Experimental Physiology

Polycystic ovary syndrome (PCOS), one of the most common endocrine disorders in reproductive‐aged women, is associated with metabolic disturbances. The present study aimed to examine changes in body weight (BW) and glucose and insulin tolerance in a prenatally‐androgenized (PNA) rat model of PCOS compared to control with increasing age. Pregnant rats in the experimental group were subcutaneously injected with 5 mg of free testosterone on the 20th day of pregnancy, while the control group received the solvent. Female offspring of both groups, PNA rats (rat model of PCOS) and control, were examined in terms of changes in BW, glucose and insulin tolerance at 3, 6, 12 and 20 months of age. BW at birth (6.53 ± 0.89 vs. 5.60 ± 1.18 g; P = 0.038), 15 (25 ± 1.15 vs. 22.36 ± 3.98 g; P = 0.019) and 30 (59.37 ± 10.19 vs.49.9 ± 9.39 g; P = 0.022) days of age was significantly increased in the rat model of PCOS compared to control, but no significant differences were observed in BW of the rat model of PCOS compared to control at 60 (P = 0.155) and 75 (P = 0.932) days or at 3 (P = 0.239), 6 (P = 0.782), 12 (P = 0.755) and 20 (P = 0.092) months of age. Rat model of PCOS showed impaired glucose tolerance (IGT) at 3 months of age (P = 0.020) and insulin resistance (IR) with increasing age (3–20 months of age) compared to control. Increased BW before puberty, IGT at 3 months of age and IR with increasing age were observed in our rat model of PCOS. This rat model may contribute to a better understanding of underlying mechanisms of changes in BW, IGT and IR in future studies.

This article provides a narrative review of the current literature and our expert opinion concerning the iliac branch endoprosthesis (IBE) and its use in the treatment of complex abdominal aortic aneurysm (AAA) cases with concomitant aneurysmal involvement of the common iliac artery (CIA) and/or the internal iliac artery (IIA). Up to 25% of those with an AAA may present with extension of the aneurysmal disease into the iliac vessels. This anatomy may complicate the standard endovascular aortic repair (EVAR) procedure, as the available length of distal landing zones is altered. The optimum treatment requires both the adequate sealing of the distal landing zone as well as the preservation of the pelvic circulation through the IIA. Extensive preoperative assessment of the anatomy, as well as an accurate deployment following all procedural steps, enables endovascular treatment of complex aorto‐iliac aneurysms safe with excellent midterm clinical outcomes. The current literature shows that the utilization of the IBE offers a durable treatment of these complicated cases with results equal to those of the open repair, without the associated morbidity. Preservation of the pelvic circulation is recommended to prevent pelvic ischaemic symptoms and can also be carried out on both sides provided certain anatomical requirements are met.

Female development includes significant size changes across the breast. Yet, whether differences in breast surface area (BrSA) modify breast sensitivity to warm, cold and wetness, and the associated epidermal properties (skin thickness and surface roughness) remain unclear. We investigated the relationship between BrSA and thermal and wetness perception, as well as epidermal properties, in 21 females (28±$\ \pm$10 years) of varying breast sizes (BrSA range: 147–502 cm²), at multiple breast sites (i.e., nipple, above and below the nipple, and bra triangle). Associations between BrSA and the perceptual and epidermal variables were determined via correlation analyses. Differences across test sites were assessed by repeated‐measures ANOVA. Our results did not support the hypothesis that larger breasts present reduced thermal and wetness sensitivity, except for the above nipple site, which presented reduced warm sensitivity with increasing BrSA (r = −0.61, P = 0.003). We also found a heterogeneous distribution of cold, but not warm or wetness, sensitivity across the breast, with the above nipple site presenting lower cold sensitivity than any other site (P < 0.015). Our findings did not indicate any association between BrSA and epidermal properties (thickness and roughness), nor any site‐dependent variation in these anatomical parameters (P > 0.15). We conclude that, while some skin‐site (i.e., above the nipple) and perceptual modality‐dependent (i.e., warm sensitivity) differences were observed, BrSA‐dependent variations in thermal and wetness sensitivity were not a generalised feature of the skin covering the breast. These observations advance our fundamental understanding of breast sensory function, and they could inform the design of user‐centred clothing such as bras.

