The relationship between muscle thickness and pennation angle is mediated by fascicle length in the muscles of the lower extremities.

Muscle morphological architecture, a crucial determinant of muscle function, has fascinated researchers since the Renaissance. Imaging techniques enable the assessment of parameters such as muscle thickness (MT), pennation angle (PA), and fascicle length (FL), which may vary with growth, sex, and physical activity. Despite known interrelationships, robust mathematical models like causal mediation analysis have not been extensively applied to large population samples. We recruited 109 males and females, measuring knee flexor and extensor, and plantar flexor MT, PA, and FL using real-time ultrasound imaging at rest. A mixed-effects model explored sex, leg (dominant vs. non-dominant), and muscle region differences. Males exhibited greater MT in all muscles (0.1 to 2.1 cm, p < 0.01), with no sex differences in FL. Dominant legs showed greater rectus femoris (RF) MT (0.1 cm, p = 0.01) and PA (1.5°, p = 0.01), while vastus lateralis (VL) had greater FL (1.2 cm, p < 0.001) and PA (0.6°, p = 0.02). Regional differences were observed in VL, RF, and biceps femoris long head (BFlh). Causal mediation analyses highlighted MT's influence on PA, mediated by FL. Moderated mediation occurred in BFlh, with FL differences. Gastrocnemius medialis and lateralis exhibited FL-mediated MT and PA relationships. This study unveils the intricate interplay of MT, FL, and PA in muscle architecture.

Controllable synthesis and morphology-dependent light emission efficiency of Zn2GeO4 nanophosphors.

Zn2GeO4 is considered a very promising alternative to current luminescent semiconductors. Previous results suggest that its emitted wavelength may depend on different variables, such as particle size and morphology, among others. In this work, we have prepared pure and highly homogeneous Zn2GeO4 nanorods under hydrothermal synthesis conditions with a willemite-like structure. Their luminescent properties have been explored and their band gap is estimated, which are distinct from those of previously reported Zn2GeO4 bulk particles. Therefore, our results identify particle morphology as a crucial factor for maximizing and fine-tuning the luminescence of Zn2GeO4 nano-phosphors.

Physiological and molecular predictors of cycling sprint performance.

The study aimed to identify novel muscle phenotypic factors that could determine sprint performance using linear regression models including the lean mass of the lower extremities (LLM), myosin heavy chain composition (MHC), and proteins and enzymes implicated in glycolytic and aerobic energy generation (citrate synthase, OXPHOS proteins), oxygen transport and diffusion (myoglobin), ROS sensing (Nrf2/Keap1), antioxidant enzymes, and proteins implicated in calcium handling. For this purpose, body composition (dual-energy X-ray absorptiometry) and sprint performance (isokinetic 30-s Wingate test: peak and mean power output, Wpeak and Wmean ) were measured in young physically active adults (51 males and 10 females), from which a resting muscle biopsy was obtained from the musculus vastus lateralis. Although females had a higher percentage of MHC I, SERCA2, pSer16 /Thr17 -phospholamban, and Calsequestrin 2 protein expressions (all p < 0.05), and 18.4% lower phosphofructokinase 1 protein expression than males (p < 0.05), both sexes had similar sprint performance when it was normalized to body weight or LLM. Multiple regression analysis showed that Wpeak could be predicted from LLM, SDHB, Keap1, and MHC II % (R 2 = 0.62, p < 0.001), each variable contributing to explain 46.4%, 6.3%, 4.4%, and 4.3% of the variance in Wpeak , respectively. LLM and MHC II % explained 67.5% and 2.1% of the variance in Wmean , respectively (R 2 = 0.70, p < 0.001). The present investigation shows that SDHB and Keap1, in addition to MHC II %, are relevant determinants of peak power output during sprinting.

Antioxidant enzymes and Nrf2/Keap1 in human skeletal muscle: Influence of age, sex, adiposity and aerobic fitness.

