Biology and Life Sciences

Abstract: Wearable devices, such as the Empatica E4, are increasingly used to assess stress-related electrodermal activity (EDA). The EmbracePlus has replaced the widely used Empatica E4. This study evaluated the validity of the EmbracePlus by comparing wrist-worn EDA measurements with the Shimmer3 GSR+ across signal-, parameter-, and event-level analyses. Healthy volunteers (n=53) completed breathing exercises, a Stroop stress task, and a virtual reality (VR) height stressor while wearing both devices simultaneously on the non-dominant wrist. Signal-level agreement was assessed using cross-correlation, parameter-level agreement using Bland–Altman analyses of mean skin conductance level (SCL), total phasic activity, skin conductance response (SCR) amplitude, and SCR count, and event-level agreement using within-device baseline-to-task comparisons and inter-device difference plots with a priori acceptability boundaries. Signal-level agreement was weak-to-moderate. Shimmer3 yielded systematically higher values across all metrics, indicating limited agreement in absolute EDA values. Shimmer3 detected significant increases across all metrics during both stress tasks. EmbracePlus detected the stronger VR stressor across all metrics, whereas during the milder Stroop task only total phasic activity and mean SCL increased. These findings indicate that EmbracePlus and Shimmer3 are not interchangeable for absolute EDA assessment and that EmbracePlus validity depends on stressor intensity and metric selection.

Abstract: Fingerprint dermatoglyphics is used in Ibero-America and Eastern Europe as a marker of physical ability for talent identification. A 2022 genome-wide study linked fingerprint loci to limb development and hand proportions, thereby supporting a morphological hypothesis. We quantified the association between quantitative fingerprint indices and objectively measured physical ability and assessed whether it persisted after adjustment for morphology. Following a registered protocol (PROSPERO CRD420261469333), we searched Web of Science and four Ibero-American databases and pooled Fisher z-transformed correlations in a correlated-and-hierarchical-effects model with cluster-robust variance estimation, with three-level and Bayesian models as companions. Twenty studies were eligible; nine contributed 122 effect estimates from 337 participants. The pooled correlation was r = 0.047 (95% confidence interval: −0.218 to 0.306); the three-level model gave r = 0.025 (−0.028 to 0.078), an anti-conservative interval. No study adjusted for anthropometry, maturation, or training; in four studies measuring all three, anthropometry correlated with performance (mean |r| = 0.45) more strongly than fingerprints (mean |r| = 0.17), and partial correlations did not increase the fingerprint–performance association. Certainty was very low. This study shows no practical association between morphological and physical capacities, which does not support using fingerprints to select young athletes.

Abstract: The evolution of the pentadactyl limbs in tetrapods is an interdisciplinary field, spanning palaeontology, evolutionary biology, human and animal physiology, biomechanics, and the theory of complex emergent systems. Research in this area has led to the formulation of various scientific hypotheses and theories that require further investigation and testing. This research continues to generate theories and approaches to solve this problem. In this paper, we analyse prevailing theories and the experimental evidence supporting them and propose our model to explain the number of fingers on the human hand. The results of palaeontological studies show that the first limbs of ancient fish that emerged from the water, consisted of eight, seven, or six digits. However, the subsequent evolution of land-dwelling organisms led to the vast majority of tetrapods, from the whole range of possible finger counts, settling on the number five. Geneticists have now studied in considerable detail the mechanism by which five digits are formed, involving the Hoxa11, Hoxa13, Hoxd13 and other genes. However, the question of why evolution chose five digits specifically, rather than six, seven or eight, remains unanswered. Another theory that the selection of five digits and the establishment of this number occurred by chance, and that the number five offers no advantage over any other number. In this paper, we formulate hypothesis that the selection of five digits was not random but purposeful, as evolution would have required, and that the reason for this choice is determined by the physical properties of three-dimensional space and time. We show that the number five is a characteristic number of our physical world, a fundamental biological constant for terrestrial creatures. Evolution’s selection of a limb with five digits is a necessary and sufficient condition for adaptation to three-dimensional terrestrial space, enabling the rapid acquisition, via the five digits, of the necessary and sufficient tactile information about the shapes of three-dimensional objects in the context of the struggle for existence. Tetrapods with any other number of digits lost out to those with five digits in the competitive struggle for survival during the course of evolution.

