Obesity is associated with biological dysfunction in skeletal muscle. As a condition of obesity accompanied by muscle mass loss and physical dysfunction, sarcopenic obesity (SO) has become a novel ...public health problem. Human fibroblast growth factor 19 (FGF19) plays a therapeutic role in metabolic diseases. However, the protective effects of FGF19 on skeletal muscle in obesity and SO are still not completely understood. Our results showed that FGF19 administration improved muscle loss and grip strength in young and aged mice fed a high‐fat diet (HFD). Increases in muscle atrophy markers (FOXO‐3, Atrogin‐1, MuRF‐1) were abrogated by FGF19 in palmitic acid (PA)‐treated C2C12 myotubes and in the skeletal muscle of HFD‐fed mice. FGF19 not only reduced HFD‐induced body weight gain, excessive lipid accumulation and hyperlipidaemia but also promoted energy expenditure (PGC‐1α, UCP‐1, PPAR‐γ) in brown adipose tissue (BAT). FGF19 treatment restored PA‐ and HFD‐induced hyperglycaemia, impaired glucose tolerance and insulin resistance (IRS‐1, GLUT‐4) and mitigated the PA‐ and HFD‐induced decrease in FNDC‐5/irisin expression. However, these beneficial effects of FGF19 on skeletal muscle were abolished by inhibiting AMPK, SIRT‐1 and PGC‐1α expression. Taken together, this study suggests that FGF19 protects skeletal muscle against obesity‐induced muscle atrophy, metabolic derangement and abnormal irisin secretion partially through the AMPK/SIRT‐1/PGC‐α signalling pathway, which might be a potential therapeutic target for obesity and SO.
A highly reversible aqueous rechargeable battery system is assembled by using a Zn anode, a room-temperature synthesized MnO2-birnessite cathode and a mild ZnSO4-based aqueous electrolyte with MnSO4 ...as an additive. Structural analysis reveal that MnO2-birnessite undergoes a structural transformation to poorly crystalline MnO2. It offers an operating voltage of 1.39 V, an energy density of 364 Wh kg−1 (cathode only) at 200 mA g−1 and shows a capacity retention of 100% over 400 cycles at 500 mA g−1. This low-cost battery system is a promising candidate for large-scale energy storage.
Low-cost birnessite with high energy density shows a capacity retention of ∼100% over 400 cycles. Display omitted
Although autophagy impairment is a well-established cause of muscle atrophy and P300 has recently been identified as an important regulator of autophagy, the effects of P300 on autophagy and muscle ...atrophy in type 2 diabetes (T2D) remain unexplored. We aimed at characterizing the role of P300 in diabetic muscle and its underlying mechanism.
Protein levels of phosphorylated P300, total P300, acetylated histone H3, LC3, p62 and myosin heavy chain, and mRNA levels of Atrogin-1 and MuRF1 were analyzed in palmitic acid (PA)-treated myotubes and db/db mice. Autophagic flux was assessed using transmission electron microscopy, immunofluorescence and mRFP-GFP-LC3 lentivirus transfection in cells. Muscle weight, blood glucose and grip strength were measured in mice. Hematoxylin and eosin (H&E) staining was performed to determine changes in muscle fiber size. To investigate the effects of P300 on autophagy and myofiber remodeling, a P300 specific inhibitor, c646, was utilized. 3-Methyladenine (3-MA) was utilized to inhibit autophagosomes formation, and chloroquine (CQ) was used to block autophagic flux.
Phosphorylation of P300 in response to PA enhanced its activity and subsequently suppressed autophagic flux, leading to atrophy-related morphological and molecular changes in myotubes. Inhibition of P300 reestablished autophagic flux and ameliorated PA-induced myotubes atrophy. However, this effect was largely abolished by co-treatment with the autophagy inhibitor CQ. In vivo results demonstrated that inhibition of P300 partially rescued muscle wasting in db/db mice, accompanied with autophagy reactivation.
The findings revealed that T2D-induced overactivation of P300 contributes to muscle atrophy by blocking autophagic flux.
•T2D-induced P300 phosphorylation increases its activity, leading to skeletal muscle atrophy.•P300 functions as an anti-autophagic regulator.•Autophagic flux is blocked in muscle under diabetes conditions.•Autophagy pathway is required for P300-mediated muscle atrophy.
