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Abstract Background The terminal stage of ischemic heart disease develops into heart failure (HF), which is characterized by hypoxia and metabolic disturbances in cardiomyocytes. The hypoxic failing heart triggers hypoxia-inducible factor-1α (HIF-1α) actions in the cells sensitized to hypoxia and induces metabolic adaptation by accumulating HIF-1α. Furthermore, soluble monocarboxylic acid transporter protein 1 (MCT1) and mitochondrial pyruvate carrier 1 (MPC1), as key nodes of metabolic adaptation, affect metabolic homeostasis in the failing rat heart. Aerobic exercise training has been reported to retard the progression of HF due to enhancing HIF-1α levels as well as MCT1 expressions, whereas the effects of exercise on MCT1 and MPC1 in HF (hypoxia) remain elusive. This research aimed to investigate the action of exercise associated with MCT1 and MPC1 on HF under hypoxia. Methods The experimental rat models are composed of four study groups: sham stented (SHAM), HF sedentary (HF), HF short-term exercise trained (HF-E1), HF long-term exercise trained (HF-E2). HF was initiated via left anterior descending coronary artery ligation, the effects of exercise on the progression of HF were analyzed by ventricular ultrasound (ejection fraction, fractional shortening) and histological staining. The regulatory effects of HIF-1α on cell growth, MCT1 and MPC1 protein expression in hypoxic H9c2 cells were evaluated by HIF-1α activatort/inhibitor treatment and plasmid transfection. Results Our results indicate the presence of severe pathological remodelling (as evidenced by deep myocardial fibrosis, increased infarct size and abnormal hypertrophy of the myocardium, etc.) and reduced cardiac function in the failing hearts of rats in the HF group compared to the SHAM group. Treadmill exercise training ameliorated myocardial infarction (MI)-induced cardiac pathological remodelling and enhanced cardiac function in HF exercise group rats, and significantly increased the expression of HIF-1α (p

IntroductionIn the evolving field of neurophysiological research, visual light flicker stimulation is recognized as a promising non-invasive intervention for cognitive enhancement, particularly in sleep-deprived conditions.MethodsThis study explored the effects of specific flicker frequencies (40 Hz and 20–30 Hz random flicker) on alertness recovery in sleep-deprived rats. We employed a multidisciplinary approach that included behavioral assessments with the Y-maze, in vivo electrophysiological recordings, and molecular analyses such as c-FOS immunohistochemistry and hormone level measurements.ResultsBoth 40 Hz and 20–30 Hz flicker significantly enhanced behavioral performance in the Y-maze test, suggesting an improvement in alertness. Neurophysiological data indicated activation of neural circuits in key brain areas like the thalamus and hippocampus. Additionally, flicker exposure normalized cortisol and serotonin levels, essential for stress response and mood regulation. Notably, increased c-FOS expression in brain regions related to alertness and cognitive functions suggested heightened neural activity.DiscussionThese findings underscore the potential of light flicker stimulation not only to mitigate the effects of sleep deprivation but also to enhance cognitive functions. The results pave the way for future translational research into light-based therapies in human subjects, with possible implications for occupational health and cognitive ergonomics.

Indoor space is the place where human beings live, and how to meet people's indoor thermal comfort needs in the context of energy scarcity is one of the important issues for sustainable development of buildings, and the evaluation of the indoor thermal environment has become the key to it. In the case of Japanese wood-framed detached houses, which contain different types of space forms, it is difficult to accurately apply the existing thermal environment evaluation results. In this study, detached houses in Kitakyushu City, Japan, were selected as the research object, and continuous measurements and subjective questionnaires of the indoor thermal environments were conducted based on three modes of no heating, continuous heating, and intermittent heating, in order to grasp the current information of the thermal comfort in detached houses. The results showed that: 1. The average indoor temperatures in both Washitsu and Yoshitsu were lower than the human thermal comfort range; 2. The thermally neutral temperature of 15.9 °C in Washitsu was lower than that of 17.7 °C in Yoshitsu, and the acceptable temperature zones were (14.3–17.5 °C) and (15.6–18.9 °C), respectively; 3. Develop modified models (PMVe) and adaptive predicted mean vote (aPMV) model suitable for thermal comfort evaluation of detached houses in Japan. The results of this study will help to improve the indoor thermal environment and thermal comfort evaluation system of Japanese detached houses, and provide a useful reference for the study of the renewal and renovation of houses in this area.