Abstract: Jump testing is widely used to assess lower-limb power, force absorption, and stretch-shortening cycle (SSC) function; however, lateral cyclic tests remain underexplored despite their relevance to change-of-direction performance. This study determined the intra- and inter-session reliability of a novel cyclic lateral leg power test using an inertial measurement unit (IMU). Seventeen female athletes completed three identical testing sessions separated by seven days. Participants performed 10 consecutive lateral bounds at distances of 1.0x, 1.25x, and 1.5x leg length on each limb. A foot-mounted IMU quantified contact time (CT) and airtime (AT), with the best five repetitions analyzed. Reliability was assessed using percent change in the mean, coefficients of variation (CV), and intraclass correlation coefficients (ICC). Between-session changes were small (-7.9% to 6.6%), with no significant session effects for CT or AT. CVs ranged from 9.2% to 21.8%, with only CT at 1.0x leg length between Sessions 1 and 2 below 10%. ICCs ranged from 0.12 to 0.76, indicating poor-to-good relative reliability. Overall, the IMU-instrumented lateral cyclic test demonstrated largely unacceptable reliability, particularly at greater jump distances, indicating that further protocol refinement is required before implementation in clinical or performance settings.

Abstract: Living connective tissue must preserve mechanical function while changing shape, yet stiffness alone does not describe this adaptability. This Hypothesis article integrates mechanical homeostasis, biotensegrity, auxetic mechanics, and extracellular-matrix (ECM) biology to develop a falsifiable model of tissue reconfiguration. Auxeticity is a condition-dependent behavior in which longitudinal extension is accompanied by transverse expansion. We propose that ECM state—including hydration, ground-substance organization, collagen architecture and crimp, cross-linking, interfibrillar mobility, and cellular prestress—may regulate reversible auxetic deformation within biological systems. Auxetic oscillation (AO) denotes repeated reversible transitions into and out of negative-Poisson deformation regimes during physiological loading. Progressive restriction of this capacity could narrow the deformation repertoire, alter fluid and energy handling, modify mechanotransductive input, and participate in maladaptive remodeling. The model does not claim that all tissues are auxetic, that auxeticity is inherently beneficial, or that any manual therapy or exercise restores auxeticity. Instead, it generates tissue-, direction-, strain-, rate-, hydration-, and scale-specific predictions. Testing these predictions requires concurrent characterization of ECM state and multiaxial deformation, with methods selected and validated by qualified investigators. Reproducible coupling would support AO as one component of mechanical homeostasis; absent coupling would require the model to be narrowed or rejected.

Abstract: Infrasound, a low-frequency physical stimulus from environmental and anthropogenic sources, is assumed to impact microvascular regulation, though the mechanism is not fully understood. This study examines the effects of bipolar infrasound exposure (1 Hz, 100 dB) on the sublingual microcirculation in mice, with a single 4-hour exposure and repeated 4-hour daily exposures for 14 days. Control mice were placed in the same chamber without infrasound exposure. Using sidestream dark-field (SDF) videomicroscopy and laser Doppler flowmetry (LDF), we assessed microvascular diameter oscillations (vasomotion) and flow changes (flowmotion), respectively. A single exposure significantly increased vasomotion oscillation amplitude in the low-frequency band, while changes in the very-low- and high-frequency bands were not significant. Flowmotion measured by LDF significantly increased in the very-low-frequency band after a single exposure, while the other frequency bands remained unchanged. In contrast, repeated exposure significantly increased vasomotion oscillation amplitude within the very-low-, low-, and high-frequency bands, while LDF-derived flowmotion did not change significantly. The findings suggest that repeated exposure to infrasound may induce irregular microvascular oscillations, primarily affecting vessel diameter rather than overall perfusion, warranting further exploration into related mechanisms.

