Exoskeletons assist and augment movement, but their effects on proprioceptive feedback remain poorly understood due to challenges in making direct measures of sensory signals in humans. Here, we leveraged a benchtop animal model to explore how mechanical context akin to an elastic exoskeleton operating on a human lower limb joint influences primary muscle spindle firing. In an anesthetized rat preparation, we applied controlled stretches to the medial gastrocnemius with engineered springs (0-0.5 N/mm) in parallel to the muscle-tendon unit (MTU) while modulating muscle activation to maintain overall system stiffness. Fascicle length was measured with sonomicrometry, force and MTU length with a servo motor, and spindle instantaneous firing rate (IFR) using dorsal root recordings. Trading off increases in exoskeleton stiffness with reductions in muscle activation decreased biological muscle force (3.1±0.6 N to 1.6±0.6 N, p<0.001) and stiffness (4.4±1.5 N/mm to 2.3±1.3 N/mm, p<0.01), and increased fascicle length (7.9±1.3 mm to 8.3±1.5 mm, p<0.005). We found significant correlations between spindle firing and each independent fascicle dynamics factor we investigated (p<0.005). Thus, parallel stiffness modified muscle fascicle dynamics but did not alter spindle firing, possibly due to internal trade-offs in the salient fascicle dynamics that drive spindle behavior. Leveraging in-situ experiments that enable monitoring of afferent feedback in complex mechanical contexts such as added parallel stiffness can provide a window into the effects of wearable devices on underlying sensory systems.

Aberrant proprioception is hypothesised to contribute to suboptimal motor adaptations that promote pain persistence. However, when these impairments in proprioception develop in the transition from acute to chronic pain is not well understood. Understanding the nature and time course of proprioceptive changes early in pain development may reveal critical insights. The primary aim of this systematic review and meta-analysis was, therefore, to evaluate the influence of acute pain on proprioception. Six databases (Pubmed, Medline, Web of Science, Psychinfo, Embase, and Scopus) were searched from inception to May 18[th], 2026 for studies examining the effect of experimentally-induced or clinical pain of < 3 months' duration on behavioural measures of proprioception. Behavioural outcomes included joint position reproduction, threshold to detect passive motion, force matching, velocity detection, and left/right judgement tasks (LRJT). Included articles (27 studies, n = 4,019 participants) were critically appraised using a modified Downs and Black checklist. Meta-analyses were performed using a random effects model on LRJT, and all other outcomes were synthesised descriptively due to study heterogeneity. The analysis revealed that individuals with acute clinical pain demonstrated worse accuracy on the LRJT when identifying images corresponding to the affected side (MD = -8.64, 95% CI = -16.93 to -0.34), with no corresponding change in response time. Acute pain was also associated with impairments in position and movement sense in a joint- and angle dependent manner. Interpretation of these findings should consider the heterogeneity of acute pain conditions included, particularly clinical and experimental models involving tissue injury or inflammation that may independently influence proprioceptive performance. Together, these findings raise the possibility that acute pain disrupts both sensory feedback relating to position and movement sense and processing of somatotopic proprioceptive representations. PERSPECTIVE: This review suggests that acute pain may alter proprioception in task-specific ways, disrupting position and movement sense as well as somatotopic body-related processing. These findings may help clarify early sensorimotor changes that contribute to maladaptive movement and provide mechanistic insight into the transition from acute to persistent pain.