Abstract Purpose Acute kidney disease (AKD) is believed to be involved in the transition from acute kidney injury (AKI) to chronic kidney disease in general populations, but little is understood about this possibility among kidney surgical populations. This study aimed to elucidate the incidence of AKD after partial nephrectomy and risk factors that promote the AKI to AKD transition. Methods From January 2010 to January 2020, this study retrospectively collected a dataset of consecutive patients with renal masses undergoing partial nephrectomy in 4 urological centers. Cox proportional regression analyses were adopted to identify risk factors that promoted the AKI to AKD transition. To avoid overfitting, the results were then verified by logistic least absolute shrinkage and selection operator (LASSO) regression. A nomogram was then constructed and validated for AKI to AKD transition prediction. Results AKI and AKD occurred in 228 (21.4%) and 42 (3.9%) patients among a total of 1062 patients, respectively. In patients with AKI, multivariable Cox regression analysis and LASSO regression identified that age (HR 1.078, 1.029–1.112, p 30 min (HR 7.284, 2.210–23.999, p = 0.001), and intraoperative blood loss > 300ml (HR 8.641, 2.751–27.171, p

Nanocellulose is a sustainable resource that combines a modifiable surface with excellent mechanical strength. It has been increasingly applied to applications in different fields. Plant-based nanocellulose primarily contains cellulose nanocrystal and cellulose nanofibrils. This review summarizes the preparation methods for cellulose nanocrystal and cellulose nanofibrils that emerged from agricultural by-products. The different sorts of cellulose nanocrystal preparation methods that have been discussed include the inorganic acid hydrolysis method, organic acid hydrolysis method, ionic liquid method, deep eutectic solvent method, and so forth. Also, several methods of pretreatment and preparation of cellulose nanofibrils are characterized, encompassing the oxidation pretreatment represented by 2,2,6,6-tetramethylpiperidine-1-oxy radical oxidation and enzymatic pretreatment. The high pressure homogenization, fine grinding, high-strength ultrasound and high pressure microfluidization techniques are used to prepare cellulose nanofibrils. This review's objective is to offer a theoretical framework for the economical and environmentally responsible manufacturing of nanocellulose.

Abstract Alzheimer’s disease (AD) is a major subtype of neurodegenerative dementia caused by long-term interactions and accumulation of multiple adverse factors, accompanied by dysregulation of numerous intracellular signaling and molecular pathways in the brain. At the cellular and molecular levels, the neuronal cellular milieu of the AD brain exhibits metabolic abnormalities, compromised bioenergetics, impaired lipid metabolism, and reduced overall metabolic capacity, which lead to abnormal neural network activity and impaired neuroplasticity, thus accelerating the formation of extracellular senile plaques and intracellular neurofibrillary tangles. The current absence of effective pharmacological therapies for AD points to the urgent need to investigate the benefits of non-pharmacological approaches such as physical exercise. Despite the evidence that regular physical activity can improve metabolic dysfunction in the AD state, inhibit different pathophysiological molecular pathways associated with AD, influence the pathological process of AD, and exert a protective effect, there is no clear consensus on the specific biological and molecular mechanisms underlying the advantages of physical exercise. Here, we review how physical exercise improves crucial molecular pathways and biological processes associated with metabolic disorders in AD, including glucose metabolism, lipid metabolism, Aβ metabolism and transport, iron metabolism and tau pathology. How metabolic states influence brain health is also presented. A better knowledge on the neurophysiological mechanisms by which exercise improves AD metabolism can contribute to the development of novel drugs and improvement of non-pharmacological interventions.

