Search Results (2,293)

Skin is a highly specialized barrier organ, which serves essential barrier, immune, and sensory functions and exhibits conserved structure. In addition, each species exhibits a unique skin transcriptional profile for adapting distinct environmental conditions and physiological demands. However, these transcriptional profiles across mammals remain incompletely understood. In this study, we integrated 61 publicly available skin RNA-seq datasets from eight mammalian species: human (Homo sapiens), macaque (Macaca fascicularis), mouse (Mus musculus), sheep (Ovis aries), goat (Capra hircus), donkey (Equus asinus), rabbit (Oryctolagus cuniculus), and pig (Sus scrofa). We identified a large number (2286 to 4588) of differentially expressed genes (DEGs) based on 10,504 one-to-one orthologous genes in all pairwise species comparisons. A total of 44 conserved genes were identified by integrating tissue specificity, expression variability, and mean expression level, which were enriched in epidermal development, keratinocyte differentiation, and desmosome organization. We also identified species-specific genes and transcription factors, such as STMN1 (donkey), COL1A1 (goat), and ACTN2 (mouse), which are associated with the cell cycle, extracellular matrix, and muscle contraction pathways, respectively. WGCNA further revealed goat-associated module 2 (M2) enriched in the negative regulation of angiogenesis. Collectively, this study provides a comprehensive cross-species transcriptional profile resource for mammalian skin, providing a valuable resource for understanding the regulatory plasticity underlying skin evolution across mammals. Full article

Background: Steel club training is a form of strength and conditioning exercise that involves swinging weighted clubs through circular and pendular movements, thereby imposing substantial rotational and multiplanar demands on the trunk. However, the core muscle activation patterns elicited by these exercises remain poorly characterized. Purpose: This study aimed to characterize global, muscle-specific, and side-to-side core muscle activation across a battery of steel club exercises and compare it with that of conventional plank variations. Methods: A within-subject experimental design was used in a single-session laboratory setting. Fourteen trained males (n = 14) performed ten steel club exercise conditions (comprising seven distinct movement patterns, with unilateral variations performed bilaterally) using 8 and 16 kg clubs and four isometric plank variations; data from n = 13 were available for the Shield Cast 16 kg condition and the omnibus ANOVA due to one excluded signal. Surface electromyography was bilaterally recorded from the rectus abdominis, external oblique, internal oblique, and multifidus muscles and normalized to maximal voluntary contraction (% MVC). Repeated-measures ANOVA was used to assess global and muscle-specific differences across exercise conditions, and paired-samples t-tests were used to evaluate side-to-side differences. Results: Global core activation significantly differed across exercises (p < 0.001, ηp² = 0.798) and was generally greater during steel club exercises than during conventional planks. The Lateral Pendulum to Shoulder Cast (54.77 ± 9.32% MVC), Gamma Cast (47.79 ± 8.96% MVC), and Shield Cast (43.96 ± 11.25% MVC), all performed with 16 kg, elicited greater global activation than each of the four plank variations (all adjusted p < 0.05). The internal oblique showed the greatest activation across most steel club exercises, reaching 69.40 ± 12.18% MVC during the Lateral Pendulum to Shoulder Cast. Several unilateral exercises also elicited significant side-to-side differences, particularly Mills and Reverse Mills (all p < 0.05). Conclusions: Among experienced steel club practitioners, these exercises elicited exercise-specific, dynamic, and multiplanar core activation patterns, with several exercises—particularly those performed with 16 kg—producing greater global activation than conventional plank variations. These findings support steel club training as a complementary modality for dynamic core training, although the independent contributions of movement pattern and external load, as well as long-term adaptations, remain to be established. Full article

The knee is a mechanically demanding synovial organ in which joint loading, tissue deformation, cellular mechanotransduction and matrix turnover are coupled. This narrative review critically links those scales and asks where the evidence is sufficiently mature for mechanistic or clinical inference. PubMed/MEDLINE and Europe PMC were searched from database inception to 20 July 2026 using structured terms for knee biomechanics, cartilage and osteochondral mechanobiology, finite element modelling, mechanosensitive channels, osteoarthritis, machine learning and digital twins. Landmark studies were selected for foundational models, while recent studies were prioritised for causal experiments, validation and translation. Instrumented implants show that common activities generate tibiofemoral forces of several times body weight, but tissue-level exposure also depends on muscle co-contraction, geometry and material properties. Biphasic and fibril-reinforced models explain how those loads become stress, strain, fluid pressure and osmotic signals. At the cell scale, TRPV4 and PIEZO1/2 participate in overlapping, context-dependent calcium signalling rather than a universal protective–pathological binary; most causal evidence remains preclinical. Osteoarthritis is therefore framed as a mechanically amplified feedback process involving cartilage, bone, synovium and systemic modifiers. Computational degeneration models and machine-learning surrogates are increasingly informative, although prospective validation, parameter identifiability and uncertainty propagation remain limiting. The review’s added value is an explicit transmission-and-validation framework that connects whole-joint observables to molecular responses while labelling the evidence source and translational readiness at every step. Full article