Ageing, a sedentary lifestyle, and obesity are associated with increased oxidative stress, while regular exercise is associated with an increased antioxidant capacity in trained skeletal muscles. Whether a higher aerobic fitness is associated with increased expression of antioxidant enzymes and their regulatory factors in skeletal muscle remains unknown. Although oestrogens could promote a higher antioxidant capacity in females, it remains unknown whether a sex dimorphism exists in humans regarding the antioxidant capacity of skeletal muscle. Thus, the aim was to determine the protein expression levels of the antioxidant enzymes SOD1, SOD2, catalase and glutathione reductase (GR) and their regulatory factors Nrf2 and Keap1 in 189 volunteers (120 males and 69 females) to establish whether sex differences exist and how age, VO2max and adiposity influence these. For this purpose, vastus lateralis muscle biopsies were obtained in all participants under resting and unstressed conditions. No significant sex differences in Nrf2, Keap1, SOD1, SOD2, catalase and GR protein expression levels were observed after accounting for VO2max, age and adiposity differences. Multiple regression analysis indicates that the VO2max in mL.kg LLM-1.min-1can be predicted from the levels of SOD2, Total Nrf2 and Keap1 (R = 0.58, P < 0.001), with SOD2 being the main predictor explaining 28 % of variance in VO2max, while Nrf2 and Keap1 explained each around 3 % of the variance. SOD1 protein expression increased with ageing in the whole group after accounting for differences in VO2max and body fat percentage. Overweight and obesity were associated with increased pSer40-Nrf2, pSer40-Nrf2/Total Nrf2 ratio and SOD1 protein expression levels after accounting for differences in age and VO2max. Overall, at the population level, higher aerobic fitness is associated with increased basal expression of muscle antioxidant enzymes, which may explain some of the benefits of regular exercise.

Determinants of the maximal functional reserve during repeated supramaximal exercise by humans: The roles of Nrf2/Keap1, antioxidant proteins, muscle phenotype and oxygenation.

When high-intensity exercise is performed until exhaustion a "functional reserve" (FR) or capacity to produce power at the same level or higher than reached at exhaustion exists at task failure, which could be related to reactive oxygen and nitrogen species (RONS)-sensing and counteracting mechanisms. Nonetheless, the magnitude of this FR remains unknown. Repeated bouts of supramaximal exercise at 120% of VO2max interspaced with 20s recovery periods with full ischaemia were used to determine the maximal FR. Then, we determined which muscle phenotypic features could account for the variability in functional reserve in humans. Exercise performance, cardiorespiratory variables, oxygen deficit, and brain and muscle oxygenation (near-infrared spectroscopy) were measured, and resting muscle biopsies were obtained from 43 young healthy adults (30 males). Males and females had similar aerobic (VO2max per kg of lower extremities lean mass (LLM): 166.7 ± 17.1 and 166.1 ± 15.6 ml kg LLM-1.min-1, P = 0.84) and anaerobic fitness (similar performance in the Wingate test and maximal accumulated oxygen deficit when normalized to LLM). The maximal FR was similar in males and females when normalized to LLM (1.84 ± 0.50 and 2.05 ± 0.59 kJ kg LLM-1, in males and females, respectively, P = 0.218). This FR depends on an obligatory component relying on a reserve in glycolytic capacity and a putative component generated by oxidative phosphorylation. The aerobic component depends on brain oxygenation and phenotypic features of the skeletal muscles implicated in calcium handling (SERCA1 and 2 protein expression), oxygen transport and diffusion (myoglobin) and redox regulation (Keap1). The glycolytic component can be predicted by the protein expression levels of pSer40-Nrf2, the maximal accumulated oxygen deficit and the protein expression levels of SOD1. Thus, an increased capacity to modulate the expression of antioxidant proteins involved in RONS handling and calcium homeostasis may be critical for performance during high-intensity exercise in humans.

Quantitative, Spectro-kinetic Analysis of Oxygen in Electron-Beam Sensitive, Multimetallic Oxide Nanostructures.

The oxygen stoichiometry of hollandite, KxMnO2-δ, nanorods has been accurately determined from a quantitative analysis of scanning-transmission electron microscopy (STEM) X-Ray Energy Dispersive Spectroscopy (XEDS) experiments carried out in chrono-spectroscopy mode. A methodology combining 3D reconstructions of high-angle annular dark field electron tomography experiments, using compressed-sensing algorithms, and quantification through the so-called ζ-factors method of XEDS spectra recorded on a high-sensitivity detector has been devised to determine the time evolution of the oxygen content of nanostructures of electron-beam sensitive oxides. Kinetic modeling of O-stoichiometry data provided K0.13MnO1.98 as overall composition for nanorods of the hollandite. The quantitative agreement, within a 1% mol error, observed with results obtained by macroscopic techniques (temperature-programmed reduction and neutron diffraction) validate the proposed methodology for the quantitative analysis, at the nanoscale, of light elements, as it is the case of oxygen, in the presence of heavy ones (K, Mn) in the highly compromised case of nanostructured materials which are prone to electron-beam reduction. Moreover, quantitative comparison of oxygen evolution data measured at macroscopic and nanoscopic levels allowed us to rationalize beam damage effects in structural terms and clarify the exact nature of the different steps involved in the reduction of these oxides with hydrogen.

