Sarcopenia is a progressive age-related skeletal muscle disorder characterized by the loss of muscle mass, strength, and physical performance, leading to frailty, disability, and increased mortality. Although its clinical consequences are well recognized, the underlying biological mechanisms remain incompletely understood, limiting the development of early diagnostic strategies and targeted therapies. Increasing evidence indicates that sarcopenia results from complex interactions among mitochondrial dysfunction, chronic low-grade inflammation (inflammaging), cellular senescence, neuromuscular junction degeneration, and anabolic resistance. The present review critically summarizes the current evidence on the principal circulating and molecular biomarkers associated with these interconnected mechanisms. Mitochondrial dysfunction appears to represent an early upstream event that promotes excessive reactive oxygen species production, defective mitophagy, inflammatory activation, and cellular senescence. Chronic inflammation, mediated primarily through IL-6 and TNF-α, further accelerates muscle catabolism and regenerative failure, whereas senescence-associated pathways impair satellite cell function and muscle repair. Neuromuscular degeneration and anabolic resistance further contribute to progressive muscle atrophy and functional decline. Among the candidate biomarkers, GDF-15, FGF-21, IL-6, TNF-α, CAF22, p16INK4a, p21/CDKN1A, IGF-1, and myostatin appear particularly promising for characterizing the biological heterogeneity of sarcopenia. However, no single biomarker currently demonstrates sufficient diagnostic accuracy for routine clinical use. Instead, integrated multi-biomarker approaches combining mitochondrial, inflammatory, senescence-associated, neuromuscular, and anabolic markers may improve early diagnosis, risk stratification, and personalized therapeutic strategies. Future prospective longitudinal studies are required to validate these biomarkers and facilitate their translation into clinical practice.
Neuromuscular performance is influenced by diurnal variation, but it remains unclear whether sex moderates these patterns in team sport athletes. This study examined whether sex moderates the effect of time of day on neuromuscular performance in volleyball players. One hundred and two volleyball players (46 males and 56 females) completed a randomized battery of tests in the morning (08:00-10:00) and evening (18:00-20:00) on separate days. The battery included vertical jumps (squat, countermovement, and spike jumps), spike performance (standing and jumping spike), agility (modified T test), isometric handgrip strength, and dynamic balance (modified star excursion balance test). A significant sex-by-time interaction was observed in squat jump (P  =  .002, ηp2=.09), with males showing higher evening values, whereas females showed no significant change. A sex-by-time interaction was also found in jumping spike (P = .045, ηp2=.04), agility (P = .027, ηp2=.05), and dynamic balance (ie, posterolateral) on the dominant leg (P = .005, d = 0.26), reflecting different response patterns between sexes. No significant changes were observed in other dynamic balance directions (P > .05). A significant time-of-day effect was observed, indicating higher evening performance in all jump tests (P = .005, ηp2=.08-.19), ball velocity in spike velocity (P = .002, ηp2=.09), and isometric handgrip strength (P = .001, ηp2≈.10). Sex-specific differences were limited to a few tasks and were generally small in magnitude, whereas a consistent enhancement in neuromuscular performance in the evening compared with the morning emerged as the primary finding, regardless of sex.
Germline pathogenic variants in the Additional Sex Combs-Like 1 (ASXL1) gene are associated with the neurodevelopmental Bohring-Opitz syndrome and cancers like Wilms' tumours. Bohring-Opitz syndrome is a phenotypically heterogeneous condition characterised by feeding difficulties, syndromic facial abnormalities, abnormal posturing and developmental delays, and it has only been reported in infant/adolescent patients. There are no reported neuromuscular phenotypes associated with ASXL1. A 71-year-old male proband exhibited congenital facial, extraocular, proximal upper limb and generalised/distal lower limb muscle weakness/wasting. This was associated with dysphagia, childhood motor developmental delay, bilateral upper limb tremor and bilateral pes cavus. He demonstrated some features of Bohring-Opitz syndrome including feeding difficulties, microcephaly, micrognathia and anteverted nares but lacked the characteristic posturing. Muscle imaging demonstrated symmetrical lower limb atrophy. His adult age diagnosis is unique among ASXL1-associated conditions. A genetic diagnosis of the ASXL1 variant (c.1210C>T; p.Arg404Ter) was achieved through phenotype-driven genetic neurodevelopmental panel testing given some overlap with neurodevelopmental patients following unsuccessful initial genetic sequencing. This expands the phenotype of ASXL1 pathogenic variants with a novel and distinct neuromuscular presentation. This case demonstrates the importance of thorough and accurate phenotype for unusual presentations, as this diagnosis was missed through routine genetic testing.
