Professor Shi Zhou

Background
Intermittent hypoxia intervention (IHI) has been shown to reduces blood glucose and improves insulin resistance in type 2 diabetes (T2D) and has been suggested as a complementary or alternative intervention to exercise for individuals with limited mobility. Previous research on IHI has assessed cellular glucose uptake rather than utilization. The purpose of this study was to determine the effect of a 4-week IHI, with or without an aerobic exercise, on skeletal muscle glucose utilization as indicated by the changes in pyruvate, lactate, NAD+, and NADH, using a mouse model of diet-induced T2D. In addition, the effects of one exposure to hypoxia (acute) and of a 4-week IHI (chronic) were compared to explore their relationship.

Methods
C57BL/6J mice were randomly assigned to normal control and high-fat-diet groups, and the mice that developed diet-induced diabetes were assigned to diabetes control, and intervention groups with 1 hour (acute) or 4 weeks (1 hour/day, 6 days/week) exposure to a hypoxic envrionment (0.15 FiO2), exercise (treadmill run) in normoxia, and exercise in hypoxia, respectively, with N = 7 in each group. The effects of the interventions on concentrations of fasting blood glucose, muscle glucose, GLUT4, lactate, pyruvate, nicotinamide adenine dinucleotide (NAD+), and NADH were measured, and statistically compared between the groups.

Results
Compared with diabetes control group, the mice treated in the hypoxic environment for 4 weeks showed a significantly higher pyruvate levels and lower lactate/pyruvate ratios in the quadriceps muscle, and the mice exposed to hypoxia without or with aerobic exercise for either for 4 weeks or just 1 hour showed higher NAD+ levels and lower NADH/NAD+ ratios.

Conclusions
Exposure to moderate hypoxia for either one bout or 4 weeks significantly increased the body’s mitochondrial NAD cyclethe in diabetic mice even in the absence of aerobic exercise. The hypoxia and exercise interventions exhibited synergistic effects on glycolysis. These findings provide mechanistic insights into the effects of IHI in respect of the management of hyperglycemia.

Pathological features of Alzheimer's Disease (AD) include alterations in the structure and function of neurons as well as of myelin sheaths. Accumulated evidence shows that aerobic type of exercise can enhance neuroplasticity in mouse models of AD. However, whether and how aerobic exercise can affect myelin sheath repair and neuroprotection in the AD models remains unclear. In this study we tested the hypotheses that 1) myelin structural alterations in 3xTg-AD mice would be related to abnormalities in oligodendrocyte lineage cells, resulting in impaired learning and memory, and 2) a 6-month aerobic exercise intervention would have beneficial effects on such alterations. Two-month-old male 3xTg-AD mice were randomly assigned to a control (AC) or an exercise (AE) group, and age-matched male C57BL/6;129 mice were also randomly assigned to a normal control (NC) or an exercise (NE) group, with n = 12 in each group. Mice in the exercise groups were trained on a motor-drive treadmill, 60 min per day, 5 days per week for 6 months. Cognitive function was assessed at the end of the intervention period. Then, brain specimens were obtained for assessments of morphological and oligodendrocyte lineage cell changes. The results of electron microscopy showed that myelin ultrastructure demonstrated a higher percentage of loose and granulated myelin sheath around axons in the temporal lobe in the AC, as compared with the NC group, along with greater cognitive dysfunction at 8-months of age. These differences were accompanied by significantly greater myelin basic protein (MBP) expression and less neuron-glial antigen-2 (NG2) protein and mRNA levels in the AC, compared to the NC. However, there were no significant between-group differences in the G-ratio (the ratio of axon diameter to axon plus myelin sheath diameter) and 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNPase) protein and mRNA levels. The aerobic exercise ameliorated cognitive deterioration and appeared to keep components of myelin sheath and oligodendrocyte precursor cells stabilized, resulting in a decrease in the percentage of loose and granulated myelin sheath and MBP protein, and an increase in NG2 protein and mRNA levels in the AE group. Therefore, the 6-month exercise intervention demonstrated beneficial effects on myelin lesions, abnormal differentiation of oligodendrocytes and general brain function in the 3xTg-AD mice, providing further insights into the role of aerobic exercise in management of neurodegeneration in AD by maintaining intact myelination.

