Biology and Life Sciences

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.

Abstract: Background: An estimated 28,900 deaths around the world in 2021 were attributed to unintentional CO poisoning. Following inhalation, CO binds to hemoglobin with an affinity 220–240 times greater than that of oxygen to form carboxyhemoglobin (COHb). While the constituents of CO exposure are known to determine CO uptake in the blood, much less is understood regarding individual variability of the response to a given CO stimulus. Thus, the purpose of this paper was to explore the relationship between hemoglobin mass (HbM, a proxy for blood hemoglobin content) and the magnitude of the ensuing carboxyhemoglobinemia. Methods: This is a theoretical work based solely on considerations and published data. Discussion: Currently considered the gold standard for HbM assessment, the CO-rebreathing technique relies on the dilution principle i.e. the lower the HbM values the higher the ΔCOHb following a standardized CO bolus administration or an outdoors exposure. Accordingly, previously published prediction equations with HbM and ΔCOHb as the predictor and outcome variables, respectively, are reviewed with particular reference to the (confounding) factor of pulmonary ventilation. As far as treatment to CO poisoning is concerned, dynamic exercise emerges as a supplement to oxygen therapy to facilitate CO removal from human body. Screening procedures aiming to identify individuals susceptible to CO poisoning should henceforth include HbM assessments.

Abstract: Although athlete monitoring can quantify training exposure and athlete status with increasing detail, conversion into daily training decisions remains inconsistent. This structured narrative review synthesizes evidence on training load, neuromuscular readiness, recovery, fatigue interpretation, measurement reliability, applied decision-making, and proposes the LOAD-R framework: a systems model linking Load, Organism response, Adaptive state, Decision, and Re-evaluation. A transparent non-PRISMA strategy was used because the aim was conceptual integration and framework development rather than effect-size pooling. Evidence was organized around field-applicable monitoring domains and their decision value. LOAD-R extends existing approaches by moving beyond single indicators, fixed thresholds, and dashboard alerts. It classifies athlete state into adaptive, functional-overload, underloaded, uncertain, or maladaptive zones, each linked to progress, maintain, modify, deload, or recover decisions. The framework also provides implementation levels and testable predictions. By shifting monitoring from passive data collection toward adaptive decision support, LOAD-R offers a scalable model that may improve decision consistency, reduce maladaptive training responses, and enhance the practical value of athlete monitoring in applied sport settings.

Abstract: Osteoporosis arises from disrupted bone remodeling, and growing evidence shows that gut microbiota and their metabolites have a major influence on skeletal health through the gut-bone and gut-brain-bone axes. In this systematic review, we synthesize findings from 932 studies to identify key microbial taxa, metabolites, and signaling pathways that modulate osteoblast and osteoclast activities. Short‑chain fatty acids (SCFA), tryptophan‑derived metabolites, and β‑D‑glucuronidase-related estrogen regulation emerge as central microbial mechanisms affecting bone formation and resorption. By integrating these data with the Phylobone extracellular matrix proteins database, we highlight Osteopontin and Cathepsin K as important downstream mediators linking microbial signals to bone matrix turnover. Probiotic strains (particularly Lactobacillus rhamnosus GG and L. reuteri) show potential to improve bone health through metabolic, immune, and endocrine pathways. Together, these findings outline a mechanistic framework connecting gut function to skeletal biology and identify promising microbiome‑based targets for osteoporosis interventions.

Abstract: Background/Objectives: This study aimed to quantify the kinetic demands of multiple hops in series, movement tasks that are commonly used in strength and conditioning and physiotherapeutic practice. Focus was placed on comparing the demands of a quintuple-hop task to a triple-hop task, with particular focus on quantifying the eccentric braking stretch-load demands. Methods: Forty-four male university athletes (age 20.1 ± 1.4 years; body mass 71.2 ± 8.6 kg; stature 171.9 ± 5.1 cm) completed the hopping tasks across track-embedded force platforms, where braking and propulsion kinetics were measured across 54x track-embedded force platforms. Results: Significant (p < 0.001) averaged in-creases in maximal vertical (~32%) and horizontal braking impulses (~56%) for both TH and QH tasks were noted across hops. The last two hops of the QH task were found to have greater averaged vertical (~58%) and horizontal (~180%) stretch-load demands than the two initial hops (p < 0.001). Conclusions: This is the first study in which an extensive summary of kinetic measures for both triple and quintuple hops has been reported. The findings highlight the biomechanical, stretch-load aspects of these exercises, which can help practitioners better prescribe and program hops for injury prevention, rehabilitation, and performance enhancement.

