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Objective To compare the effects of chronic intermittent hypoxia exposure on different fiber types of muscle and investigate its possible mechanism. Methods Sixteen SD rats were randomly divided into normoxia control group (C group, placed in a normoxic chamber) and chronic intermittent hypoxia group (H group, placed in a hypoxic chamber with an oxygen concentration of 12.4%, 8 h per day, for 4 weeks). Their body mass was weighed during the intervention, and the grasping force and lean body mass were tested after the intervention. The wet masses of soleus muscle (SOL) and musculi tibialis anterior (TA), muscle fiber cross-sectional area (FCSA) were measured. The protein levels of puromycin (Puro) and ubiquitin (Ub) were detected with Western blotting. RNA sequencing was carried out for TA tissues to screen the differential genes between the 2 groups. And the biological process and pathways enriched by these differential genes were analyzed. Results ① During the intervention, the body mass of the C and H groups continued to increase, but it of the H group was always lower than that of the C group at each time point. The intervention also resulted in the decreases in the lean body mass and its percentage, grasping force and relative grasping force in the H group than the C group, but there were no statistical differences. ② The wet mass of TA was significantly lower in the H group than the C group (P < 0.05). In H group, both SOL and TA muscle fibers were damaged, and the FCSA of SOL was significantly lower than C group (P < 0.05). ③Puro and Ub in SOL tissues were obviously higher in the H group than the C group. The ratio of Puro/Ub was decreased significantly in SOL tissues (P < 0.05), but increased significantly in TA tissues (P < 0.01). ④ There were 665 differential genes found in SOL tissues and 228 differential genes in TA tissues between the 2 groups. Among them, 58 differential genes were up-regulated and 35 were down-regulated in both muscles. Those up-regulated differential genes in SOL tissues were mainly enriched in inflammatory response and protein synthesis and involved in TNF and Jak/STAT signaling pathways. The up-regulated differential genes in TA tissues were mainly enriched in antioxidant and glucose metabolism and glucocorticoid and involved in PPAR signaling pathway and glutathione metabolism. The down-regulated genes were concentrated in oxidative stress and transformation between fast- and slow-twitch muscles. Conclusion Chronic intermittent hypoxia could promote SOL atrophy by enhancing inflammatory response, and TA may resist hypoxia-induced muscle atrophy by improving antioxidant capacity.

Due to the widespread application of nonlinear optical materials, the design and synthesis of such materials with excellent performance has always been a research hotspot. In this paper, based on the reported TIDC-Cl, five new molecules were designed by introducing donor or acceptor units and their combination. By utilizing density functional theory and time-dependent density functional theory, the linear and nonlinear optical properties of molecules TIDC-Cl and 1–5 were investigated in detail. It was found that except for molecule 1, they are all narrowband compounds (1.41–2.22 eV), and their absorption spectra underwent a red shift, especially for molecules 2 and 4, which have reached the infrared region at long wavelengths. Molecule TIDC-Cl is a candidate for bipolar transport materials and molecules 2–5 are expected to serve as electron transport materials. Given that the studied molecules all have a large first hyperpolarizability, especially molecule 5, which is 807 times larger than that of the organic urea molecule, they are expected to serve as high-performance nonlinear optical materials. In addition, the origin of nonlinearity was studied through DR analysis, hyperpolarizability density analysis and the unit sphere representation method. The discussion of frequency-dependent (hyper)polarizability indicates that the frequency dispersion of the first hyperpolarizability appears in the studied molecules. It is hoped that this study will better promote the understanding of the nonlinear optical response of push–pull materials and pave the way for the development of high-tech nonlinear optical materials. [ABSTRACT FROM AUTHOR]

To improve exercise performance, the supplement of nutrients has become a common practice before prolonged exercise. Trimethylamine N-oxide (TMAO) has been shown to ameliorate oxidative stress damage, which may be beneficial in improving exercise capacity. Here, we assessed the effects of TMAO on mice with exhaustive swimming, analyzed the metabolic changes, and identified significantly altered metabolic pathways of skeletal muscle using a nuclear magnetic resonance-based (NMR-based) metabolomics approach to uncover the effects of TMAO improving exercise performance of mice. We found that TMAO pre-administration markedly prolonged the exhaustive time in mice. Further investigation showed that TMAO pre-administration increased levels of 3-hydroxybutyrate, isocitrate, anserine, TMA, taurine, glycine, and glutathione and disturbed the three metabolic pathways related to oxidative stress and protein synthesis in skeletal muscle. Our results provide a metabolic mechanistic understanding of the effects of TMAO supplements on the exercise performance of skeletal muscle in mice. This work may be beneficial in exploring the potential of TMAO to be applied in nutritional supplementation to improve exercise performance. This work will lay a scientific foundation and be beneficial to exploring the potential of TMAO to apply in nutritional supplementation. [ABSTRACT FROM AUTHOR]