It is known that resistance exercise using one limb can affect motor function of both the exercised limb and the unexercised contralateral limb, a phenomenon termed cross-education. It has been suggested that cross-education has clinical implications, e.g. in rehabilitation for orthopaedic conditions or post-stroke paresis. Much of the research on the contralateral effect of unilateral intervention on motor output is based on voluntary exercise. This scoping review aimed to map the characteristics of current literature on the cross-education caused by three most frequently utilised peripheral neuromuscular stimulation modalities in this context: electrical stimulation, mechanical vibration and percutaneous needling, that may direct future research and translate to clinical practice. A systematic search of relevant databases (Ebsco, ProQuest, PubMed, Scopus, Web of Science) through to the end of 2020 was conducted following the PRISMA Extension for Scoping Review. Empirical studies on human participants that applied a unilateral peripheral neuromuscular stimulation and assessed neuromuscular function of the stimulated and/or the unstimulated side were selected. By reading the full text, the demographic characteristics, context, design, methods and major findings of the studies were synthesised. The results found that 83 studies were eligible for the review, with the majority (53) utilised electrical stimulation whilst those applied vibration (18) or needling (12) were emerging. Although the contralateral effects appeared to be robust, only 31 studies claimed to be in the context of cross-education, and 25 investigated on clinical patients. The underlying mechanism for the contralateral effects induced by unilateral peripheral stimulation remains unclear. The findings suggest a need to enhance the awareness of cross-education caused by peripheral stimulation, to help improve the translation of theoretical concepts to clinical practice, and aid in developing well-designed clinical trials to determine the efficacy of cross-education therapies.

The reactive oxygen species (ROS) produced during exercise act as a double-edged sword because they may cause oxidative damage but also play a role in the signaling pathways. A supplementation of exogenous antioxidants can reduce the total amount of ROS during exercise while it may also affect the ROS’ role in the signaling pathways of mitochondrial biogenesis. It has been suggested that hydrogen gas, as an antioxidant, can selectively scavenge hydroxyl radicals but does not affect superoxide anion’s signal transduction. The aim of this study was to compare the effects of 1-h hydrogen gas inhalation 30min prior to a treadmill exercise on the key biomarkers of mitochondrial biogenesis and related signaling pathways, and the activities of endogenous antioxidant enzymes, with those of vitamin C, in the rat skeletal muscle. Eighty-one 8-week-old male Sprague–Dawley (SD) rats were randomly assigned to three interventions (exercise-only, exercise+4%H2, and exercise+vitamin C at 500mg/kg weight, with 27 rats under each intervention), and sampled at pre-, immediately post and 4h post a 60-min treadmill exercise at speed of 27m/min and flat inclination, with nine rats in each sub-group. Expression of mitochondrial biogenetic markers and related signaling molecules in gastrocnemius muscle, and concentrations of oxidative stress markers in serum were measured. Two-way ANOVA or Kruskal–Wallis analyses showed that both hydrogen inhalation and vitamin C supplementation significantly reduced serum levels of MDA immediately after exercise and AGEs 4h after exercise. The pre-exercise supplement of vitamin C significantly reduced mitochondrial complex IV concentrations and PGC-1α, NRF-1, TFAM gene expression levels compared to the pre-exercise group, but the hydrogen gas intervention did not result in a reduction in these measurements. Unlike vitamin C, hydrogen inhalation did not blunt post-exercise mitochondrial biogenetic signals, but resulted in an increase in complex IV concentration, activation of PGC-1α, and TFAM and NRF-2 gene transcription, and up-regulation of PGC-1α protein expression. The findings indicated that hydrogen gas inhalation could play the role as an effective antioxidant in response to the exercise, whilst it did not significantly affect mitochondrial biogenesis. The dose–response relationship and antioxidant effects in different types of exercise for hydrogen inhalation require further investigation.

