Experimental Physiology最新文献

{"title":"Clinical significance and immune microenvironment association of cuproptosis-related genes in pan-cancer.","authors":"Xinyu Ge, Kaijing Wang, Tian Zhao, Jinyi Wang, Jie Liu, Zhengliang Sun, Zhengjun Chai, Wen Zhang, Chengbao Li, Yan Xu, Guohan Chen","doi":"10.1113/EP092310","DOIUrl":"https://doi.org/10.1113/EP092310","url":null,"abstract":"<p><p>Recent studies highlight the important roles of cuproptosis in cancer cells. However, the roles of the cuproptosis-related genes (CRGs) in different cancers are still not fully understood. Comprehensive analysis was performed using open-source bioinformatic platforms to disclose the expression profiles, prognostic significance, genomic and epigenetic characteristics, immune microenvironment, and drug sensitivity of CRGs including FDX1, LIAS, LIPT1, DLD, DLAT, PDHA1, PDHB, SLC31A1, MTF1, GLS, CDKN2A, HSPA4 and ATP7B. The colon cancer samples were further obtained to verify the correlation between CDKN2A expression and immune cell infiltration by fluorescence staining. We demonstrated the expression level, methylation and the copy number variant feature, as well as the prognostic significance of CRGs in pan-cancers. The expression of CRGs, especially PDHB, LITP1, ATP7B, HSPA4 and CDKN2A, was significantly correlated with pathological stages. The genetic alteration of CRGs was explored, and CDKN2A was the most frequently altered gene with alteration rate as high as 17% in 10,953 tumour patients. In addition, we revealed a relationship to the tumour immune microenvironment (TIME) and drug resistance in pan-cancer. Moreover, CDKN2A, which was closely correlated to pan-cancer prognosis, was especially analysed including TIME alteration, genomic heterogeneity and tumour stemness. Fluorescence images of colon cancer from different patients demonstrated a positive correlation between CDKN2A expression and the number of CD45⁺ immune cells. Our research has provided a comprehensive understanding of cuproptosis regulators and revealed potential prognostic biomarkers and therapeutic targets for cancers.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144495407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of repeated cryostimulation exposures on sleep quality in swimmers during an intense training period.","authors":"Coralie Arc-Chagnaud, Benoit Dugué, Robin Pla, Romain Bouzigon, Laurent Bosquet, Olivier Dupuy","doi":"10.1113/EP092293","DOIUrl":"https://doi.org/10.1113/EP092293","url":null,"abstract":"<p><p>The aim of this study was to evaluate the effects of daily partial body cryostimulation exposures on sleep and recovery parameters in elite swimmers undergoing an intense training period. Twenty-three elite French swimmers (7 females and 16 males) were involved in this controlled cross-over protocol. The experiment took place during 2 weeks of intense training load. Each week (5 days and 5 nights) represented one of the two experimental conditions: partial body cryostimulation exposures (CRYO) or control sessions (CONT). Daily partial body cryostimulation exposure of 3 min at -110°C was performed (or not) during a consecutive period of 5 days, after the evening training session. Perceived wellness (anxiety, tiredness, depression and mood profile), sleep quality (via actimetry and cerebral recording) and nocturnal heart rate variability were evaluated. Collection of saliva samples permitted the measurement of C-reactive protein and melatonin. Perceived anxiety, tiredness and depression were reduced after the CRYO week, concomitant with an improved mood profile. Recordings of cerebral activity during the night highlighted increased slow-wave sleep duration in the first sleep cycle during the CRYO week. Other sleep parameters, including total sleep time, sleep latency, efficiency or movements during the night, remained unchanged. The concentration of C-reactive protein in saliva was lower during the CRYO week compared with the CONT week. Moreover, sleep analysis allowed a distinction between better sleepers and poor sleepers. In the latter group, only poor sleepers among the male swimmers obtained a benefit on their sleep from cryotherapy. Repeated cryostimulation exposures during 1 week of intense training improved perceived wellness in elite swimmers, reduced inflammation, and modulated sleep architecture by increasing slow-wave sleep duration.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Computing muscle mechanical state variables from combined proprioceptive sensory feedback.","authors":"Jacob D Stephens, Lena H Ting, Timothy C Cope","doi":"10.1113/EP092351","DOIUrl":"https://doi.org/10.1113/EP092351","url":null,"abstract":"<p><p>Proprioceptive sensory feedback is crucial for the control of movement. In many ways, sensorimotor control loops in the neuromuscular system act as state feedback controllers. These controllers combine input commands and sensory feedback regarding the mechanical state of the muscle, joint or limb to modulate the mechanical output of the muscles. To understand how these control circuits function, it is necessary to understand fully the mechanical state variables that are signalled by proprioceptive sensory (propriosensory) afferents. Using new computational approaches, we demonstrate how combinations of group Ia and II muscle spindle afferent feedback can allow for tuned responses to force and the rate of force (or length and velocity) and how combinations of muscle spindle and Golgi tendon organ feedback can