Muscle Contraction Research Articles

Distinct modulation of calcium-activated chloride channel TMEM16A by drug-binding sites

TMEM16A is a calcium-activated chloride channel with significant role in epithelial fluid secretion, sensory transduction, and smooth muscle contraction. Several TMEM16A inhibitors have been identified; however, their binding sites and inhibitory mechanisms remain unclear. Using magnolol and honokiol, the two regioisomeric inhibitors, as chemical probes, we have identified a drug-binding site distinct from the pore region, in TMEM16A, which is described here. With electrophysiology, unbiased molecular docking and clustering, molecular dynamics simulations, and experimental validation with mutant cycle analysis, we show that magnolol and honokiol utilize different drug-binding sites, pore and nonpore pockets. The pore blocker utilizes amino acids crucial for chloride passage, whereas the nonpore blocker allosterically modulates the pore residues to hinder ion permeation. Among 17 inhibitors tested, 11 were pore blockers and 6 were nonpore blockers, indicating the importance of this nonpore pocket. Our study provides insights into drug-binding mechanism in TMEM16A together with a rationale for future drug development.

Smooth Muscle Mechanosensitivity Generates and Maintains Pressure Gradients Across the Intestine.

The gut, the ureter, or the Fallopian tube all transport biological fluids by generating trains of propagating smooth muscle constrictions collectively known as peristalsis. These tubes connect body compartments at different pressures. We extend here Poiseuille's experiments on liquid flow in inert tubes to an active, mechanosensitive tube: the intestine. We use as a miniature myogenic peristaltic pump model, the fetal chicken gut, and measured the flow and contractile wave propagation as a function of the initially applied pressures and pressure gradients. We dissect the molecular pathways of smooth muscle mechanosensitivity by measuring the force generated by gut rings in different pharmacological conditions. We demonstrate that smooth muscle contractions in response to stretch or pressure is mediated by L-type Ca2+ channels and IP3 receptors. We show that this positive-feedback mechanosensitive behavior can spontaneously generate pressure gradients across gut segments initially subject to equal pressure; this same mechanism tends to stabilize initially applied pressure gradients; it can act jointly or compete with the pressure gradient induced by directional peristaltic waves. We demonstrate that high pressure differentials can reverse the physiological propagation direction of contractile waves imparted by interstitial cell of Cajal pacemaker activity. We find that flow rate increases with tube length, but that the maximum pressure differential generated depends solely on smooth muscle contractile force and on the initial resting pressure applied inside the organ. We provide fundamental mechanical and hydrodynamic insight into the myogenic mechanisms of transport in the gastrointestinal tract. We scale up our results to other human peristaltic organs and discuss their implications for pathophysiology of intestinal obstruction, vesicoureteral reflux and endometriosis.

The effect of fatiguing muscle contractions on kicking performance in experienced soccer players

ABSTRACT The objective of this study was to clarify the effects of fatiguing muscle contractions of the m. quadriceps femoris on kicking abilities of experienced soccer players. 16 male professional (n = 5) and amateur players (n = 11) performed kicking tests in two conditions (fatigue and control) on separate days in a randomised crossover design. The fatiguing protocol performed with the kicking leg consisted of 5 sets of 10 maximal voluntary concentric and eccentric knee extensions. Maximal voluntary isometric contraction force (MVIC), 15 hz/50 hz stimulation force ratio (force ratio), and kicking abilities were assessed before and after completion of the fatiguing protocol or rest (control). The fatiguing protocol successfully induced fatigue of 14.0 ± 2.7% (mean ± SE) reduced MVIC and 14.0 ± 3.7% reduced force ratio while no reductions occurred in the control condition. Between group difference showed ball speed declined 2.1 ± 0.95% more following the fatigue protocol compared to control condition. On the control day shooting accuracy improved by 13.3 ± 5.6% and was numerically impaired on the intervention day by 1.0 ± 9.2%. Despite this, no significant between group difference was observed in shooting accuracy (p = 0.18). The study demonstrated that fatigue induced by prior muscle contractions impairs maximal shooting speed, but we observed no significant impairment of shooting accuracy.