High prevalence of physical inactivity and obesity in children and adolescents has become a global problem. This systematic review aimed to examine the existing literature regarding the factors that influence participation in physical activity (PA) in children and adolescents with reference to the social ecological model (SEM) proposed by McLeroy et al. (1988). The SEM provides a framework under which the influencing factors are categorized into five levels: intrapersonal, interpersonal, organizational, community, and public policy. A systematic search of relevant literature published before July 2020 was conducted through Ebsco, ProQuest, PubMed Central, Scopus, and Web of Science. A total of fourteen studies met the inclusion criteria. The selected articles were all of high quality as assessed using the Mixed Methods Appraisal Tool (2018). The results indicated that gender, age, ethnicity, and self-concept were the most common influencing factors at the intrapersonal level. At the interpersonal and organization levels, supports from friends, parents, and teachers were positive predictors of students' PA participation. Accessibility of facilities and safe neighborhoods was a crucial factor that influenced children and adolescents' participation in PA at the community level. Future studies on the effective types of policies or practices that could successfully promote facilities' accessibility and improve neighborhood safety are required. The outcomes of this systematic review are expected to inform practice and support the development and implementation of sound policies for the promotion of PA participation in children or adolescents from a comprehensive social ecological viewpoint.

The objectives of this study were to compare the antidepressant effects between endurance and resistance exercise for optimizing interventions and examine the metabolomic changes in different types of skeletal muscles in response to the exercise, using a rat model of chronic unpredictable mild stress (CUMS)-induced depression. There were 32 male Sprague-Dawley rats randomly divided into a control group (C) and 3 experimental groups: CUMS control (D), endurance exercise (E), and resistance exercise (R). Group E underwent 30 min treadmill running, and group R performed 8 rounds of ladder climbing, 5 sessions per week for 4 weeks. Body weight, sucrose preference, and open field tests were performed pre and post the intervention period for changes in depressant symptoms, and the gastrocnemius and soleus muscles were sampled after the intervention for metabolomic analysis using the

Physical inactivity is identified by the World Health Organisation as the fourth risk factor for global mortality and has major implications on the prevalence of non-communicable diseases and general health of the populations. There has been substantial evidence indicating that adequate levels of physical activity, such as prescribed exercise, can be an effective intervention for prevention and treatment of many chronic health conditions, as well as for improvement of mental health, quality of life and well-being. Many countries in the world have developed policies and guidelines for promotion of participation in physical activity and application of prescribed exercise as a means of intervention for chronic health conditions. Subsequently, the roles of exercise professionals in the community and health care system who provide services to the general community members, individuals with various health conditions, as well as elite athletes, and their professional training, qualifications and standards need to be defined and implemented.
This article provides a preliminary comparison of the exercise professionals and their current roles in the community and health care systems between Australia and China (including mainland, Taiwan and Hong Kong, as they have different health care systems), aiming to promote the recognition of exercise professionals in the health care systems, and facilitate the global development of the exercise-related professions, for a healthier world.

The aim of this systematic review is to analyse the current evidence reported in the literature on the efficacy of resting in normobaric hypoxia as a potential intervention for patients with impaired fasting blood glucose. Available databases was searched, under the PRISMA guidelines, throughout to the end of August 2017. A total of four empirical studies (out of 3281 filtered) were identified as eligible for the review. Two studies were on the acute effects of one-hour exposure to moderate hypoxia, and reported a reduction of blood glucose by 0.74 to 2.1 mM. The other two studies were on the effects of repeated exposure with nine to ten sessions in two to three weeks, however did not shown sustained decrease in fasting blood glucose. These studies employed selfcontrolled design with relatively small numbers of participants (n= 6-18). Similar findings were also reported in studies on the effects of exercising in hypoxia with single bout or several weeks of intervention. Further research, particularly randomised controlled clinical trials, is required to determine the efficacy and hormetic dosage range of long-term IH intervention for pre-diabetes and type 2 diabetes, and to elucidate the underlying mechanisms of the treatment effects.