parse external and internal (self-generated) force. These models suggest that muscle spindle feedback might be used to monitor and control muscle forces in addition to length and velocity and, when combined with tendon organ feedback, can distinguish self-generated from externally imposed forces. Given that these models combine feedback from different sensory afferent types, they emphasize the utility of analysing muscle propriosensors as an integrated population, rather than independently, to gain a better understanding of propriosensory-motor control. Furthermore, these models propose a framework that links neural connectivity in the spinal cord with neuromechanical control. Although considerable work has been done on propriosensory-motor pathways in the CNS, our aim is to build upon this work by emphasizing the mechanical context.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of short-term exercise on plasma metabolic and lipidomic profiles of individuals with type 2 diabetes.","authors":"Maartje Cox, Aaron Raman, Timothy Fairchild, John P Beilby, Bu B Yeap, Jeremy K Nicholson, Julien Wist, Jeremiah Peiffer, Nathan G Lawler","doi":"10.1113/EP092768","DOIUrl":"https://doi.org/10.1113/EP092768","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a common metabolic disorder characterized by chronic hyperglycaemia, with physical inactivity and excessive adiposity as predisposing factors. This clinical trial aimed to investigate the effects of an exercise intervention on the metabolome of T2DM participants, fasting and in response to an oral glucose tolerance test (OGTT) and an acute exercise stimulus. Thirteen people with T2DM (age 51 ± 7 years; body mass index 32.7 ± 4.9 kg/m²) completed 45 min of moderate-intensity treadmill exercise on 12 days consecutively. Blood samples were collected before and after the first and last training sessions and during a pre- and postintervention OGTT. Fasted blood samples were collected from 198 healthy control subjects and 208 people with T2DM from an independent cohort for comparison. Samples were analysed using high-resolution ¹H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry. The exercise intervention did not induce a shift towards a healthier fasted metabolome in people living with T2DM. In response to consumption of a glucose bolus (OGTT), glycolysis-related metabolites increased and free fatty acids decreased, with no effect of the exercise intervention. In response to acute exercise, glucose and amino acids decreased and free fatty acids increased, with similar responses on the last day of training as on the first day, indicating no effect of the intervention. The clinical trial was registered prospectively in the Australian New Zealand Clinical Trials Registry ACTRN12617000286347 on 24 February 2017.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Faecal microbiome, gastrointestinal integrity, inflammation and thermoregulation in recent exertional heat illness patients and matched controls.","authors":"Alex A M Gould, Neil P Walsh, Michael J Tipton, Michael J Zurawlew, Omar Tayari, Carol House, Simon K Delves, Samuel C Robson, Janis J Shute, Joy E M Watts, Andrew J Roberts, Alex J Rawcliffe, Megan R Robinson, Jo Corbett","doi":"10.1113/EP092849","DOIUrl":"https://doi.org/10.1113/EP092849","url":null,"abstract":"<p><p>The gastrointestinal (GI) microbiota and GI barrier integrity are hypothesised to contribute to exertional heat illness (EHI) aetiology. We compared the faecal microbiome, GI barrier integrity, inflammation and thermoregulation of 29 recent (∼4 months) EHI patients (a group with elevated EHI risk) and 29 control individuals without prior EHI history, matched for variables influencing thermoregulation and GI microbiota. Participants completed an exercise heat tolerance assessment (HTA), with faecal microbiome assessed by 16S rRNA gene amplicon sequencing of stool samples and blood biomarkers of GI barrier integrity and inflammation measured pre- and post-HTA. With the exception of the Simpson index (patient = 0.97 ± 0.01 vs. control = 0.98 ± 0.00, P = 0.030), there were no between-groups differences in faecal microbiome composition (α-diversity, β-diversity, relative abundance, differential abundance), GI barrier integrity, inflammation or terminal thermoregulatory indices. Individuals were subsequently classified as heat tolerant (n = 46) or intolerant (n = 12) on the basis of the HTA. Heat intolerant individuals demonstrated lower sudomotor response (intolerant = 0.53 (0.17) vs. tolerant = 0.62 (0.20) L m^-2 h^-1, P = 0.011) despite greater thermoregulatory strain (e.g., terminal T_rec: intolerant = 39.20 ± 0.31 vs. tolerant = 38.80 ± 0.31°C, P < 0.001), lower Firmicutes:Bacteroidota ratio (intolerant = 3.7 (0.6) vs. tolerant = 4.5 (2.0), P = 0.019) and higher plasma [sCD14] (P = 0.014), but other aspects of faecal microbiome, GI integrity or inflammation did not differ from heat tolerant individuals. In conclusion, the faecal microbiome composition and the GI barrier integrity and inflammatory responses to exercise heat-stress showed limited differences between recent EHI patients and matched controls, or between individuals classified as heat intolerant or heat tolerant and are unlikely to explain elevated EHI risk in recent EHI patients, or heat intolerance.