Osteoporosis (OP) is a prevalent bone disease characterized by reduced bone density and quality, increasing fragility and fracture risk. Osteoclast (OC) activity and circadian rhythm play a role in the pathogenesis of OP. Melatonin is a circadian regulator that affects bone metabolism, but its molecular mechanism has not been studied in detail. This study aimed to identify the relationship between melatonin‐related genes and OP through bioinformatics methods and to verify it experimentally.We analysed microarray data from the GSE35959 dataset, identifying differentially expressed genes in OP patients. Circadian rhythm‐related genes and melatonin‐related genes intersect with these differentially expressed genes, highlighting that CSNK1D is a central gene. Functional enrichment, correlation and protein–protein interaction analyses were conducted. Experimental validation involved in vitro differentiation assays using RAW264.7 cells and in vivo studies with an ovariectomy‐induced rat model of OP to evaluate the role of CSNK1D in osteoclastogenesis to verify its effect on OP. Differential expression analysis revealed 272 significant genes, with CSNK1D identified as central to the circadian rhythm and to melatonin and OP interplay. Functional analyses showed involvement of CSNK1D in OC differentiation and inflammatory pathways. in vitro experiments confirmed CSNK1D upregulation during OC differentiation, and small interfering RNA‐mediated knockdown reduced OC marker expression and TRAP⁺ cell formation. in vivo, CSNK1D expression is associated with bone loss in OP rats. Melatonin‐related CSNK1D promotes OC differentiation and promotes the development of OP. These findings suggest CSNK1D as a potential therapeutic target for OP, offering insights into new treatment strategies integrating circadian rhythm regulation.

Adipose tissue has an established endocrine function through the secretion of adipokines. However, a role for bioactive metabolites and lipids, termed metabokines and lipokines, is emerging in adipose tissue‐mediated autocrine, paracrine and endocrine signalling and inter‐organ communication. Traditionally seen as passive entities, metabolites are now recognized for their active roles in regulating cellular signalling and local and systemic metabolism. Distinct from white adipose tissue, specific endocrine functions have been attributed to thermogenic brown and beige adipose tissues. Brown and beige adipose tissues have been identified as sources of metabokines and lipokines, which influence diverse metabolic pathways, such as fatty acid β‐oxidation, mitochondrial function and glucose homeostasis, across a range of tissues, including skeletal muscle, adipose tissue and heart. This review explores the intricate signalling mechanisms of brown and beige adipose tissue‐derived metabokines and lipokines, emphasizing their roles in maintaining metabolic homeostasis and their potential dysregulation in metabolic diseases. Furthermore, we discuss the therapeutic potential of targeting these pathways, proposing that precise modulation of metabokine receptors and transporters could offer superior specificity and efficacy in comparison to conventional approaches, such as β‐adrenergic signalling‐stimulated activation of brown adipose tissue thermogenesis. Understanding the complex interactions between adipokines, metabokines and lipokines is essential for developing a systems‐level approach to new interventions for metabolic disorders, underscoring the need for continued research in this rapidly evolving field.

Position sense is arguably more important than any of the other proprioceptive senses, because it provides us with information about the position of our body and limbs in relationship to one another and to our surroundings; it has been considered to contribute to our self‐awareness. There is currently no consensus over the best method of measuring position sense. We have recently measured position sense with three commonly used methods. These were two‐arm matching, one‐arm pointing and one‐arm repositioning, all carried out by blindfolded subjects with their lightly loaded forearms moving in the sagittal plane. It is currently believed that muscle spindles are the principal position sensors. We posed the question, was there evidence for spindles participating in the generation of position sense with each method? The indicator of spindle activity we used was the presence of thixotropic errors in the position signal, in response to conditioning voluntary contractions of forearm muscles. Based on this criterion, there was evidence of spindles contributing to position sense with all three methods. It was concluded that the spindle contribution to the position signal and the extent to which this was processed centrally was different with each method. It is argued that a case could be made for the existence of more than one position sense. Differences between the methods have implications for their meaning in a clinical setting.

