Ferroptosis connects disrupted iron handling, phospholipid peroxidation, and insufficient antioxidant defense with cardiovascular injury. Whether exercise can modify ferroptosis-related vulnerability in the heart and vasculature remains an important but incompletely resolved question. This mechanism-centered narrative review evaluates exercise-related evidence across cardiovascular injury contexts and distinguishes direct cardiovascular experiments from supportive marker studies, indirect mechanistic evidence, and human clinical contexts. PubMed was searched through June 2026, with supplementary retrieval from the Web of Science Core Collection and citation tracing. Among available exercise-specific studies, current evidence is most informative in preclinical models, particularly doxorubicin cardiotoxicity, where endurance exercise preconditioning has been linked to reduced iron accumulation, lipid-peroxide injury, mitochondrial damage, and myocardial dysfunction in studies incorporating ferroptosis-sensitive perturbation. Additional evidence from ischemia-reperfusion injury, diabetic cardiomyopathy, cardiac fibrosis, and experimental heart failure suggests that exercise may influence iron handling, the system Xc--GSH-GPX4 axis, NRF2-related antioxidant regulation, lipid peroxidation, mitochondrial resilience, and inflammatory signaling. However, many studies remain marker-based, and evidence for resistance or combined training in tissue-level cardiovascular ferroptosis is limited. Human exercise studies provide translational context through improvements in vascular, metabolic, inflammatory, and oxidative-stress outcomes, but they do not yet establish ferroptosis modulation in cardiovascular tissue. Future studies require clearer exercise-dose reporting, serial sampling, tissue-level ferroptosis assays, pathway perturbation, clinically relevant models, and validated human biomarkers. Overall, exercise is best interpreted as a promising modifier of ferroptosis-related cardiovascular biology rather than an established ferroptosis-targeted therapy.
The tunica adventitia of blood vessels is a highly heterogeneous microenvironment comprising diverse cell types. Beyond providing structural scaffolding, adventitial fibroblasts act as dynamic, responsive cells that contribute to vascular homeostasis mainly through regulation of collagen, fibronectin and elastin expression and paracrine effects that promote vascular inflammation. Their dysregulation leads to the onset and progression of several diseases. Signaling pathways in adventitial fibroblasts, particularly DDR2, hypoxia-ERK1/2 MAPK and PI3K/Akt signaling, impact cell proliferation, pro-fibrotic gene expression and cellular response to stress. Furthermore, non-coding RNAs and novel epigenetic mechanisms significantly impact adventitial fibroblast function. Adventitial fibroblasts promote sex-related variations in the prevalence and severity of vascular diseases. Rapid advances in single-cell transcriptomics, biomarker development and other molecular and imaging techniques promise deeper insights into adventitial fibroblast biology, unravelling their heterogeneity and functional variability, and their role in extracellular matrix remodeling and paracrine signaling. These in turn would pave the way for innovative strategies to target pro-fibrotic fibroblast subpopulations and prevent adverse vascular remodeling. This review provides an overview of adventitial fibroblast function and the role of these cells in atherosclerosis, hypertension, diabetes, aneurysm and age-related vascular dysfunction, underscoring the need for a paradigm shift in vascular biology, positioning the adventitia as a critical regulator of vascular health and disease.
IntroductionSleep inertia, characterized by impaired cognitive and psychomotor performance post-waking, poses a significant safety concern in operational settings, particularly when exacerbated by prior sleep loss. Existing reactive countermeasures demonstrate limited efficacy within the critical initial minutes following awakening. This study aimed to evaluate the effectiveness of two reactive interventions—cognitive stimulation and physiological dynamization —in mitigating sleep inertia, examining their impact after both a 9-hour time in bed baseline night and a 3-hour recovery night following total sleep deprivation.MethodsForty-two healthy participants were randomized into Control, Cognitive Stimulation, or Dynamization (respiratory and muscular exercises) groups, performing a 5-minute countermeasure immediately upon awakening. Primary outcomes included Psychomotor Vigilance Test reaction times and attentional lapses, Karolinska Sleepiness Scale, and the Operational Assessment of Sleep Inertia State, measured at predefined intervals of 5, 20, 35, 40, 55 minutes post awakening. In the absence of a pre-protocol, true rested baseline, the 55 minutes measure was taken as the within-session reference point.ResutlsWe confirmed that sleep inertia was significantly more pronounced following the 3-hour recovery night. Crucially, physiological dynamization significantly reduced sleep inertia within the first 20 minutes post-awakening, evidenced by lower reaction times (-49 ms, Cohen’d=0.81, p=0.02) and lapses (-2.3 lapses, d=0.71, p=0.02) at the Psychomotor Vigilance Task, and decreased subjective sleep inertia scores compared to the control group. Cognitive stimulation also conferred some benefits, notably reducing lapses and subjective sleepiness inertia scores, though its effect was not as consistent as that of dynamization. Participants in the cognitive stimulation group showed higher subjective and objective measures of sleep inertia after waking up, while no such significant differences were observed for the dynamization group.ConclusionThese findings indicate that physiological dynamization, incorporating brief respiratory and muscular exercises, is a highly promising reactive countermeasure for rapidly dissipating sleep inertia. Implementing such interventions post-awakening holds substantial potential value for enhancing immediate performance, though field studies are required to validate operational implications in demanding professional environments.