Cold acclimation with shivering improves metabolic health in adults with overweight or obesity.

Cold acclimation increases insulin sensitivity, and some level of muscle contraction appears to be needed for provoking this effect. Here 15 men and (postmenopausal) women with overweight or obesity, the majority of whom had impaired glucose tolerance, were intermittently exposed to cold to induce 1 h of shivering per day over 10 days. We determined the effect of cold acclimation with shivering on overnight fasted oral glucose tolerance (primary outcome) and on skeletal muscle glucose transporter 4 translocation (secondary outcome). We find that cold acclimation with shivering improves oral glucose tolerance, fasting glucose, triglycerides, non-esterified fatty acid concentrations and blood pressure. Cold acclimation with shivering may thus represent an alternative lifestyle approach for the prevention and treatment of obesity-related metabolic disorders. ClinicalTrials.gov registration: NCT04516018 .

The ARK2N (C18ORF25) Genetic Variant Is Associated with Muscle Fiber Size and Strength Athlete Status

Background: Data on the genetic factors contributing to inter-individual variability in muscle fiber size are limited. Recent research has demonstrated that mice lacking the Arkadia (RNF111) N-terminal-like PKA signaling regulator 2N (Ark2n; also known as C18orf25) gene exhibit reduced muscle fiber size, contraction force, and exercise capacity, along with defects in calcium handling within fast-twitch muscle fibers. However, the role of the ARK2N gene in human muscle physiology, and particularly in athletic populations, remains poorly understood. The aim of this study was threefold: (a) to compare ARK2N gene expression between power and endurance athletes; (b) to analyze the relationship between ARK2N gene expression and muscle fiber composition; and (c) to investigate the association between the functional variant of the ARK2N gene, muscle fiber size, and sport-related phenotypes. Results: We found that ARK2N gene expression was significantly higher in power athletes compared to endurance athletes (p = 0.042) and was positively associated with the proportion of oxidative fast-twitch (type IIA) muscle fibers in untrained subjects (p = 0.017, adjusted for age and sex). Additionally, we observed that the ARK2N rs6507691 T allele, which predicts high ARK2N gene expression (p = 3.8 × 10−12), was associated with a greater cross-sectional area of fast-twitch muscle fibers in strength athletes (p = 0.015) and was over-represented in world-class strength athletes (38.6%; OR = 2.2, p = 0.023) and wrestlers (33.8%; OR = 1.8, p = 0.044) compared to controls (22.0%). Conclusions: In conclusion, ARK2N appears to be a gene specific to oxidative fast-twitch myofibers, with its functional variant being associated with muscle fiber size and strength-athlete status.

Macrophages excite muscle spindles with glutamate to bolster locomotion.

The stretch reflex is a fundamental component of the motor system that orchestrates the coordinated muscle contractions underlying movement. At the heart of this process lie the muscle spindles (MS), specialized receptors finely attuned to fluctuations in tension within intrafusal muscle fibres. The tension variation in the MS triggers a series of neuronal eventsincluding an initial depolarization of sensory type Ia afferents that subsequently causes the activation of motoneurons within the spinal cord1,2. This neuronal cascade culminates in the execution of muscle contraction, underscoring a presumed closed-loop mechanism between the musculoskeletal and nervous systems. By contrast, here we report the discovery of a new population of macrophages with exclusive molecular and functional signatures within the MS that express the machinery for synthesizing and releasing glutamate. Using mouse intersectional genetics with optogenetics and electrophysiology, we show that activation of MS macrophages (MSMP) drives proprioceptive sensory neuron firing on a millisecond timescale. MSMP activate spinal circuits, motor neurons and muscles by means of a glutamate-dependent mechanism that excites the MS. Furthermore, MSMP respond to neural and muscle activation by increasing the expression of glutaminase, enabling them to convert the uptakenglutamine released by myocytes during muscle contraction into glutamate. Selective silencing or depletion of MSMP in hindlimb muscles disrupted the modulation of the stretch reflex for force generation and sensory feedback correction, impairing locomotor strategies in mice. Our results have identified a new cellular component, the MSMP, that directly regulates neural activity and muscle contraction. The glutamate-mediated signalling of MSMP and their dynamic response to sensory cues introduce a new dimension to our understanding of sensation and motor action, potentially offering innovative therapeutic approaches in conditions that affect sensorimotor function.