Water-resistance rowing machines are widely used in fitness and rehabilitation; however, the neuromuscular effects of different resistance levels remain unclear. This study investigated resistance-dependent muscle activation during water-resistance rowing using surface electromyography (sEMG). Participants performed rowing exercise under four water-resistance conditions (MIN, Level 2, Level 3, and MAX) while maintaining a fixed stroke rate of 40 cycles/min. sEMG signals from the biceps brachii, triceps brachii, deltoid, latissimus dorsi, rectus femoris, and tibialis anterior were collected using a Delsys wireless system (1000 Hz) and normalized to maximal voluntary isometric contraction (MVIC). Results revealed significant interaction effects between resistance level and muscle group. The biceps brachii exhibited the greatest activation across all resistance conditions, whereas overall muscle activation remained below 40% MVIC. Activation differences were limited among the first three resistance levels but increased substantially at the highest resistance level. These findings support the use of sEMG for quantifying resistance-dependent neuromuscular adaptations and optimizing exercise prescription monitoring.
This study aimed to compare the short-term neuromuscular impairments resulting from a single session of isometric and dynamic strength training in youth soccer players. Twenty-one male youth soccer players (aged 16.8 ± 0.9 years) participated in this counterbalanced crossover trial, and were randomly assigned to a training sequence, starting with either a dynamic (3 sets of 4 repetitions of squats and deadlifts at 75% and 80% of 1RM, respectively) or an isometric training session (3 sets of 4 maximal 4-second repetitions of isometric squats and mid-thigh pulls) with protocols standardized for the number of exercises, sets, repetitions, and recovery intervals. A one-week washout period was allowed before participants switched training conditions. A repeated-measures ANOVA was used to assess the differences in countermovement jump (CMJ) height, bar velocity during half-squats, and perceived soreness and fatigue across different time points (baseline, 30 minutes, and 24 hours post-exercise). CMJ height was significantly greater in the isometric condition 30 minutes post-exercise compared to the dynamic condition (d = 0.71; p < .001). Additionally, the isometric condition exhibited significantly higher bar velocity 24 hours post-exercise (d = 0.69; p < .001). While no significant differences were detected in perceived soreness between groups at any time point, perceived fatigue was significantly reduced in the isometric condition at the 24-hour mark (d = 0.70; p < .05). These findings suggest that dynamic strength training may impair neuromuscular function to a greater extent than isometric training.
Cerebral palsy (CP) is predominantly characterized by spasticity. While botulinum neurotoxin type A (BoNT-A) effectively reduces spasticity, its transient efficacy represents a major clinical limitation. Elucidating the mechanisms that limit its duration of action may inform strategies to prolong therapeutic benefit. A spastic CP rat model was established via carotid artery ligation and hypoxia in 7-day-old Wistar rats. On postnatal Day 21, BoNT-A (5 U/kg) was administered to the gastrocnemius muscle. Behavioral and molecular biological assessments were performed at 4 and 12 weeks post-injection. At 4 weeks after injection, the motor performance improved, spasticity decreased (p < 0.05), neuromuscular junction density increased, and neurotrophic factors IGF-1, GAP 43, and S100 increased (all p < 0.05). However, these functional and molecular changes diminished by 12 weeks. Further proteomic analysis revealed a shift in pathway enrichment, from protein synthesis and vesicular transport at 4 weeks to metabolic regulation at 12 weeks. Among the differentially expressed proteins, Sar1b and Rtn1, whose expression patterns paralleled with nerve sprouting, may be key regulatory factors. These findings indicate that BoNT-A facilitates NMJ recovery through temporal regulation of energy metabolism, protein synthesis, and vesicular transport. Rtn1 and Sar1b may represent candidate molecular targets for extending the therapeutic effects of BoNT-A, although further functional validation is required.