Heterostructured Cobalt Silicide Nanocrystals: Synthesis in Molten Salts, Ferromagnetism, and Electrocatalysis.

Nanoscale heterostructures of covalent intermetallics should give birth to a wide range of interface-driven physical and chemical properties. Such a level of design however remains unattainable for most of these compounds, due to the difficulty to reach a crystalline order of covalent bonds at the moderate temperatures required for colloidal chemistry. Herein, we design heterostructured cobalt silicide nanoparticles to trigger magnetic and catalytic properties in silicon-based materials. Our strategy consists in controlling the diffusion of cobalt atoms into silicon nanoparticles, by reacting these particles in molten salts. By adjusting the temperature, we tune the conversion of the initial silicon particles toward homogeneous CoSi nanoparticles and core-shell nanoparticles made of a CoSi shell and a silicon-rich core. The increased interface-to-volume ratio of the CoSi component in the core-shell particles yields distinct properties compared to the bulk and homogeneous nanoparticles. First, the core-shell particles exhibit increased ferromagnetism, despite the bulk diamagnetic properties of cobalt monosilicide. Second, the core-shell nanoparticles act as efficient precatalysts for alkaline water oxidation, where the nanostructure is converted in situ into a layered cobalt silicon oxide/(oxy)hydroxide with high and stable oxygen evolution reaction (OER) electrocatalytic activity. This work demonstrates a route to design heterostructured nanocrystals of covalent intermetallic compounds and shows that these new structures exhibit very rich, yet poorly explored, interface-based physical properties and reactivity.

Characterization of Tunneled Wide Band Gap Mixed Conductors: The Na2O-Ga2O3-TiO2 System.

This article focuses on the Na2O-Ga2O3-TiO2 system, which is barely explored in the study of transparent conductive oxides (TCOs). NaxGa4+xTin-4-xO2n-2 (n = 5, 6, and 7 and x ≈ 0.7-0.8) materials were characterized using neutron powder diffraction and aberration-corrected scanning transmission electron microscopy. Activation energy, as a function of different structures depending on tunnel size, shows a significant improvement in Na+ ion conduction from hexagonal to octagonal tunnels. New insights into the relationship between the crystal structure and the transport properties of TCOs, which are crucial for the design and development of new optoelectronic devices, are provided.

A Mango Leaf Extract (Zynamite®) Combined with Quercetin Has Exercise-Mimetic Properties in Human Skeletal Muscle.

Zynamite PX®, a mango leaf extract combined with quercetin, enhances exercise performance by unknown molecular mechanisms. Twenty-five volunteers were assigned to a control (17 males) or supplementation group (8 males, receiving 140 mg of Zynamite® + 140 mg quercetin/8 h for 2 days). Then, they performed incremental exercise to exhaustion (IE) followed by occlusion of the circulation in one leg for 60 s. Afterwards, the cuff was released, and a 30 s sprint was performed, followed by 90 s circulatory occlusion (same leg). Vastus lateralis muscle biopsies were obtained at baseline, 20 s after IE (occluded leg) and 10 s after Wingate (occluded leg), and bilaterally at 90 s and 30 min post exercise. Compared to the controls, the Zynamite PX® group showed increased basal protein expression of Thr287-CaMKIIδD (2-fold, p = 0.007) and Ser9-GSK3ß (1.3-fold, p = 0.005) and a non-significant increase of total NRF2 (1.7-fold, p = 0.099) and Ser40-NRF2 (1.2-fold, p = 0.061). In the controls, there was upregulation with exercise and recovery of total NRF2, catalase, glutathione reductase, and Thr287-CaMKIIδD (1.2-2.9-fold, all p < 0.05), which was not observed in the Zynamite PX® group. In conclusion, Zynamite PX® elicits muscle signaling changes in resting skeletal muscle resembling those described for exercise training and partly abrogates the stress kinases responses to exercise as observed in trained muscles.