Ageing‐related neuromuscular dysfunction is associated with reduced tropomyosin‐related kinase receptor subtype B (TrkB) signalling and accumulation of damaged cytoplasmic aggregates in motor neurons. Autophagy functions to remove these damaged aggregates, and we previously reported increased cervical motor neuron expression of LC3 and p62 in old age. We hypothesized that inhibition of TrkB kinase activity results in an increase in the relative expression of both LC3 and p62 in cervical motor neurons, consistent with impaired progression of autophagy. TrkBF616A mice, which possess a mutation that renders TrkB kinase activity susceptible to rapid inhibition by 1NMPP1, were treated at 6, 18 or 24 months of age with vehicle or 1NMPP1 for 7 days. Immunofluorescence intensity was measured to determine LC3 and p62 expression in choline acetyltransferase‐positive motor neurons in the cervical spinal cord. The effect of inhibiting TrkB kinase activity on progression of autophagy was age dependent. In 6‐month‐old mice, inhibiting TrkB kinase activity increased cervical motor neuron expression of LC3 by 11% (P < 0.001) and p62 by 8% (P = 0.019) compared with vehicle treatment. In 18‐ and 24‐month‐old mice, there was no effect of inhibiting TrkB kinase activity on motor neuron LC3 or p62 expression. We provide evidence that inhibition of TrkB signalling impairs progression of autophagy in motor neurons of young mice, similar to the response to ageing. Accordingly, a reduction of TrkB signalling in old age might contribute to neuromuscular dysfunction by impairing progression of autophagy in motor neurons.

Less than 7% of the world's population live at an altitude above 1500 m. Yet, as many as 67% of medalists in the 2020 men's and women's Olympic marathon, and 100% of medalists in the 2020 men's and women's Olympic 5000 m track race may have been born or raised above this otherwise rare threshold. As a possible explanation, research spanning nearly a quarter of a century demonstrates that indigenous highlanders exhibit pulmonary adaptations distinct from their lowland counterparts. These adaptations may then promote endurance performance. Indeed, healthy indigenous highlanders often exhibit a larger aerobic exercise capacity compared to sea‐level residents who travel to high altitude. However, questions remain on whether high‐altitude birth is advantageous for sea‐level competitions. In this review, we ask whether being born at a high altitude generates an ergogenic advantage for endurance performance in the Summer Olympics—a venue that is generally held at sea level. In so doing, we distinguish between three groups of high‐altitude residents: (i) the indigenous highlander, (ii) the highland newcomer, and (iii) the highland sojourner. Concentrating specifically on altitude‐induced alterations to pulmonary physiology beginning in the perinatal period, we propose that if altitude‐related maladaptations are avoided, genomic and developmental alterations accompanying highland birth may present benefits for endurance competitions at sea level.

Traumatic brain injury (TBI) affects neural function at the local injury site and also at distant, connected brain areas. However, the real‐time neural dynamics in response to injury and subsequent effects on sensory processing and behaviour are not fully resolved, especially across a range of spatial scales. We used in vivo calcium imaging in awake, head‐restrained male and female mice to measure large‐scale and cellular resolution neuronal activation, respectively, in response to a mild/moderate TBI induced by focal controlled cortical impact (CCI) injury of the motor cortex (M1). Widefield imaging revealed an immediate CCI‐induced activation at the injury site, followed by a massive slow wave of calcium signal activation that travelled across the majority of the dorsal cortex within approximately 30 s. Correspondingly, two‐photon calcium imaging in the primary somatosensory cortex (S1) found strong activation of neuropil and neuronal populations during the CCI‐induced travelling wave. A depression of calcium signals followed the wave, during which we observed the atypical activity of a sparse population of S1 neurons. Longitudinal imaging in the hours and days after CCI revealed increases in the area of whisker‐evoked sensory maps at early time points, in parallel to decreases in cortical functional connectivity and behavioural measures. Neural and behavioural changes mostly recovered over hours to days in our M1‐TBI model, with a more lasting decrease in the number of active S1 neurons. Our results in unanaesthetized mice describe novel spatial and temporal neural adaptations that occur at cortical sites remote to a focal brain injury.