Dysphagia is a major complication after ischemic stroke. Although neuromuscular electrical stimulation (NMES) and pharyngeal ice stimulation both improve swallowing function, evidence for their combined efficacy remains limited. This retrospective study analysed a prospective cohort of inpatients with post-stroke dysphagia admitted to Mianyang Central Hospital between January 1, 2022, and August 31, 2025. The primary outcome was 90-day swallowing function assessed by the Water Swallowing Test (WST); a score < 3 indicated a favourable prognosis and ≥ 3 indicated a poor prognosis. Baseline characteristics were compared between groups, and multivariable logistic regression was used to evaluate the independent association between treatment and outcome. A total of 1033 patients were enrolled in the final analysis. Overall, 778 patients (75.31%) achieved a favourable prognosis, and 255 (24.69%) had a poor prognosis. Compared with the NMES alone group, the NMES combined with ice stimulation group exhibited a significantly higher favourable prognosis rate (77.3% vs. 73.3%, p < 0.001) and a more concentrated distribution of lower WST scores (median [IQR]: 2.0 [1.0, 2.0] vs. 2.0 [1.0, 3.0], p = 0.029). After adjusting for confounding variables, multivariable regression analysis confirmed combined therapy as an independent protective factor against poor prognosis (OR = 0.533, 95% CI: 0.389-0.732, p < 0.001). NMES combined with ice stimulation therapy is associated with a lower risk of a poor prognosis compared to NMES alone therapy in post-ischemic stroke dysphagia patients, suggesting a synergistic effect that could inform optimised clinical management.
This pilot study compared the effects of load-matched isometric resistance training and dynamic resistance training on neuromuscular and sport-related performance in collegiate Kho-Kho athletes. Seventeen athletes completed the study and were included in the final analysis: nine in the isometric training group and eight in the dynamic training group. Both groups completed a five-week training program, with intensity regulated using modality-specific rating of perceived exertion scales: the Isometric Exercise Scale for the isometric group and the Borg CR-10 scale for the dynamic group. Pre- and post-intervention assessments included knee extension and flexion torque at multiple angles and velocities, squat linear sprint performance, vertical jump metrics, and reactive strength index. The isometric group showed significant within-group improvements in 75° knee-extension peak torque and jump height, and both groups improved selected strength and sprint outcomes. Significant Group × Time interactions were observed for 75° right knee-extension peak torque and initial squat-start sprint speed, suggesting greater improvement in the isometric group for these selected outcomes. However, vertical jump improvement did not show a significant Group × Time interaction, and isokinetic torque outcomes showed no clear modality-specific superiority. These preliminary findings suggest that RPE-regulated isometric training may provide short-term benefits for selected joint-angle-specific strength and initial acceleration outcomes in Kho-Kho athletes. However, definitive superiority over dynamic resistance training cannot be concluded from this exploratory pilot study.
To compare the therapeutic effects of proprioceptive neuromuscular facilitation (PNF) versus traditional rehabilitation (electroacupuncture combined with infrared irradiation) on tendon-bone healing in a rat model of rotator cuff tear. Thirty-two male SD rats were randomly divided into four groups (n=8 each): sham operation (Sham), rotator cuff tear model without treatment (Model), traditional treatment (Traditional: electroacupuncture + infrared), and PNF treatment (PNF: daily passive stretching with resistance). The rotator cuff tear model was established by transverse incision of 1/2 of the supraspinatus tendon. After 4 weeks of intervention, tendon-bone healing was evaluated by biomechanical testing (maximum failure load), ELISA (IL-1β, IL-6, TNF-α), qPCR (inflammatory gene expression), histology (H&E, Safranin O, Sirius Red, Masson's trichrome), immunohistochemistry (collagen type I), and Western blot (VEGF, TGF-β). PNF treatment significantly increased the maximum failure load of the tendon-bone interface compared to the Model and Traditional groups (p < 0.05). Both PNF and Traditional treatments reduced pro-inflammatory cytokine levels (IL-1β, IL-6, TNF-α) at both protein and mRNA levels, with PNF showing a more pronounced anti-inflammatory effect. Histologically, PNF group exhibited better-organized collagen fibers (Masson's trichrome), increased fibrocartilage regeneration (Safranin O), and a higher ratio of mature type I to type III collagen (Sirius Red under polarized light) compared to the Traditional group. Immunohistochemistry revealed stronger type I collagen deposition in the PNF group. Western blot demonstrated that PNF upregulated VEGF and TGF-β expression more effectively than Traditional treatment. PNF therapy outperforms traditional electroacupuncture combined with infrared therapy in promoting tendon-bone healing after rotator cuff tear in rats, as evidenced by superior biomechanical strength, enhanced collagen maturation, and better modulation of inflammation and growth factors. PNF is a promising non-invasive rehabilitation approach that warrants further clinical investigation in patients with chronic rotator cuff injury.
