Frontiers in Physiology

Drug-induced liver injury (DILI) is a leading cause of drug withdrawal, a particular cause for concern among patients receiving anti-cancer treatment. This review summarizes the available evidence on the efficacy of hepatoprotective drugs in normalizing liver enzyme abnormalities among patients with DILI due to treatment with anti-cancer therapies. Across relevant publications, the effects of several compounds on anti-cancer therapy-induced DILI were assessed. Treatment with hepatoprotective agents which is usually initiated after DILI has been detected and involves cessation of causative anti-cancer therapy, has demonstrated improvements in liver enzyme elevation. However, prophylactic treatment with two agents in particular, ademetionine and bicyclol have shown hepatoprotective effects that enabled patients to continue with their anti-cancer therapy with a reduced subsequently reduced risk of hepatotoxicity. While these publications show some evidence for the benefits of hepatoprotective agents among patients with DILI due to anti-cancer therapy, more research is needed to fully determine the effects of hepatoprotective drugs in resolving DILI signs and symptoms among patients receiving treatment for cancer.

Remodeling and relaxation of the mouse pubic symphysis (PS) are responsible for separating the pubic bone, allowing the passage of the full-term fetus, and ensuring safe delivery. PS in postpartum mice can rapidly return to a similar non-pregnant state, providing mechanical stability for the reproductive tract. During pregnancy and postpartum recovery, PS changes in mice are involved in many aspects, including extracellular matrix (ECM), matrix metalloproteinases (MMPs), cell phenotypes, hormones, and immune cells. The changes in PS in mice during pregnancy and postpartum convalescence were reviewed, and the possible mechanisms were discussed. We hope to attract more research interest to explore the biological mechanisms of this process better.

Skeletal muscle atrophy, characterized by the loss of muscle mass and function, can result from disuse, aging, disease, drug. Exercise preconditioning—a form of exercise training performed before these harmful threats—induces notable remodeling and extensive biochemical adaptations in skeletal muscle, creating a protective phenotype in muscle fibers, and thus serving as an effective intervention for preventing skeletal muscle atrophy. Here, we review the current understanding relating to how exercise preconditioning protects skeletal muscle from damage caused by inactivity, sarcopenia, disease, or pharmacological intervention, with an emphasis on the cellular mechanisms involved. Key mechanisms highlighted as making a significant contribution to the protective effects of exercise on skeletal muscle fibers include mitochondria; the expression of cytoprotective proteins such as HSP72, SOD2, SESN2, PGC-1α and AMPK; and the regulation of oxidative stress. These findings underscore the potential of exercise preconditioning as a non-pharmacological intervention for preserving muscle mass and function, as well as preventing muscular atrophy, ultimately improving the quality of life for at-risk populations.

Acute and chronic hypoxia modulate the expression of inflammatory mediators known as cytokines. However, studies in chronic and intermittent hypobaric or normobaric hypoxia, like those described in miner’s population, are scarce or absent. In this study, we evaluate the effect of chronic intermittent normobaric hypoxia (CINH) on the hematological response and the expression of lymphocyte cytokines IL-1, IL-2, IL-6, and IL-10 in rats. A total of 20 Sprague-Dawley rats were divided into two groups: a) CINH (FiO 2 10%, n = 10) and b) Control (normoxic, n = 10). Systolic arterial pressure and heart rate were measured using a tail-cuff sensor. Blood samples were obtained from both groups for hematological studies, and expression of cytokines obtained from lymphocytes was determined by RT-PCR. Hematocrit, hemoglobin, platelet count, and hematological constant were elevated, and leucocyte count decreased in CINH rats. In addition, systolic arterial pressure in CINH rats was significantly increased (over 50%). Cytokine expression from lymphocytes showed that IL-2, and IL-10 increased by 140% and 38%, respectively; IL-6 showed no significant change, while IL-1β expression decreased by 18%. In this regard, CINH could activate an inflammatory response mediated by IL-2. However, this response could be attenuated by increased IL-10 expression, a known anti-inflammatory cytokine, and decreased IL-1β and IL-6 expression, indicative of an adaptation mechanism to CINH.