Tuning Magnetoconductivity in LaMnO3 NPs through Cationic Vacancy Control.

The inclusion of La-Mn vacancies in LaMnO3 nanoparticles leads to a noticeable change in conductivity behavior. The sample retains its overall insulator characteristic, with a typical thermal activation mechanism at high temperatures, but it presents high magnetoconductivity below 200 K. The activation energy decreases linearly with the square of the reduced magnetization and vanishes when the sample is magnetized at saturation. Therefore, it turns out that electron hopping between Mn3+ and Mn4+ largely contributes to the conductivity below the Curie temperature. The influence of the applied magnetic field on conductivity also supports the hypothesis of hopping contribution, and the electric behavior can be explained as being due to an increase in the hopping probability via spin alignment.

Molten Salts-Driven Discovery of a Polar Mixed-Anion 3D Framework at the Nanoscale: Zn4 Si2 O7 Cl2 , Charge Transport and Photoelectrocatalytic Water Splitting.

Mixed-anion compounds widen the chemical space of attainable materials compared to single anionic compounds, but the exploration of their structural diversity is limited by common synthetic paths. Especially, oxychlorides rely mainly on layered structures, which suffer from low stability during photo(electro)catalytic processes. Herein we report a strategy to design a new polar 3D tetrahedral framework with composition Zn4 Si2 O7 Cl2 . We use a molten salt medium to enable low temperature crystallization of nanowires of this new compound, by relying on tetrahedral building units present in the melt to build the connectivity of the oxychloride. These units are combined with silicon-based connectors from a non-oxidic Zintl phase to enable precise tuning of the oxygen content. This structure brings high chemical and thermal stability, as well as strongly anisotropic hole mobility along the polar axis. These features, associated with the ability to adjust the transport properties by doping, enable to tune water splitting properties for photoelectrocatalytic H2 evolution and water oxidation. This work then paves the way to a new family of mixed-anion solids.

Architectural anatomy of the human tibialis anterior presents morphological asymmetries between superficial and deep unipennate regions.

The tibialis anterior muscle plays a critical role in human ambulation and contributes to maintaining the upright posture. However, little is known about its muscle architecture in males and females. One hundred and nine physically active males and females were recruited. Tibialis anterior muscle thickness, pennation angle, and fascicle length were measured at rest in both unipennate regions of both legs using real-time ultrasound imaging. A linear mixed model was used with muscle thickness, pennation angle, or fascicle length as the dependent variables. All models were carried out with and without total leg lean mass and shank length as covariates. Causal mediation analysis was computed to explore the effect of muscle thickness on the relationship between fascicle length and pennation angle. There were no significant differences between dominant and nondominant legs regarding muscle architecture. Muscle thickness and pennation angle were greater in the deep than the superficial unipennate region in males (1.9 mm and 1.1°, p < 0.001) and women (3.4 mm and 2.2°, p < 0.001). However, the fascicle length was similar in both regions for both sexes. The differences remained significant after accounting for differences in leg lean mass and shank length. In both regions, muscle thickness was 1-3 mm greater in males and superficial pennation angle 2° smaller in females (both, p < 0.001). After accounting for leg lean mass and shank length, sex differences remained for muscle thickness (1.6 mm, p < 0.05) and pennation angle (3.4°, p < 0.001) but only in the superficial region. In both regions, leg lean mass and shank-adjusted fascicle length were 1.4 mm longer in females than males (p < 0.05). The causal mediation analysis revealed that the estimation of fascicle length was positive, suggesting that a 10% increase in muscle thickness would augment the fascicle length, allowing a 0.38° pennation angle decrease. Moreover, the pennation angle increases in total by 0.54° due to the suppressive effect of the increase in fascicle length. The estimated mediation, direct, and total effects were all significantly different from zero (p < 0.001). Overall, our results indicate that the architectural anatomy of the tibialis anterior shows sexual dimorphism in humans. Tibialis anterior presents morphological asymmetries between superficial and deep unipennate regions in both sexes. Lastly, our causal mediation model identified a suppressive effect of fascicle length on the pennation angle, suggesting that increments in muscle thickness are not always aligned with increments in fascicle length or the pennation angle.