A maximal apnoea provides significant challenges to one's physiological systems, including significantly altered arterial blood gases, and requires a highly integrative response from multiple systems, that is, changes in blood pressure, maintenance of cerebral blood flow, etc. Previous work and reviews have focused on the cardiovascular responses to a maximal apnoea, but very little work has focused upon the responses of the respiratory muscles and respiratory mechanics. This is important because of the changes to arterial blood gases leading to an increased drive to breath and the appearance of involuntary respiratory muscle contractions. This review outlines what is known about how the respiratory system responds to a maximal apnoea. We put forth the hypothesis that the respiratory muscles may become fatigued following a maximal apnoea and that the respiratory muscles of elite divers may be more fatigue‐resistant, which could be an important feature of these individuals which allows them to be successful in this sport. Finally, we provide direction for future work to explore the long‐term health of apnoea diving.

We explored the association between aerobic capacity (AC) and the skeletal muscle proteome of McArdle (n = 10) and wild‐type (n = 8) mice, as models of intrinsically ‘low’ and ‘normal’ AC, respectively. AC was determined as total distance achieved in treadmill running until exhaustion. The quadriceps muscle proteome was studied using liquid chromatography with tandem mass spectrometry, with the Search Tool for the Retrieval of Interacting Genes/Proteins database used to generate protein–protein interaction (PPI) networks and enrichment analyses. AC was significantly associated (P‐values ranging from 0.0002 to 0.049) with 73 (McArdle) and 61 (wild‐type) proteins (r‐values from −0.90 to 0.94). These proteins were connected in PPI networks that enriched biological processes involved in skeletal muscle structure/function in both groups (false discovery rate <0.05). In McArdle mice, the proteins associated with AC were involved in skeletal muscle fibre differentiation/development, lipid oxidation, mitochondrial function and calcium homeostasis, whereas in wild‐type animals AC‐associated proteins were related to cytoskeleton structure (intermediate filaments), cell cycle regulation and endocytic trafficking. Two proteins (WEE2, THYG) were associated with AC (negatively and positively, respectively) in both groups. Only 14 of the 132 proteins (∼11%) associated with AC in McArdle or wild‐type mice were also associated with those previously reported to be modified by aerobic training in these mice, providing preliminary evidence for a large divergence in the muscle proteome signature linked to aerobic training or AC, irrespective of AC (intrinsically low or normal) levels. Our findings might help to gain insight into the molecular mechanisms underlying AC at the muscle tissue level.

Menopause marks a major milestone in female reproductive ageing. It is characterized by the cessation of ovarian function and a concomitant decline in hormones such as oestradiol. Subsequently, females undergoing menopausal transition experience a progressive increase in cardiovascular and cerebrovascular disease risk. During menopause, reductions in nitric oxide (NO) bioavailability, endothelial dysfunction, increases in systemic inflammation, oxidative stress, and impaired vascular remodelling may contribute towards an accelerated decline in the function of cerebral and peripheral vascular systems. Historically, hormone therapy (HT) has been used as a means of managing vascular disease risk and reducing menopause‐associated vasomotor symptoms such as hot flushes, though some studies suggest regular exercise has the potential to be a promising alternative. Regular aerobic exercise during early postmenopause may slow vascular decline by improving NO and oestradiol bioavailability, promoting positive vascular remodelling and lowering systemic inflammation. However, exercise‐mediated improvements in markers of vascular function are not consistently observed in oestradiol‐deficient postmenopausal women. Emerging evidence suggests that due to the greater oestradiol bioavailability during early postmenopause, vascular adaptations to exercise may be enhanced during this stage, as opposed to late postmenopause. Subsequently it may be important to begin regular exercise in the years preceding and immediately following the final menstrual period to slow the progression of vascular disease risk during perimenopause and beyond. The present review will provide a summary of our current understanding of how vascular function is affected during menopause and the role of regular aerobic and resistance exercise training in managing vascular disease risk.