Epilepsy detection using artificial intelligence (AI) networks has gained significant attention. However, existing methods face challenges in accuracy, computational cost, and speed. CNN excel in feature extraction but suffer from high computational latency and power consumption, while SVM rely heavily on feature quality and expensive kernel computations, limiting real-time performance. Additionally, most CNN-SVM hybrid model lack hardware optimization, leading to inefficient implementations with poor accuracy-latency trade-offs. To address these issues, this paper designs a hybrid AI network-based method for epilepsy detection using electroencephalography (EEG) signals. First, a hybrid AI network was constructed using three convolutional layers, three pooling layers, and a Gaussian kernel SVM to achieve EEG epilepsy detection. Then, the design of the multiply-accumulate circuit was completed using a parallel-style row computation method, and a pipelined convolutional computation circuit was used to accelerate the convolutional computation and reduce the computational overhead and delay. Finally, a single-precision floating-point exponential and logarithmic computation circuit was designed to improve the speed and accuracy of data computation. The digital back-end of the hardware circuit was realized under the TSMC 65 nm process. Experimental results show that the circuit occupies an area of 3.20 mm ² , consumes 4.28 mW of power, operates at a frequency of 10 MHz, and has an epilepsy detection latency of 0.008 s, which represents a 32% reduction in latency compared to those reported in the relevant literature. The database test results showed an epilepsy detection accuracy of 97.5%, a sensitivity of 97.6%, and a specificity of 97.2%.

Atherosclerosis (AS), a prime causative factor in cardiovascular disease, originates from endothelial cell dysfunction (ECD). Comprising a vital part of the vascular endothelium, endothelial cells play a crucial role in maintaining vascular homeostasis, optimizing redox balance, and regulating inflammatory responses. More evidence shows that ECD not only serves as an early harbinger of AS but also exhibits a strong association with disease progression. In recent years, the treatment strategies for ECD have been continuously evolving, encompassing interventions ranging from lifestyle modifications to traditional pharmacotherapy aimed at reducing risk factors, which also have demonstrated the ability to improve endothelial cell function. Additionally, novel strategies such as promising biotherapy and gene therapy have drawn attention. These methods have demonstrated enormous potential and promising prospects in improving endothelial function and reversing AS. However, it is essential to remain cognizant that the current treatments still present significant challenges regarding therapeutic efficacy, long-term safety, and ethical issues. This article aims to provide a systematic review of these treatment methods, analyze the mechanisms and efficacy of various therapeutic strategies, with the goal of offering insights and guidance for clinical practice, and further advancing the prevention and treatment of cardiovascular diseases.

Introduction: The mitral valve annulus naturally adopts a saddle shape in systole, likely concentrating systolic stress on the commissures where fibrous trigones are located. This study hypothesized that in patients with dilated cardiomyopathies, where the annulus is large and planar, the stress would be redirected. Methods: Computational modeling was employed to compare the stress distribution in saddle-shaped mitral valves (n.10 patients) with planar annuli seen in dilated cardiomyopathy (n.10 patients) using kinematics of the mitral valve annulus from systole to diastole extrapolated from computed tomography angiography. Results: Simulations revealed high stress near the anterolateral and posteromedial commissures in normal valves, in contrast to high leaflet stress in planar annuli. Significant differences in stress distribution were observed near the anterolateral (S = 0.427 ± 0.053 MPa in normal valves vs S = 0.211 ± 0.123 MPa in diseased valves, p < 0.001) and posterolateral commissures (S = 0.340 ± 0.008 MPa in normal valves vs S = 0.208 ± 0.060 MPa in diseased valves, p < 0.001). Additionally, mitral annulus disjunction was present in healthy patients but absent in those with annulus planarity due to dilated cardiomyopathy. Discussion: This study suggests that while the saddle-shaped annulus focuses leaflet stress on commissures, planar annuli distribute systolic stress over leaflet surfaces. This may trigger embryonic pathways and alter mitral leaflet collagen content, ultimately leading to valve remodeling. Identifying patients with early annular planarity prior to substantial leaflet remodeling may provide early treatments to prevent increasing mitral regurgitation.

Background IPC has been suggested to boost skeletal muscle performance, though its effectiveness remains controversial. This study evaluates whether IPC influences local hemodynamic responses and surface electromyographic (sEMG) activity during non-fatiguing voluntary sustained and intermittent contractions. Methods Ten male participants were subjected to IPC (3 cycles, 5-min ON/5-min OFF right arm ischemia, cuff pressure: 250 mmHg) and SHAM (same protocol at 20 mmHg) in two different sessions. Near-infrared spectroscopy was used to monitor tissue oxygenation (TOI) and deoxy-hemoglobin (HHb) in extensor and flexor forearm muscles. sEMG was also recorded. Measurements were taken during sustained (20-s duration) and intermittent (5 s ON/5 s OFF) isometric contractions at 20, 30, and 40% of the maximal voluntary contraction. These non-fatiguing exercise tasks were performed before and 30 min after the IPC/SHAM intervention. Results sEMG exhibited a significant increase post vs. pre-treatment in both IPC and SHAM in extensors. A significant decrease in TOI at rest was noted pre vs. post-treatment for both IPC and SHAM (p < 0.01). In general, no main effect of treatment was observed, except for HHb changes during contraction in extensor muscles, associated with no effect of time and no time-treatment interaction. All variables exhibited a main effect of force level (p < 0.05), with no interaction with treatment or time. Conclusion IPC had no effect on hemodynamic and electromyographic variables during sustained and intermittent handgrip. These results do not support IPC-related ergogenic effects at the muscle level, aligning with previous findings on electrically stimulated contractions.