Myostatin (GDF8) is a member of the transforming growth factor-β (TGF-β) superfamily. Myostatin gene mutations or inhibition of the Myostatin/Activin pathway results in increased skeletal muscle mass, demonstrating its role as a negative regulator of skeletal muscle. Myostatin blockade is a promising strategy for increasing muscle mass in myopathies such as Duchenne Muscular Dystrophy (DMD); however, it faces considerable challenges in clinical translation, in part due to the progressive nature of the disease. Here we tested the ability of JA16 monoclonal antibody-mediated myostatin blockade to improve the dystrophic phenotype in newborn mdx mice (an animal model of DMD). Myostatin inhibition led to significant increases in muscle size, fiber number and cross-sectional area along with increased absolute force alongside reduced post-eccentric contraction force drop and reduced serum creatine kinase. We used the Multiparametric Muscle Improvement Score (MMIS) to objectively quantitate benefits in this preclinical study and determined that the magnitude of improvements exceeded those reported using the exact same intervention in older mdx mice treated for the same duration. This study demonstrates an age-dependent aspect of this intervention and suggests that earlier interventions may provide greater therapeutic benefits. Full article

Pelvic floor dysfunctions are highly prevalent and can substantially impair quality of life. Physiotherapy is considered a first-line conservative treatment, and the integration of technologies such as ultrasound may enhance outcomes through visual biofeedback. Objectives: To evaluate the effectiveness of ultrasound as a biofeedback tool in physiotherapeutic interventions for pelvic floor dysfunctions across different populations. Methods: A systematic review was conducted following PRISMA guidelines and registered in PROSPERO (CRD420261278982). The literature search was conducted between February and March 2025 in PubMed, Web of Science, Scopus, Medline, and PEDro. Randomized controlled trials using ultrasound as biofeedback in physiotherapy interventions were included. Methodological quality was assessed using the PEDro scale, and risk of bias was evaluated with the RoB 2 tool. Results: Two randomized controlled trials involving 75 women were included. One study investigated older women with urinary incontinence, whereas the other included postpartum women with pregnancy-related pelvic girdle pain. In Galea et al., transabdominal ultrasound biofeedback was not superior to conventional feedback based on vaginal palpation for urinary leakage, incontinence frequency, or quality of life, although the ultrasound group showed a significant within-group reduction in leakage episodes. In Kuo et al., ultrasound-guided biofeedback combined with pelvic floor and stabilization exercises reduced pain and disability compared with education alone and improved walking performance, but it was not consistently superior to exercise without biofeedback and did not significantly improve pelvic floor muscle contractility. The small number of studies, heterogeneity of populations and interventions, and low to very low certainty of the evidence limited the strength of the findings. Conclusions: Ultrasound-based biofeedback may be a useful adjunct to pelvic floor physiotherapy, particularly for facilitating correct muscle contraction and supporting motor learning. However, the available evidence does not demonstrate a consistent additional clinical benefit over conventional feedback or exercise alone. These findings should therefore be interpreted cautiously. Further high-quality randomized controlled trials with larger samples, standardized protocols, and longer follow-up are required. Full article

Background: Transcranial direct current stimulation (tDCS) applied unilaterally to the cerebellum (c-tDCS) can improve several aspects of human motor performance. The purpose of the study was to examine the influence of dual source tDCS delivered bilaterally over the cerebellar cortices (dsc-tDCS) on the time to task failure (TTF) of a fatiguing contraction in young adults. Methods: The study utilized a double-blind, randomized, SHAM-controlled, within-subjects, crossover design, and participants were given either dsc-tDCS or SHAM stimulation in two different experiments held 7 days apart in a fully counterbalanced order. Every aspect of the two experiments was the same except the type of stimulation (dsc-tDCS or SHAM) delivered during the fatiguing contraction. The fatiguing contraction was executed with a precision grip at 15% of the maximum voluntary contraction (MVC) force, and participants were instructed to maintain the contraction for as long of time as possible. Results: The TTF and fatigue index were both similar for the dsc-tDCS and SHAM stimulation conditions. In addition, the electromyographic (EMG) activity, force error, and standard deviation (SD) of force measured during the fatiguing contraction were also not statistically different between the dsc-tDCS and SHAM stimulation conditions. Conclusions: The findings suggest that dsc-tDCS does not decrease the rate of progression of muscle fatigue. Full article