Objective To investigate the effects of different phosphorylation sites of FoxO1 on protein synthesis and proteolysis in rat skeletal muscle L6 cells under the condition of hypoxia. Methods Adenoviral vectors (FoxO1, FoxO1T24A/D, FoxO1S250A/D, and FoxO1AS313A/D) were constructed, and then used to infect the differentiated rat skeletal muscle cells respectively with appropriate multiples of infection (MOI). These L6 cells were corresponding named to 8 groups: EGFP, rFoxO1, T24A, T24D, S250A, S250D, S313A and S313D, and then each transfection group was divided into normoxic group (C) and hypoxic group (H). Adenovirus transfection was observed using a fluorescence confocal microscope. Puromycin-binding peptides, ubiquitin labeling protein, synthesis and decomposition-related proteins were detected using Western blotting. Results Compared with the C-EGFP group, the expression levels of puromycin-binding polypeptide (1.38±0.06), mTOR (1.54±0.21) and p-mTOR (1.57±0.34) were significantly increased in the C-rFoxO1 group (all P < 0.05). The levels of mTOR (1.33±0.35) and p-mTOR (1.60 ± 0.44) were also elevated in the C-T24D group than the C-EGFP group (P < 0.01). The level of mTOR in the H-T24D group was notably reduced when compared with the C-T24D group (P < 0.01). Protein accumulation was remarkably increased in the C-S250A group than the C-EGFP group (P < 0.01), and was statistically decreased in the H-S250A group than the C-S250A group (P < 0.05). But no such differences were seen in the protein accumulation in the S313A and S313D groups when compared with that in the C-EGFP group (P>0.05). Conclusion FoxO1 can improve protein synthesis by enhancing the activity of mTOR, but this process is strictly regulated by hypoxia. Under hypoxic condition, FoxO1 inhibits protein synthesis via phosphorylation sites Thr24 and Ser250.

Aims: This study aims to investigate the effect of aerobic exercise training on BKCa channel in diabetic vascular smooth muscle and explore the underlying mechanism. Methods: Control m/m mice and diabetic db/db mice were randomly assigned to sedentary groups (W and D) and exercise training groups (WE and DE). Mice in exercise groups underwent training sessions lasting for 12 weeks, with a speed of 12 m/min for 60 min, five times per week. The thoracic aorta was extracted isolated and examined for measurement of vascular structure, global levels of reactive oxygen species (ROS), vasodilation, and protein expression. Rat thoracic aorta vascular smooth muscle cells (USMCs) were cultured, and siRNA transfection was conducted to detect whether AMPK contributed to the regulation. ROS level and protein expression were measured. Results: Compared with control mice, diabetic mice had a larger vascular medium thickness, impaired BKCa-mediated vasodilation, a higher level of ROS, and a lower expression of BKCa α, BKCa β1, Nrf2, p-Nrf2, p-Nrf2/Nrf2, HO-1, and p-AMPK/AMPK. Exercise training increased the expression of BKCa α, Nrf2, p-Nrf2, p-Nrf2/Nrf2, HO-1, and p-AMPK/AMPK. AMPK deletion led to lower ROS levels and expression of BKCa α, β1, Nrf2, and HO-1 in USMCs cultured in high glucose conditions. Conclusions: BKCa channel protein expression reduction in VSMCs contributes to vasodilation and vascular remodeling dysfunction in diabetes mellitus. Aerobic exercise can promote the expression of BKCa channel and improve BKCa-mediated vascular dysfunction in diabetic VSMCs through AMPK/Nrf2/HO-1 signaling pathway. [ABSTRACT FROM AUTHOR]

This study aims to explore the role of FoxO1 and its acetylation in the alleviation of hypoxia‐induced muscle atrophy by resistance training. Forty male Sprague–Dawley rats were randomly divided into four groups: normoxic control group (C), normoxic resistance training group (R), hypoxic control group (H) and hypoxic resistance training group (HR). Rats in R and HR groups were trained on an incremental weight‐bearing ladder every other day, while those in H and HR groups were kept in an environment containing 12.4% O2. After 4 weeks, muscles were collected for analysis. Differentiated L6 myoblasts were analysed in vitro after hypoxia exposure and plasmids transfection (alteration in FoxO1 acetylation). The lean body mass loss, wet weight and fibre cross‐sectional area of extensor digitorum longus of rats were decreased after 4 weeks hypoxia, and the adverse reactions above was reversed by resistance training. At the same time, the increase in hypoxia‐induced autophagy was suppressed, which was accompanied by a decrease in the expression of nuclear FoxO1 and cytoplasmic Ac‐FoxO1 by resistance training. The L6 myotube diameter increased and the expression of autophagic proteins were inhibited under hypoxia via intervening by FoxO1 deacetylation. Overall, resistance training alleviates hypoxia‐induced muscle atrophy by inhibiting nuclear FoxO1 and cytoplasmic Ac‐FoxO1‐mediated autophagy. [ABSTRACT FROM AUTHOR]

In this paper, in order to study the relationship between structure and performance, four new non‐fullerene acceptor (NFA) derivatives were designed based on the two reported NFA molecules BO‐4Cl and BTP‐S2 by replacing the benzothiadiazole unit with a less‐electron deficient benzotriazole unit and inserting another ethylene double bond between the central core and the terminal groups. Density functional theory (DFT) and Time‐dependent DFT were applied to investigate linear and nonlinear optical (NLO) properties, such as electronic structure, electronic absorption, reorganization energy, and the second‐order NLO properties. The investigation demonstrates that they are all narrow bandgap derivatives, the absorption spectrum extends to the near‐infrared region and using two ethylene double bond is the most effective way to reduce the energy gap, redshift the maximum absorption peak and the middle absorption band, and enhance second‐order NLO response. Considering the smaller electron and hole reorganization energy and the larger static first hyperpolarizability value, the studied NFA derivatives have great potential to become ambipolar charge transport materials and large second‐order NLO materials. [ABSTRACT FROM AUTHOR]