Abstract: Lumbar spinal stenosis (LSS) is a major cause of pain and disability, yet its pathophysiology remains incompletely understood. Although spinal decompression is the standard surgical treatment for LSS with disabling pain or with progressive neurological symptoms, clinical outcomes are often suboptimal, with reoperation required in 5-23% of cases. While degenerative changes of the vertebral canal have been extensively investigated, the potential contribution of the thoracolumbar fascia (TLF) has never been explored at the molecular level. We hypothesized that the TLF undergoes extracellular matrix remodeling and inflammatory changes in LSS. Thoracolumbar fascia biopsies were collected from 14 patients undergoing spinal surgery (7 with LSS and 7 controls with traumatic vertebral fractures). Total collagen content was quantified by hydroxyproline assay, collagen subtypes (I, III, VI and XII) by Western blotting, and inflammatory remodeling by ELISA quantification of TNF-α and MMP-2. LSS patients showed significantly higher hydroxyproline content (p = 0.026), indicating increased collagen deposition and fascial fibrosis, together with elevated MMP-2 levels (p = 0.038), supporting the presence of active chronic extracellular matrix remodeling. TNF-α levels did not differ significantly between groups, although marked inter-individual variability was observed. Collagen subtype expression showed distinct trends but no significant differences. These findings provide the first molecular evidence of fibrotic remodeling and altered extracellular matrix turnover in the TLF of LSS patients, supporting its role as an active contributor to disease pathophysiology and a potential diagnostic biomarker and therapeutic target.

Abstract: Dendrodoris arborescens (Mollusca: Gastropoda) is a dorid nudibranch species for which internal anatomical details have remained undocumented. In September 2024, a total of 20 specimens were collected from the low intertidal zone at Heishijiao, Dalian, Liaoning, China (38.865°N, 121.548°E), representing the first record of this species from the area. Here we present a comprehensive description of both external mor-phology and internal anatomy, based on external observation, anatomical dissection, histological sectioning, and scanning electron microscopy (SEM). The body is elon-gate-elliptical and uniformly black; the mantle surface is smooth without tubercles, bordered by a narrow orange-red marginal band. The rhinophores are clavate, bearing densely arranged, obliquely oriented lamellae on their surface. The branchial plumes are dendritic and encircle the anus. The digestive system features a suctorial oral ap-paratus lacking radula. The reproductive system exhibits a tri-duct hermaphroditic configuration, with the hermaphroditic gonad embedded within the digestive gland. These findings provide foundational morphological data for understanding the repro-ductive biology of Dendrodoris and offer a reference baseline for future studies on spe-cies identification and cultivation of this genus.

Abstract: Two leading paradigms dominate discussions of obesity: the Energy Balance Model (EBM), which attributes weight gain to a surplus of caloric intake over expenditure, and the Carbohydrate-Insulin Model (CIM), which emphasizes carbohydrate-driven hormonal shifts that promote fat storage. Here we introduce the Protein Partitioning Model (PPM), a muscle-centric framework proposing that dietary protein and muscular activity interact to influence energy partitioning and thereby shape body composition even under constant caloric intake. By integrating PPM with the Rational Addiction framework from economics, we model how food choices and body composition co-evolve over time through their effects on lean and fat tissue. The model predicts that, when paired with resistance exercise, protein intake supports functional lean mass, which in turn enhances insulin sensitivity and increases the marginal utility of protein consumption. This creates a virtuous feedback loop characterized by bounded escalation, converging on stable states with relatively low adiposity. In contrast, carbohydrate-consumption feedback can produce relatively volatile, binge-prone trajectories with much higher steady-state adiposity. By treating muscle as an active regulator of nutrient partitioning rather than a passive consequence of energy balance, PPM unifies key features of both existing paradigms while suggesting a proactive, muscle-centric approach to obesity prevention and long-term metabolic health.