Aims: The aims of this study were to determine the effects of four weeks of intermittent exposure to a moderate hypoxia environment (15% oxygen), and compare with the effects of exercise in normoxia or hypoxia, on glucose homeostasis, insulin sensitivity, GLUT4 translocation, insulin receptor phosphorylation, Akt-dependent GSK3 phosphorylation and Akt activity in skeletal muscle of obese mice with type 2 diabetes.
Methods: C57BL/6J mice that developed type 2 diabetes with a high-fat-diet (55% fat) (fasting blood glucose, FBG = 13.9 ± 0.69 (SD) mmol/L) were randomly allocated into diabetic control (DC), rest in hypoxia (DH), exercise in normoxia (DE), and exercise in hypoxia (DHE) groups (n = 7, each), together with a normal-diet (4% fat) control group (NC, FBG = 9.1 ± 1.11 (SD) mmol/L). The exercise groups ran on a treadmill at intensities of 75-90% VO2max. The interventions were applied one hour per day, six days per week for four weeks. Venous blood samples were analysed for FBG, insulin (FBI) and insulin sensitivity (QUICKI) pre and post the intervention period. The quadriceps muscle samples were collected 72 hours post the last intervention session for analysis of GLUT4 translocation, insulin receptor phosphorylation, Akt expression and phosphorylated GSK3 fusion protein by western blot. Akt activity was determined by the ratio of the phosphorylated GSK3 fusion protein to the total Akt protein.
Results: The FBG of the DH, DE and DHE groups returned to normal level (FBG = 9.4 ± 1.50, 8.86 ± 0.94 and 9.0 ± 1.13 (SD) mmol/L for DH, DE and DHE respectively, P < 0.05), with improved insulin sensitivity compared to DC (P < 0.05), after the four weeks treatment, while the NC and DC showed no significant changes, as analysed by general linear model with repeated measures. All three interventions resulted in a significant increase of GLUT4 translocation to cell membrane compared to the DC group (P < 0.05). The DE and DH showed a similar level of insulin receptor phosphorylation compared with NC that was significantly lower than the DC (P < 0.05) post intervention. The DH and DHE groups showed a significantly higher Akt activity compared to the DE, DC and NC (P < 0.05) post intervention, as analysed by one-way ANOVA.
Conclusions: This study produced new evidence that intermittent exposure to mild hypoxia (0.15 FiO2) for four weeks resulted in normalisation of FBG, improvement in whole body insulin sensitivity, and a significant increase of GLUT4 translocation in the skeletal muscle, that were similar to the effects of exercise intervention during the same time period, in mice with diet-induced type 2 diabetes. However, exercise in hypoxia for four weeks did not have additive effects on these responses. The outcomes of the research may contribute to the development of effective, alternative and complementary interventions for management of hyperglycaemia and type 2 diabetes, particularly for individuals with limitations in participation of physical activity.

The aim of this study was to determine whether unilateral manual needling at nonacupoints could result in bilateral strength gain similar to that found in electroacupuncture at specific acupoints. Fifty healthy male volunteers with an age range of 19–27 years were recruited and randomly allocated into five groups: (1) manual acupuncture and (2) electroacupuncture at two acupoints (ST-36 and ST-39); (3) manual acupuncture and (4) electroacupuncture at two nonacupoints on the tibialis anterior muscle; and (5) control group. The intervention groups received needling in each session on the right leg for 15 minutes in Week 1, 20 minutes in Week 2, and 30 minutes in Weeks 3–8, three sessions per week. The maximal isometric ankle dorsiflexion strength and muscle activation (as determined by twitch interpolation) of both legs were assessed pre, post, 2 weeks post, and 3 weeks post the experimental period. Mixed models (linear) with repeated-measures analysis identified significant strength gains (p < 0.01) after the intervention period in both limbs, while no significant differences were detected between the intervention groups and between the two legs, and no change was found in the control group. A significant improvement in muscle activation (p < 0.01) was also observed in both legs in the intervention groups. It was concluded that both unilateral manual and electric needling caused significant bilateral strength gain, and this effect was not specific to the selected acupoints or electric stimulation. The strength gain was sustained for at least 3 weeks after the 8-week intervention.