The pathological deposition of amyloid-β (Aβ) in the walls of cerebral blood vessels as cerebral amyloid angiopathy (CAA) is a key feature of Alzheimer’s disease (AD) and is linked to impaired clearance of Aβ via intramural periarterial drainage (IPAD). The spontaneous contractions of cerebral smooth muscle cells (SMCs) are thought to drive IPAD, but the relationship between vascular aging and Aβ accumulation remains unclear. We propose a unified framework centered on cerebral intramural cells (CICs), including arterial SMCs, specialized pericyte subtypes, as mediators of vascular dysfunction and neurodegeneration. We integrate current evidence from studies of cerebral small vessel disease, blood–brain barrier (BBB) dysfunction, pericyte biology, vascular aging, cerebral perfusion, and IPAD. CICs regulate vasomotion, capillary flow, BBB integrity, and IPAD. Their dysfunction impairs perfusion and protein clearance, increasing vulnerability in white matter and the hippocampus. These vascular alterations interact with amyloid and inflammatory processes, contributing to synaptic dysfunction, network disconnection, and neurodegeneration. CICs represent potential therapeutic targets. A CIC-centered framework may help explain the links between vascular dysfunction, impaired Aβ clearance, and neurodegeneration in AD and CAA. Full article

Foam rolling (FR) is widely used to acutely enhance range of motion, yet the influence of different application volumes on neuromuscular, structural, and biochemical responses remains unclear. This study investigated the acute effects of low- and high-volume hamstrings FR interventions. Fifty-seven healthy male participants were randomly assigned to a high-volume FR group (IG10; 10 min per posterior thigh), a low-volume FR group (IG2; 2 min per posterior thigh), or a control group (CG; 20 min rest). Pre- and post-intervention assessments included sit-and-reach (SAR) performance, shoulder circumduction (SC) (mobility), maximal voluntary isometric contraction (MVIC), biceps femoris muscle stiffness (MS), and creatine kinase (CK) levels. Linear mixed-effects models revealed significant Time effects for SAR performance and SC, as well as a Group effect for SC (p < 0.05), whereas no significant Group × Time interactions were observed for any outcome (all p > 0.05). Significant improvements in SC were observed in both intervention groups compared with the CG, whereas no differences were detected between the two intervention durations. In contrast, no differential effects were observed for MS, maximal strength, or CK concentrations between the intervention groups, indicating that extending the FR duration from 2 to 10 min did not provide additional acute benefits. Full article

Sprint performance improves throughout adolescence as a result of both structural and neuromuscular development. In particular, increases in body height, lower limb length, and muscle volume have been consistently linked to improvements in sprint performance. However, allometric scaling of force, speed, and power remain lower in adolescents compared to adults even after structural differences are accounted for, implicating neural factors as independent contributors to performance development. The purpose of this study was to investigate differences in neuromuscular activation patterns of the lower limb muscles during maximal sprinting between youth male athletes across two age groups (U19: 17–19 years; U16: 13–16 years). Eighteen athletes performed a 50 m maximal sprint. Spatiotemporal variables (running speed, step frequency, step length) were measured over 30–50 m using a high-speed camera (240 Hz) and timing gates. Electromyographic (EMG) signals were recorded simultaneously from ten lower limb muscles using wireless EMG sensors (2000 Hz): rectus femoris (RF), biceps femoris (BF), semitendinosus (ST), gluteus maximus (Gmax), gluteus medius (Gmed), vastus lateralis (VL), vastus medialis (VM), tibialis anterior (TA), gastrocnemius (GAS), and soleus (SOL). Root mean square (RMS) amplitude was calculated across four gait phases (contact, early-swing, mid-swing, late-swing) and normalised to maximal voluntary Isometric contraction (%MVIC). The U19 group demonstrated significantly greater running speed (U19: 9.49 ± 0.39 vs. U16: 8.67 ± 0.25 m·s⁻¹, p < 0.001), step frequency (U19: 4.49 ± 0.12 vs. U16: 4.35 ± 0.16 Hz, p = 0.004), and step length (U19: 2.12 ± 0.12 vs. U16: 1.99 ± 0.06 m, p = 0.010) than U16. The overall pattern of lower limb muscle activation across the gait cycle was broadly similar between groups; however, a significant group × phase interaction was observed for RF (p = 0.003, F = 5.257, η² = 0.247), with post hoc analysis revealing greater RF activation during early swing in U19 (p = 0.033). These findings may indicate that sprint-specific training in youth athletes is associated with not only structural but also neuromuscular differences, specifically reflecting enhanced RF recruitment during the phase-critical moment of early swing—a window in which high-threshold motor unit activation is most mechanically decisive. EMG-based assessment of hip flexor activation during maximal sprinting may provide a complementary tool, pending further validation, for talent identification and training prescription in youth track and field. Full article