Abstract: Purpose: The anaerobic speed reserve (ASR), defined as the difference between maximal sprint speed (MSS) and maximal aerobic speed (MAS), has been used in track and field to establish locomotor profiles and individualize training. In cross-country (XC) skiing, training encompasses varied activities that involve lower and upper body engagement and present distinct biomechanical and cardiometabolic characteristics. This study aimed to determine whether the locomotor profile of youth XC skiers depends on the locomotion mode. Methods: Twelve regional-level female skiers completed two field performance assessments in running (RUN) and roller skiing (SKI): a half-Cooper 6-minute test to determine MAS and a 40-m sprint to establish MSS. Three profiles (endurance, hybrid, or sprint) were determined from the ASR. Results: MAS was higher in SKI than RUN (17.2 ± 1.24 km·h⁻¹ vs 13.9 ± 1.0 km·h⁻¹; t (11) = 10.19, p < 0.001). MSS was also higher in SKI than RUN (23.0 ± 1.35 km·h⁻¹ vs 20.0 ± 1.3 km·h⁻¹; t (11) = 8.15; p < 0.001). However, the ASR did not significantly differ between modalities (p = 0.606). Most athletes were classified as hybrids in RUN (n = 7) and SKI (n = 6). Conclusion: Our findings indicate that most athletes retain a hybrid profile regardless of the modality, which is probably due to modern XC ski racing requirements. The stability of ASR across modalities suggests that this parameter reflects athlete’s intrinsic characteristics rather than modality-specific demands. The ASR may therefore represent a useful indicator for comparing athletes across different testing modalities.

Abstract: Background: Pilonidal sinus disease (PSD) is a chronic inflammatory condition predominantly affecting young adults. Minimally invasive techniques such as pit-picking have gained increasing popularity; however, recurrence rates remain a significant concern. Microwave ablation (MWA) has recently emerged as a novel adjunctive modality that may improve treatment durability through enhanced destruction of residual sinus epithelium. Materials and Methods: This retrospective multicenter comparative cohort study included 403 consecutive patients treated for PSD between January 2022 and January 2024. Among these, 200 patients underwent pit-picking combined with MWA (MWA group) and 203 underwent pit-picking alone (PP group). Recurrence was defined as any clinical reappearance of pit, abscess, or discharging sinus confirmed at follow-up. Primary outcome was disease recurrence; secondary outcomes included operative time, postoperative pain (VAS), complications, SSI, wound healing time, pain-free sitting, and return to work. Multivariable logistic regression and Kaplan–Meier analysis were performed. Results: MWA group demonstrated superior postoperative outcomes: shorter pain-free sitting (2 vs 4 days), healing time (11 vs 16 days), and return to work (3 vs 5 days). Overall complication rates were lower (4.5% vs 11.3%; OR 0.37, 95% CI 0.16–0.84; p=0.018). Recurrence rates were significantly reduced (5.5% vs 13.8%; OR 0.36, 95% CI 0.17–0.75; p=0.006). MWA treatment remained an independent predictor of reduced recurrence on multivariable analysis (adjusted OR 0.35, 95% CI 0.16–0.76; p=0.007). Conclusion: Pit-picking combined with microwave ablation is a safe and effective minimally invasive treatment strategy for PSD, significantly improving postoperative recovery, reducing morbidity, and lowering recurrence rates. Further prospective randomized studies with longer follow-up are warranted.

Abstract: Playing position influences soccer match demands, but comparisons may be biased by unequal playing time and repeated observations from the same players. This retrospective observational study compared GPS-derived running and change-of-velocity demands across five positional groups while accounting for within-player clustering and match exposure. The primary analysis included 84 player-match observations from 21 male professional outfield players across six competitive matches. Linear mixed-effects models included playing position and match as fixed effects, log-transformed playing duration as a covariate, and player as a random intercept. After Holm correction, position was associated with total distance, high-intensity running distance at ≥19 km/h, distance at ≥25 km/h, sprint count, peak speed, accelerations at ≥3 m/s², and decelerations at ≤−3 m/s² (adjusted p ≤ 0.020). At equivalent exposure, central defenders recorded approximately 49% less high-intensity running than wingers and fewer sprints, accelerations, and decelerations than several other groups. Midfielders achieved a 3.06 km/h lower adjusted peak speed than side defenders/full-backs. Findings were robust to two sensitivity analyses. Position-specific monitoring should combine accumulated match dose with exposure-adjusted estimates and account for repeated observations when players contribute data from multiple matches.