Effect of Ankle-Foot Orthosis on Paretic Gastrocnemius and Tibialis Anterior Muscle Contraction of Stroke Survivors During Walking: A Pilot Study

Ankle-foot orthoses (AFOs) have been commonly prescribed for stroke survivors with foot drop, but their impact on the contractions of paretic tibialis anterior (TA) and medial gastrocnemius (MG) has remained inconclusive. This study thus investigated the effect of AFOs on these muscle contractions in stroke survivors. The contractions of paretic TA and MG muscles were assessed in twenty stroke patients and compared between walking with and without AFOs, using a novel wearable dynamic ultrasound imaging and sensing system. The study found an increase in TA muscle thickness throughout a gait cycle (p > 0.05) and a significant increase in TA muscle surface mechanomyography (sMMG) signals during the pre- and initial swing phases (p < 0.05) when using an AFO. MG muscle thickness generally decreased with the AFO (p > 0.05), aligning more closely with trends seen in healthy adults. The MG surface electromyography (sEMG) signal significantly decreased during the initial and mid-swing phases when wearing an AFO (p < 0.05). The TA-MG co-contraction index significantly decreased during initial and mid-swing phases with the AFO (p < 0.05). These results suggest that AFOs positively influenced the contraction patterns of paretic ankle muscles during walking in stroke patients, but further research is needed to understand their long-term effects.

Accelerating Precision: Using AI to Fine-Tune Workout Form and Motion Speed

This is an extension of the paper that we published earlier on AI for workout Form Optimization. In the earlier paper, we presented a software solution for workout form optimization using joint angles. Just like the effectiveness of the workout is in the precision of the body form, it also gets hugely impacted by the workout speed, i.e., muscle contraction and relaxation speed. This paper covers a software solution that can be used to give users feedback on their workout speed for specific workout exercises. It uses computer vision and artificial intelligence libraries. The sample implementation is provided on GitHub GitHub - pythonioncoder/Fit-Form-AI. Keywords— Pose Detection AI Libraries, Media pipe, AI Programming, Computer Vision, Artificial Intelligence, Fit Form AI

The impact of eccentric muscle contractions on peripheral nerve integrity.

Besides muscle damage, eccentric contractions also impose significant mechanical loads on peripheral nerves. However, the impact of eccentric contractions on peripheral nerve properties remains unclear. We aimed to reveal the immediate (i.e., <2 h and short-term (i.e., <10 days) effects of eccentric contractions on functional, structural, morphological, physiological and biomechanical properties of peripheral nerves. Four electronic databases (PubMed, Science Direct, PEDro and Cochrane) were searched for animal and human studies which evaluated the immediate and/or short-term impact of eccentric contractions of upper or lower limb muscles on outcomes related functional, structural, morphological, physiological and biomechanical properties of peripheral nerves. From a total of 2415 articles, two human and two animal studies met the selection criteria. Several signs of nerve damage following eccentric exercises were observed, such as reductions in myelin sheath thickness, nerve fibre diameter, sensory and motor nerve conduction velocity, and protein zero levels, alongside increased levels of macrophage-related protein and tropomyosin receptor kinase C. No significant changes were identified in growth-associated protein 43. It is worth noting that some variables exhibited differences in their time course between human and animal studies. Animal studies revealed that the effects were more pronounced when eccentric contractions were performed at higher velocities. Current evidence is suggestive that eccentric contractions has the potential to alter the peripheral nerves structural, morphological, functional and physiological properties, which are indicative of nerve damage. CRD42021285767.