Abstract
Age-related loss of skeletal muscle mass and function, termed sarcopenia, could impair the quality of life in the elderly. The mechanisms involved in skeletal muscle aging are intricate and ...largely unknown. However, more and more evidence demonstrated that mitochondrial dysfunction and apoptosis also play an important role in skeletal muscle aging. Recent studies have shown that mitochondrial calcium uniporter (MCU)-mediated mitochondrial calcium affects skeletal muscle mass and function by affecting mitochondrial function. During aging, we observed downregulated expression of mitochondrial calcium uptake family member3 (MICU3) in skeletal muscle, a regulator of MCU, which resulted in a significant reduction in mitochondrial calcium uptake. However, the role of MICU3 in skeletal muscle aging remains poorly understood. Therefore, we investigated the effect of MICU3 on the skeletal muscle of aged mice and senescent C2C12 cells induced by
d
-gal. Downregulation of MICU3 was associated with decreased myogenesis but increased oxidative stress and apoptosis. Reconstitution of MICU3 enhanced antioxidants, prevented the accumulation of mitochondrial ROS, decreased apoptosis, and increased myogenesis. These findings indicate that MICU3 might promote mitochondrial Ca
2+
homeostasis and function, attenuate oxidative stress and apoptosis, and restore skeletal muscle mass and function. Therefore, MICU3 may be a potential therapeutic target in skeletal muscle aging.
Inflatable anchors have been applied to reinforce foundations because soft soil deposits have a low bearing capacity. However, previous research on the mechanical behaviors of inflatable anchors has ...focused on a single anchor. Since anchors are always used in a group, the uplift behavior of multiple inflatable anchors in soft soil should be investigated. A series of pull-out tests were conducted in this framework by changing the number, spacing, and layout of inflatable anchors. Additionally, the effect coefficient (ECO) of multiple inflatable anchors is discussed. It is found that the failure behavior of multiple inflatable anchors exhibits a three-stage curve: an initial linear stage, followed by nonlinear, and steady-state stages. In addition, the ultimate bearing capacity of multiple inflatable anchors is maximized if the ratio of the spacing of inflatable anchors to the equivalent expanding section diameter of an inflatable anchor is 6.84. It is recognized that the ECO of this new multiple inflatable anchor group is sometimes greater than 1, unlike that of conventional anchors, which have ECOs of less than 1. In addition, the layout of multiple inflatable anchors in the shape of a cinquefoil is recommended due to its high ECO.
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•Purifying simulated biogas by hydrate process with synergic additives.•Synergic additives comprise DMSO and TBAB or THF.•Microcosmic structure analysis, kinetic and separation ...efficiency were studied.•Synergic additives can enhance the hydrate-based separation process due to DMSO.
Treatment and subsequent use of biogas are garnering huge interest for both energy recovery and mitigation of environmental impact. However, separation process is pivotal for increasing its calorific value and removing CO2. This work presents the kinetic and separation efficiency study as well as microcosmic structure analysis for purifying simulated biogas (45.0mol% CO2/CH4 binary mixture) through hydrate crystallization approach. Particularly, synergic additives comprise gas solvent (dimethyl sulfoxide (DMSO)) and traditional hydrate promoter (tetrahydrofuran (THF) or tetra-n-butyl ammonium bromide (TBAB)) were proposed to enhance the hydrate-based separation process. The promotion mechanism was explored through in-situ Raman spectroscopy. The residual gas phase and the decomposition gas phase from the hydrate slurry were sampled and analyzed. Based on the experimental data, the gas storage capacity, unit system gas consumed rate, gas selectivity and separation efficiency were calculated for evaluating the separation process. It was found that, the synergic additives could promote the mixture hydrate formation process due to DMSO (acid gas solvent) could improve both rate and selectivity of CO2 during the dissolution and diffusion processes. In addition, the Raman analysis reveals that the simulated biogas forms structure II hydrate and semiclathrate framework with THF–DMSO and TBAB–DMSO respectively, and CH4 molecules are only found in the smaller (512) cages of the mixture hydrates. It is inferred that DMSO just performs as an acid gas solvent during the gas dissolution and diffusion processes but not participate in the hydrate framework formation. It will be of practical interest in relation to resolving the bottleneck of hydrate-based biogas purification technology and of potential importance for the industry application of gas hydrate.
•Barrier effect of metro station in dewatering of large-scale excavation is studied.•Responses of groundwater and soil to dewatering under barrier effect are revealed.•Barrier effect causes decrease ...of water yield but increase of groundwater drawdown.•Distance of barrier to excavation can determine the nature of the barrier effect.•Excavation scale can only affect the intensity of the barrier effect.