This study investigated the effect of glutamine (Gln) on paralytic symptoms in rats poisoned by Bungarus multicinctus and explored the underlying mechanism, focusing on the Agrin-MuSK signaling pathway in neuromuscular transmission recovery.An ex vivo diaphragm tension assay assessed Gln's reversal of venom-induced neuromuscular blockade. A rat poisoning model was established with Bungarus multicinctus venom (0.15 mg/kg). Rats were divided into normal, venom, and venom+Gln groups. We evaluated survival, paralysis, blood gases (PaO2, PaCO2, PaSO2), diaphragm histopathology and ultrastructure, and oxidative stress markers (SOD, MDA). RT-qPCR and Western Blot analyzed key Agrin-MuSK pathway components (mRNA: Agrin, Chrne, Chrna, LRP4, MuSK, Rapsyn; protein: Agrin, p-MuSK/MuSK, α1- subunit of nAChR, ε- subunit of nAChR). Gln significantly reversed venom-induced diaphragm tension decline ex vivo (P<0.05). In vivo, high-dose Gln (750 mg/kg) significantly improved survival (P<0.05), alleviated paralysis and hypoxia (increased PaSO2, PaO2; decreased PaCO2, P<0.05), reduced diaphragm ultrastructural damage, and enhanced antioxidant capacity (increased SOD, decreased MDA, P<0.05). Venom significantly suppressed key Agrin-MuSK pathway elements (Agrin, p-MuSK/MuSK; P<0.01). Gln intervention significantly upregulated the expression of pathway molecules (Agrin, Chrne, LRP4, MuSK, Rapsyn mRNA and Agrin, p-MuSK/MuSK protein; P<0.05 or P<0.01).Gln effectively alleviates paralysis and improves survival in Bungarus multicinctus-poisoned rats. This protection is associated with improved neuromuscular junction ultrastructure, reduced oxidative stress, and activation of the Agrin-MuSK signaling pathway, promoting neuromuscular transmission recovery. The study provides experimental evidence and potential therapeutic targets for Gln in treating Bungarus multicinctuspoisoning, especially respiratory paralysis.
Despite widespread clinical use and Food and Drug Administration (FDA) approval for use in patients from birth to < 2 years old in 2024, data regarding the safety and monitoring practices of sugammadex in infants with congenital heart disease (CHD) remains limited. While its efficacy has been demonstrated, adverse effects have been documented including bradycardia and allergic reactions, including anaphylaxis. These effects may be of particular concern in infants with CHD, who may be at a higher risk for hemodynamic instability. The current study retrospectively evaluated a random sample of patients over a 10-year period to determine the efficacy, perioperative adverse effects, and neuromuscular monitoring practices associated with the administration of reversal agents for neuromuscular blocking agents in patients less than 2 years of age with CHD. The study cohort included 497 encounters across 375 unique patients with a median age of 7 months who received either sugammadex or neostigmine, which served as a historical comparator. Bradycardia occurred at a low and comparable rate in both groups (1.4%), and no cases of anaphylaxis were documented. Additional adverse events were heterogeneous and were likely attributable to the underlying CHD, associated comorbidities, and the hemodynamic complexity of the surgical procedures rather than to the reversal agent alone. Successful tracheal extubation was achieved in over 90% of encounters, with a similar rate between groups. Rate of residual neuromuscular blockade was also comparable between groups, though quantitative train-of-four (TOF) monitoring was inconsistently documented. Furthermore, wide variability in sugammadex dosing was observed, highlighting an opportunity for standardization in this high-risk pediatric population. In the current cohort of infants with CHD, sugammadex was associated with a low incidence of perioperative adverse effects and rates of successful tracheal extubation similar to neostigmine. These patterns held despite higher ASA status among patients receiving sugammadex, which suggests greater baseline illness severity. Observed adverse events were heterogeneous and likely reflect the underlying clinical context in addition to any reversal agent effects. This study also highlights practice variability, including inconsistent documentation of quantitative TOF monitoring, which limits the ability to assess residual blockade and may contribute to variable dosing of sugammadex. In this physiologically vulnerable population, standardized monitoring and prospective data would help clarify how to best dose sugammadex. Taken together, these findings support the continued use of sugammadex in infants with CHD while highlighting the limits of current evidence. Larger, prospective studies with consistent monitoring are needed to better define the safe use of sugammadex in this population and to more clearly separate drug-related effects from other perioperative contributions to adverse events.