Coordination among cytoskeletal organization, cell contraction, and extracellular matrix development is dependent on LOX for aneurysm prevention.

Distinct and seemingly independent cellular pathways affecting intracellular machinery or extracellular matrix (ECM) deposition and organization have been implicated in aneurysm formation. One of the key genes associated with this pathology in both humans and mice is lysyl oxidase (LOX), a secreted ECM-modifying enzyme, highly expressed in medial vascular smooth muscle cells. To dissect the mechanisms leading to aneurysm development, we conditionally deleted Lox in smooth muscle cells. We find that cytoskeletal organization is lost following Lox deletion. Cell culture assays and in vivo analyses demonstrate a cell-autonomous role for LOX affecting myosin light-chain phosphorylation and cytoskeletal assembly resulting in irregular smooth muscle contraction. These results not only highlight new intracellular roles for LOX, but notably, they provide a link between multiple processes leading to aneurysm formation, suggesting LOX coordinates ECM development, cytoskeletal organization, and cell contraction required for media development and function.

Multiomics profiling of DNA methylation, microRNA, and mRNA in skeletal muscle from monozygotic twin pairs discordant for type 2 diabetes identifies dysregulated genes controlling metabolism

BackgroundA large proportion of skeletal muscle insulin resistance in type 2 diabetes (T2D) is caused by environmental factors.MethodsBy applying multiomics mRNA, microRNA (miRNA), and DNA methylation platforms in biopsies from 20 monozygotic twin pairs discordant for T2D, we aimed to delineate the epigenetic and transcriptional machinery underlying non-genetic muscle insulin resistance in T2D.ResultsUsing gene set enrichment analysis (GSEA), we found decreased mRNA expression of genes involved in extracellular matrix organization, branched-chain amino acid catabolism, metabolism of vitamins and cofactors, lipid metabolism, muscle contraction, signaling by receptor tyrosine kinases pathways, and translocation of glucose transporter 4 (GLUT4) to the plasma membrane in muscle from twins with T2D. Differential expression levels of one or more predicted target relevant miRNA(s) were identified for approximately 35% of the dysregulated GSEA pathways. These include miRNAs with a significant overrepresentation of targets involved in GLUT4 translocation (miR-4643 and miR-548z), signaling by receptor tyrosine kinases pathways (miR-607), and muscle contraction (miR-4658). Acquired DNA methylation changes in skeletal muscle were quantitatively small in twins with T2D compared with the co-twins without T2D. Key methylation and expression results were validated in muscle, myotubes, and/or myoblasts from unrelated subjects with T2D and controls. Finally, mimicking T2D-associated changes by overexpressing miR-548 and miR-607 in cultured myotubes decreased expression of target genes, GLUT4 and FGFR4, respectively, and impaired insulin-stimulated phosphorylation of Akt (Ser473) and TBC1D4.ConclusionsTogether, we show that T2D is associated with non- and epigenetically determined differential transcriptional regulation of pathways regulating skeletal muscle metabolism and contraction.

Stochastic force generation in an isometric binary mechanical system.

Accurate models of muscle contraction are necessary for understanding muscle performance and the molecular modifications that enhance it (e.g., therapeutics, posttranslational modifications, etc.). As a thermal system containing millions of randomly fluctuating atoms that on the thermal scale of a muscle fiber generate unidirectional force and power output, muscle mechanics are constrained by the laws of thermodynamics. According to a thermodynamic muscle model, muscle's power stroke occurs with the shortening of an entropic spring consisting of an ensemble of force-generating myosin motor switches, each induced by actin binding and gated by inorganic phosphate release. This model differs fundamentally from conventional molecular power stroke models that assign springs to myosin motors in that it is physically impossible to describe an entropic spring in terms of the springs of its molecular constituents. A simple two-state thermodynamic model (a binary mechanical system) accurately accounts for muscle force-velocity relationships, force transients following rapid mechanical and chemical perturbations, and a thermodynamic work loop. Because this model transforms our understanding of muscle contraction, it must continue to be tested. Here, we show that a simple stochastic kinetic simulation of isometric muscle force predicts four phases of a force-generating loop that bifurcates between periodic and stochastic beating through mechanisms framed by two thermodynamic equations. We compare these model predictions with experimental data including observations of spontaneous oscillatory contractions (SPOCs) in muscles and periodic force generation in small myosin ensembles.