Lysosomal membrane failure contributes to cellular injury by disrupting degradation, metabolism, immune signaling, and compartmental integrity, yet the physical principles that determine whether a mechanically loaded lysosome adapts or ruptures remain incompletely resolved. This review integrates biophysical and molecular evidence to examine lysosomal membrane tension as an organelle-state variable and TMEM63A as an emerging determinant of lysosomal mechanoresilience. We distinguish membrane tension from hydrostatic and osmotic pressure, organelle volume, membrane permeabilization, and rupture, and evaluate how surface-area-to-volume constraints, luminal solute accumulation, ion and water flux, membrane potential, lipid composition, and force-from-lipid gating shape mechanical failure thresholds. The strongest evidence comes from Drosophila TMEM63 and mouse TMEM63A lysosomal mechanosensitivity and macrophage models in which TMEM63A-dependent cation efflux lowers acute membrane tension and rupture susceptibility. Together, these findings support a pressure-relief model coupling mechanically activated conductance to lysosomal membrane stability. Evidence from lysosome-related organelles, lipid scrambling, myelination, infection, and pressure-sensitive mTORC1-TFEB/TFE3 signaling broadens the mechanistic scope without establishing a universal TMEM63A-dependent pathway. Accordingly, TMEM63A is best viewed as a system- and condition-dependent regulator of acute lysosomal mechanical vulnerability, not a general lysosomal controller or validated therapeutic target. Importantly, TMEM63A-linked disease phenotypes in humans and Tmem63a-deficient mice have not been causally linked to impaired lysosomal mechanoresilience, and the macrophage pressure-relief mechanism remains unvalidated in vivo. Resolving these uncertainties will require simultaneous, time-resolved measurements of tension, geometry, ion composition, membrane potential, permeability, and repair, combined with compartment-specific localization and rescue using wild-type, pore-defective, localization-defective, and disease-associated variants.

Despite the quadriceps being a large muscle group with distinct heads, no study has compared motor unit discharge rates (MUDRs) of the three superficial portions in the same participants. Further, day-to-day variability of quadriceps MUDRs and the influence of limb dominance have not been evaluated. Thus, during submaximal contractions, we assessed MUDRs of the vastus lateralis (VL), rectus femoris (RF), and vastus medialis (VM) of the dominant and non-dominant limbs on two separate days. We hypothesized that MUDRs of the RF would be faster than VM and VL but not different between the VM and VL. Additionally, MUDRs would not be different between limbs, or days. During two identical sessions (≥72h apart), 16 healthy, young adults (8 females, 27±7y) performed repeated (7-14 per limb) 15-s isometric contractions at 25% of maximal knee extensor force. Motor unit trains (≥24 per muscle) were recorded from concentric needle electrodes inserted separately into the VL, RF, and VM, and analyzed using decomposition-based quantitative electromyography software. Muscle order was pseudorandomized, though consistent for each limb within a participant. A total of 5391 motor unit trains were included for analysis (26.9±5.5 per muscle per participant). Independent of limb dominance and day (main effects and interactions all P≥0.115), the mean MUDR for RF (12.6±1.8Hz) was faster than VL (10.2±1.5Hz) and VM (10.9±1.7Hz), and VM was faster than VL (all P≤0.001). The results indicate the three superficial quadriceps muscles have unique motor unit rate modulation, possibly reflecting different relative contributions to knee extension force production.

Many species of gecko and all but one species of anole possess enlarged, serially arranged scales on the ventral surfaces of their digits that collectively are referred to as toe pads. These are commonly considered key innovations and have been the subject of many studies within and beyond the biological sciences. The definition of squamate toe pads, however, remains vague. This is particularly problematic for comparative morphological and biomechanical studies wherein toe pad area is commonly employed as a dependent or independent variable or covariate. Lack of a standardized means of delimitation of toe pads impedes accurate measurement of these ecologically and evolutionarily important features and compromises effective comparison between species and studies. Herein, we take a comprehensive approach to the delimitation of the toe pads of the Tokay gecko (Gekko gecko), the species of gecko most frequently studied in relation to the phenomenon of gecko adhesion. In addition to consideration of the broadly adopted, but somewhat arbitrarily delineated, circumscription of toe pads based on characteristics of scale dimensions alone, we also investigate their boundaries by examining the relationship between subdigital scales and subcutaneous anatomical features (employing osteological and tendon-based [TB] criteria). We find that the methods employing only external dimensions of subdigital scales to delimit toe pads overestimate their area, thereby resulting in functional studies that likely underestimate toe pad adhesive stress (force per unit area). Of the two approaches that anatomically delimit toe pads, that based upon tendinous connections (demarcating what we refer to as the LDT region of the digits) encompasses all epidermal filaments that are true setae (those bearing spatulate tips), the only structures empirically validated to facilitate whole-animal adhesion. As such, we encourage future studies to employ the TB approach to accurately delimit gekkotan (and anoline) toe pads in a functionally and anatomically meaningful (and standardized) fashion and provide guidelines about how this can be achieved.