Diabetic peripheral neuropathy (DPN) causes progressive sensorimotor dysfunction of the lower extremities, impairing mobility and increasing fall risk. Phase-specific neuromuscular activation during repeated sit-to-stand (STS) transfers in DPN remains poorly characterized. This study compared lower-limb muscle activation during repeated STS transfers in fifteen ambulatory DPN patients and fifteen age- and gender-matched healthy controls. Bilateral surface electromyography (sEMG) was recorded from the vastus lateralis, vastus medialis, biceps femoris, gluteus maximus, and gluteus medius; normalized to maximum voluntary contractions (MVCs), and analyzed separately for STS and stand-to-sit phases. No significant between-group differences were observed for any muscle during either phase (all p > 0.05). Effect sizes were small-to-medium, with confidence intervals indicating uncertainty around the estimated between-group differences. Notably, gluteus maximus activation during STS demonstrated the largest between-group effect size, favoring the DPN group (d = 0.54), although this difference was not statistically significant. This finding may indicate a possible proximal hip-extensor strategy that requires confirmation in larger studies. Both groups demonstrated significantly greater vastus lateralis and gluteus maximus activation during STS than stand-to-sit, reflecting greater neuromuscular demand during rising. Overall, the non-significant between-group findings, together with the effect-size and confidence-interval analysis, suggest that MVC-normalized EMG amplitude alone may have limited sensitivity for detecting neuropathic neuromuscular alterations during transitional tasks in ambulatory patients with DPN.
Peripheral nerve injuries often result in prolonged skeletal muscle denervation, leading to progressive atrophy, fibrosis, neuromuscular instability, and loss of regenerative capacity before axons can reinnervate distal targets. Here, we developed a non-viral strategy using tissue nanotransfection (TNT) to deliver the neurogenic transcription factor cocktail Ascl1 , Brn2 , and Myt1l ( ABM ) directly to denervated skeletal muscle. In vitro , ABM -transfected myoblasts sustained expression of the reprogramming factors, acquired neuron-like morphologies, upregulated neuronal markers including Tuj1, Map2, and Syp, and exhibited electrophysiological properties consistent with membrane excitability. RNA sequencing confirmed broad activation of neurogenic transcriptional programs, with enrichment of pathways associated with neuronal fate commitment, neuron differentiation, axon guidance, synaptogenesis, and developmental signaling. In a mouse model of sciatic nerve transection, TNT enabled localized ABM expression in denervated gastrocnemius muscle. ABM -TNT treatment accelerated resolution of denervation-associated fibrillation potentials and showed trends toward improved twitch and tetanic torque, compound muscle action potential amplitudes, and muscle mass preservation. Transcriptomic profiling of treated muscles 5 weeks after injury revealed distinct gene expression programs enriched for muscle regeneration, neuromuscular organization, trophic support, extracellular matrix remodeling, angiogenesis, myogenesis, and metabolic adaptation. Network analyses further identified activation of neurogenic regulators, neurotrophic signaling, and vascular-support pathways. These findings establish TNT-mediated ABM delivery as a non-viral platform for inducing neurogenic and myoprotective programs in denervated muscle, suggesting a potential strategy to preserve muscle viability during the prolonged interval required for peripheral nerve regeneration.