How to make full use of geographical advantage to improve the indoor thermal environment of passive buildings in plateau area has become a hot topic, which is of great significance for building energy conservation and thermal engineering design of passive buildings. This study took a residential house in Lhasa, Tibetas as the research object, obtained indoor air temperature distribution through field measurement. A multiple regression model was used to explore the influence of outdoor meteorological factors on indoor thermal environment. Results showed that the temperature near the south window was the highest mostly higher than 16 °C, and the vertical temperature gradient was higher than 7.5 °C with the solar radiation and outdoor temperature gradually raised during daytime. Besides, the vertical temperature difference is less than 3 °C as the distance from the south window increases, and the air temperature gradually goes down. The standardized regression coefficient (Beta) illustrated that solar radiation has the greatest influence on the indoor thermal environment compared with the outdoor temperature. Therefore, for direct gain passive buildings in Tibetan areas, the potential of reasonably setting transparent heat generation structures to improve the indoor thermal environment is far greater than that of improving the thermal insulation of non-transparent enclosures.

In this paper, the effect of the magnetic field on the optical properties of cellulose nanocrystal (CNC) films with different surface groups was investigated. T-CNC with carboxyl groups on its surface was prepared from cellulose sulfate nanocrystals (S-CNC) by 2,2,6,6-tetramethylpiperidine-1-oxy radical (TEMPO) oxidation. Its basic structure was characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, and zeta potential. The effects of magnetic field on CNC films with different surface charges were observed in four modes: no magnetic field, vertical magnetic field, inclined magnetic field, and horizontal magnetic field. The results showed that T-CNC had carboxyl groups on its surface and S-CNC had sulfate groups on its surface. The absolute value of T-CNC potential was lower than that of S-CNC due to the different surface charges. The two kinds of CNC exhibited different self-assembly modes due to the difference in surface charges, in which T-CNC was concentric self-assembly and S-CNC was chiral nematic self-assembly, and the difference in self-assembly modes was not changed by the magnetic field. However, the arrangement of T-CNC and S-CNC in self-assembly process was affected by the magnetic field. With the different orientations of the magnetic field, the color of the two films was affected by the change in the arrangement of CNC. Among them, the vertical magnetic field had the most significant effect on the two kinds of CNC films, which could make the arrangement of CNC in the films more uniform and closer, thus improving the uniformity of film color. The color response of CNC self-assembled films with different surface groups under different magnetic fields lays a foundation for the subsequent regulation of CNC iridescent films and their application in the field of packaging.

The benefit of regular exercise on the heart has been well documented but the role of RNA m6A modification in exercise-induced cardiac remodelling remains largely unknown. In this study, the authors report that METTL14 plays an important role in RNA m6A modification in exercise-induced physiological cardiac hypertrophy.

Abstract Background Moderate physical exercise is conducive to the brains of healthy humans and AD patients. Previous reports have suggested that treadmill exercise plays an anti-AD role and improves cognitive ability by promoting amyloid clearance, inhibiting neuronal apoptosis, reducing oxidative stress level, alleviating brain inflammation, and promoting autophagy–lysosome pathway in AD mice. However, few studies have explored the relationships between the ubiquitin–proteasome system and proper exercise in AD. The current study was intended to investigate the mechanism by which the exercise-regulated E3 ubiquitin ligase improves AD. Methods Both wild type and APP/PS1 transgenic mice were divided into sedentary (WTC and ADC) and exercise (WTE and ADE) groups (n = 12 for each group). WTE and ADE mice were subjected to treadmill exercise of 12 weeks in order to assess the effect of treadmill running on learning and memory ability, Aβ plaque burden, hyperphosphorylated Tau protein and E3 ubiquitin ligase. Results The results indicated that exercise restored learning and memory ability, reduced Aβ plaque areas, inhibited the hyperphosphorylation of Tau protein activated PI3K/Akt/Hsp70 signaling pathway, and improved the function of the ubiquitin–proteasome system (increased UCHL-1 and CHIP levels, decreased BACE1 levels) in APP/PS1 transgenic mice. Conclusions These findings suggest that exercise may promote the E3 ubiquitin ligase to clear β-amyloid and hyperphosphorylated Tau by activating the PI3K/Akt signaling pathway in the hippocampus of AD mice, which is efficient in ameliorating pathological phenotypes and improving learning and memory ability.