Introduction:Professional Formula racing often requires multiple high-stakes on-track sessions within the same competition day, creating a need to characterize pre-performance physiological state under field constraints. Salivary cortisol is a widely used marker of hypothalamic-pituitary-adrenal axis activity, but field-ready options for its immediate assessment during competition remain limited. Wearable heart-rate monitoring during on-track driving may provide an immediately available field signal reflecting composite cardiovascular load. This multi-season single-case field study examined the within-athlete association between wearable heart-rate data and same-day pre-performance salivary cortisol change in one professional Formula racing driver. Materials and methods:The primary observational series comprised 23 race-day observations across three competitive seasons. During each morning on-track session, the driver wore a wearable electrocardiogram device, and the peak heart rate (HRpeak) was extracted. Saliva samples were collected approximately 30 and 10 min before each morning and afternoon session and assayed for cortisol. Within-day cortisol change (ΔCortisol) was defined as afternoon minus morning pre-session cortisol, averaged across the two samples. The primary analysis included 18 dry-track observations with complete HRpeak and cortisol data. Five additional observations were examined in an exploratory post hoc analysis. Results:In the primary analytical sample, morning HRpeak was positively associated with ΔCortisol (r = 0.720). The positive direction was retained in sensitivity checks using 5-s and 10-s average heart rates anchored on the HRpeak and addressing serial dependence, season/session characteristics, and -30 min and -10 min sample-specific cortisol changes. Including the single wet-track observation reduced the correlation to r = 0.316. In the post hoc analysis, standardized ΔCortisol residuals were negative for the three planned-timing nap opportunities. No inferential comparison was performed. Discussion:Wearable on-track HRpeak may provide an immediately available field signal of composite cardiovascular load associated with later same-day endocrine variation in the participating driver. This interpretation is limited to dry-track conditions and does not support the use of HRpeak as a stress-specific marker, prediction method, or decision rule; the association does not establish causality. The post hoc observations provide no evidence regarding nap efficacy. Nevertheless, these descriptive findings may inform future prospective studies.
Background:Ballet requires high levels of postural control, coordination, and movement precision. This study examined whether adding unstable-surface balance training to resistance training improves balance and agility performance in college ballet dancers. Methods:Thirty male college ballet dancers were randomly assigned to an unstable-surface combined training group (CT, n = 15) or a stable-surface comparison group (ST, n = 15). Both groups completed a 12-week training program, with three sessions per week. Each session comprised 40 min of resistance training and 20 min of balance training. Static balance, dynamic balance, sensory organization, Y-Balance Test performance, and change-of-direction outcomes were assessed before and after the intervention. Results:Significant time effects and group × time interactions were observed for all static-balance variables under the eyes-open and eyes-closed conditions (all p < 0.05), with broader improvements in the CT group than in the ST group. Significant time effects and group × time interactions were also observed for VIS, VEST, toes-up and toes-down adaptation, YBT-N, YBT-D, and closed-eye stepping performance (all p < 0.05). No significant time effects or group × time interactions were found for the SOT composite score, SOM, or PREF. All three change-of-direction outcomes improved over time, but none showed a significant group × time interaction. Conclusions:Unstable-surface balance training combined with resistance training produced broader improvements in static and dynamic balance than stable-surface balance training. Evidence for superior agility improvement, however, remained limited.