Background/Objectives: L-2-hydroxyglutaric aciduria (L2HGA) is a rare autosomal recessive neurometabolic disorder marked by developmental delay, intellectual disability, and progressive movement abnormalities. Variants in RYR1 can cause congenital myopathies, but data on the co-occurrence of variants in populations are limited. The aim of this study was to characterize the clinical and genetic basis of the neurometabolic and neuromuscular abnormalities and to investigate the potential interaction between the identified variants. Methods: Patients with complex, previously undiagnosed clinical presentations underwent neurological evaluation, including brain magnetic resonance imaging, electromyography, biochemical testing, and whole-exome sequencing (WES). Identified variants were analyzed in silico and confirmed by Sanger sequencing in the patient and her parents. Three cases were reviewed, and one of these patients exhibited developmental delay, hypotonia, intellectual disability, and progressive motor dysfunction. Biochemical tests revealed markedly elevated urinary 2-hydroxyglutaric acid levels, consistent with L2HGA. Results: WES identified a homozygous likely pathogenic variant in L2HGDH (c.589_590insGGC, p.Q197insG), confirming the molecular diagnosis of L2HGA. In addition, a heterozygous missense variant in RYR1 (c.7268T>A, p.M2423K), classified as a variant of uncertain significance, was detected and was inherited from her mildly affected father. The L2HGDH variant explains the neurometabolic phenotype of the patient, whereas the RYR1 variant remains of uncertain significance, and its clinical contribution cannot be clearly established. Conclusions: To our knowledge, this case illustrates the co-occurrence of a likely pathogenic L2HGDH variant and a heterozygous RYR1 variant of uncertain significance. The findings expand the mutational spectrum of L2HGA and underscore the value of comprehensive genomic testing in complex neurometabolic and neuromuscular disorders.
Evidence on powered wearable exoskeleton gait training in patients with chronic hypoxic-ischemic encephalopathy (HIE) is virtually absent, and existing studies have focused on macroscopic functional outcomes while neglecting joint-level neuromuscular force-generation characteristics such as rate of force development (RFD). To examine the effects of a six-week powered exoskeleton gait training program on isometric hip strength and RFD, sit-to-stand (STS) performance, frontal-plane hip strength, and center-of-pressure (CoP) dynamics in a patient with chronic HIE-induced quadriparesis. A case report with pre- and post-intervention evaluation was conducted. A 47-year-old male with chronic HIE-induced quadriparesis (onset 2017) completed 18 sessions (three per week, six weeks) of powered lower-limb exoskeleton gait training. Outcomes included isometric hip peak force and RFD (DynaMo, Vald Performance), STS peak force and body mass-normalized RFD (ForceDecks, Vald Performance), frontal-plane hip strength (ForceFrame, Vald Performance), and CoP path length and mean velocity. Hip extension peak force increased by 247-256% bilaterally, and hip extension RFD increased by 174-188%, whereas hip flexion peak force showed minimal change (+3.3-5.2%). Body mass-normalized STS RFD increased by 250% (10 to 35 N·s-1·kg-1), representing the largest relative gain. Hip abduction strength increased by 27.1-36.8% with improved bilateral symmetry; hip adduction imbalance reversed from right to left dominance. CoP path length and mean velocity each decreased by 3.7%. Six weeks of powered exoskeleton gait training selectively enhanced time-dependent neuromuscular output-particularly RFD-beyond maximal strength gains, with meaningful improvements in functional weight acceptance during STS. These findings support exoskeleton-based training as a promising rehabilitation strategy for patients with chronic CNS injury.