Background and Objectives: Overactive bladder (OAB) has been associated with pelvic floor dysfunction, but the associations of vaginal pressure (VP) and transversus abdominis (TVA) thickness with OAB remain unclear. We examined these associations in women with lower urinary tract symptoms. Materials and Methods: This retrospective cross-sectional study included 213 women; 106 met the prespecified Overactive Bladder Symptom Score criteria and 107 did not. Maximal VP during voluntary pelvic floor contraction and ultrasonographic TVA thickness at rest, during maximal inspiration and maximal expiration, and during the abdominal drawing-in maneuver were compared between groups. Multivariable logistic regression adjusted for age, body mass index, number of deliveries, postmenopausal status, and hypertension. Results: Maximal VP and TVA thickness during the abdominal drawing-in maneuver were lower in the OAB group. In the continuous-variable model, higher VP (per 5-cmH₂O increase: OR = 0.704, 95% CI 0.576–0.845) and greater TVA thickness during the abdominal drawing-in maneuver (per 1-mm increase: OR = 0.500, 95% CI 0.343–0.708) were associated with lower odds of OAB. Neither measure showed a consistent stepwise relationship with OAB severity. Exploratory ROC analyses yielded moderate apparent AUCs, but the cohort-derived cutoffs require external validation and should not inform clinical decisions. Conclusions: Lower VP and lower TVA thickness during the abdominal drawing-in maneuver were associated with OAB in this selected cohort. Concurrent cross-sectional assessment cannot establish causality or temporal relationships and cannot exclude reverse causation. Prospective studies are required before considering predictive or preventive roles, and cohort-derived cutoffs require external validation before clinical use. Full article

Purpose: The aim of this study was to assess within-session reliability and concurrent validity of a wireless surface electromyography device (MR EMG) relative to a wireless criterion system (Delsys Trigno) during dynamic leg extension at varying loading intensities. Methods: Thirty-one resistance-trained adults performed four repetitions at 30%, 60%, and 90% of their predicted one-repetition maximum (1RM) on the plate-loaded leg extension machine, with EMG amplitude recorded simultaneously by both systems for the vastus lateralis (VL) and vastus medialis obliquus (VMO). Root mean square (RMS) amplitudes were normalized to maximal voluntary isometric contraction and compared across devices using intraclass correlation coefficients (ICC), coefficients of variation (CV%), standard error of measurement, Pearson correlations, and Bland–Altman analyses. Results: Both devices demonstrated excellent within-session reliability (ICC = 0.92–0.97; CV = 7.8–11.3%). Validity differed by muscle. Across all loads, VMO agreement was good (ICC = 0.82–0.85; r = 0.83–0.86), while VL agreement was moderate (ICC = 0.53–0.57; r = 0.54–0.64). Bland–Altman analyses revealed systematic positive bias across all conditions, with proportional bias present for the VL but absent for the VMO. Conclusions: MR EMG demonstrated excellent within-session reliability but muscle-dependent concurrent validity, with good VMO agreement and moderate VL agreement with the criterion system. Full article

Glycogenolysis is an important contributor to ATP production in contracting skeletal muscle. However, the activation of glycogen phosphorylase in resting muscle does not by itself trigger significant glycogenolysis. To elucidate the mechanisms underlying this regulation, we analyzed the functional coupling between glycogenolysis and glycolysis using a mathematical model of energy metabolism in mammalian fast-twitch (white) skeletal muscle. A system-level analysis of the model reveals an important role for inorganic phosphate (a substrate for glycogen phosphorylase) in regulating glycogenolysis rates in both resting and contracting muscle. In contracting muscle, at sufficiently high concentrations of inorganic phosphate, the activation of glycogen phosphorylase markedly increases the rate of glycogenolysis, thereby enhancing ATP production and stabilizing the cellular energy charge. In contrast, glycogen phosphorylase activation in resting muscle is unable to support glycogen breakdown due to a significant decrease in inorganic phosphate levels. Moreover, the analysis shows that forced acceleration of the glycogen phosphorylase reaction under resting conditions does not increase ATP production; instead, it promotes the accumulation of phosphorylated glycolytic intermediates, which may induce osmotic stress and cause damage to muscle cells. Full article