Abstract: Background: Coronary artery calcification complicates percutaneous coronary intervention (PCI) by promoting stent underexpansion and increasing rates of stent thrombosis, restenosis, and major adverse cardiovascular events (MACE). Four principal lesion preparation strategies are available: conventional balloon angioplasty, modified balloons (cutting/scoring), atherectomy (rotational/orbital), and intravascular lithotripsy (IVL). Prior evidence derives largely from pairwise trials; no study has simultaneously compared all four modalities. Methods: A systematic review and frequentist random-effects network meta-analysis (NMA) was conducted per Cochrane and PRISMA guidelines. Eight studies were included: ROTAXUS, ECLIPSE, BALI, PREPARE-CALC, ROTA-SHOCK, ROLLING STONE, COPS, and ROLLER COASTER-EPIC22. Treatment nodes comprised plain balloon angioplasty, modified balloon (cutting/scoring), atherectomy, and IVL. Procedural, angiographic, and follow-up clinical outcomes were analyzed using odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals. Treatment hierarchy was estimated via P-scores/SUCRA. Prespecified sensitivity and node-splitting analyses assessed robustness and consistency. Results: Across 8 studies and 4 lesion preparation strategies, IVL ranked highest for procedural success (P-score 47.9%) and procedure-related MACE (31.5%), while modified balloon ranked best for minimizing periprocedural MI (P-score 46.2%). Atherectomy was the only strategy associated with a statistically significant increase in coronary perforation risk compared to plain balloon angioplasty (OR 2.02; 95% CI 1.08–3.77; p=0.028), with plain balloon ranking most favorably for dissection risk. Procedure-related mortality was comparable across all strategies, with no statistically significant pairwise differences. At follow-up, IVL demonstrated the most favorable profile for all-cause mortality (P-score 89.4%), MI (50.6%), and target lesion revascularization (57.7%), while modified balloon ranked highest for follow-up MACE (58.4%). Sensitivity and node-splitting analyses confirmed robustness and consistency of findings across all endpoints. Conclusion: In this NMA simultaneously comparing all four calcified lesion preparation strategies, IVL and modified balloon techniques demonstrated consistently favorable profiles across procedural efficacy and follow-up ischemic outcomes, while atherectomy was associated with a significantly higher perforation risk. These findings, to be interpreted in the context of moderate certainty evidence and largely non-significant pairwise comparisons, provide a comprehensive comparative framework to guide operator decision-making for heavily calcified coronary lesions.

Abstract: Inadequate sleep is common, with up to 40% of adults worldwide getting less than 7 h of sleep per night. Inadequate sleep increases the risk of glucose intolerance, a precursor to type 2 diabetes. While most laboratory studies have focused on severe sleep loss (< 5 h per night), the impact of moderate sleep loss (< 7 h per night), a pattern more representative of modern society, on glucose tolerance has received less attention. Emerging evidence suggests that sleep-loss-induced glucose intolerance may partly result from alterations in mitochondrial characteristics, although direct mechanistic evidence remains limited. It is also unclear whether these changes persist or can be reversed by recovery sleep, during which adequate sleep is restored. This review summarises the effects of varying severities of inadequate sleep on glucose tolerance and highlights current evidence linking alterations in mitochondrial characteristics and changes in glucose tolerance to periods of inadequate sleep. We also discuss whether recovery sleep may restore mitochondrial characteristics and improve glucose tolerance and investigate the potential role of allostasis in these changes. Understanding these mechanisms is critical for assessing the potential reversibility of sleep-loss-induced changes in glucose tolerance and informing strategies to mitigate the adverse health effects associated with inadequate sleep.