ObjectiveTo examine how acupuncture at Shousanli (LI10) influences blood oxygen metabolism in tissues beneath acupoints along the Hand-Yangming Large Intestine Meridian, as well as at non-meridian sites, with the aim of validating acupoint specificity and meridian transmission.Methods60 healthy volunteers were randomized to acupoint (n=30, LI10) or non-meridian (n=30, 2 cm medial to LI10) groups. Photoacoustic imaging assessed oxygen saturation (SO2) at LI10, LI11, LI8, LI4, and corresponding non-meridian sites at baseline, post-deqi, post-withdrawal, and 15/30 min post-withdrawal.ResultsFollowing acupuncture at LI10, local SO2 at LI10 increased significantly (P<0.01), with transmission along the meridian to LI11 and LI8. No significant changes were observed at non-meridian non-acupoint sites.ConclusionAcupuncture at Shousanli can specifically regulate blood oxygen metabolism at acupoint regions and demonstrates meridian-oriented transmission characteristics, providing visualized evidence for acupoint specificity.
BackgroundFibromyalgia (FM) and irritable bowel syndrome (IBS) are overlapping functional somatic syndromes characterized by gut-brain axis dysregulation and low-grade systemic inflammation. We investigated whether a 16-week supervised combined exercise program is associated with phenotype-specific biomarker changes in patients with FM, IBS, or their comorbidity (FM+IBS).MethodsIn this prospective, single-center, pre-post interventional study, 55 patients (FM, n=15; FM+IBS, n=21; IBS, n=19) completed a 16-week supervised program of aerobic, resistance, and flexibility training three times weekly. Pre- and post-intervention assessments included a panel of intestinal barrier, neuroimmune, and inflammatory biomarkers, together with the Global Physical Capacity Score (GPCS).ResultsIn the FM+IBS group, exercise was associated with significant reductions in urinary lactulose excretion (mean delta: -0.160%, p=0.001), L/M ratio (mean delta: -0.011, p=0.026), serum zonulin (mean delta: -6.2 ng/mL, p=0.016), fecal zonulin (mean delta: -65.9 ng/mL, p=0.007), and urinary indoxyl sulfate (mean delta: -23.6 mg/L, p=0.046), with post-intervention L/M values falling below the 0.030 pathological threshold. In the IBS group, serum 5-HT increased (mean delta: +30.0 ng/mL, p=0.028) and IBS-SSS decreased by 85.8 points (p<0.001), exceeding the minimally important difference; both findings were confirmed in a sensitivity analysis restricted to 14 female patients (5-HT: p=0.033; IBS-SSS: p=0.004). In the FM group, IL-6 increased (mean delta: +0.37 pg/mL, p=0.013) and GPCS improved (p=0.047). BDNF, I-FABP, DAO, and LPS remained unchanged across all groups.ConclusionsSixteen weeks of combined exercise were associated with phenotype-specific biological patterns. FM+IBS patients showed reductions in barrier-related markers, supported by two independent assays (L/M ratio and indoxyl sulfate), while IBS patients exhibited enhanced serotonergic signaling and symptom relief, both robust to sex-stratified sensitivity analysis. The isolated IL-6 increase in FM patients requires caution, since an acute myokine effect and a chronic inflammatory drift are both compatible with a single measurement taken 16 weeks apart. These exploratory findings, constrained by this proof-of-concept design, support phenotype-stratified randomized controlled trials with active comparators to validate and characterize these differential responses.
ObjectiveTo investigate the associations between seminal plasma inflammatory biomarkers, particularly the sTLR4/IL-1β ratio, and sperm chromatin condensation deficiency (SCCD) in men undergoing fertility evaluation, and to assess its potential utility in identifying individuals at risk for SCCD.Methods74 men undergoing fertility evaluation were enrolled and categorized into a Normal SCCD group (SCCD ≤ 30%, n = 37) and an Impaired SCCD group (SCCD > 30%, n = 37) based on aniline blue staining. Seminal plasma levels of inflammatory markers, including HMGB1, sTLR4, IL-1β, TNF-α and oxidative stress markers, including 8-iso-PGF2α, total antioxidant capacity (T-AOC) were measured. Spearman correlation analysis, Firth’s penalized logistic regression, and receiver operating characteristic (ROC) curve analysis was employed to evaluate the discriminative performance of the biomarkers and the combined score, respectively.ResultsUnivariate Firth regression analysis revealed that the sTLR4/IL-1β ratio was a factor associated with reduced risk against SCCD (OR approaching 0, 95% CI: 0.00 - 0.04, P = 0.006), while T-AOC was significantly associated with increased risk of SCCD (OR = 200.99, 95% CI: 1.52 - 38205.02, P = 0.033). Multivariable analysis confirmed that sTLR4/IL-1β remained an independent factor associated with reduced SCCD risk after adjusting for confounders (P < 0.001), whereas T-AOC was not statistically significant in the multivariable model (P = 0.472). ROC curve analysis yielded an area under the curve (AUC) of 0.786 for sTLR4/IL-1β, indicating moderate-to-good discriminative ability.ConclusionA higher seminal plasma sTLR4/IL-1β ratio is independently associated with reduced SCCD risk, suggesting that preserved immunological buffering may protect sperm chromatin integrity. The sTLR4/IL-1β ratio demonstrates moderate-to-good discriminatory ability (AUC = 0.786) and, as an exploratory finding, may serve as a potential auxiliary assessment tool in future larger validation studies.