When an excavation is close to an existing underground structure which exactly penetrates aquifers, the structure would exert water-blocking (WB) and soil-blocking (SB) effects by changing the groundwater seepage and restricting the strata movement. These two barrier effects would make the dewatering-induced behaviours of groundwater and strata be different from the case with no nearby structure. In this study, a typical metro station was selected as an underground barrier, and its barrier effect on the responses of groundwater and strata to dewatering of adjacent large-scale excavations were numerically investigated. Results indicate that regardless of the excavation scale, the overall water yield of the excavation would be reduced by considering the WB effect, while in the meantime, the induced groundwater drawdown would be enlarged, meaning the number of the designed pumping wells could be reduced to achieve the same dewatering effect. The strata behaviour under barrier effect is more complicated, depending on the coupled action of the WB and SB effects; both the excavation width (B) and the distance of station to the excavation (D) could largely affect the intensity of the WB and SB effects, further determining the ground settlement amount (either larger or smaller than that without barrier effect). Designers should consider the barrier effect based on practical D and B to realize the optimal or economic design and meanwhile to prevent the appearance of unexpected large responses of groundwater and strata during dewatering construction.
CU test and CD test were performed to capture the stress-strain characteristics of the clay in Dongting Lake area, China. Since the classical constitutive model cannot ideally describe the strain ...hardening behavior of the clay, an improved constitutive model that involved three damage factors was proposed. The damage first factor D1, which represents elemental volume strength F, was fitted by the Weibull function. The second and third damage factors D2 and D3, which represent the porosity ratio e and the drainage rate Pε respectively, were fitted by Harris function. The CD test damage model is constructed by D1, D2, and D3. In the CU test, the porosity ratio e is a constant value, and the drainage volume is 0, so that D2 is constant value and D3 is 0. Therefore, the CU test damage model of the clay was constructed using the damage first factor D1. In the end, the accuracy of the proposed CU/CD damage constitutive models of the clay was validated with the experimental results. It is found that the results fitted by the proposed methodology are in good agreement with the experimental results.
This study aimed to test the association between personality traits and affect among boxers and to figure out whether loneliness mediated this relationship. This study used The Big Five Personality ...Traits Scale, The UCLA Loneliness Scale, and The Positive and Negative Affect Scale (PANAS) which were administered to
= 231 boxers (age: M = 20.28;
= 2.60), of which 62% were male (
= 144) and 38% were female (
= 87). The results showed that (1) conscientiousness, extraversion, and agreeableness were negatively related with negative affect, neuroticism was positively associated with negative affect, and openness showed no relationship with negative affect; (2) conscientiousness, extraversion, and agreeableness were all positively correlated with positive affect, neuroticism was negatively associated with positive affect, and openness showed no relationship with positive affect; (3) conscientiousness, extraversion, openness, and agreeableness were negatively related with loneliness and neuroticism was positively associated with loneliness; and (4) loneliness was positively associated with negative affect; loneliness was negatively associated with positive affect; and loneliness had mediating effect on the relationship between the personality traits and affect. Furthermore, these findings suggest that loneliness might be one mechanism explaining how boxer's personality traits influence their athletic performance. Therefore, in the future, we should start by helping them reduce their loneliness to reduce their negative affect and improve their positive affect and also, in some degree, to enhance boxers' athletic ability and mental quality health.
Fibrosis is a key pathological event during muscle aging that accelerates the development of sarcopenia. We show that sarcolipin (SLN) is highly expressed during aging, promotes intracellular calcium ...overload and participates in impaired myogenic differentiation. d-Galactose (D-gal) was used to induce senescence in C2C12 myoblasts. Conventional AAV-mediated SLN knockdown cells were used to study the role of SLN in muscle physiology and pathophysiology. C2C12 cells were treated with D-gal, which promoted fibrosis and SLN upregulation. The expression of TGF-β1 and α-SMA, which participate in myogenic transdifferentiation, were also elevated. C2C12 cells with reduced sarcolipin expression produced decreased amounts of collagen. Our study identified an unrecognized role of SLN in regulating myogenic transdifferentiation during aging-associated skeletal muscle cell fibrosis. Targeting SLN may be a novel therapeutic strategy to relieve sarcopenia-associated muscle fibrosis.
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