The present review aimed to investigate the effectiveness of aerobic exercise (AE) compared to other interventions in decreasing pain intensity and reducing disability in individuals with neck pain. A systematic review (SR) of randomized controlled trials was conducted. This SR was registered in PROSPERO (CRD42021231231). Searches were conducted in five electronic databases (MEDLINE, Embase, CINAHL, Cochrane and SCOPUS). Studies were selected if they included adults over 18 years old with neck pain. The primary outcomes were pain intensity and physical function. A meta‐analysis was conducted when applicable. Cochrane RoB Tool‐2 was used to determine the risk of bias of included studies, and the certainty of the evidence was determined using the GRADE approach. Out of 4669 initial records screened, six studies published in 12 articles were included. AE was not statistically different compared to no‐treatment or other interventions (e.g., localized exercise or acupuncture) on pain intensity measured with a visual analogue scale (VAS) (mean difference (MD) [95%CI]: 5.16 mm [−6.38, 16.70]). Contrarily, strengthening exercise was better than AE for pain intensity (MD [95%CI]: −11.34 mm [−21.6, −1.09]) after treatment. However, when AE was combined with other therapy (strengthening exercises or acupuncture), the combined therapy was better than isolated treatments (MD [95%CI]: 7.71 mm [1.07, 14.35]). A high heterogeneity was observed between protocols, comparisons, and results (magnitudes and directions). In conclusion, AE had positive results only when combined with other therapies to reduce pain intensity and disability in patients with neck pain. However, the evidence is limited, low‐quality, and heterogeneous.

This study applied alterations in partial pressure of end‐tidal carbon dioxide (PETCO2${{P}_{{\mathrm{ETC}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$) to challenge dynamic cerebral autoregulation (dCA) responses across the cardiac cycle in both biological sexes. A total of 20 participants (10 females and 10 males; aged 19–34 years) performed 4‐min bouts of repeated squat–stand manoeuvres (SSMs) at 0.05 and 0.10 Hz (randomized orders) with PETCO2${{P}_{{\mathrm{ETC}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ clamped at ∼40 mmHg. The protocol was repeated for hypercapnic (∼55 mmHg) and hypocapnic (∼20 mmHg) conditions. Middle cerebral artery (MCA) and posterior cerebral artery (PCA) were insonated via transcranial Doppler ultrasound. Dynamic end‐tidal forcing clamped PETCO2${{P}_{{\mathrm{ETC}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$, and finger photoplethysmography quantified beat‐to‐beat changes in blood pressure. Linear regressions were performed for transfer function analysis metrics including power spectrum densities, coherence, phase, gain and normalized gain (nGain) with adjustment for sex. During hypercapnic conditions, phase metrics were reduced from eucapnic levels (all P < 0.009), while phase increased during the hypocapnic stage during both 0.05 and 0.10 Hz SSMs (all P < 0.037). Sex differences were present with females displaying greater gain and nGain systole metrics during 0.10 Hz SSMs (all P < 0.041). Across PETCO2${{P}_{{\mathrm{ETC}}{{{\mathrm{O}}}_{\mathrm{2}}}}}$ stages, females displayed reduced buffering against systolic aspects of the cardiac cycle and augmented gain. Sex‐related variances in dCA could explain sex differences in the occurrence of clinical conditions such as orthostatic intolerance and stroke, though the effect of fluctuating sex hormones and contraceptive use on dCA metrics is not yet understood.

Gravity, an invisible but constant force , challenges the regulation of blood pressure when transitioning between postures. As physiological reserve diminishes with age, individuals grow more susceptible to such stressors over time, risking inadequate haemodynamic control observed in orthostatic hypotension. This prevalent condition is characterized by drops in blood pressure upon standing; however, the contrary phenomenon of blood pressure rises has recently piqued interest. Expanding on the currently undefined orthostatic hypertension, our study uses continuous non‐invasive cardiovascular data to explore the full spectrum of blood pressure profiles and their associated frailty outcomes in community‐dwelling older adults. Given the richness of non‐invasive beat‐to‐beat data, artificial intelligence (AI) offers a solution to detect the subtle patterns within it. Applying machine learning to an existing dataset of community‐based adults undergoing postural assessment, we identified three distinct clusters (iOHYPO, OHYPO and OHYPER) akin to initial and classic orthostatic hypotension and orthostatic hypertension, respectively. Notably, individuals in our OHYPER cluster exhibited indicators of frailty and sarcopenia, including slower gait speed and impaired balance. In contrast, the iOHYPO cluster, despite transient drops in blood pressure, reported fewer fallers and superior cognitive performance. Surprisingly, those with sustained blood pressure deficits outperformed those with sustained rises, showing greater independence and higher Fried frailty scores. Working towards more refined definitions, our research indicates that AI approaches can yield meaningful blood pressure morphologies from beat‐to‐beat data. Furthermore, our findings support orthostatic hypertension as a distinct clinical entity, with frailty implications suggesting that it is worthy of further investigation.