Abstract Background Gut microbiota plays important roles in health maintenance and diseases. Physical exercise has been demonstrated to be able to modulate gut microbiota. However, the potential role of gut microbiome in exercise protection to myocardial infarction (MI) remains unclear. Results Here, we discovered exercise training ameliorated cardiac dysfunction and changed gut microbial richness and community structure post-MI. Moreover, gut microbiota pre-depletion abolished the protective effects of exercise training in MI mice. Furthermore, mice receiving microbiota transplants from exercised MI mice had better cardiac function compared to mice receiving microbiota transplants from non-exercised MI mice. Mechanistically, we analyzed metabolomics in fecal samples from exercised mice post-MI and identified 3-Hydroxyphenylacetic acid (3-HPA) and 4-Hydroxybenzoic acid (4-HBA), which could be applied individually to protect cardiac dysfunction post-MI and apoptosis through NRF2. Conclusions Together, our study provides new insights into the role of gut microbiome in exercise protection to MI, offers opportunities to modulate cardiovascular diseases by exercise, microbiome and gut microbiota-derived 3-HPA and 4-HBA. Video Abstract

Mitochondrial ORF of the 12S rRNA Type-C (MOTS-c) is a mitochondrial-derived peptide composed of 16 amino acids encoded by the 12S rRNA region of the mitochondrial genome. The MOTS-c protein is transferred to the nucleus during metabolic stress and directs the expression of nuclear genes to promote cell balance. Different tissues co-expressed the protein with mitochondria, and plasma also contained the protein, but its level decreased with age. In addition, MOTS-c has been shown to improve glucose metabolism in skeletal muscle, which indicates its benefits for diseases such as diabetes, obesity, and aging. Nevertheless, MOTS-c has been used less frequently in disease treatment, and no effective method of applying MOTS-c in the clinic has been developed. Throughout this paper, we discussed the discovery and physiological function of mitochondrial-derived polypeptide MOTS-c, and the application of MOTS-c in the treatment of various diseases, such as aging, cardiovascular disease, insulin resistance, and inflammation. To provide additional ideas for future research and development, we tapped into the molecular mechanisms and therapeutic potentials of MOTS-c to improve diseases and combined the technology with synthetic biology in order to offer a new approach to its development and application.

Despite being one of the greatest global challenges for health and social care in the 21st century, Alzheimer’s disease (AD) lacks specific medicine. Irisin, an exercise-generated muscle factor, emerges as a potential hormone for AD prevention and treatment because of its role in promoting the browning of white adipose tissue, accelerating energy expenditure, regulating energy metabolism, and improving insulin resistance. The study reviews classic hallmarks of AD and irisin’s physiology before discussing the possible mechanism by which irisin protects against AD in terms of its effects related to molecular biology and cellular biology. Results reveal that irisin sharpens learning memory by inducing the production of brain-derived neurotrophic factor (BDNF), lowers the production of inflammatory factors, protects neurology through astrocytes, and ameliorates AD symptoms by improving insulin resistance. The review aims to facilitate future experimental studies and clinical applications of irisin in preventing and treating AD.