Pulmonary ventilation and gas exchange during prolonged exercise in humans: Influence of dehydration, hyperthermia and sympathoadrenal activity.

NEW FINDINGS: What is the central question of the study? Ventilation increases during prolonged intense exercise, but the impact of dehydration and hyperthermia, with associated blunting of pulmonary circulation, and independent influences of dehydration, hyperthermia and sympathoadrenal discharge on ventilatory and pulmonary gas exchange responses remain unclear. What is the main finding and its importance? Dehydration and hyperthermia led to hyperventilation and compensatory adjustments in pulmonary CO2 and O2 exchange, such that CO2 output increased and O2 uptake remained unchanged despite the blunted circulation. Isolated hyperthermia and adrenaline infusion, but not isolated dehydration, increased ventilation to levels similar to combined dehydration and hyperthermia. Hyperthermia is the main stimulus increasing ventilation during prolonged intense exercise, partly via sympathoadrenal activation. ABSTRACT: The mechanisms driving hyperthermic hyperventilation during exercise are unclear. In a series of retrospective analyses, we evaluated the impact of combined versus isolated dehydration and hyperthermia and the effects of sympathoadrenal discharge on ventilation and pulmonary gas exchange during prolonged intense exercise. In the first study, endurance-trained males performed two submaximal cycling exercise trials in the heat. On day 1, participants cycled until volitional exhaustion (135 ± 11 min) while experiencing progressive dehydration and hyperthermia. On day 2, participants maintained euhydration and core temperature (Tc ) during a time-matched exercise (control). At rest and during the first 20 min of exercise, pulmonary ventilation ( V ̇ E ${\skew2\dot V_{\rm{E}}}$ ), arterial blood gases, CO2 output and O2 uptake were similar in both trials. At 135 ± 11 min, however, V ̇ E ${\skew2\dot V_{\rm{E}}}$ was elevated with dehydration and hyperthermia, and this was accompanied by lower arterial partial pressure of CO2 , higher breathing frequency, arterial partial pressure of O2 , arteriovenous CO2 and O2 differences, and elevated CO2 output and unchanged O2 uptake despite a reduced pulmonary circulation. The increased V ̇ E ${\skew2\dot V_{\rm{E}}}$ was closely related to the rise in Tc and circulating catecholamines (R2  ≥ 0.818, P ≤ 0.034). In three additional studies in different participants, hyperthermia independently increased V ̇ E ${\skew2\dot V_{\rm{E}}}$ to an extent similar to combined dehydration and hyperthermia, whereas prevention of hyperthermia in dehydrated individuals restored V ̇ E ${\skew2\dot V_{\rm{E}}}$ to control levels. Furthermore, adrenaline infusion during exercise elevated both Tc and V ̇ E ${\skew2\dot V_{\rm{E}}}$ . These findings indicate that: (1) adjustments in pulmonary gas exchange limit homeostatic disturbances in the face of a blunted pulmonary circulation; (2) hyperthermia is the main stimulus increasing ventilation during prolonged intense exercise; and (3) sympathoadrenal activation might partly mediate the hyperthermic hyperventilation.

Fast regulation of the NF-κB signalling pathway in human skeletal muscle revealed by high-intensity exercise and ischaemia at exhaustion: Role of oxygenation and metabolite accumulation.

The NF-κB signalling pathway plays a critical role in inflammation, immunity, cell proliferation, apoptosis, and muscle metabolism. NF-κB is activated by extracellular signals and intracellular changes in Ca2+, Pi, H+, metabolites and reactive oxygen and nitrogen species (RONS). However, it remains unknown how NF-κB signalling is activated during exercise and how metabolite accumulation and PO2 influence this process. Eleven active men performed incremental exercise to exhaustion (IE) in normoxia and hypoxia (PIO2:73 mmHg). Immediately after IE, the circulation of one leg was instantaneously occluded (300 mmHg). Muscle biopsies from m. vastus lateralis were taken before (Pre), and 10s (Post, occluded leg) and 60s after exercise from the occluded (Oc1m) and free circulation (FC1m) legs simultaneously together with femoral vein blood samples. NF-κB signalling was activated by exercise to exhaustion, with similar responses in normoxia and acute hypoxia, as reflected by the increase of p105, p50, IKKα, IκBß and glutathione reductase (GR) protein levels, and the activation of the main kinases implicated, particularly IKKα and CaMKII δD, while IKKß remained unchanged. Postexercise ischaemia maintained and stimulated further NF-κB signalling by impeding muscle reoxygenation. These changes were quickly reverted at the end of exercise when the muscles recovered with open circulation. Finally, we have shown that Thioredoxin 1 (Trx1) protein expression was reduced immediately after IE and after 1 min of occlusion while the protein expression levels of glutathione peroxidase 1 (Gpx1) and thioredoxin reductase 1 (TrxR1) remained unchanged. These novel data demonstrate that exercising to exhaustion activates NF-κB signalling in human skeletal muscle and regulates the expression levels of antioxidant enzymes in human skeletal muscle. The fast regulation of NF-κB at exercise cessation has implications for the interpretation of published studies and the design of new experiments.