Ageing is an escalating global health issue, with the World Health Organization (WHO) reporting that one in six individuals will be 60 years or older by the year 2030. Therefore, understanding the mechanisms of complex biological ageing processes and associated healthcare challenges has become increasingly important. Intrinsic capacity (IC), defined by WHO as the composite of all physical and mental capacities an individual possesses, can be used as a proxy for defining healthy ageing. IC has five key components: locomotion, cognition, psychological, sensory, and vitality capacity (VC). This review paper specifically focuses on exercise as an effective tool to preserve VC in ageing populations. The physiological domains of VC discussed include energy and metabolism, neuromuscular function, immune and stress response, mitochondrial function, and the methylation clock. Additionally, we highlight potential outcome measures for assessing each of these domains. This review also covers areas of focus for future research and possible interventions. We ultimately conclude that ageing is a complex, multifaceted process resulting in deficits across multiple VC components. However, regular exercise is capable of producing physiological adaptations that may be beneficial in the context of healthy ageing and improving or preserving the status of VC components.

The relationship between mechanistic target of rapamycin complex 1 (mTORC1) activation after resistance exercise and acetylcholine receptor (AChR) subunit gene expression remains largely unknown. Therefore, we aimed to investigate the effect of electrical stimulation‐induced intense muscle contraction, which mimics acute resistance exercise, on the mRNA expression of AChR genes and the signalling pathways involved in neuromuscular junction (NMJ) maintenance, such as mTORC1 and muscle‐specific kinase (MuSK). The gastrocnemius muscle of male adult Sprague–Dawley rats was isometrically exercised. Upon completion of muscle contraction, the rats were euthanized in the early (after 0, 1, 3, 6 or 24 h) and late (after 48 or 72 h) recovery phases and the gastrocnemius muscles were removed. Non‐exercised control animals were euthanized in the basal state (control group). In the early recovery phase, Agrn gene expression increased whereas LRP4 decreased without any change in the protein and gene expression of AChR gene subunits. In the late recovery phase, Agrn, Musk, Chrnb1, Chrnd and Chrne gene expression were altered and agrin and MuSK protein expression increased. Moreover, mTORC1 and protein kinase B/Akt‐histone deacetylase 4 (HDAC) were activated in the early phase but not in the late recovery phase. Furthermore, rapamycin, an inhibitor of mTORC1, did not disturb changes in AChR subunit gene expression after muscle contraction. However, rapamycin addition slightly increased AChR gene expression, while insulin did not impact it in rat L6 myotube. These results suggest that changes in the AChR subunits after muscle contraction are independent of the rapamycin‐sensitive mTORC1 pathway.

Females likely experience larger performance benefits from androgenic-anabolic steroids than males. We set out to determine if there were temporal differences in select athletics (track and field) records between females and males. Exploratory aims included: (1) evaluating the improvements in female and male world records over time, and (2) investigating the influence of doping programs on male and female world records before and after 1990, when sports governing bodies began to implement random out-of-competition and systematic in-competition drug testing. We collected the top 500 performances of all time for both sexes from an online database (worldathletics.org) in four running events (100, 200, 400 and 800 m) and two throwing events (discus throw and shot-put). Data were stratified into quintiles based on world record ranking (1st to 100th, 101st to 200th, etc.). The temporal distribution of the top 100 female performers was significantly earlier than the top 100 male performers (year: 2000 ± 1 vs. 2005 ± 1, respectively; P < 0.0001). Within the event, the top performances occurred significantly earlier for females in the 800 m (year: 1995 ± 15 vs. 2003 ± 12; P = 0.0007) and shot-put (year: 1992 ± 14 vs. 2003 ± 17; P = 0.0004). Among females, world records rapidly improved through the 1980s, but following 1990, the world records ceased to improve. Geographically, there was a greater representation of countries with state-sponsored doping programs, specifically among female performances. We postulate these sex differences in the temporal distribution of top performances are likely associated with enhanced effectiveness of exogenous androgens (steroid doping) among female athletes with lower endogenous androgen hormones compared to males.