Lactate accumulation will appear in athlete skeletal muscle after intense exercise. If the high lactate level maintains, athletes will sustain fatigue and athletic capacity decline due to internal environment and normal metabolism disruption. In order to enhance athlete physical recovery and exercise performance in high-intensity sport events, it is of great significance to explore the scientific intervention procedures based on quicker lactate clearance in skeletal muscle and blood after exercise. This article collects classic and novel literature in terms of lactate metabolism, lactate clearance and fatigue monitoring during exercise by searching PubMed database and then summarizes comprehensive insights into athlete physical recovery with corresponding figures and charts. We introduce the generation and transformation process of lactate, lactate clearance pathways and the fatigue monitoring methods for athletes in detail. The lactate clearance pathways involve biochemical pathways (oxygen inhalation, amino acids supplement, targeting free radical, alkaline reserve, targeting vasomotion, ribose supplement), physical activities (exercise-mediated activities, non-exercise activities) and training methods (interval training, altitude training) to accelerate lactate metabolism. The biochemical factors for monitoring athletic fatigue level involve blood, urine, sweat, saliva and exhaled gas. We hope this review can offer some significant and scientific assistance for athlete recovering after exercise and improving sport achievements based on quicker lactate clearance.

Myokines released by skeletal muscle in response to contraction may contribute to the health-promoting effects of exercise. Previous studies with cultured rodent and human myotubes have revealed highly complex patterns of myokine secretion. However, the commonalities and differences in the secretory response of the different cell models have not been explored, limiting the interpretation of these results. In the present study, we performed a comprehensive analysis of contraction-regulated secretomes using the most commonly used skeletal muscle cell models, cultured murine C2C12 myotubes and satellite cell-derived primary human myotubes (HSkMC). The cells were subjected to low-frequency electrical pulse stimulation (EPS) for 6 h followed by high-resolution mass spectrometry analysis of secreted proteins in the culture medium. We identified 5,710 and 3,285 proteins in the secretomes of C2C12 myotubes and HSkMC, with 80% of human myokines also detected in the murine secretome. Additionally, we found 518 and 336 secreted proteins that were differentially regulated during contraction in murine and human cells, respectively, along with 1,440 and 385 previously unknown potential myokines secreted by murine and human myotubes. Bioinformatic prediction analyses revealed that the majority of the newly identified myokines were secreted via unconventional protein secretion pathways (UPS) in the murine secretome, whereas most novel proteins in the human secretome were secreted via the classical endoplasmic reticulum (ER)-to-Golgi pathway. Moreover, ontology analysis indicates cell type-specific differences in cellular compartments involved in myokine secretion. Collectively, our results provide a comprehensive overview of the secretomes of two of the most commonly used cell models and may provide guidance for further studies of myokines.

Background Advanced epithelial ovarian cancer (EOC) patients often receive neoadjuvant platinum-based chemotherapy (NAC), with interval surgery (after three cycles of chemotherapy) considered as a major prognostic factors. We examined how changes in body composition (muscle and adipose tissue) during NAC influence prognosis. Objective Using CT images acquired before and during NAC in a cohort of women with advanced EOC, the aim of this study was to analyze body composition (muscle and fat mass) and see whether these parameters, at diagnosis or as they evolve during chemotherapy, can be linked to recurrence-free survival and overall survival (RFS and OS). Material and methods The study included 53 patients with FIGO stage III-IV epithelial ovarian cancer. CT images were analyzed to calculate skeletal muscle index (SMI), subcutaneous adipose tissue index visceral adipose tissue index estimated lean body mass (LBM) and estimated whole-body fat mass (WFM). Changes in tissue composition were normalized for 100 days and expressed as % change to account for intervals between scans at baseline and after three cycles of chemotherapy. The impact on survival was assessed by Log-rank test. Results At diagnosis, clinical criteria such as age or BMI did not correlate with RFS or OS. 60% of patients were considered sarcopenic (low SMI), including mainly underweight and normal-weight patients. Low SMI was not associated with RFS or OS. Twenty-six patients who underwent interval surgery demonstrated longer relapse-free intervals ( p = 0.01). Notably, while muscle parameters showed minimal changes (−2%), parameters assessing adipose tissue showed significant decreases of 10, 12% and 7.6% per 100 days (VATI, SATI and estimated WFM, respectively). Obese patients were particularly affected by this loss of muscle and fat, compared with patients in other BMI categories. Rapid and severe loss of VATI (−28% per 100 days) and estimated WFM (−18% per 100 days) were significantly associated with shorter OS ( p = 0.031 and p = 0.046 respectively). Conclusion Our findings suggests that early and substantial loss of visceral adipose tissue during NAC is a significant predictor of poor survival in advanced EOC. This highlights an urgent need for targeted nutritional or pharmaceutical strategies to mitigate fat loss and improve patients outcomes.