Myasthenia gravis (MG) is a B-cell-mediated autoimmune disease characterized by impaired neuromuscular transmission. Although genetic predisposition and thymic abnormalities are well recognized, they cannot fully explain the increasing incidence and regional heterogeneity of MG, highlighting the potential contribution of environmental factors. Bisphenol A (BPA), a ubiquitous endocrine-disrupting chemical, exhibits estrogenic activity, immunomodulatory effects, and mitochondrial toxicity, and has been implicated in multiple autoimmune disorders. However, the potential role of BPA in MG pathogenesis remains largely unexplored. BPA-related targets and MG-associated genes were collected from public databases, and overlapping targets were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to explore the biological functions and pathways of the overlapping targets. Candidate targets were screened using four machine-learning algorithms, including least absolute shrinkage and selection operator (LASSO) regression, support vector machine-recursive feature elimination (SVM-RFE), random forest (RF), and extreme gradient boosting (XGBoost). Differential expression and diagnostic performance were validated using the Gene Expression Omnibus (GEO) dataset GSE85452. Immune infiltration was assessed using CIBERSORT. Molecular docking and molecular dynamics (MD) simulations were conducted to evaluate the potential binding stability and interaction modes between BPA and key target proteins. In addition, C2C12 myoblasts were treated with different concentrations of BPA for 24 h, and cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. Based on the cell viability results, 50 μM BPA was selected for quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analyses of key genes. A total of 225 overlapping targets were identified between BPA exposure-related targets and MG-associated genes. Enrichment analyses showed that these targets were mainly associated with ion transport, membrane potential regulation, muscle system processes, immune signaling, apoptosis, endocrine resistance, and AGE-RAGE signaling pathways.Four machine-learning algorithms identified cholinergic receptor nicotinic beta 1 subunit (CHRNB1), KRAS proto-oncogene, GTPase (KRAS), phosphomannomutase 2 (PMM2), and toll-like receptor 4 (TLR4) as candidate targets. Validation in the GSE85452 dataset showed that CHRNB1, PMM2, and TLR4 were significantly upregulated in MG samples compared with control samples, whereas KRAS showed no significant difference. receiver operating characteristic (ROC) analysis further demonstrated that CHRNB1, PMM2, and TLR4 had good diagnostic performance, with area under the ROC curve (AUC) values of 0.827, 0.856, and 0.821,respectively. Immune infiltration analysis revealed altered immune cell infiltration patterns and associations between key targets and specific immune cell subsets. Molecular docking predicted favorable binding of BPA to CHRNB1, PMM2, and TLR4, with binding energies of -7.4, -5.7, and -5.8 kcal/mol, respectively. MD simulations further supported the potential stability of these BPA-target complexes. In vitro experiments showed that BPA reduced C2C12 cell viability in a concentration-dependent manner. qRT-PCR validation showed that treatment with 50 μM BPA significantly upregulated Chrnb1 expression, while downregulating Pmm2 and Tlr4 expression.Western blot analysis further confirmed that BPA exposure significantly decreased the protein expression of TLR4 and PMM2, while increasing that of CHRNB1 in C2C12 cells. This study provides integrated computational and experimental evidence that BPA exposure may be associated with MG-related molecular alterations. BPA may affect MG-related biological processes through the regulation of ion transport, neuromuscular signaling, immune activation, and glycosylation-related metabolism. CHRNB1, PMM2, and TLR4 may serve as potential molecular links between BPA exposure and MG-related pathological processes.
Background and Objectives: The back squat is widely used in resistance training, performance enhancement, and rehabilitation, and barbell position and squat depth are key modifiable variables that may influence neuromuscular demand. This study investigated the effects of barbell position and squat depth on trunk and lower-extremity muscle activation during the back squat. Materials and Methods: Twenty-two adult men with at least 2 years of back-squat experience performed high-bar and low-bar back squats to knee-flexion angles of 50°, 90°, and 130° using a standardized external load corresponding to 80% of each participant's habitual one-repetition maximum (1RM). Conditions were presented in randomized order. Surface electromyography was used to record the rectus femoris, vastus medialis, vastus lateralis, gluteus maximus, semitendinosus, biceps femoris, rectus abdominis, and erector spinae. Electromyographic activity was analyzed separately for eccentric and concentric phases and normalized to maximal voluntary isometric contraction (%MVIC). Results: Increasing squat depth most consistently increased quadriceps and erector spinae activation, indicating greater knee extensor and trunk extensor demand at deeper positions. Rectus abdominis activation showed a depth-related effect during the concentric phase, with only isolated pairwise differences during the eccentric phase, whereas gluteus maximus activation showed limited modulation. Barbell position produced selective phase- and depth-dependent responses: the low-bar squat showed greater hamstring and erector spinae activation in specific comparisons, whereas the high-bar squat showed greater knee-extensor activation at selected depths, most clearly in the rectus femoris. Conclusions: Barbell position and squat depth modify relative neuromuscular demand during the back squat and may be used to adjust the emphasis on knee extensor, trunk stabilizer, and posterior-chain demands rather than to target a single muscle group in isolation.