Muscle spindles are stretch‐sensitive mechanoreceptors found in the skeletal muscles of most four‐limbed vertebrates. They are unique amongst sensory receptors in the ability to regulate their sensitivity by contraction of the intrafusal muscle fibres on which the sensory endings lie. Muscle spindles have revealed a remarkable diversity of functions, including reflex action in posture and locomotion, contributing to bodily self awareness, and influencing wound healing. What were the circumstances which gave rise to the evolution of such complex end‐organs? We argue that spindles first appeared in early amniotes and only later in frogs and toads. This was considered an example of convergent evolution. Spindles in amphibians and reptiles are characterised by their simple structure, pointing to key features essential for spindle function. Spindle sensitivity in amphibians and reptiles is controlled by intrafusal fibre contractions evoked by branches of motor axons supplying extrafusal muscle. Modern phylogenetic evidence has revised our views on the origin of birds, placing them closer to the dinosaurs than had previously been thought. Birds are the only group, other than mammals, which has a dedicated fusimotor innervation of spindles, another example of convergent evolution, given the widely different origins of the two groups. One factor that may have played a role here was that both groups are endotherms, allowing motor control to develop further in an optimal internal environment. This, as well as other changes within the spindle, has led to the astonishing sophistication of motor control observed especially in many modern mammals.

Exposure to the spaceflight environment causes adaptations in most human physiological systems, many of which are thought to affect women differently from men. Since only 11.5% of astronauts worldwide have been female, these issues are largely understudied. The physiological nuances affecting the female body in the spaceflight environment remain inadequately defined since the last thorough published review on the subject. A PubMed literature search yielded over 2200 publications. Using NASA's 2014 review series ‘The effects of sex and gender on adaptation to space’ as a benchmark, we identified substantive advancements and persistent knowledge gaps in need of further study from the nearly 600 related articles that have been published since the initial review. This review highlights the most critical issues to mitigate medical risk and promote the success of missions to the Moon and Mars. Salient sex‐linked differences observed terrestrially should be studied during upcoming missions, including increased levels of inflammatory markers, coagulation factors and leptin levels following sleep deprivation; correlation between body mass and the severity of spaceflight‐associated neuro‐ocular syndrome; increased incidence of orthostatic intolerance; increased severity of muscle atrophy and bone loss; differences in the incidence of urinary tract infections; and susceptibility to specific cancers after exposure to ionizing radiation. To optimize health and well‐being among all astronauts, it is imperative to prioritize research that considers the physiological nuances of the female body. A more robust understanding of female physiology in the spaceflight environment will support crew readiness for Artemis missions and beyond.

Athletes frequently compete only a few days after long‐haul travel. Longitudinal real‐world data on athletes’ sleep and sleep–wake cycle in competitive settings remain scarce. This study assessed the impact of a long‐haul travel across ∼13 time zones on sleep patterns, rest–activity circadian rhythms (RAR), and their subsequent effects on neuromuscular function and race performance in the Canadian Short‐Track Speed Skating Team. Nineteen athletes (24 ± 4 years, 11 women) travelled from Montréal (UTC‐5) to Asia (UTC+8, UTC+9) for World Cup races between 2017 and 2019. Actigraphy data were collected before (Baseline) and during travel, during the stay in Asia (SIA), and during competition days. RAR were computed using cosinor analyses on accelerometry data with 24 h phase periods. Countermovement jump height (CMJ) was measured in a subsample (n = 10). Compared to baseline (7:08 ± 0:53), athletes obtained less sleep during travel (6:16 ± 1:27) and competition days (6:35 ± 1:10), and more during SIA (7:32 ± 0:46; time effect P < 0.0001). Sleep efficiency and CMJ were greater in SIA than baseline (P = 0.007 and P = 0.0004, respectively). During SIA, sleep time increased by 9 min per night until the fifth day (P < 0.0001), with a slight decrease in sleep efficiency (P = 0.005) and an increase in CMJ (P < 0.0001). For RAR, mean activity peaked on day 2, shifting from late evening to ∼15:00. Race performance was not different from other races of the same season (P > 0.254). Our results demonstrated that, despite the possible sleep debt from the long‐haul travel, athletes recovered within 5 days, highlighting their adaptability to manage sleep debt and jetlag without impacting competitive outcomes.