A previous investigation on limonene (LM), perillyl alcohol (POH), and carveol (CV), focused on the structure–activity relationship and hydroxyl group, documented that the presence of the hydroxyl group influences the pharmacodynamic potency of these agents, inhibiting smooth muscle contraction with the order of potency: POH > CV > LM. That investigation also suggested a mechanism of action, which importantly included activity on the voltage-dependent calcium channel. Here, we investigated whether this structure–activity relationship also applies to nerve excitability (an activity greatly dependent on sodium channels) using compound action potential (CAP) recordings from mouse sciatic nerves and in silico simulations. POH, CV, and LM inhibited both the positive amplitudes and conduction velocities of the two CAP components in a concentration-dependent manner, with IC₅₀ values of 0.8, 1.0, and 4.3 mM (1st component) and 0.6, 0.6, and 3.0 mM (2nd component) for amplitude, and 2.4, 2.4, and 7.1 mM (1st component) and 1.0, 2.6, and 4.3 mM (2nd component) for conduction velocity. The order of pharmacodynamic potency, thus, was POH = CV > LM. In silico simulation demonstrated that POH and CV penetrate the Nav 1.6 and accommodate in the channel at the interface between the selectivity filter and the central cavity, a position very favorable to block the channel pore. In contrast, LM exhibited a markedly different docking profile, suggesting that LM binding is less likely to directly obstruct sodium permeation. In conclusion, the three substances investigated inhibited nerve excitability, but those with a hydroxyl group demonstrated greater pharmacodynamic potency. Full article

Facial aging is a multifactorial process characterized by progressive structural and functional changes involving skin, soft tissues, muscles, and skeletal support. Current conceptual models primarily rely on static anatomical descriptions and regional assessment scales that evaluate visible signs such as wrinkles, folds, and volume loss. Although these approaches provide useful clinical reference points, they may only partially capture the dynamic interactions between muscular activity, tissue aging, and gravitational forces that shape facial morphology over time. In this article, we propose a conceptual framework for interpreting facial aging based on the vectorial dynamics generated by facial mimic muscles. Within this perspective, facial muscles can be considered sources of contraction vectors that exert mechanical influences on facial tissues throughout life. Under physiological conditions, facial appearance reflects a dynamic equilibrium between opposing vectorial influences. However, progressive tissue weakening combined with repetitive muscular activity may gradually alter this balance. This hypothesis-generating, vector-based model integrates muscular dynamics with tissue aging and gravitational effects to offer a complementary interpretative framework for facial aging. It is not intended as a validated biomechanical theory, but rather as a conceptual tool to stimulate further anatomical, imaging-based, and clinical investigation. Full article

Hydrogel-based three-dimensional culture systems are widely used in tissue engineering; however, their maturation is often limited under static conditions. This study investigates the combined effects of dynamic perfusion and initial cell seeding density on remodeling behavior and mechanical properties of bioprinted collagen hydrogel constructs, with additional assessment of smooth muscle cell-like (SMC) differentiation. Rectangular constructs (30 × 15 × 1.5 mm) were fabricated using high-concentration collagen (30 mg/mL) with cell densities of 10 and 20 million cells/mL. MCDB- and DMEM-based media were first compared using growth curves, leading to the selection of MCDB differentiation medium for subsequent experiments. Constructs were then cultured statically or under dynamic perfusion (20 mL/min) for up to 7 days. Remodeling was evaluated by monitoring changes in construct dimensions over time. Static constructs exhibited non-uniform deformation and rolling, whereas dynamically perfused samples retained their geometry and underwent homogeneous contraction. Mechanical testing revealed a transition from stiff and brittle to more compliant and ductile behavior, with preserved load-bearing capacity at large strains. Remodeling and mechanical outcomes were strongly influenced by cell density and culture medium, with differentiation conditions promoting more stable constructs. These changes were accompanied by increased expression of smooth muscle–related markers under dynamic culture. Overall, dynamic perfusion and cell seeding density jointly govern remodeling and mechanical maturation of bioprinted collagen constructs, highlighting their importance for functional hydrogel-based tissue development. Full article