Exploring the ’EarSwitch’ concept: a novel ear based control method for assistive technology

BackgroundLoss of communication with loved ones and carers is one of the most isolating and debilitating effects of many neurological disorders. Assistive technology (AT) supports individuals with communication, but the acceptability of AT solutions is highly variable. In this paper a novel ear based control method of AT, the concept of ’EarSwitch’, is presented. This new approach is based on detecting ear rumbling, which is the voluntary contraction of the tensor tympani muscle (TTM), resulting in observable movement of the eardrum and a dull rumbling sound. ’EarSwitch’ has the potential to be a discreet method that can complement existing AT control methods. However, only a subset of the population can ear rumble and little is known about the ability of rumbling in populations with neurological disorders.MethodsTo explore the viability of the ’EarSwitch’ concept as an AT control method we conducted in-depth online surveys with (N=1853) respondents from the general population and (N=170) respondents with self-declared neurological disorders including Motor Neurone Disease (MND) and Multiple Sclerosis (MS).This is the largest ever study to explore ear rumbling and the first to explore whether rumbling is preserved among individuals with neurological disorders. In addition, we validated rumbling, and investigated usability of the ’EarSwitch’ concept as a control input, using in-person otoscopic examination with a subset of participants.ResultsA significant proportion of the population with neurological disorders could benefit from ’EarSwitch’ controllable AT. The upper bound prevalence of the ability to rumble without accompanying movements was 55% in the general population, 38% in the neurological population, and 20% of participants with MND (N=95) reported this ability. During the validation procedure, participants achieved high accuracy in self-reporting the ability to rumble (80%) and proved concept of using the ’EarSwitch’ method to control a basic interface.Discussion’EarSwitch’ is a potential new AT control method control, either by itself or as a supplement to other existing methods. Results demonstrate self-reported ear rumbling is present among patients with different neurological disorders, including MND. Further research should explore how well the ability to rumble is preserved in different types and stages of neurological disorders.

Co-culture of postnatal mouse spinal cord and skeletal muscle explants as an experimental model of neuromuscular interactions.

The intercommunication between nerves and muscles plays an important role in the functioning of our body, and its failure leads to severe neuromuscular disorders such as spinal muscular atrophy and amyotrophic lateral sclerosis. Understanding the cellular and molecular mechanisms underlying nerve-muscle interactions and mediating their mutual influence is an integral part of strategies aimed at curing neuromuscular diseases. Here, we propose a novel ex vivo experimental model for the spinal cord (SC) and skeletal muscle interactions which for the first time utilizes only fully formed (but not yet quite functional) postnatal tissues. The model represents an organotypic co-culture comprising a longitudinal slice of the mouse postnatal SC and an extensor digitorum longus (EDL) muscle explant placed in the "damage zone" of transversally dissected longitudinal slice of the SC. Using this model, we have shown that SC tissue stimulates muscle contractions and reduces the area occupied by acetylcholine receptors on muscle surface. In turn, EDL muscles stimulate the growth of SC-derived neurites. Thus, our organotypic model allows one to assess the mutual influence of neurons and muscles in a nearly natural setting which maintains the architecture and cellular composition of intact tissues. Therefore, this model may provide an effective platform for studying molecular and cellular mechanisms linked to defective neuromuscular interactions in associated pathologies.

Fibroblast diversification is an embryonic process dependent on muscle contraction

Fibroblast diversification is an embryonic process dependent on muscle contraction

Botulinum toxin treatment of refractory vaginismus: a prospective study.