Abstract: Physical exercise is a major determinant of health and functional capacity, yet direct com-parisons among contemporary gym-based exercise modalities remain limited. This cross-sectional study compared the physiological and nutritional profile of 148 healthy recreational adults (72 men and 76 women; aged 18–45 years) engaged in mixed aero-bic-resistance training (n = 52), Pilates (n = 46), or CrossFit (n = 50). Participants under-went cardiopulmonary exercise testing to determine maximal oxygen uptake (VO₂max), ventilatory anaerobic threshold (VAT), and metabolic equivalents (METs), alongside body composition analysis, handgrip strength assessment, flexibility testing, and question-naire-based evaluation of dietary habits and supplement use. CrossFit and mixed training were associated with higher VO₂max and functional capacity than Pilates, whereas Pilates demonstrated higher VAT expressed as a percentage of VO₂max. Mixed training and CrossFit also showed more favorable body composition profiles, while mixed training demonstrated superior handgrip strength, particularly in men. Flexibility did not differ significantly among exercise modalities. Mediterranean diet adherence differed signifi-cantly among men, while protein supplements and creatine were among the most fre-quently reported supplements. Overall, exercise modality was associated with distinct physiological and nutritional characteristics, with CrossFit and mixed training showing greater cardiorespiratory and body composition benefits, whereas Pilates was linked to a different submaximal exercise profile and specific lifestyle-related patterns.

Abstract: Background: Due to the difficulty of identifying the window of receptivity, a molecular understanding of endometrial changes after fertilization is essential for improving the effectiveness of in vitro fertilization (IVF). This multi-level study examines the compo-sition of cytokines and extracellular vesicles (EVs) in uterine lavage samples obtainable via a noninvasive procedure in mice. The goal is to offer a new perspective on the tim-ing of embryo transfer. Methods: We performed flow cytometric analyses of inflamma-tory cytokines and EVs in uterine lavage samples collected from CD1 mice at the pre-receptive stage (2.5 days post coitum [dpc]) and the receptive stage (4.5 dpc). We also assessed endometrial progesterone receptor expression via immunohistochemistry and evaluated the expression of adhesion molecules related to implantation by RT-PCR. Re-sults: Significant differences were found in the concentrations of inflammatory cyto-kines (IL-6, IFN-γ, and MCP-1), the EV pattern in uterine lavage fluid, and the expres-sion of some genes related to implantation (CD44, CD81, and CD29). These results re-veal uterine lavage fluid markers associated with endometrial receptivity. Using these noninvasive markers can improve the effectiveness of IVF by enabling more precise timing of embryo transfer.

Abstract: Backround: Musculoskeletal disorders associated with muscular strain on the neck and shoulders affect women in administration more often than men. Ergonomic guidelines have historically been derived from male models, often ignoring biomechanical differences between the sexes. The study aims to quantify the acute biomechanical response of the neck muscles of men and women to a standardized writing task. Methods: The research involved 57 healthy university students (34 women, 23 men; age 19–24 years). Muscle tone (F), stiffness (S), and viscoelastic decrement (D) in sternocleidomastoideus muscle (SCM), trapezius muscle (UT), and semispinalis capitis muscle (SSC) were assessed by the non-invasive MyotonPRO device before and after 20 minutes of continuous writing. Results: The results were statistically quantified and showed significant differences in muscle strategy between the sexes (p < 0.05). While women experienced a fatigue decrease in tone after exercise, the SCM as a superficial neck flexor and the deeper neck extensor SSC recorded a significant compensatory increase in tone, the opposite was true for men. Conslusion: These objective data show that identical office work causes a different physiological burden in women. Prevention of musculoskeletal disorders should therefore abandon a one-size-fits-all approach and move towards gender-specific solutions.