BackgroundContinuous vital signal monitoring is essential for patients undergoing hemodialysis sessions in which physiological instability, body fatigue, and cardiovascular complications may occur and require early medical interventions. However, conventional contactbased sensors such as electrocardiogram (ECG) have several limitations due to increased skin sensitivity, skin irritation, and interference with clinical procedures.ObjectiveThis study proposes a remote photoplethysmography (rPPG) framework for continuous heart rate monitoring of stage-5 chronic kidney disease (CKD-5) patients.MethodsA pilot cohort of eight patients diagnosed with stage-5 chronic kidney disease undergoing hemodialysis sessions were monitored using synchronized RGB video and ECG reference measurements to generate 32 hours of video data. The proposed framework incorporates an automated facial landmark tracking and a dual-masking-based skin detection approach to robustly define regions-of-interest (ROI). A multimethod ensemble fusion is integrated through spectral analysis, peak detection, and harmonic product spectrum analysis for confidence-weighted final heart rate estimation.ResultsThe proposed framework achieved a mean absolute error (MAE) of 1.16 beats per minute (BPM) and root mean squared error (RMSE) of 1.86 BPM with a mean bias error of −0.68 BPM among all patients irrespective of lower visibility due to mask and partial occlusion.ConclusionThese findings suggest that noncontact heart rate monitoring of patients diagnosed with advanced renal diseases is feasible using visible imaging and the rPPG method. By addressing clinical variability, the proposed framework suggests the potential of remote heart rate monitoring in a controlled dialysis-unit environment.
BackgroundGastrointestinal motility disturbances rank among the most frequently reported medical complications of spaceflight. Astronauts experience delayed gastric emptying, erratic small intestinal transit and reduced colonic propulsion. The underlying mechanisms are multifactorial. Microgravity alters intra-abdominal physical mechanics, disrupts autonomic and enteric neural circuits, shifts gastrointestinal hormone secretion profiles, inflicts oxidative stress upon effector cells, and perturbs gut microbial communities. Cross-model comparisons reveal substantial disagreement, suggesting that no single ground-based analog fully captures the pathophysiology of orbital flight.AimTo critically review how weightlessness affects gastric emptying, small intestinal transit and colonic motility; to critically evaluate contradictory findings across simulation platforms; and to delineate the neural, humoral, cellular and microbiological mechanisms involved.MethodsWe searched PubMed, Web of Science and the NASA Technical Reports Server for articles published between January 1990 and June 2026 (last search 30 June 2026). Search terms included: “microgravity”, “weightlessness”, “spaceflight”, “gastrointestinal motility”, “gastric emptying”, “intestinal transit”, “gut microbiome”, “interstitial cells of Cajal” and “oxidative stress”. Studies using head-down bed rest, hindlimb unloading, clinorotation, parabolic flight and actual spaceflight were included. The review follows a critical narrative design; the full search strategy and the framework used to appraise the evidence are described in Section 1.1.ResultsAltered-gravity studies suggest that gastrointestinal dysmotility may involve neurohumoral dysregulation, oxidative injury to interstitial cells of Cajal and smooth muscle, barrier dysfunction and altered enteric signaling; however, most mechanistic evidence derives from simulated models and has not been directly validated during human spaceflight. Direct human motility measurements remain sparse, and the evidence comprises a mixture of direct observations, model-dependent inferences and testable hypotheses. Cross-study agreement is poor: some head-down bed rest trials report accelerated small-bowel transit, whereas tail-suspension models and limited flight observations suggest motor suppression. These divergences may reflect model-specific confounding rather than a uniform effect of microgravity.ConclusionCurrent ground-based models each capture only partial aspects of orbital GI pathophysiology. Future work should combine multi-omics profiling with next-generation simulation platforms to develop evidence-based countermeasures for long-duration missions.