Background Stroke, a major global health concern, is responsible for high mortality and long-term disabilities. With the aging population and increasing prevalence of risk factors, its incidence is on the rise. Existing risk assessment tools have limitations, and there is a pressing need for more accurate and personalized stroke risk prediction models. Smoking, a significant modifiable risk factor, has not been comprehensively examined in current models regarding different smoking types. Methods Data were sourced from the 2015–2018 National Health and Nutrition Examination Survey (NHANES) and the 2020–2021 Behavioral Risk Factor Surveillance System (BRFSS). Tobacco use (including combustible cigarettes and e-cigarettes) and stroke history were obtained through questionnaires. Participants were divided into four subgroups: non-smokers, exclusive combustible cigarette users, exclusive e-cigarette users, and dual users. Covariates such as age, sex, race, education, and health conditions were also collected. Multivariate logistic regression was used to analyze the relationship between smoking and stroke. Four machine-learning models (XGBoost, logistic regression, Random Forest, and Gaussian Naive Bayes) were evaluated using the area under the receiver-operating characteristic curve (AUC), and Shapley’s additive interpretation method was applied for feature importance ranking and model interpretation. Results A total of 273,028 individuals were included in the study. Exclusive combustible cigarette users had an elevated stroke risk (β: 1.36, 95% CI: 1.26–1.47, P < 0.0001). Among the four machine-learning models, the XGBoost model showed the best discriminative ability with an AUC of 0.794 (95% CI = 0.787–0.802). Conclusion This study reveals a significant association between smoking types and stroke risk. An XGBoost-based stroke prediction model was established, which has the potential to improve the accuracy of stroke risk assessment and contribute to personalized interventions for stroke prevention, thus alleviating the healthcare burden related to stroke.

Objective This study aims to enhance the efficiency and accuracy of thyroid nodule segmentation in ultrasound images, ultimately improving nodule detection and diagnosis. For clinical deployment on mobile and embedded devices, DeepLabV3+ strives to achieve a balance between a lightweight architecture and high segmentation accuracy. Methodology A comprehensive dataset of ultrasound images was meticulously curated using a high-resolution ultrasound imaging device. Data acquisition adhered to standardized protocols to ensure high-quality imaging. Preprocessing steps, including noise reduction and contrast optimization, were applied to enhance image clarity. Expert radiologists provided ground truth labels through meticulous annotation. To improve segmentation performance, we integrated MobileNetV2 and Depthwise Separable Dilated Convolution into the Atrous Spatial Pyramid Pooling (ASPP) module, incorporating the Pyramid Pooling Module (PPM) and attention mechanisms. To mitigate classification imbalances, we employed Tversky loss functions in the ultrasound image classification process. Results In semantic image segmentation, DeepLabV3+ achieved an impressive Intersection over Union (IoU) of 94.37%, while utilizing only 12.4 MB of parameters, including weights and biases. This remarkable accuracy demonstrates the effectiveness of our approach. A high IoU value in medical imaging analysis reflects the model’s ability to accurately delineate object boundaries. Conclusion DeepLabV3+ represents a significant advancement in thyroid nodule segmentation, particularly for thyroid cancer screening and diagnosis. The obtained segmentation results suggest promising directions for future research, especially in the early detection of thyroid nodules. Deploying this algorithm on mobile devices offers a practical solution for early diagnosis and is likely to improve patient outcomes.