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiology of nitrogen: A life or death matter.","authors":"Damian M Bailey, Vaughan G Macefield, David C Poole","doi":"10.1113/EP092946","DOIUrl":"10.1113/EP092946","url":null,"abstract":"<p><p>With each breath, four out of every five molecules we inspire are nitrogen (N₂), since this gas constitutes ∼80% of the atmospheric air that surrounds us. Despite its abundance and unlike molecular oxygen, N₂ has traditionally held less appeal among physiologists given its lack of reactivity and corresponding inability to support combustion or life, rendering it metabolically nugatory. The controversial application of N₂ asphyxiation for the inhumane purposes of human execution of convicted criminals and assisted suicide of a terminally ill patient has thrust this important gas into the scientific and public spotlight, sparking widespread condemnation. In the current review, we take an opportunity to explore the molecular bases and clinical consequences linked to the Janus-faced physiology of N₂ to better explain its life-and-death qualities. We highlight the complex history that led to its discovery and the physio-geochemical evolution of Earth's uniquely N₂-rich atmosphere, including intimate links with oxygen (O₂), another life-and-death homonuclear diatomic gas that preceded aerobic respiration and the emergence of complex multicellular life. Diving deep into N₂'s quantum state, we expose its unique physiochemical properties to better understand why this gas is metabolically inert and physiologically deadly when in excess and especially to the exclusion of O₂. We apply this integrated physiological knowledge to further inform the controversial public debate and directly challenge the misconceived notion that N₂ gas asphyxiation offers a quick, indolent and dignified death for the inhumane purposes of human execution and assisted suicide.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of soluble guanylyl cyclase stimulation on muscle oxygenation and exercise capacity in heart failure with mildly reduced ejection fraction.","authors":"Ramona E Weber, Kiana M Schulze, Andrew G Horn, Tyler E McCoach, Zachary J White, K Sue Hageman, Stephanie E Hall, Peter Sandner, Brad J Behnke, Timothy I Musch, David C Poole","doi":"10.1113/EP092756","DOIUrl":"10.1113/EP092756","url":null,"abstract":"<p><p>Heart failure (HF) with a mildly reduced ejection fraction (HFmrEF; 40%-49%) is present in ≤25% of HF patients. Therapeutic treatment options for HFmrEF-associated exercise intolerance are limited. Nitric oxide (NO)-independent stimulation of soluble guanylyl cyclase to improve peripheral vasodilatation offers a novel approach to enhance skeletal muscle oxygenation (interstitial pressure of O₂) and exercise capacity. We tested the hypotheses that the soluble guanylyl cyclase stimulator BAY 41-2272 (BAY41) would increase exercise tolerance, skeletal muscle interstitial pressure of O₂ during contractions and NO sensitivity in rats with HFmrEF. Healthy Sprague-Dawley rats (n = 20) and rats with experimentally induced HFmrEF (n = 25) (3-4 months old) were used for this investigation. HFmrEF was confirmed via echocardiography, and rats were randomized and treated with 1.0 mg/kg of BAY41 or vehicle for 2 weeks, followed by exercise testing and spinotrapezius muscle phosphorescence quenching measurements during 1 Hz contractions. The HFmrEF rats had a lower exercise capacity than healthy rats (834 ± 169 vs. 1138 ± 214 s; p < 0.001). BAY41 increased exercise capacity (1158 ± 223 s; p = 0.006) and muscle oxygenation index (1461 ± 427 vs. 1108 ± 239 mmHg·s; p = 0.047) during 1 Hz contractions versus HFmrEF vehicle control rats. Sodium nitroprusside superfusion elicited a faster response time in BAY41-treated HFmrEF rats versus vehicle-treated control animals (150 ± 58 vs. 220 ± 50 s; p = 0.022). After sodium nitroprusside superfusion, BAY41-treated HFmrEF rats had a significantly elevated muscle oxygenation index during steady-state contractions versus vehicle-treated control animals (3104 ± 703 vs. 2365 ± 682 mmHg·s; p = 0.027). These data suggest that stimulation with soluble guanylyl cyclase can improve skeletal muscle oxygenation and increase the exercise capacity in HFmrEF rats, potentially via enhanced vascular smooth muscle NO sensitivity.</p>","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332701","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From fatigue to physiology: Submaximal 2-day cardiopulmonary exercise test and emerging standards in long COVID.","authors":"Michael G Risbano","doi":"10.1113/EP092958","DOIUrl":"https://doi.org/10.1113/EP092958","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Galloyl-bis-hexahydroxydiphenoyl glucose and endothelial remodelling: nutrigenomic insights into blackberry's superior vasorelaxant efficacy over mugwort.","authors":"Shan Tao, Yinuo Qin, Chengqiang Jin","doi":"10.1113/EP092901","DOIUrl":"https://doi.org/10.1113/EP092901","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reply to: Galloyl-bis-hexahydroxydiphenoyl glucose and endothelial remodelling: Nutrigenomic insights into blackberry's superior vasorelaxant efficacy over mugwort.","authors":"Afaf Mehiou, Anca Lucau-Danila, Zachee L E Akissi, Chaimae Alla, Nourelhouda Bouanani, Abdelkhaleq Legssyer, Jean-Louis Hilbert, Sevser Sahpaz, Abderrahim Ziyyat","doi":"10.1113/EP092989","DOIUrl":"https://doi.org/10.1113/EP092989","url":null,"abstract":"","PeriodicalId":12092,"journal":{"name":"Experimental Physiology","volume":" ","pages":""},"PeriodicalIF":2.6,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324850","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}