Surface electromyography (sEMG) normalized to mechanical output can describe electrical activation amplitude relative to torque, but such ratios should not be interpreted automatically as neuromuscular efficiency. This exploratory cross-sectional study compared quadriceps activation-to-torque ratios at 45° and 75° knee flexion and examined hypothesis-generating associations with countermovement jump (CMJ) outcomes. Seventeen participants performed two brief unilateral maximal isometric knee-extension trials at each angle. Wireless sEMG from the vastus lateralis (VL), vastus medialis (VM), and rectus femoris (RF) and Biodex torque were acquired separately and manually matched by participant, knee angle, and test set. Ratios were calculated as Noraxon-exported mean EMG amplitude divided by Biodex average peak torque. Ratios were higher at 45° than at 75° for VL (mean difference = 0.74 μV/(N·m), BCa 95% CI: 0.34-1.34; Holm-adjusted p = 0.020), VM (0.52, 0.09-0.72; p = 0.009), and RF (0.69, 0.22-1.32; p = 0.028). Exploratory Spearman correlations with CMJ outcomes ranged from -0.38 to 0.32 and were nonsignificant after false-discovery-rate correction. The findings indicate protocol-specific, angle-dependent differences, whereas CMJ associations remain inconclusive and require larger, reliability-focused studies with synchronized acquisition and fully documented signal processing.
Background/Objectives: The aim of this study was to assess the association between physical activity (PA), in accordance with the WHO recommendations for weekly activities, and the occurrence of falls over a one-year period. The study was conducted among 150 individuals aged 48 to 88 years living in the Polish city of Łódź during the Community Festive event. Methods: Data from 150 participants (131 women and 19 men) were assessed using the Tinetti scale, Time Up & Go (TUG), Hand Grip Strength (HGS), and a structured face-to-face interview regarding retrospective fall incidents over the past 12 months and the weekly volume of PA. Results: A total of 29 participants experienced a fall (all of whom were women) while 121 individuals reported no fall. In the non-fall group, higher percentage of individuals met the WHO physical activity guidelines compared to the fall group (74% vs. 61.1% to 48.3%). Furthermore, individuals without the history of falls achieved better results in the RHGS (p = 0.02) and Tinetti tests (p = 0.04). Notably, individuals in the fall group reported engaging in more aerobic activity on average than those in the non-fall group. Conclusions: The study demonstrated that older adults and middle-aged individuals without a history of falls reported a higher compliance with weekly resistance training. While multivariable models show that raw physical activity volume is not an independent predictor of fall risk, training compliance aligns with superior objective neuromuscular performance, showing positive associations with RHGS and Tinetti scores.
Dyspnoea is a severe symptom, causing immediate distress and significantly impairing health-related quality of life, particularly in chronic conditions. Pulmonary rehabilitation is a cornerstone in the management of chronic obstructive pulmonary disease, as supported by evidence highlighting its efficacy in improving dyspnoea, aerobic capacity, and health-related quality of life. In this multidisciplinary approach, much of those physical effects are enabled by a physiotherapist-led intensive training strategy: exercise training. In recent years, numerous studies have supported the benefits of exercise training as an effective intervention for several other chronic diseases (including interstitial lung disease, long-covid, obesity, neuromuscular disorders). Despite differences in pathophysiology, these populations share common mechanisms responsible for the chronicity of dyspnoea, including deconditioning and peripheral muscle dysfunction, which can be targeted by exercise training. After exploring the physiological mechanisms by which exercise training alleviates chronic dyspnoea, this state-of-the-art narrative review aimed to provide a readable practical synthesis to help both those learning about exercise training in pulmonary rehabilitation and those treating the individuals affected by chronic dyspnoea. A comprehensive search strategy was employed to identify relevant studies, with publications ranging from January 2020 to April 2025 from MEDLINE, the Cochrane Database, and ClinicalTrials.gov. We support the importance of the higher intensities of exercise training as a pivotal component in enhancing the individualised therapeutic potential of exercise training across diverse disease states. We also summarise evidence on muscle-level adaptations and special attention is given to the potential role of eccentric contractions in enhancing mechanical efficiency and reducing fatigue resistance, which could be a promising area for future research. Finally, we provide practical guidance on subjects' selection, baseline assessment, intensity prescription and monitoring.