Background Amyloid-β protein (Aβ) accumulation is a defining characteristic of Alzheimer’s disease (AD), resulting in neurodegeneration and a decline in cognitive function. Given orexin’s well-documented role in enhancing memory and cognition, this study investigates its potential to regulate Aβ-induced neurotoxicity, offering new perspectives into AD management. Methods This paper simulated Aβ accumulation in the hippocampus of AD patients by administering Aβ 1-42 oligomers into the bilateral hippocampal dentate gyrus of ICR mice. Inflammatory cytokines (IL-6, TNF-α) and orexin-A levels were measured by ELISA. Additionally, the excitability of orexinergic neurons was assessed by IHC targeting c-Fos expression. These methodologies evaluated the Aβ-induced neuroinflammation, orexinergic system functionality, and dexamethasone’s (Dex) effects on these processes. Results Injection of Aβ 1-42 oligomer resulted in elevated levels of IL-6, TNF-α, and orexin-A in the hippocampus, as well as increased excitability of orexinergic neurons in the lateral hypothalamus (LH). Dex treatment reduced neuroinflammation, causing a reduction in orexin-A levels and the excitability of orexinergic neurons. Conclusion Aβ-induced neuroinflammation is accompanied by enhanced levels of orexin-A and orexinergic neuron excitability. These findings suggest that the enhanced functionality of the orexinergic system may become a compensatory neuroprotective mechanism to counteract neuroinflammation and enhance cognitive function.

Introduction: Men and women have different performance abilities, where women have greater tolerance for fatigue in long-distance exercise. Part of this greater tolerance may be due, in part, differences in men’s and women’s mental fatigue capacity during exercise. Thus, the aim of this study was to examine the effect of cycling endurance exercise, along with mental fatigue, on the sex dependent differences in exercise tolerance. Methods: Twenty-five (15 women and 10 men) cyclists in a randomized, controlled, and crossover protocol performed three experimental sessions. In the first session, the cycling peak power output (PPO) was determined and 65% of PPO was used for intensity of the experimental sessions. In sessions 2 and 3, participants performed Cycling + Mental Exertion (ME) (cycling endurance exercise with a ME-stroop task) and Cycling + Movie (cycling endurance exercise while watching a movie). Serum cortisol concentration and a psychomotor vigilance task (PVT) were measured pre- and post-sessions. During the experimental sessions rate of perceived exertion (RPE) and heart rate (HR) were recorded every 10 min and participants completed the NASA-TLX questionnaire directly following the post- PVT. Results: Performing Cycling + ME was associated with a longer time to exhaustion (p < 0.05) and higher RPE following 40-70 min in women than men (p < 0.05). Cycling + ME increased HR following 40-70 min in women (p < 0.05). For both men and women cortisol concentration level was higher pre- to post-Cycling + ME with no difference between sexes. Women exhibited faster reaction times compared to men in both pre- and post-sessions. Discussion: Performing mental exertion with cycling endurance exercise impairs endurance performance. While our findings align with some previous research, we suggest that men may be more prone to mental fatigue; however, further research needed to confirm this.

The poultry industry faces a major impediment in dealing with highly pathogenic avian influenza (HPAI). Large outbreaks have resulted in depletion of available resources needed for desired depopulation methods, leading to the need for alternative methods. This study was conducted to explore alternative ventilation shutdown procedures and how they affect laying hens throughout the process. Three treatments evaluated were ventilation shutdown plus heat (VSDH), ventilation shutdown plus heat and relative humidity (VSDHRh), and ventilation shutdown plus carbon dioxide (VSDCO 2 ). There were two phases used: one phase was used to study treatment effects on the hens’ EEG responses from beginning to time of death and how laying hens behaved. Phase 2 examined how these treatments affected hen blood chemistry and HSP70 during the process. VSDCO 2 had a significantly quicker time of death (P = 0.0003), and VSDH and VSDHRh were not different. There were no differences in pre- or post-corticosterone levels in Phase 1; however, there was a trend (P = 0.07) toward significance in the post corticosterone levels. Heat shock protein 70 (HSP70) levels were higher (P = 0.0001) in the VSDCO 2 treatment, which could be due to the protein upregulation to prevent apoptosis. In Phase 2, VSDH corticosterone had a significantly greater treatment effect compared to VSDHRh and VSDCO 2 . corticosterone levels were significantly greater than those of VSDHRh. There were no significant treatment effects in Phase 2 for HSP70 expression; however, the sequence was significant, with the HSP70 being significantly greater at 75% to the average time of death than at 100% to the average time of death. Overall, VSDHRh could be a good alternative for the industry to use to rapidly depopulate laying hen facilities. However, more research on this treatment and more in-depth stress parameters measured needs to be conducted to fully determine how it affects laying hens.