Rhythmic light flickers have emerged as useful tools to modulate cognition and rescue pathological oscillations related to neurological disorders by entrainment. However, a mechanistic understanding of the entrainment for different brain oscillatory states and light flicker parameters is lacking. To address this issue, we proposed a biophysical neural network model for thalamocortical oscillations (TCOs) and explored the stimulation effects depending on the thalamocortical oscillatory states and stimulation parameters (frequency, intensity, and duty cycle) using the proposed model and electrophysiology experiments. The proposed model generated alpha, beta, and gamma oscillatory states (with main oscillation frequences at 9, 25, and 35 Hz, respectively), which were successfully transmitted from the thalamus to the cortex. By applying light flicker stimulation, we found that the entrainment was state-dependent and it was more prone to induce entrainment if the flicker perturbation frequency was closer to the endogenous oscillatory frequency. In addition, endogenous oscillation would be accelerated, whereas low-frequency oscillatory power would be suppressed by gamma (30–50 Hz) flickers. Notably, the effects of intensity and duty cycle on entrainment were complex; a high intensity of light flicker did not mean high entrainment possibility, and duty cycles below 50% could induce entrainment easier than those above 50%. Further, we observed entrainment discontinuity during gamma flicker stimulations with different frequencies, attributable to the non-linear characteristics of the network oscillations. These results provide support for the experimental design and clinical applications of the modulation of TCOs by gamma (30–50 Hz) light flicker.

Abstract Air pollution, via ambient PM2.5, is a big threat to public health since it associates with increased hospitalisation, incidence rate and mortality of cardiopulmonary injury. However, the potential mediators of pulmonary injury in PM2.5‐induced cardiovascular disorder are not fully understood. To investigate a potential cross talk between lung and heart upon PM2.5 exposure, intratracheal instillation in vivo, organ culture ex vivo and human bronchial epithelial cells (Beas‐2B) culture in vitro experiments were performed respectively. The exposed supernatants of Beas‐2B were collected to treat primary neonatal rat cardiomyocytes (NRCMs). Upon intratracheal instillation, subacute PM2.5 exposure caused cardiac dysfunction, which was time‐dependent secondary to lung injury in mice, thereby demonstrating a cross‐talk between lungs and heart potentially mediated via small extracellular vesicles (sEV). We isolated sEV from PM2.5‐exposed mice serum and Beas‐2B supernatants to analyse the change of sEV subpopulations in response to PM2.5. Single particle interferometric reflectance imaging sensing analysis (SP‐IRIS) demonstrated that PM2.5 increased CD63/CD81/CD9 positive particles. Our results indicated that respiratory system‐derived sEV containing miR‐421 contributed to cardiac dysfunction post‐PM2.5 exposure. Inhibition of miR‐421 by AAV9‐miR421‐sponge could significantly reverse PM2.5‐induced cardiac dysfunction in mice. We identified that cardiac angiotensin converting enzyme 2 (ACE2) was a downstream target of sEV‐miR421, and induced myocardial cell apoptosis and cardiac dysfunction. In addition, we observed that GW4869 (an inhibitor of sEV release) or diminazene aceturate (DIZE, an activator of ACE2) treatment could attenuate PM2.5‐induced cardiac dysfunction in vivo. Taken together, our results suggest that PM2.5 exposure promotes sEV‐linked miR421 release after lung injury and hereby contributes to PM2.5‐induced cardiac dysfunction via suppressing ACE2.

Circular RNAs take crucial roles in several pathophysiological processes. The regulatory role and its underlying mechanisms of circ-ZNF609 in the heart remains largely unknown. Here, we report that circ-ZNF609 is upregulated during myocardial ischemia/reperfusion (I/R) remodeling. Knockdown of circ-ZNF609 protects against acute I/R injury and attenuates left ventricle dysfunction after I/R remodeling in vivo. In vitro, circ-ZNF609 regulates cardiomyocyte survival and proliferation via modulating the crosstalk between Hippo-YAP and Akt signaling. Mechanically, N6-methyladenosine-modification is involved in the regulatory role of circ-ZNF609 on YAP. An in-depth study indicates that knockdown of circ-ZNF609 decreases the expression of YTHDF3 and further fine-tuned the accessibility of Yap mRNA to YTHDF1 and YTHDF2 to regulate YAP expression. circ-ZNF609 knockdown represents a promising therapeutic strategy to combat the pathological process of myocardial I/R injury.