The Role of Transmission Electron Microscopy in the Early Development of Mesoporous Materials for Tissue Regeneration and Drug Delivery Applications.

For the last 20 years, silica-based mesoporous materials have provided a sound platform for the development of biomedical technology applied to tissue engineering and drug delivery. Their unique structural and textural characteristics, chiefly, the ordered distribution of homogeneous and tunable pores with high surface areas and large pore volume, and their excellent biocompatibility provide an excellent starting point for bone tissue regeneration on the mesoporous surface, and also to load species of interest inside the pores. Adequate control of the synthesis conditions and functionalization of the mesoporous surface are critical factors in the design of new systems that are suitable for use in specific medical applications. Simultaneously, the use of appropriate characterization techniques in the several stages of design and manufacture of mesoporous particles allows us to ascertain the textural, structural and compositional modifications induced during the synthesis, functionalization and post-in vitro assays processes. In this scenario, the present paper shows, through several examples, the role of transmission electron microscopy and associated spectroscopic techniques in the search for useful information in the early design stages of mesoporous systems, with application in the fields of tissue regeneration and drug delivery systems.

Treatment of hypertension with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and resting metabolic rate: A cross-sectional study.

Hypertension in obese and overweight patients is associated with an elevated resting metabolic rate (RMR). The aim of this study was to determine whether RMR is reduced in hypertensive patients treated with angiotensin-converting enzyme inhibitors (ACEI) and blockers (ARB). The RMR was determined by indirect calorimetry in 174 volunteers; 93 (46.5 %) were hypertensive, of which 16 men and 13 women were treated with ACEI/ARB, while 30 men and 19 women with untreated hypertension served as a control group. Treated and untreated hypertensives had similar age, BMI, physical activity, and cardiorespiratory fitness. The RMR normalized to the lean body mass (LBM) was 15% higher in the untreated than ACEI/ARB-treated hypertensive women (p = .003). After accounting for LBM, whole-body fat mass, age, the double product (heart rate x systolic blood pressure), and the distance walked per day, the RMR was 2.9% lower in the patients taking ACEI/ARB (p = .26, treatment x sex interaction p = .005). LBM, age, and the double product explained 78% of the variability in RMR (R2  = 0.78, p < .001). In contrast, fat mass, the distance walked per day, and total T4 or TSH did not add predictive power to the model. Compared to men, a greater RMR per kg of LBM was observed in untreated hypertensive overweight and obese women, while this sex difference was not observed in patients treated with ACEI or ARBs. In conclusion, our results indicate that elevated RMR per kg of LBM may be normalized by antagonizing the renin-angiotensin system.

Angiotensin-Converting Enzyme 2 (SARS-CoV-2 receptor) expression in human skeletal muscle.

