Objective To investigate whether commuting mode is associated with biological aging, including KDM 's Biological Age Acceleration (KDM-BAA), PhenoAge Acceleration (PhenoAA) and leukocyte telomere length (LTL) based on the UK Biobank (UKB). Methods We performed a cross-sectional study of 225,018 UKB participants recruited 2006–2010. Commuting mode was categorized into non-active, walking only, mixed mode walking, cycling, and mixed mode cycling. The sign of LTL was reversed, then the three biological aging biomarkers were standardized and dichotomized according to whether the standardized value was greater than 0. A series of logistic regression models were fitted with progressive covariate adjustment. Subgroup analyses assessed effect modification, and sensitivity analyses tested robustness to alternative analytic specifications. Results In fully-adjusted models, the walking group (ORP = 0.928, 95% CI 0.874–0.984, p = 0.013; ORK = 0.922, 95% CI 0.859–0.989, p = 0.022) and the mixed cycling (ORP = 0.852, 95% CI 0.816–0.890, p < 0.001; ORK = 0.881, 95% CI 0.839–0.925, p < 0.001) exhibited lower biological age accelerations relative to non-active commuting. The cycling group exhibited lower Z-PhenoAA and longer LTL (ORP = 0.890, 95% CI 0.837–0.947, p < 0.001; ORT = 0.944, 95% CI 0.893–0.998, p = 0.044). The findings in the sensitivity analyses remained consistent with the main results. Conclusion Active commuting, especially cycling, is associated with slower biological aging and replacing car use with bicycle commuting may offer a simple, low-cost and time-efficient strategy that may effectively delay biological aging.
Background Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer, characterized by high incidence and mortality rates. Long noncoding RNAs (lncRNAs) have gained increasing attention for their regulatory roles in tumors, but the functions of many lncRNAs remain poorly understood. Previous studies have suggested that LINC02126 is downregulated in LUAD, yet its specific biological function remains unclear. This study aimed to investigate the role of LINC02126 in LUAD and to elucidate the underlying molecular mechanisms. Methods RT-qPCR and Western blotting were employed to detect mRNA and protein expression levels. Cell viability, proliferation, cell cycle distribution, apoptosis, migration, and invasion were assessed using CCK-8, colony formation, EdU, flow cytometry, wound healing, and transwell assays. MeRIP-qPCR, m6A-IP-qPCR, RNA pull-down, dual-luciferase reporter, and RNA stability assays were used to evaluate LINC02126 m6A modification and its interaction with YTHDC1. The target miRNA was identified via bioinformatics combined with dual-luciferase reporter, Ago2-RIP, and RNA pull-down assays. A nude mouse xenograft model was used to examine tumor growth in vivo. Results LINC02126 was significantly downregulated in LUAD and associated with poor prognosis. Overexpression of LINC02126 inhibited proliferation, migration, invasion, and EMT, while promoting apoptosis and cell cycle arrest. YTHDC1 bound to LINC02126 m6A sites and enhanced its stability. LINC02126 directly bound to and reduced miR-501–5p levels. Inhibition of miR-501–5p mimicked LINC02126’s antitumor effects, while miR-501–5p overexpression reversed them. In vivo, LINC02126 overexpression suppressed tumor growth and decreased miR-501–5p expression. Conclusion YTHDC1 enhanced LINC02126 stability via m6A modification, and LINC02126 inhibited LUAD progression through miR-501–5p.
Chronic kidney disease (CKD) represents a significant global health challenge, with its progression and complications associated with dysbiosis of the gut microbiota. Patients with CKD demonstrate stage-dependent alterations in the composition of gut microbiota and a reduction in diversity, which is characterized by a decline in beneficial bacteria (e.g., Bifidobacterium, Lactobacillus) and an increase in pathogenic species. This dysbiosis disrupts the gut-kidney axis, resulting in a depletion of protective metabolites such as short-chain fatty acids (SCFAs) and secondary bile acids, while facilitating the accumulation of toxic metabolites including trimethylamine N-oxide (TMAO), indoxyl sulfate (IS), and p-cresyl sulfate (pCS). These toxins contribute to the progression of CKD and cardiovascular complications through mechanisms that involve oxidative stress, inflammation (e.g., NF-ĸB/NLRP3 activation), fibrosis (e.g., TGF-β/Smad signaling), and endothelial dysfunction. Therapeutic strategies aimed at modulating the gut microbiota encompass dietary interventions (such as increasing fiber and plant-based protein), microecological agents (including probiotics and prebiotics), fecal microbiota transplantation (FMT), and adsorbents (e.g., targeting uremic toxins). Although these approaches show promise in delaying CKD progression and alleviating complications, they necessitate further validation through large-scale clinical trials to confirm their efficacy, safety, and the development of personalized protocols. Investigating the gut-kidney axis may provide novel biomarkers and therapeutic opportunities for enhancing CKD outcomes.