Abstract: Background: Motor precision is a highly innate trait, while ambidexterity in high-precision tasks remains rare and biologically regulated. Few sports necessitate bilateral precision; however, the indigenous sport of picigin uniquely requires symmetrical palm-striking proficiency. Methods: This study investigated bilateral precision and ball velocity in 22 experienced players, divided into competitive (n=11) and recreational (n=11) groups. A specialized bilateral palm-precision test was developed to measure performance across both dominant and non-dominant hands. Key metrics included the asymmetry index for speed and accuracy, and the speed-accuracy trade-off (SAT). Results: Results indicate that competitors significantly outperform recreational players in both precision and velocity. Notably, the SAT analysis suggests that the dominant hand of recreational players performs at a level comparable to the non-dominant hand of competitors. While recreational players exhibited slightly lower asymmetry indices, the inter-manual gap remained stable despite years of experience. Conclusions: Findings suggest that bilateral training induces linear improvements on both sides, maintaining a constant asymmetry ratio rather than diminishing it through long-term practice.

Abstract: Dental pain due to dentine hypersensitivity or pulpitis is characterized by short or lasting episodes of pain triggered by normally innocuous stimuli originating from exposed dentine. Both represent the most frequent pain of the orofacial region. Transient receptor potential (TRP) superfamily of ion channels participates in the detection of different modalities of sensibility in the mammalian sensory teeth system, i.e., trigeminal neurons and odontoblasts. In particular, some members of the melastatin family (TRPM) serve as molecular thermal sensors, and temperature is one of the most potent stimuli in triggering dentine hypersensitivity. Here we review and update the information about the distribution of TRPM channels in the trigeminal ganglion and dental pulp cells, especially odontoblast, in humans and animal models. In addition to the well know sensory roles of TRPM, other functions such as in development and mineralization of teeth are considered.

Abstract: To maintain homeostatic conditions and optimal function during stressors, mitochondria initiate nuclear retrograde signaling. The mitochondrial Integrated Stress Response (ISR) and Unfolded Protein Response (UPR^mt) are critical quality control mechanisms activated during instances of mitochondrial perturbations. Restoration of mitochondrial homeostasis is orchestrated by three transcription factors, ATF4, CHOP, and ATF5, which upregulate protective genes to counteract stress. As the health and function of skeletal muscle is heavily dependent on a highly adaptive mitochondrial network, defining how mitochondrial health is maintained across various conditions is essential. Although several studies demonstrate the importance of these responses following instances of stress, the signaling mechanisms required to initiate such pathways remain poorly characterized in skeletal muscle. This review examines how the mitochondrial ISR/UPRmt and related transcription factors respond to organellar stress by emphasizing the molecular events that occur during exercise, aging and muscle disuse. Through consolidating the literature, this work aims to highlight the current understanding of mitochondrial stress response signaling within skeletal muscle and thus emphasize areas for future research and potential therapeutic strategies during divergent metabolic conditions.

Abstract: The teaching of human anatomy has historically relied on cadaveric dissection, atlases, and static imaging. While these approaches remain foundational, they insufficiently reflect the dynamic, bedside-oriented realities of modern clinical practice. Point-of-care ultrasound (POCUS) enables real-time visualization of living anatomy and physiology and is increasingly integral to clinical decision-making across specialties. I argue that sonographic anatomy should be incorporated longitudinally into all undergraduate medical curricula. Such integration enhances spatial understanding, reinforces clinical relevance, and accelerates the development of diagnostic reasoning. I propose a scalable, phased implementation model and address common barriers, including faculty training and resource constraints. The integration of ultrasound into anatomy education represents not an addition, but a necessary evolution.