Irisin, as one of the myokines induced by exercise, has attracted much attention due to its important physiological functions such as white fat browning, the improvement in metabolism, and the alleviation of inflammation. Despite the positive role that irisin has been proven to play in the prevention and treatment of cardiovascular diseases, whether it can become a biomarker and potential target for predicting and treating cardiovascular diseases remains controversial, given the unreliability of its detection methods, the uncertainty of its receptors, and the species differences between animals and humans. This paper was intended to review the role of irisin in the diagnosis and treatment of cardiovascular diseases, the potential molecular mechanism, and the urgent problems to be solved in hopes of advancing our understanding of irisin as well as providing data for the development of new and promising intervention strategies by discussing the causes of contradictory results.

Hypoxia at high-altitude leads to osteoporosis. Resveratrol (RES), as an antioxidant, has been reported to promote osteoblastogenesis and suppress osteoclastogenesis. However, the therapeutic effect of RES against osteoporosis induced by high-altitude hypoxia remains unclear. Thus, this study was intended to investigate the potential effects of RES on high-altitude hypoxia-induced osteoporosis both in vivo and in vitro. Male Wistar rats were given RES (400 mg/kg) once daily for nine weeks under hypoxia, while the control was allowed to grow under normoxia. Bone mineral density (BMD), the levels of bone metabolism-related markers, and the changes on a histological level were measured. Bone marrow-derived mesenchymal stem cells (BMSCs) and RAW264.7 were incubated with RES under hypoxia, with a control growing under normoxia, followed by the evaluation of proliferation and differentiation. The results showed that RES inhibited high-altitude hypoxia-induced reduction in BMD, enhanced alkaline phosphatase (ALP), osteocalcin (OCN), calcitonin (CT) and runt-related transcription factor 2 (RUNX2) levels, whereas it reduced cross-linked carboxy-terminal telopeptide of type I collagen (CTX-I) levels and tartrate-resistant acid phosphatase (TRAP) activity in vivo. In addition, RES attenuated histological deteriorations in the femurs. In vitro, RES promoted osteoblastogenesis and mineralization in hypoxia-exposed BMSCs, along with promotion in RUNX2, ALP, OCN and osteopontin (OPN) levels, and inhibited the proliferation and osteoclastogenesis of RAW264.7. The promotion effects of RES on osteoblastogenesis were accompanied by the down-regulation of reactive oxygen species (ROS) and hypoxia inducible factor-1α (HIF-1α) induced by hypoxia. These results demonstrate that RES can alleviate high-altitude hypoxia-induced osteoporosis via promoting osteoblastogenesis by suppressing the ROS/HIF-1α signaling pathway. Thus, we suggest that RES might be a potential treatment with minimal side effects to protect against high-altitude hypoxia-induced osteoporosis.

This paper aims to provide data support for rural sustainable development through analyzing the spatio-temporal characteristics of the interactions of the outdoor thermal environment. The ordinary and representative rural settlements in the Guanzhong area were selected to analyze the dynamic process of the rural thermal environment through field measurements and numerical simulations. RMSE (root mean square error) and MAPE (mean absolute percentage) were used to verify the numerical simulation model, and physiological equivalent temperature (PET) was used to evaluate the outdoor thermal environment. Results show that the ENVI-met model reliably predicts the thermal environment of a rural settlement, as the air temperature and relative humidity values range of the RMSE and MAPE were 0.85–1.79 and 2.04–5.11%, respectively. Moreover, the air temperature rose by 3.08% and relative humidity dropped by 4.42% from 2003 to 2018 as the amount of artificial surfaces increased by 35.4% and the PET index gradually increased by 27.43% at daytime and 34.03% at nighttime. Furthermore, trees could improve the outdoor thermal environment significantly, mainly because the average air temperature decreased by 3.6% and relative humidity increased by 8%, and the PET index decreased by 12.4% and 13.1%, respectively, for daytime and nighttime. This case study is representative of rural settlements in the Guanzhong plain, and thus is an appeal to rural planners to pay attention to the thermal environment issues caused by increased artificial underlay surfaces and to focus on trees in rural areas.