IntroductionSepsis is a leading cause of acute kidney injury (AKI) in patients treated in intensive care units. Due to close resemblance between porcine and human anatomy and physiology, porcine models are increasingly utilized in investigations of pathophysiological mechanisms behind sepsis associated AKI.ObjectiveThe aim of this review was to assess the renal function in untreated porcine models of sepsis using the Risk, Injury, Failure, Loss, End-stage kidney disease (RIFLE) criteria at the group level.DesignThe review was pre-registered in the Open Science Framework, DOI 10.17605/OSF.IO/FC29M. A systematic literature search was performed to identify porcine sepsis models which fulfilled the RIFLE criteria in the absence of active treatment. Three databases (Medline, Embase, and Web of Science) were systematically searched from 1946 until April 29th, 2025. In vivo studies aiming to induce sepsis or sepsis like conditions were included if the RIFLE criteria could be assessed at the group level in at least one study group. A meta-analysis was performed to study the relation between sepsis induction method and the likelihood of fulfilling the RIFLE criteria.Results1270 records were retrieved via databases and registers. Additional 309 records were identified from citation searching. 64 studies were included in the systematic review. 30 of 64 (47%) studies fulfilled one of the RIFLE criteria. 16, 9 and 5 studies fulfilled the RIFLE Risk, Injury and Failure criteria, respectively. 28 out of 64 studies (44%) reported renal dysfunction, but only two studies defined AKI using a diagnostic criterion. Exogenous markers of glomerular filtration rate (GFR) were applied in three studies. Fulfilment of the RIFLE criteria was associated with GFR being reported (p = 0.007), while the meta-analysis found no difference in the rate of AKI between different sepsis induction methods (Q_between = 2.49, p = 0.48).ConclusionsAKI at the group level was identified in 47% of the included studies. Exploratory meta-analyses did not identify any statistically robust differences in RIFLE fulfilment between sepsis induction methods, but methodological heterogeneity significantly limited the interpretability of the meta-analysis. Measurement of GFR was associated with a higher likelihood of RIFLE fulfilment, while the use of precise markers appeared limited.
Medical education traditionally presents physiological regulation through homeostatic feedback loops—reactive mechanisms that correct deviations from set points. More recently, allostatic models have emphasized the brain’s anticipatory role in regulation. However, presenting these frameworks as competing paradigms creates conceptual confusion for learners. This paper proposes a unified, three-tiered model of physiological regulation that positions reflexive, homeostatic, and predictive mechanisms as complementary systems operating across different timescales. Tier 1 encompasses local reflexive responses providing millisecond-to-second protection. Tier 2 comprises systemic homeostatic feedback maintaining core variables over minutes to hours. Tier 3 involves brain-centered predictive regulation integrating cognition, emotion, and context to anticipate demands. Critically, these tiers interact hierarchically: reflexive mechanisms provide immediate protective boundaries, homeostatic systems coordinate whole-body stability, and predictive processes adjust regulatory set points in anticipation of future needs. In turn, reflexive and homeostatic mechanisms constrain predictive regulation within biological limits. This hierarchical framework provides medical educators with coherent scaffolding for teaching regulation and prepares students to understand how psychological and contextual factors influence health outcomes.
Pancreatitis remains a common gastrointestinal disease with no mechanism-specific therapy. Its pathogenesis was long explained by the autodigestion hypothesis: a single linear cascade initiated by premature intra-acinar trypsinogen activation. This trypsin-centric view cannot account for the amplification of inflammation, the switching of cell-death modality, the acute-to-chronic transition, organ failure, or the chronic pancreatitis caused by protein-misfolding genes that act outside the protease system. Here we synthesize evidence from genetically engineered mouse models (GEMMs); their loss- and gain-of-function designs, spanning global and conditional knockouts, knock-ins, and CRISPR/Cas9 editing, can separate molecular events that are necessary, sufficient, or merely correlated. These models show, for example, that enhanced trypsinogen autoactivation alone is sufficient for spontaneous disease, that NF-κB-driven inflammation can be initiated independently of trypsin, and that loss of autophagy alone disrupts acinar homeostasis. On this basis we reframe pancreatitis as a network pathophysiology with two coupled layers. First, acinar homeostasis is maintained by several semi-independent control modules (digestive-enzyme safety, endoplasmic reticulum protein quality control, the autophagy–lysosome system, the calcium–mitochondria axis, and NF-κB signaling), so that disease can be initiated at any of several independent nodes. Second, the injured acinar cell dies through an interconnected, switchable network of regulated cell death (apoptosis, necroptosis, pyroptosis, ferroptosis, and PANoptosis), sharing nodes such as caspase-8, RIPK3, and GPX4, whose configuration, more than the initiating trigger, determines severity. This framework recasts the heterogeneity of human pancreatitis as different entry points into one network and argues for therapies directed at shared nodes rather than single pathways.