Introduction Cell pacing is a fundamental procedure for generating action potentials (AP) in excitable tissues. Various pulse shapes have been proposed for this purpose, with the aim of either facilitating the achievement of the excitation threshold or minimizing energy delivery to the patient. This study seeks to identify the optimal pulse shape for each of these objectives. Methods To determine the most effective pulse forms, we employed a mathematical model simulating nonlinear tissue responses to a range of pulse shapes. Results Our results demonstrate that the rectangular pulse is optimal for reaching the excitation threshold, while the Gaussian pulse is superior in minimizing energy delivery. Other pulse shapes examined, including ramp-up, ramp-down, half-sine, and triangular (tent-like), fall between these two in terms of performance. Discussion From a clinical perspective, the appropriate pulse shape should be selected based on the specific goal. For minimizing the pulse amplitude required to cross the excitation threshold, the rectangular pulse is recommended. In contrast, if reducing energy delivery to the patient is paramount, the Gaussian pulse is the preferred choice. In other scenarios, a judicious selection can be made based on the outcomes of our model and the clinical requirements.

Objectives To investigate the influence of plaque distribution and vascular bifurcation angle on hemodynamics within the carotid artery bifurcation and to explore the role these factors play in the development of vulnerable carotid plaques. The study aims to provide a more comprehensive understanding of how complex hemodynamic patterns affect plaque formation, vulnerability, and progression. Methods Patient-specific carotid bifurcation models were reconstructed using 3D rotational angiography and CT angiography, validated by digital subtraction angiography. Computational fluid dynamics (ANSYS Fluent) with non-Newtonian modeling simulated hemodynamics under patient-specific boundary conditions. Plaque morphology and hemodynamic parameters (TAWSS, OSI, ECAP) were quantified. Statistical analyses included Spearman’s correlations and non-parametric tests for bifurcation angles/plaque locations. Results Numerical simulations demonstrated that plaque subtypes and bifurcation angles critically modulate carotid hemodynamics. Elevated wall shear stress (WSS) upstream of plaques (sites M/N) increased rupture susceptibility, whereas low WSS at the outer bifurcation (site P) exacerbated atherogenesis. Larger bifurcation angles reduced peak velocities, expanded low-velocity zones, and diminished WSS, amplifying atherosclerosis risk. Vortex-driven low-shear regions prolonged platelet residence, enhancing thrombotic propensity. Fluid-structure interactions revealed arterial wall deformation near bifurcations, correlating with endothelial injury and plaque progression. These hemodynamic alterations underscore the biomechanical interplay driving plaque vulnerability and thrombosis in carotid atherosclerosis. Conclusion Carotid plaque vulnerability arises from bifurcation angle-dependent hemodynamic disturbances, where elevated upstream wall shear stress predisposes to rupture, while low-shear zones at the outer bifurcation accelerate atherogenesis. Vortex-driven platelet retention and fluid-structure interactions exacerbate endothelial dysfunction, underscoring hemodynamic targeting for clinical risk mitigation.

Introduction Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide. However, the role of folate in MASLD remains controversial. This study aimed to investigate the association between two folate indicators [serum folate and red blood cell (RBC) folate] and MASLD prevalence using data from the 2017–2020 National Health and Nutrition Examination Survey (NHANES). Methods A total of 3,879 participants without liver disease or significant alcohol consumption were included in the final analysis. Hepatic steatosis was assessed via transient elastography, with MASLD defined as a controlled attenuation parameter (CAP) ≥285 dB/m and the presence of at least one cardiometabolic risk factor. Logistic regression and generalized additive models (GAMs) were used to evaluate associations between folate levels and MASLD, with subgroup analyses stratified by age, gender, and body mass index (BMI). Results After full adjustment for confounders, RBC folate exhibited a significant positive association with MASLD (OR = 1.111 and 95% CI: 1.015–1.216 per 1-unit increase). In contrast, serum folate showed a transient negative association in minimally adjusted models (OR = 0.869 and 95% CI: 0.802–0.941), which disappeared after further adjustments. Subgroup analyses confirmed that age, gender, and BMI did not modify the RBC folate–MASLD relationship. Discussion These findings suggest that elevated RBC folate levels are independently associated with MASLD prevalence, whereas serum folate may lack clinical relevance due to susceptibility to confounding factors. RBC folate, as a stable biomarker of long-term folate status, may serve as a superior indicator for investigating folate–MASLD associations.