Asthenoteratozoospermia represents a leading cause of idiopathic male infertility, characterized by diminished sperm motility and aberrant morphology. Testis-expressed protein 44 (Tex44) is essential for sperm flagellar development in mice, yet its pathogenic contribution to human asthenoteratozoospermia and clinical translational relevance remain largely undefined. This study aimed to characterize the role of TEX44 in sperm structure and function, identify pathogenic TEX44 variants in infertile men, and evaluate intracytoplasmic sperm injection (ICSI) as a fertility-rescue strategy. A Tex44-knockout (Tex44⁻/⁻) mouse model was generated using CRISPR/Cas9. Sperm parameters were analyzed by computer-assisted sperm analysis (CASA), coupled with ultrastructural, transcriptomic, and functional fertility assays (in vivo fertilization, IVF, ICSI). Whole-exome sequencing (WES) was performed in 535 well-phenotyped infertile men, and candidate TEX44 variants were verified by Sanger sequencing. Protein structure prediction and clinical ICSI outcome analysis were also performed. Tex44⁻/⁻ mice displayed asthenoteratozoospermia, marked by disrupted axonemal 9 + 2 microtubule organization, defective mitochondrial sheath assembly, and compromised fertility, all of which were effectively rescued by ICSI. Transcriptomic profiling demonstrated dysregulation of pathways governing flagellar structure and mitochondrial function. In humans, three pathogenic TEX44 variants were identified in seven affected individuals. All patients presented with severe semen abnormalities. ICSI resulted in favorable reproductive outcomes, including healthy live births. Tex44 deficiency causes asthenoteratozoospermia by impairing sperm axonemal integrity and mitochondrial sheath assembly. Pathogenic TEX44 variants are associated with human asthenoteratozoospermia, and ICSI serves as an effective therapeutic intervention for affected patients. These findings establish TEX44 as a novel diagnostic biomarker, broaden the genetic architecture of male infertility, and strengthen the translational bridge between basic science and clinical reproductive care.
Abstract Background The objective of this study was to evaluate and compare the safety, efficacy, and cost-effectiveness of different mobility aids during the early rehabilitation phase following surgical repair of acute Achilles tendon rupture (AATR). Methods This prospective cohort study included 198 patients who underwent surgical repair for AATR between April 2023 and February 2025, with 171 males (86.4%) and a mean age of 36.4 years. Based on the mobility aid used weeks 3–6 postoperatively, participants were categorized into four groups: Wheelchair (n = 43), Knee Scooter (n = 41), Axillary Crutches (n = 78), and Leg Support (LS) Walker (n = 36). Patients were scheduled for assessments at 2, 4, 6, 12, and 24 weeks, with an additional telephone follow-up conducted approximately one year after surgery. Primary outcomes included the rate of unplanned Emergency Department (ED) visits, the affected-to-unaffected (A: U) calf circumference ratio, and expected rehabilitation costs. Secondary outcomes encompassed the Visual Analog Scale, the Achilles Tendon Total Rupture Score, the American Orthopedic Foot & Ankle Society Ankle-Hindfoot Score, and time to key recovery milestones, including single-leg heel raise to 50% of contralateral side, return to light exercise, return to work, and return to pre-injury exercise. Continuous variables were analyzed using one-way ANOVA or Kruskal-Wallis test, and categorical variables using chi-square or Fisher’s exact test, while linear mixed-effects models were employed for longitudinal outcomes. Results During the early rehabilitation phase (Weeks 3–6), unplanned ED visit rates differed significantly among the four groups (p = 0.032), with the Axillary Crutches showing significantly higher odds than the Wheelchair (OR = 8.24, 95% CI 1.16–58.53, p = 0.040). A significant difference in the A: U ratio was observed among the four groups at 6 weeks postoperatively (p = 0.037), and post-hoc comparisons showed significant differences for LS Walker vs. Wheelchair (p < 0.001), Axillary Crutches vs. Wheelchair (p = 0.002), and LS Walker vs. Knee Scooter (p = 0.038). The LS Walker and Axillary Crutches also demonstrated superior performance in VAS, ATRS, and AOFAS scores from Week 4 to Week 12, and achieved key recovery milestones significantly earlier (p < 0.001). Economic analysis revealed the lower direct treatment costs in the Axillary Crutches (477 RMB) and Knee Scooter (539 RMB), followed by the Wheelchair (664 RMB) and LS Walker (1126 RMB) (p < 0.001). Conclusions LS Walker demonstrated superior efficacy in preserving muscle and accelerating functional recovery, while Knee Scooter offered a favorable profile for fall prevention and cost-effectiveness. Trial registration ClinicalTrials.gov (NCT04663542), registered on 22 September 2020.