PurposeThis study investigated the non-linear, time-dependent alterations in cardiorespiratory fitness, running economy (RE), and metabolic kinetics during the first week of acute exposure to a sub-high altitude (1,300 m) in elite youth endurance athletes.MethodsFourteen male national-level middle- and long-distance runners (age: 19.8 ± 0.7 years; sea-level V˙O2max: 67.2 ± 3.8 mL·kg-¹·min-¹) completed field-based incremental exhaustion tests on a standard 400-m outdoor track at sea level (T0) and on day 1 (T1, within 18 h post-arrival), day 4 (T2), and day 6 (T3) after rapid rail-based ascent to 1,300 m. Maximal oxygen uptake (V˙O2max), peak running speed (vV˙O2max), and submaximal RE (steady-state V˙O2 at 12, 14, and 16 km·h-¹) were assessed using an automated metabolic cart. Blood lactate concentration ([La-]b) and maximal heart rate (HRmax) were measured. Daily waking morning heart rate (morning HR) and resting arterial oxygen saturation (SpO2) were continuously monitored. Training volume was strictly standardized to 70% of the habitual sea-level load.ResultsOne-way RM ANOVA revealed a significant main effect of time on V˙O2max (F[3,39]=18.42,p<0.001,ηp2=0.59). Crucially, polynomial contrasts confirmed a highly significant quadratic trend (Fquadratic[1,13]=34.21,ptrend<0.001,ηp2=0.72), statistically validating a non-linear V-shaped temporal kinetic profile. V˙O2max dropped from T1 to a distinct nadir at T2 (−7.0%, 95% CI:[60.1,64.7] mL·kg−1·min−1,p<0.001), and partially rebounded at T3. Concurrently, submaximal RE at 14 km/h significantly deteriorated at T2, as evidenced by a 5.3% increase in distance-specific oxygen cost (from 210.5±12.4 at T1 to 221.7±14.2 mL·kg−1·km−1 at T2, p=0.010), which also exhibited a significant quadratic pattern (ptrend=0.008). Post-exercise blood lactate peaked at T2 (11.2±1.4 mmol·L−1,p=0.015), while HRmax remained statistically stable (F[3,39]=0.21,p=0.885,ηp2=0.015).ConclusionAcute relocation to 1,300 m induces a distinct physiological nadir on Day 4, which may be related to transient autonomic adjustments and respiratory muscle work, rather than hematological adaptations. Early adaptation emerges by Day 6. Coaches may consider closer monitoring and temporary adjustment of training intensity during the early days following ascent, particularly around day 4.
BackgroundDespite the decline in secondhand smoke (SHS) exposure since the implementation of smoking bans in public places, SHS exposure remains a significant health risk factor affecting about 1/3 of non-smokers worldwide. We previously showed that 12 weeks of SHS exposure reduces heart rate variability, an effect that peaks at week 4. We further showed that 4 weeks of SHS exposure significantly reduces cardiac vagal neuron’s (CVN) excitability that is associated with a reduced small conductance calcium-dependent potassium (SK) channel activity.ObjectivesThis study aimed to test whether the reduced excitability in CVNs also wanes with longer exposure duration (12 weeks) and whether 4-aminopyridine sensitive voltage-gated potassium channels contribute to the SHS-induced decreases in neuronal excitability.MethodsAdult male mice were exposed to 12 weeks of filtered air or SHS at an environmental-relevant concentration (3 mg/m3, 6 hr/d, 5d/wk). We performed whole-cell patch-clamp recordings on anatomically identified CVNs in the nucleus ambiguus.Results12 weeks of SHS exposure significantly increased action potential (AP) thresholds and reduced spiking responses to excitation. SHS exposure did not significantly alter resting membrane potential, or 4-aminopyridine sensitive channel activity, suggesting that leak potassium channels and voltage gated potassium channels were unlikely to contribute to the reduced excitability. We found two adaptations that may serve to counteract the reduced excitability. First, APs inactivated at higher voltages that helped to maintain the spiking response range and increase maximum discharge frequency. Second, blocking SK channels with apamin had smaller effects on the spiking response in CVNs from SHS-exposed mice, suggesting that a reduced SK channel activation during spiking activity may help to dampen the reduced excitability.ConclusionEnvironmentally relevant SHS exposure reduces neuronal excitability of CVNs through mechanisms other than enhanced SK and voltage-gated potassium channel functions.