Introduction Among theorists and practitioners, there is a consensus regarding the significant role of optimizing sports training in high-altitude conditions. This stems from the specific combination of environmental variables that determine the dynamics of changes in broadly understood training adaptation. The aim of this study was to evaluate the impact of an experimental training program, Hypoxic Boxing (under normobaric hypoxia conditions), on the development of the functional profile (motor and specialized fitness) within a national elite group of boxers. Methods A randomized controlled trial was conducted with 20 elite-level boxers representing the national championship level (mean age: 23.9 ± 3.0 years; height: 181.3 ± 7.14 cm; body weight: 79.3 ± 8.84 kg; BMI: 24.15 ± 2.21; training experience: 10 ± 4.0 years). The participants were assigned to either the experimental group (Hypoxic Boxing - HB; n = 10) or the control group (Normoxic Boxing - NB; n = 10). Both groups followed the same 6-week training program, which included two daily training sessions (morning and afternoon). The afternoon training sessions for the HB group were conducted under normobaric hypoxic conditions in a hypoxic chamber, while the NB group trained in non-simulated normoxic conditions. The profile of changes was assessed before and after the intervention (pretest vs. posttest) by analyzing the results of selected motor ability tests from the Eurofit battery and specialized fitness using the Pawluk Boxing Test. Results The HB group (within-group analysis) demonstrated a significant improvement in test performance for strength endurance and resistance to fatigue in the abdominal, arm, and back muscles. Specifically, the number of sit-ups increased from 27.5 ± 4.0 to 28.8 ± 3.4 ( p = 0.007, d c = 0.35), and the number of pull-ups improved from 14.9 ± 4.5 to 16.4 ± 4.6 ( p = 0.005, d c = 0.33). The intervention also led to a notable enhancement in specialized fitness, including anaerobic capacity and technical efficiency, as reflected in the number of punches delivered in 20 s (72.6 ± 9.6 to 74.3 ± 9.5, p = 0.008, d c = 0.18), post-exercise recovery (HR 1 min: 143.3 ± 6.6 to 138.4 ± 5.8 bpm, p = 0.004, d c = 0.79), and the multidimensional Index of Specialized Performance (4.5 ± 0.5 to 4.3 ± 0.5, p = 0.005 , d c = 0.40). These changes were not observed in the NB group ( p > 0.05). Additionally, the HB group showed increased homogeneity in performance outcomes during the post-test phase. The intergroup comparison of training effects after the experiment revealed significant differences in the overall dimension of special fitness ( p > 0.05), with a more favorable improvement observed in the HB group. Conclusion Hypoxic Boxing demonstrates the benefits of an extended, combinatory training program compared to standard protocols. Our findings hold both scientific and practical significance, as Hypoxic Boxing appears effective in enhancing selected motor abilities and multidimensional specialized fitness. Further research is needed to better understand the potential benefits and limitations of hypoxic training for combat sports athletes.

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Skeletal muscle atrophy due to critical illness is a common phenomenon in the intensive care unit (ICU) and is referred to as ICU-acquired weakness (ICU-AW). The occurrence of ICU-AW in patients with sepsis is known as sepsis-acquired weakness (SAW). Furthermore, it is well known that maintaining normal muscle function closely relates to mitochondrial homeostasis. Once mitochondrial function is impaired, both muscle quality and function are affected. Copper plays a key role in mitochondrial homeostasis as a transition metal that regulates the function and stability of various enzymes. Copper is also involved in oxidation-reduction reactions, and intracellular copper overload causes oxidative stress and induces cell death. Previous studies have shown that excess intracellular copper induces cell death by targeting lipid-acylated proteins that regulate the mitochondrial tricarboxylic acid (TCA) cycle, which differs from the known canonical mechanisms of regulated cell death. Furthermore, inhibitors of cell death, such as apoptosis, necroptosis, pyroptosis and ferroptosis, are not effective in preventing copper-induced cell death. This new form of cell death has been termed “Cuproptosis”; however, the mechanism by which copper-induced cell death is involved in SAW remains unclear. In this paper, we review the possible relationship between cuproptosis and SAW. Cuproptosis may be involved in regulating the pathological mechanisms of SAW through mitochondria-related signaling pathways, mitochondria-related ferroptosis mechanisms, and mitochondria-related genes, and to provide new ideas for further investigations into the mechanism of SAW.