Vaginismus is a common sexual dysfunction. A few studies have indicated that botulinum neurotoxin type A (BoNTA) can help treat refractory vaginismus by alleviating muscle tension. However, such studies did not use standardized methodology and BoNTA dosage. The aim is to evaluate the efficacy of intravaginal BoNTA injection in treating refractory vaginismus. Also, we intended to assess the effectiveness and safety of modest doses, that is, 100 to 200 IU of submucosal BoNTA injections. A prospective study was conducted in an outpatient surgical center over 18 months. Twenty patients aged 29 to 49 years (mean, 30.9 years) with refractory vaginismus were enrolled. All patients had been sexually inactive at the time of treatment. All participants had received various treatments such as psychotherapy, vaginal dilatator therapy, muscle relaxants, and lubricants with no relief. A dose of 100 to 200 IU of BoNTA was injected submucosally in the lateral sides of the bulbospongiosus, pubococcygeus, and puborectalis muscle areas. The patients were followed over 4 months posttreatment. Nineteen patients (95%) achieved satisfactory intercourse by the end of the 4-month follow-up period. A repeat BoNTA injection was not required as there were no recurrences. None of the participants reported adverse effects. A small sample size and lack of a control group. Injecting submucosally modest BoNTA doses is an effective and safe treatment for refractory vaginismus. When conventional therapies fail, BoNTA can be used to lessen muscle contraction, alleviate pain, and facilitate dilator treatments. Our standardized protocol, which involves a careful submucosal injection technique, can minimize risks and make the procedure easy to perform for daily practice.

Reducing electrocardiographic interference in the multichannel electromyogram to help muscle fatigue assessment in low-intensity contractions.

Surface electromyography (EMG) can be used in the rehabilitation of musculoskeletal disorders, for evaluating the coordination of muscles that stabilize a joint, or as an objective tool in assessing muscle fatigue. This latter may be achieved by evaluating the low-frequency content of the EMG. However, the electrocardiogram (ECG) interference is also recorded when EMG is acquired close to the heart. It may mask or even modify the information of interest in the EMG. Different signal processing techniques have been proposed to eliminate ECG artifacts from the EMG signals, the high-pass filter being the most used one. Nevertheless, this classic filtering approach would also attenuate EMG activities below 30 Hz, which contain information from low-intensity muscle contractions. This work addresses the automatic ECG attenuation when multichannel EMG is collected on the left pectoralis major muscle during a muscle fatigue test. The proposed ECG artifact mitigation extends a successful automatic template subtraction (TS) approach, which does not require an extra reference channel and is now applied to independent EMG source signal components extracted using a blind source separation technique (ICA, Independent Component Analysis). The automatic detection of ECG components was performed through two alternative measures: entropy and Kullback-Leibler divergence. While the ECG interference seems to hamper the detection of muscle fatigue in the low-contraction regime, the association ICA+TS preserved better the EMG low-frequency content, and the entropy-based automatic detection was found to be more suitable, avoiding possible errors that might arise from manual detection procedures.

Overexpression of enhanced yellow fluorescent protein fused with Channelrhodopsin-2 causes contractile dysfunction in skeletal muscle.

Skeletal muscle activation using optogenetics has emerged as a promising technique for inducing noninvasive muscle contraction and assessing muscle function both invivo and invitro. Transgenic mice overexpressing the optogenetic fusion protein, Channelrhodopsin 2-EYFP (ChR2-EYFP) in skeletal muscle are widely used; however, overexpression of fluorescent proteins can negatively impact the functionality of activable tissues. In this study, we characterized the contractile properties of ChR2-EYFP skeletal muscle and introduced the ChR2-only mouse model that expresses light-responsive ChR2 without the fluorescent EYFP in their skeletal muscles. We found a significant reduction in the contractile ability of ChR2-EYFP muscles compared with ChR2-only and WT mice, observed under both electrical and optogenetic stimulation paradigms. Bulk RNAseq identified the downregulation of genes associated with transmembrane transport and metabolism in ChR2-EYFP muscle, while the ChR2-only muscle did not demonstrate any notable deviations from WT muscle. The RNAseq results were further corroborated by a reduced protein-level expression of ion channel-related HCN2 in ChR2-EYFP muscles and gluconeogenesis-modulating FBP2 in both ChR2-EYFP and ChR2-only muscles. Overall, this study reveals an intrinsic skeletal dysfunction in the widely used ChR2-EYFP mice model and underscores the importance of considering alternative optogenetic models, such as the ChR2-only, for future research in skeletal muscle optogenetics.