Intestinal ischaemia–reperfusion (I/R) is a common clinical pathology with high incidence and mortality rates. However, the mechanisms underlying intestinal I/R injury remain unclear. In this study, we investigated the role and mechanism of chitinase 3‐like 1 (CHI3L1) during intestinal I/R injury. Therefore, we analysed the expression levels of CHI3L1 in the intestinal tissue of an intestinal I/R rat model and explored its effects and mechanism in a hypoxia–reoxygenation (H/R) IEC‐6 cell model. We found that intestinal I/R injury elevated CHI3L1 levels in the serum, ileum and duodenum, whereas H/R enhanced CHI3L1 expression in IEC‐6 cells. The H/R‐induced inhibition of proliferation and apoptosis was alleviated by CHI3L1 knockdown and aggravated by CHI3L1 overexpression. In addition, CHI3L1 knockdown alleviated, and CHI3L1 overexpression aggravated, the H/R‐induced inflammatory response and oxidative stress. Mechanistically, CHI3L1 overexpression weakened the activation of the phosphoinositide 3‐kinase (PI3K)/AKT pathway, suppressed the nuclear translocation of Nrf2, and promoted the nuclear translocation of nuclear factor κB (NF‐κB). Moreover, CHI3L1 knockdown had the opposite effect on the PI3K/AKT pathway, Nrf2, and NF‐κB. Moreover, the PI3K inhibitor LY294002 blocked the effect of CHI3L1 knockdown on the H/R‐induced inhibition of proliferation, apoptosis, inflammatory response and oxidative stress. In conclusion, CHI3L1 expression was induced during intestinal I/R and H/R injury in IEC‐6 cells, and CHI3L1 overexpression aggravated H/R injury in IEC‐6 cells by inhibiting the PI3K/AKT signalling pathway. Therefore, CHI3L1 may be an effective target for controlling intestinal I/R injury.

CD34⁺ progenitor cells with angiogenic capabilities traffic into blood during exercise and extravasate afterwards but the magnitude of this response varies between people. We examined whether exercise‐induced progenitor cell trafficking is influenced by cardiorespiratory fitness (maximum oxygen uptake; V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_2}{\mathrm{max}}}}$). Ten males (age: 23 ± 3 years; V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_2}{\mathrm{max}}}}$: 61.88 ± 4.68 mL kg min⁻¹) undertook 1 h of treadmill running at 80% of V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_2}{\mathrm{max}}}}$. Blood samples were collected before exercise (Pre), in the final minute of exercise (0 h) and afterwards at 0.25, 1 and 24 h. Pan‐progenitor cells (CD34⁺, CD34⁺CD45dim) and putative endothelial progenitor cells (CD34⁺CD133⁺, CD34⁺VEGFR2⁺, CD34⁺CD45dimVEGFR2⁺) were quantified using flow cytometry. Progenitor subpopulations (except for CD34⁺CD45dimVEGFR2⁺) increased at 0 h (P < 0.05) and returned to pre‐exercise levels by 1 h. V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_2}{\mathrm{max}}}}$ was positively associated with the exercise‐induced progenitor cell response and there were statistically significant time × V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_2}{\mathrm{max}}}}$ interactions for CD34⁺, CD34⁺CD45dim and CD34+CD133⁺ subpopulations but not VEGFR2‐expressing progenitor cells. There were statistically significant correlations between V̇O2max${{\dot{V}}_{{{{\mathrm{O}}}_2}{\mathrm{max}}}}$ and ingress (r > 0.70, P < 0.025) and egress (r > −0.77, P < 0.009) of progenitor cell subsets (CD34⁺, CD34⁺CD45dim, CD34⁺CD133⁺), showing that cardiorespiratory fitness influences the magnitude of progenitor cell mobilisation into the blood and subsequent extravasation. These data may provide a link between high levels of cardiorespiratory fitness and vascular health.