BackgroundDysregulation of neutrophil and consistent vascular calcification(VC) contributes to the pathogenesis and progression of chronic IgA nephropathy(C-IgAN). However, its integrated mechanism in IgAN has not yet been elucidated.MethodsWe integrated GSVA, CIBERSORT and WGCNA algorithms in C-IgAN patient bulk profiles(GSE35487 and GSE93798) downloaded from GEO database for identified VC and neutrophil (VN)-related shared DEGs. Next, explainable and systemic machine learning algorithms in C-IgAN training and validation bulk profiles identified VN-associated diagnostic model and hub gene. In addition, based on VN-associated shared gene signature, we performed NMF analysis for identification of VN-related molecular subgroups, and then we also investigated the molecular and immune patterns between subgroups. Besides, we also investigated hub gene, VC and neutrophil molecular landscapes at C-IgAN patient single-cell level via advanced analytical frameworks, such as sctenifoldknk and Bayes-prism algorithms. Novelty, deep learning algorithm (DrugRefLector) and molecular docking based on C-IgAN identified optimal therapeutic agent targeting hub gene. Finally, in vitro assays examined the expression pattern of hub gene.ResultsOur study first traced dynamic VN patterns in C-IgAN and identified VN-associated diagnostic and molecular subgroups. Besides, CLEC4D can be considered as neutrophil-distributed hub gene involved in VC and C-IgAN pathogenesis, which also can be considered as a drug target of BRD-K27184429 in C-IgAN.ConclusionOur study first identified VN-related patterns for C-IgAN patients, which provides novel idea into clinical applications.
ObjectivesThis study aimed to compare the educational performance of six mainstream LLMs for neuromyelitis optica spectrum disorder (NMOSD) and evaluated patient satisfaction during real-world interactions.MethodsThis study was conducted from March to April 2026. In the first Phase, Twenty NMOSD-related questions derived from clinical guidelines and patient concerns were submitted to six LLMs (ChatGPT-5.4, Gemini-3.1-pro, Claude-4.6-Sonnet, DeepSeek-3.2, Kimi-2.5, and Qwen-3.5-plus). Responses were anonymized and independently evaluated by three neuro-ophthalmology specialists using Likert framework assessing accuracy, completeness, readability, safety, and humanity. Inter-rater reliability was assessed using the intraclass correlation coefficient (ICC). In the second Phase, the three best-performing models were subsequently evaluated through real-world interactions with ten NMOSD patients, and satisfaction scores were analyzed using linear mixed-effects models.ResultsA total of 120 chatbot responses were evaluated. With a comprehensive evaluation, significant differences were observed across all assessment domains. Gemini-3.1-pro achieved the highest scores for accuracy and safety, while Qwen-3.5-plus demonstrated superior completeness and humanity. DeepSeek-3.2 generated the most accessible responses, exhibiting the lowest reading difficulty score. However, its completeness advantage should be interpreted with caution, as it may be partially influenced by its longer response length. Inter-rater reliability was good, with single-measure ICC values ranging from 0.535 to 0.759, and average-measure ICC values ranging from 0.775 to 0.904. In patient interactions, Qwen-3.5-plus achieved the highest satisfaction score, significantly outperforming Gemini-3.1-pro and DeepSeek-3.2. Although all LLMs demonstrate superior performance in patient education, the real-world interaction with patient needs to pay attention.ConclusionsLLMs demonstrate considerable potential for NMOSD patient education but exhibit variability across educational dimensions, and require further validation in larger cohorts. These findings highlight the importance of selecting LLMs according to specific patient education goals and underscore the importance of clinicians in rare disease counseling.