Comprehensive RNA-seq Analysis Identifies Network Hub Genes and Biomarkers Differentiating Desmoid-type Fibromatosis from Reactive Fibrosis

Desmoid-type fibromatosis (DTF) is a benign but locally aggressive neoplasm characterized by the persistent fibroblast activation, unlike reactive fibrosis (RF), where fibroblast activation is transient. Although the Wnt/β-catenin signaling pathway is known to play a role in DTF pathogenesis, the specific genetic drivers contributing to this abnormal fibroblast activation are not fully understood.To identify additional driver genes that underlie the persistent activation of fibroblasts in DTF, we conducted a comparative transcriptome analysis between 29 DTF and 14 RF tissue samples, identifying 4,267 differentially expressed genes (DEGs) specific to DTF. These DTF-specific DEGs were significantly associated with pathways involved in embryonic limb morphogenesis and muscle contraction, whereas RF-specific DEGs were linked to immune response and apoptosis.Using weighted gene co-expression network analysis (WGCNA) to further elucidate the key regulatory circuits associated with the persistent activation of DTF fibroblasts, we identified a highly DTF-specific gene module comprising 120 genes. This module was also significantly enriched in other fibro-proliferative conditions showing the persistent fibroblasts activation, such as keloid disease and idiopathic pulmonary fibrosis. Subsequent analyses identified seven driver transcription factors (ZNF536, IRX5, TWIST2, NKD2, PAX9, SHOX2, and SALL4) within this DTF-specific module that may contribute to the sustained activation of DTF fibroblasts.We further assessed the utility of five key genes from this module (TWIST2, LRRC15, CTHRC1, SHOX2, and SALL4) as potential biomarkers to distinguish DTF from RF using immunohistochemistry. All markers demonstrated excellent diagnostic performance, with TWIST2 showing exceptionally high sensitivity and specificity, surpassing β-catenin, the current standard biomarker for DTF.In conclusion, our study identifies gene modules and driver transcription factors that are highly specific to DTF, offering new insights into the genetic underpinnings of abnormal fibroblast activation in DTF. We also propose novel biomarkers that could improve the diagnostic accuracy and clinical management of DTF.

Impedance for Assistance: Upper-Limb Assistive Soft Robotic Suit Using Linked-Layer Jamming Mechanisms.

Wearable robots, especially those composed of soft materials, are increasingly attracting interest due to their comfort, ease of donning and doffing, and their ability to provide assistance across various applications. In wearable robotics, striking a balance between ensuring low impedance for wearer comfort and providing sufficient assistive force is a notable design challenge. In this study, we propose exploiting impedance variation in accordance with the types of muscle contraction in the human body. Particularly in eccentric muscle contraction, the impedance can help reduce the muscular load, since it exerts force in the same direction as the muscles. To utilize the relation, we proposed a linked-layer jamming mechanism, which adjusts its impedance largely in various directions. This mechanism allows not only a broad variable range of impedance in multiple rotation directions but also directional torque design, even when equipped in human multi-degree-of-freedom (DoF) joints. By constructing a wearable robot prototype equipped with the proposed linked-layer jamming mechanisms, the effectiveness of this impedance-based assistance approach was confirmed through experiments. The findings from this study present new possibilities in wearable robot design, showing that suitably amplified impedance can assist human motion, potentially enhancing task efficiency and lowering injury risk. This work thus offers a new perspective for researchers in the field of wearable robots, demonstrating that impedance, often minimized in existing designs, can be utilized beneficially when properly amplified.