The study aimed to determine the levels of skeletal muscle angiotensin-converting enzyme 2 (ACE2, the SARS-CoV-2 receptor) protein expression in men and women and assess whether ACE2 expression in skeletal muscle is associated with cardiorespiratory fitness and adiposity. The level of ACE2 in vastus lateralis muscle biopsies collected in previous studies from 170 men (age: 19-65 years, weight: 56-137 kg, BMI: 23-44) and 69 women (age: 18-55 years, weight: 41-126 kg, BMI: 22-39) was analyzed in duplicate by western blot. VO2 max was determined by ergospirometry and body composition by DXA. ACE2 protein expression was 1.8-fold higher in women than men (p = 0.001, n = 239). This sex difference disappeared after accounting for the percentage of body fat (fat %), VO2 max per kg of legs lean mass (VO2 max-LLM) and age (p = 0.47). Multiple regression analysis showed that the fat % (ß = 0.47) is the main predictor of the variability in ACE2 protein expression in skeletal muscle, explaining 5.2% of the variance. VO2 max-LLM had also predictive value (ß = 0.09). There was a significant fat % by VO2 max-LLM interaction, such that for subjects with low fat %, VO2 max-LLM was positively associated with ACE2 expression while as fat % increased the slope of the positive association between VO2 max-LLM and ACE2 was reduced. In conclusion, women express higher amounts of ACE2 in their skeletal muscles than men. This sexual dimorphism is mainly explained by sex differences in fat % and cardiorespiratory fitness. The percentage of body fat is the main predictor of the variability in ACE2 protein expression in human skeletal muscle.

Atomic Resolution Electron Microscopy: A Key Tool for Understanding the Activity of Nano-Oxides for Biomedical Applications.

Transition metal oxides constitute one of the most fruitful sources of materials with continuously increasing potential applications prompted by the expectations derived from the reduction of the particle size. The recent advances in transmission electron microscopy, because of the development of lenses, have made it possible to reach atomic resolution, which can provide answers regarding the performance of the transition metal nano-oxides. This critical information is related not only to the ability to study their microstructural characteristics but also their local composition and the oxidation state of the transition metal. Exploring these features is a well-known task in nano-oxides for energy and electronic technologies, but they are not so commonly used for elucidating the activity of these oxides for biomedical applications. Nevertheless, the identification at the atomic level of a certain dopant or the unambiguous determination of the oxidation state of a transition metal in a nano-oxide can be important questions to be answered in a certain biomedical application. In this work, we provide several examples in transition metal nano-oxides to show how atomic-resolution electron microscopy can be a key tool for its understanding.

Functional reserve and sex differences during exercise to exhaustion revealed by post-exercise ischaemia and repeated supramaximal exercise.

KEY POINTS: Females have lower fatigability than males during single limb isometric and dynamic contractions, but whether sex-differences exist during high-intensity whole-body exercise remains unknown. This study shows that males and females respond similarly to repeated supramaximal whole-body exercise, and that at task failure a large functional reserve remains in both sexes. Using post-exercise ischaemia with repeated exercise, we have shown that this functional reserve depends on the glycolytic component of substrate-level phosphorylation and is almost identical in both sexes. Metaboreflex activation during post-exercise ischaemia and the O2 debt per kg of active lean mass are also similar in males and females after supramaximal exercise. Females have a greater capacity to extract oxygen during repeated supramaximal exercise and reach lower PETCO2 , experiencing a larger drop in brain oxygenation than males, without apparent negative repercussion on performance. Females had no faster recovery of performance after accounting for sex differences in lean mass. ABSTRACT: The purpose of this study was to ascertain what mechanisms explain sex differences at task failure and to determine whether males and females have a functional reserve at exhaustion. Exercise performance, cardiorespiratory variables, oxygen deficit, and brain and muscle oxygenation were determined in 18 males and 18 females (21-36 years old) in two sessions consisting of three bouts of constant-power exercise at 120% of V̇O2max until exhaustion interspaced by 20 s recovery periods. In one of the two sessions, the circulation of both legs was occluded instantaneously (300 mmHg) during the recovery periods. Females had a higher muscle O2 extraction during fatiguing supramaximal exercise than males. Metaboreflex activation, and lean mass-adjusted O2 deficit and debt were similar in males and females. Compared to males, females reached lower PETCO2 and brain oxygenation during supramaximal exercise, without apparent negative consequences on performance. After the occlusions, males and females were able to restart exercising at 120% of V̇O2max , revealing a similar functional reserve, which depends on glycolytic component of substrate-level phosphorylation and its rate of utilization. After ischaemia, muscle O2 extraction was increased, and muscle V̇O2 was similarly reduced in males and females. The physiological response to repeated supramaximal exercise to exhaustion is remarkably similar in males and females when differences in lean mass are considered. Both sexes fatigue with a large functional reserve, which depends on the glycolytic energy supply, yet females have higher oxygen extraction capacity, but reduced PETCO2 and brain oxygenation.