Abstract: Previous studies on rats showed a deterioration of left ventricular (LV) function and myocardial injury characterized by oxidative/nitrosative stress, PARylation, and apoptosis in the heart after three days of hypoxia. In the present study on rats, we investigated whether a three-day recovery period in normoxia can reverse myocardial injury and dysfunction. Further, we studied the effects of norepinephrine (NE) administration as a model of strong sympathetic activation on hypoxia-induced LV dysfunction and myocardial damage, as well as their reversibility. Three days of normobaric hypoxia (10% O2) significantly decreased LV systolic function. Contrary to our expectations, NE infusion even aggravated the depression in LV function. These dysfunctions were completely reversed after three days of normoxic recovery. In contrast, nitrotyrosine as a marker of oxidative/nitrosative stress receded only partially, and poly-ADP-ribose (PAR) increased even further during the recovery period. Apoptosis-inducing factor receded at least partially indicating that PAR-related apoptosis (parthanatos) is not a major cause of hypoxia-induced LV dysfunction. Additional administration of NE mildly aggravated oxidative/nitrosative stress but did not significantly intensify PARylation and consequently, parthanatos. The findings demonstrate that hypoxia-induced LV dysfunction is reversible suggesting that subchronic hypoxia and subsequent reoxygenation has a better prognosis for the LV than classical ischemia/reperfusion injury.

Abstract:

Background: The local twitch response (LTR) elicited during ultrasound-guided fascial hydrorelease (FHR) is conventionally attributed to dysfunctional motor endplates. However, in a related observational paper under concurrent submission, 89/89 evaluable archived LTR events were observed within stacking fascia at sites incompatible with direct endplate excitation. Hypothesis: We propose the Fascial Capacitor Model: stacking fascia functions as a multilayer biological capacitor in which collagen sublayers act as electrodes and the interposed densified hyaluronic-acid (HA)-rich loose layer acts as the dielectric, with the LTR reinterpreted as a transient electrophysiological discharge when a needle bridges its layers. This biophysical model is explicitly grounded in the established molecular and histological architecture of human deep fascia. Supporting evidence: Each premise is independently supported by primary literature from at least eight research lines spanning roughly seventy years. Voltage gap: The apparent gap between estimated bulk discharge voltages and motor neuron threshold is resolved by reconsidering needle-tip geometry and stimulation modality, anchored by the ±6 V triboelectric measurements of Ouyang et al. (2022). Implications: The model is the immediate-phase complement to the Fascial Memory Reset Hypothesis (Int J Mol Sci 2026, 27, 3720), explains intra-procedural symptom relief, and yields falsifiable predictions. A direct empirical validation programme using insulating-needle SEA recording is in preparation at the corresponding author’s institution.

Abstract: Time-restricted feeding (TRF) has emerged as a promising intervention to improve metabolic health and promote healthy aging, yet the cellular mechanisms underlying its effects remain incompletely understood. Here, we applied imaging-based and quantitative cellular analyses to investigate how TRF modulates aging-associated and neurodegeneration-related phenotypes in vitro. Human fibroblasts and AC16 cardiomyocytes were used as models of cellular aging, alongside fibroblast-based models of neurodegeneration. TRF was simulated through cyclic nutrient availability, and cellular responses were evaluated using microscopy-based assessment of cellular morphology, senescence-associated features, metabolic state, and circadian rhythm-associated gene expression dynamics. Imaging analyses demonstrated that TRF modulated key hallmarks of cellular senescence, including changes in cell morphology and intracellular organization, consistent with enhanced cellular resilience and altered metabolic adaptation. In AC16 cardiomyocytes, TRF influenced aging-associated cellular phenotypes, indicating that its effects extend beyond proliferative cell systems to cardiac-relevant models. In neurodegeneration-associated fibroblast models, TRF altered disease-related cellular signatures and stress-associated phenotypes, supporting a potential protective role in neurodegenerative conditions. Quantitative analyses further revealed significant TRF-induced changes in circadian rhythm characteristics across all models, including altered oscillatory amplitude, supporting a mechanistic link between nutrient timing and cellular timekeeping. Together, these findings demonstrate that TRF induces measurable changes in cellular architecture and circadian regulation associated with improved aging- and neurodegeneration-related phenotypes. This work highlights the utility of imaging-based approaches for investigating the spatiotemporal cellular effects of metabolic interventions and supports TRF as a potential therapeutic strategy for age-associated diseases.