Backgrounds: Numerous studies have revealed that hypobaric hypoxia exposure elicited imbalance of homeostasis. However, the effects of intermittent hypobaric hypoxia (IHH) exposure on the female reproductive system have been rarely reported. This study aims to assess the effects of IHH on rat female reproductive system and explore the corresponding mechanism at the histological, endocrine and molecular levels. Methods: The female rats were randomly divided into control and IHH groups. Multiple pathophysiological parameters, including body weight gain, organ coefficients, estrus cycle, and health signs were measured. Also, the reproductive hormones, hormone receptor mRNA expression and oxidant/antioxidant level were evaluated. Results: Significant increases of the heart, liver and lung coefficients were observed after IHH exposure. There were no statistically significant differences in ovarian and uterine coefficients, but changes were found in the morphology of the ovary and uterus. Additionally, the diestrus phase duration was significantly increased during IHH exposure. Furthermore, estrogen increased and the Luteinizing hormone and progesterone decreased after IHH exposure. Altered expression of ER, PR and LHR were also found in the IHH exposed rats. Importantly, IHH exposure significantly repressed the activities of GSH-Px and T-SOD and improved the contents of MDA. Conclusions: Our results evince that IHH exposure caused estrus cycle irregularity. IHH induced oxidative stress along with ovarian and uterine structure damages, reproductive hormone disturbances and unusual expression of hormone receptors, thus suggesting a potential mechanism underlying IHH-induced reproductive system dysfunction.

Circulating microRNAs (miRNAs, miRs) have great potential as cardiac biomarkers and they are also being explored for their roles in intercellular communication and gene expression regulation. The analysis of circulating miRNAs in response to exercise would provide a deeper understanding of the molecular response to physical activity and valuable information for clinical practice. Here, eight male college students were recruited to participate in cardiopulmonary exercise testing (CPET) and 1 h acute exercise training (AET). Blood samples were collected and serum miRNAs involved in angiogenesis, inflammation and enriched in muscle and/or cardiac tissues were analyzed before and after cardiopulmonary exercise and acute exercise. The miRNAs we detected were miR-1, miR-20a, miR-21, miR-126, miR-133a, miR-133b, miR-146, miR155, miR-208a, miR-208b, miR-210, miR-221, miR-222, miR-328, miR-378, miR-499, and miR-940. We found that serum miR-20a was decreased significantly after CPET and serum miR-21 was increased after AET. In addition, no robust correlation was identified between the changes of these miRNAs and makers of cardiac function and exercise capacity, which indicates a distinct adaptation of these miRNAs to exercise. Future studies are highly needed to define the potential use of these circulating miRNAs as useful biomarkers of exercise training, and disclose the biological function of circulating miRNAs as physiological mediators of exercise-induced cardiovascular adaptation.

The spectral radius minimization problem (SRMP), which aims to minimize the spectral radius of a network by deleting a given number of edges, turns out to be crucial to containing the prevalence of an undesirable object on the network. As the SRMP is NP-hard, it is very unlikely that there is a polynomial-time algorithm for it. As a result, it is proper to focus on the development of effective and efficient heuristic algorithms for the SRMP. For that purpose, it is appropriate to gain insight into the pattern of an optimal solution to the SRMP by means of checking some regular networks. Hypercubes are a celebrated class of regular networks. This paper empirically studies the SRMP for hypercubes with two/three/four missing edges. First, for each of the three subproblems of the SRMP, a candidate for the optimal solution is presented. Second, it is shown that the candidate is optimal for small-sized hypercubes, and it is shown that the proposed candidate is likely to be optimal for medium-sized hypercubes. The edges in each candidate are evenly distributed over the network, which may be a common feature of all symmetric networks and hence is instructive in designing effective heuristic algorithms for the SRMP.