diseases. Given the increasing prevalence of osteoporosis worldwide and the increasing incidence of osteoporosis, understanding the molecular mechanisms underlying bone loss is imperative for developing targeted therapies. Recent evidence suggests that ferroptosis plays a pivotal role in osteoporosis by influencing the balance between osteoblast and osteoclast activity. This review examines the mechanistic basis of ferroptosis and its pathological implications in osteoporosis. By delineating the interplay between ferroptosis and skeletal remodeling, we highlight potential therapeutic strategies aimed at modulating ferroptosis to mitigate osteoporosis progression.

Background: Objective body-fluid biomarkers may help characterize exercise-induced physical fatigue; however, heterogeneity in exercise protocols, biological matrices, and analytical platforms complicates biomarker interpretation. Purpose: This study aimed to identify candidate acute exercise-responsive metabolic biomarkers associated with physical fatigue assessment by integrating conventional biomarker evidence, exercise-related metabolomics, and exploratory targeted Liquid chromatography–mass spectrometry (LC-MS) analysis. Methods: We conducted three complementary analyses: (1) a systematic review and random-effects meta-analysis of quantitative biomarkers measured in body-fluid matrices, including blood, plasma, serum, saliva, sweat, urine, and interstitial fluid, at pre-exercise and post-exercise time points; (2) a descriptive fold-change-based synthesis of exercise-related metabolomics studies; and (3) an exploratory paired plasma–saliva liquid chromatography–mass spectrometry pilot analysis in seven apparently healthy young male volunteers. Eligible studies included apparently healthy human participants without reported acute or chronic diseases, major injuries, pregnancy, or clinically diagnosed pathological fatigue, undergoing endurance, resistance, high-intensity interval, or mixed exercise protocols. Biomarkers reported in ≥10 independent comparisons were pooled using log-transformed post-exercise/pre-exercise response ratios. Results: The systematic review and meta-analysis included 110 articles, 129 experiments, and 1826 participants. Lactate showed the strongest pooled response after exercise (response ratio = 4.43, 95% CI: 3.74–5.25, p < 0.00001; I² = 98%), followed by IL-6 (2.15, 95% CI: 1.50–3.07, p < 0.0001; I² = 87%), CK (1.70, 95% CI: 1.56–1.86, p < 0.00001; I² = 90%), and LDH (1.23, 95% CI: 1.11–1.35, p < 0.0001; I² = 93%). Metabolomics synthesis identified lactate, pyruvate, hypoxanthine and xanthine as frequently reported exercise-responsive metabolites related to glycolysis and purine degradation. Exploratory LC-MS analysis showed consistent directional changes in these metabolites in paired plasma and saliva samples. Conclusions: Lactate, pyruvate, hypoxanthine, and xanthine represent candidate metabolism-based acute exercise-responsive biomarkers associated with physical fatigue. However, their fatigue specificity remains to be established and requires validation using independent fatigue criteria, non-fatiguing exercise controls, matrix-specific analyses, and adequately powered diverse cohorts.

Mitochondrial function is critical for spermatogenesis and male fertility. MOTS-c, a mitochondrially encoded regulatory peptide, has recently been reported to effectively protect testicular spermatogenesis in mice, but its specific role and mechanism remain unclear. This study first demonstrated that MOTS-c levels were significantly reduced in the serum of patients with oligoasthenozoospermia, and these levels correlated with semen quality parameters. Spermatogenic dysfunction, including decreased sperm concentration, disrupted seminiferous tubule architecture, and a reduction in spermatogonia, was induced by mechanical stress through microgravity model. Notably, exogenous MOTS-c ameliorated spermatogenic impairment by suppressing oxidative stress and ferroptosis induced by mechanical stress. Solute Carrier Family 7 Member 11 (SLC7A11), a key molecule in ferroptosis, was identified as a target of MOTS-c. Moreover, loss- and gain-of-function studies showed that SLC7A11 inhibited ferroptosis and oxidative stress and promoted spermatogonia proliferation. Furthermore, MOTS-c enhanced the protection against spermatogenic impairment by increasing SLC7A11 levels under mechanical stress. Collectively, this study elucidates the crucial role of MOTS-c in protecting spermatogenesis by antagonizing ferroptosis, providing a theoretical foundation for its potential therapeutic use in male infertility associated with spermatogenic defects.

Glucocorticoid‐induced osteoporosis (GIO) is driven by a pathogenic shift in bone marrow mesenchymal stem cell (BMSC) lineage commitment from osteogenesis to adipogenesis. Here, we identify Microtubule Actin Cross‐linking Factor 1 (MACF1) as a critical regulator of MSC fate that is severely suppressed during long‐term glucocorticoid (GC) exposure. We demonstrate that MACF1 deficiency phenocopies GC‐induced marrow adiposity and bone loss. Crucially, restoring endogenous MACF1 via promoter‐targeted small activating RNA (saRNA) effectively corrects this fate bias and reverses microarchitectural deterioration in GIO mice. Mechanistically, MACF1 acts as a key facilitator of vesicular trafficking. By orchestrating the assembly of the Rab14/KIF16B complex, MACF1 drives the precise anterograde transport of Fibroblast Growth Factor Receptors (FGFRs) to the plasma membrane. GC exposure downregulates MACF1, disrupting this transport machinery and causing intracellular FGFR sequestration. This transport failure depletes functional cell‐surface FGFRs, thereby blunting osteogenic signaling and triggering the adipogenic shift. Collectively, our findings establish the MACF1‐governed intracellular trafficking network as an important determinant of FGFR spatial distribution and MSC fate, highlighting it as a promising therapeutic target for restoring bone‐fat equilibrium in GIO.

With the rapid expansion of terahertz (THz) technologies across communications, imaging, sensing, and biomedicine, defining their biological effects, safety boundaries, and controlled intervention has become a critical scientific priority for their responsible deployment. Although diverse biological responses have been observed at different levels of biological organization, the findings are highly dependent on exposure parameters and biological models. Moreover, how molecular perturbations propagate across scales to produce higher-order biological effects remains poorly understood. Because biomacromolecules and their hydration environments constitute the primary interface which THz radiation interacts with biological systems, elucidating THz bioeffects at the molecular scale is essential for mechanistic understanding. Here, we systematically review recent advances in THz interactions with key biological targets, including proteins, nucleic acids, ion channels, and biological membranes, and examine how local molecular perturbations translate into higher-level phenotypes. On this basis, we critically assess the major challenges facing the field and propose an integrative framework for mechanistic validation. By consolidating dispersed findings and emphasizing methodological standardization, this review provides a coherent conceptual basis for interpreting THz bioeffects and guiding their biomedical translation.