Introduction The “no pain, no gain” philosophy has long influenced athletic training approaches, particularly in high-intensity workouts like metabolic resistance training (MRT). However, the necessity of discomfort-inducing training for optimal athletic performance remains debatable. This systematic review and meta-analysis examined whether MRT provided comparable or better results than traditional training methods in trained athletes. Methods A systematic search of PubMed/MEDLINE, Web of Science, Scopus, and SPORTDiscus (January 2004 - December 2024) identified RCTs comparing MRT with traditional training in athletes. Two reviewers screened studies and assessed bias risk using Cochrane RoB 2. Random - effects meta - analyses were conducted for outcomes like VO2max, peak power, sprint performance, blood lactate, time to exhaustion, and jump height. GRADE was used to evaluate evidence certainty. Results Eleven studies (n = 276 participants) met inclusion criteria. MRT demonstrated a statistically significant improvement in sprint performance (SMD = 1.18, 95% CI: 0.00 to 2.36, p < 0.0001) and countermovement jump height (SMD = 0.80, 95% CI: −0.04 to 1.64, p = 0.0007), indicating notable gains in explosive power. VO2max improvements were observed (SMD = 0.30, 95% CI: −0.19 to 0.79, p = 0.10) but did not reach statistical significance. Peak power output showed a moderate but non-significant positive effect (SMD = 0.54, 95% CI: −2.05 to 3.13, p = 0.55), while blood lactate changes varied widely (SMD = −1.68, 95% CI: −8.58 to 5.22, p = 0.29), reflecting high heterogeneity across studies. Time to exhaustion presented a small positive effect (SMD = 0.23, 95% CI: 0.00 to 0.46, p = 0.18), but without statistical significance. Subgroup analyses revealed that younger adults (19–25 years) and experienced athletes benefited the most from MRT, with low-frequency training (≤2 sessions/week) yielding the most favorable adaptations. Moderator analysis confirmed that sprint performance had the strongest response to MRT, while aerobic measures exhibited more variability. Conclusion The evidence demonstrates the capacity of MRT to enhance athletic performance comparable to or exceeding traditional training methods while requiring reduced time commitment. These findings suggest that optimal performance adaptations can be achieved through well-designed MRT protocols without necessitating excessive training volumes. Systematic Review Registration https://inplasy.com/inplasy-2024-11-0024 , identifier: 36 INPLASY2024110024.

Background lderly individuals are more susceptible to chronic constipation, which may be linked to imbalanced mucosa secretion and absorption. Our research aims to explore the age-related alterations in epithelial chloride secretion within the human colon. Methods Colonic mucosal tissues were obtained from 9 young patients (aged 28–35 years), 10 middle-aged patients (aged 48–56 years), 10 elderly patients without constipation (aged 66–75 years), and 12 elderly patients with constipation (aged 65–78 years) who underwent surgery for colonic carcinoma. The epithelial chloride (Cl ⁻ ) secretion was assessed using the short-circuit current (Isc) method. Comparative analysis was conducted on Cl ⁻ secretion induced by spontaneous activity, bethanechol, forskolin, veratridine, and electrical field stimulation (EFS) in the four groups. Additionally, investigations were carried out on changes in cholinergic and VIPergic Cl ⁻ secretion. Results The spontaneous Cl ⁻ secretion was not affected by aging. The increase in Isc induced by bethanechol and forskolin remained unaltered in aged colon. However, the veratridine-induced neurogenic Isc increment were significantly reduced with aging and constipation. The EFS-evoked Isc rising, which typically exhibiting a biphasic pattern, was inhibited by aging in a frequency-dependent manner. Administration of scopolamine and VIP 6-28 to block cholinergic and vasoactive intestinal peptide (VIP) receptors led to smaller increases in the first and second phases of the EFS-evoked response in aged colons compared to young colons. Conclusion Significant impairments in neurogenic Cl ⁻ secretion occur in the aged colon, correlating with the degeneration of cholinergic and VIPergic nerves in the mucosa. This study could enhance our understanding of the pathophysiology of elderly constipation.

In recent years, the study of gut microbiota has gradually become a research hotspot in the field of medicine, as gut microbiota dysbiosis is closely related to various diseases. Thalassemia, as a hereditary hemoglobinopathy, has a complex pathophysiological mechanism, and traditional treatment methods show limited efficacy. With a deeper understanding of the gut microbiome, researchers have begun to focus on its role in the pathogenesis of thalassemia and its therapeutic effects. This article aims to review the role of gut microbiota in thalassemia and its potential therapeutic prospects, analyze the latest research findings, and explore the impact and mechanisms of gut microbiota on patients with thalassemia, with the goal of providing new ideas and directions for future research and clinical treatment of thalassemia.