AimsTo explore the mechanisms involved in esophageal body longitudinal muscle contraction induced by electrical field stimulation.MethodsIsometric contractions of esophageal segments from wistar rats in an organ bath were induced by electrical field stimulation (duration 1 s, frequency 1-100 Hz, intensity 30-90 V) before and after application of pharmacological probes to test involvement of muscarinic receptors, Rho kinase, Ca2+ release, protein kinase C, calmodulin and L-type Ca2+ channels.ResultsElectrical field stimulation (EFS) induced contractions showed a frequency and intensity-dependent behavior. Based on the effect size, expressed by the Cohen’s d, they were insensitive to the muscarinic receptor blocker atropine (1 µM), the Rho kinase inhibitor Y-27632 (10 µM) as well as the inhibitors of Ca2+ release 2-aminoethoxydiphenylborane (2-APB, 100µM) and 1,1’-diheptyl-4,4’-bipyridinium (DHBP, 100 µM). In contrast, contractions were reduced by the protein kinase C inhibitor chelerythrine (10µM) and by the calmodulin antagonist N-[6-aminohexyl]-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7, 100 µM). Verapamil (100 µM) abolished EFS-induced contractions.ConclusionsBased on our findings with 2-APB, DHBP, and verapamil, extracellular Ca²+ appears to be the source of the increase in intracellular Ca²+ underlying EFS-induced EB contractions. Furthermore, the effects observed with chelerythrine and W-7 may suggest that this increase in intracellular Ca²+ may subsequently activate PKC- and calmodulin-dependent signaling pathways.
BackgroundTable tennis training requires appropriate intensity distributions to improve physical conditioning without impairing skill execution. This study compared the effects of an 8-week polarized training (POL) model with those of a threshold training (THR) protocol in table tennis players.MethodsThirty-two male table tennis players (Tier 2) were randomly allocated (1:1) to either the POL intervention (80% Zone 1, 5% Zone 2, and 15% Zone 3) or the THR intervention (50% Zone 1, 45% Zone 2, and 5% Zone 3). Participants completed five supervised on-court training sessions per week, with internal workload monitored and targeted to be similar between groups. Cardiopulmonary exercise testing was used to quantify maximal oxygen uptake (V˙O2max) and ventilatory thresholds (VT1 and VT2). An incremental topspin protocol was used to assess sport-specific time to exhaustion (TTE), target accuracy during the terminal stage of the incremental protocol, and heart rate recovery at 60 s (HRR60).ResultsThe POL intervention produced greater physiological and performance adaptations than the THR intervention. VT1 increased to a greater extent in the POL group than in the THR group (+9.8% vs. +6.4%, p = 0.03). VT2 improved only in the POL group (+5.0% vs. −1.0%, p < 0.001). The POL protocol also increased sport-specific TTE (+2.7%, p = 0.049), improved target accuracy under fatigue (+7.8%, p = 0.041), and enhanced HRR60 (+11.7%, p = 0.040). The THR group showed no statistically significant improvements in these outcomes. No significant group-by-time interaction was observed for absolute V˙O2max (p = 0.821).ConclusionThis study suggests that an 8-week polarized training program may be more effective than threshold training for improving submaximal cardiorespiratory fitness, sport-specific endurance, fatigue-induced technical stability, and autonomic recovery in competitive male table tennis players.
Several studies have shown that honeybees have a remarkable ability to detect, learn, and discriminate different floral qualities such as colour patterns and odour bouquets. However, how they integrate this multi-sensory information at the neuronal level is less understood. The sites for multi-sensory convergence in honeybees and other insects are the mushroom bodies (MB). In this study, we focus on MB output neurons (MBON) to examine how different MBONs process olfactory, visual, and olfactory-visual compound stimuli using extracellular multi-unit recordings. By analysing functional responses, we defined three MBON subpopulations: “bimodal”, “unimodal light”, and “unimodal odour”. All three groups exhibit compound-mediated modulation in both directions, meaning that compared to the unimodal response, the response strength to the compound can be either higher or lower. This suggests the presence of a separate compound-activated pathway, especially for unimodal MBONs. Comparing our results to the morphology of the MB input regions, the calyces, which are both divided into the lip (olfaction), collar (vision), and the basal ring (bimodal), we provide evidence that the latter region might play a key role in compound signalling. By establishing a model based on information flow through the MB circuitry, we reproduced the functional phenotypes exhibited by the different MBON types.