Eccentric exercise is widely used in rehabilitation protocols for older adults. However, the age-related behavior of the muscle-tendon unit (MTU) during eccentric actions remains incompletely understood, especially regarding muscle-tendon decoupling and its influence on fascicle dynamics and force production. Better characterizing these mechanisms would help optimize the design of rehabilitation protocols in older individuals. This study aimed to investigate age-related differences, while ensuring comparable physical activity levels between groups, in gastrocnemius medialis (GM) MTU behavior during eccentric exercises performed at maximal and submaximal intensities, during controlled conditions on an isokinetic dynamometer and during a typical eccentric training exercise which can be done at home, i.e., heel-drop exercise. GM muscle fascicle length and tendon strain were simultaneously measured with ultrasonography during the eccentric exercises, while ankle angle, ankle torque and GM muscle activation were monitored. The results did not show any statistically significant between-group differences in GM MTU behavior during eccentric exercise between age groups, regardless of intensities (i.e., maximal versus submaximal) and conditions of the exercise (i.e., dynamometer versus heel-drop). Specifically, no statistically significant differences were detected in GM tendon strain, muscle fascicle length and velocity between active young adults and active non- or pre-frail older adults, in all exercise conditions and intensities (all p > 0.05). No significant differences were reported in Achilles tendon stiffness between groups (p > 0.05). These results suggest that the effects of aging on the MTU behavior and muscle-tendon interactions may be mitigated by maintaining important physical activity with increasing age.

Naturally occurring Ra-226 is routinely detected in scrap metal entering Taiwan's steel recycling industry; of the 69 radiation anomaly cases reported during 2022-2023, 38 involved Ra-226, motivating the contamination case examined here. However, the potential for Ra-226 to migrate into the underlying vadose zone through rainfall infiltration during interim outdoor storage, and the consequent Rn-222 gas-phase release has not been systematically evaluated. This study employs numerical simulation with HYDRUS-1D to model Rn-222 transport through unsaturated soil columns under an idealized, hypothetical case, using site-realistic climate forcing derived from five-year (2021-2025) meteorological records at three stations spanning northern, central, and southern Taiwan. Twenty-six cases were constructed, encompassing three co-located soil-climate pairings (clay loam, loam, sandy loam), a source-depth series, sustained-rainfall and drought perturbations, a water-table series, and a soil-climate factorial that separates the soil and climate contributions. Because the site-specific Ra-226 inventory is unknown, fluxes are reported per unit source term (in cm[-2] day[-1] for an unspecified solute-mass unit), and comparisons across cases are interpreted on a relative basis. Results show that soil texture is the dominant control: sandy loam produces roughly twice the annual mean surface flux of clay loam with minimal seasonal variation, while clay loam exhibits nearly sixfold seasonal modulation. Adding 10 cm of overburden reduces flux by approximately 37% in clay loam but only marginally in sandy loam. A pronounced climate asymmetry emerges: drought increases summer flux substantially, whereas the sustained-rainfall-induced suppression, though substantial in fine-textured soil, is smaller than the drought enhancement. Across the fifteen baseline and perturbation cases, surface flux spans less than half an order of magnitude, governed primarily by the inherent soil-climate combination at the source location rather than engineering measures or extreme weather.

Hereditary sensory and autonomic neuropathy type IV, commonly known as congenital insensitivity to pain with anhidrosis (CIPA), is a rare autosomal recessive disorder. It is characterized by a profound dysfunction of the sensory and autonomic nervous systems, leading to a global inability to perceive pain or temperature alongside a complete absence of sweating. Clinically, affected individuals typically present with a classic triad of symptoms: severe analgesia, a total lack of pain perception that frequently results in self-mutilation (such as biting the tongue, lips, and fingertips), recurrent fractures, and joint deformities; anhidrosis, which impairs body temperature regulation and often triggers life-threatening hyperpyrexia; and varying degrees of neurological involvement, including intellectual disability and behavioral challenges. This report details a case series within a single extended family involving two sisters and two of their paternal cousins (a brother and sister). All four patients presented with classic clinical hallmarks of CIPA, which were subsequently confirmed through genetic analysis. The patients exhibited multiple complications, including chronic infections and orthopedic injuries resulting from their lack of protective pain sensation. Managing CIPA requires a highly specialized, multidisciplinary approach to mitigate self-injury and manage febrile episodes.