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.

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 Ca2+ 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.

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Diabetes mellitus is a metabolic disorder that can lead to cognitive dysfunction. The hippocampus plays an important role in the cognitive function. Research has identified correlations between hippocampal impairment and diabetes, yet their intermediate remains unclear. Soluble epoxide hydrolase (sEH) is an enzyme that degrades epoxyeicosatrienoic acids (EETs), which have multiple protective effects by suppressing inflammation, apoptosis and oxidative stress. In this study, under diabetic conditions both hippocampal injury and cognitive decline are accompanied by upregulation of sEH. Moreover, the sEH inhibitor trans‐4‐[4‐(3‐adamantan‐1‐y1‐ureido)‐cyclohexyloxy]‐benzoic acid (t‐AUCB) prevents cognitive dysfunction and decreased ROS accumulation and apoptosis in the diabetic hippocampus. t‐AUCB treatment restored neuronal synaptic plasticity by restoring the expression of the postsynaptic proteins Postsynaptic density protein‐95 (PSD95) and N‐methyl‐d‐aspartate receptor subunit 2B (NR2B), the levels of which were positively correlated with Proline‐rich tyrosine kinase 2 (Pyk2) levels under diabetic conditions. Thus, we suggest that hippocampal protection via sEH inhibition might be a potential therapeutic approach to attenuate the progression of cognitive decline in diabetes.

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CFG pile (i.e., pile constructed by granular materials of cement, fly-ash and gravel) composite foundation is applied in subsoil treatment widely and successfully. In order to have a further study of this kind of subsoil treatment technology, the influencing factors and calculation methods of the vertical bearing capacity of single CFG pile and the CFG pile composite foundation were discussed respectively. And based on the obtained solutions, effects by the cushion and measurements to reduce negative friction area were analyzed. Moreover, the developing law of settlement and bearing capacity eigenvalue controlled by the material strength with the increase of load were given for the CFG composite foundation. The in-situ static load test was tested for CFG pile. The results of test show that the maximum test load or half of the ultimate load is used from all the points of test, the average bearing capacity eigenvalue of single pile is 390 kN, and slightly greater than the design value of bearing capacity. The bearing capacity eigenvalues of composite foundation for 3 piles are greater than 300 kPa, and the mechanical properties of CFG pile composite foundation are almost identical in the case of the same load and cushion thickness. The pile-soil stress ratio and the load-sharing ratio can be adjusted through setting up cushion thickness.

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