Skeletal muscle (SKM) has crucial roles in locomotor activity and posture within the body and also functions have been recognized as an actively secretory organ. Numerous bioactive molecules are secreted by SKM and transported by extracellular vesicles (EVs), a novel class of mediators of communication between cells and organs that contain various types of cargo molecules including lipids, proteins and nucleic acids. SKM-derived EVs (SKM-EVs) are intercellular communicators with significant roles in the crosstalk between SKM and other organs. In this review, we briefly describe the biological characteristics, composition, and uptake mechanisms of EVs, particularly exosomes, comprehensively summarize the regulatory effects of SKM-EVs on the function of, which include myogenesis, muscle repair and regeneration, as well as metabolic regulation. Furthermore, we explore the impact of SKM- EVs on various organs including bone, the cardiovascular system, adipose tissue, and nervous system. As emerging evidence suggests that SKM-EVs are involved in the development and regulation of type 2 diabetes (T2D), systemic inflammation, and other chronic diseases, we also highlight the potential of SKM-EVs as therapeutic targets and diagnostic biomarkers, emphasizing the need for further research to elucidate the complex mechanisms underlying intercellular communication in physiological and pathological contexts.

Background: Muscle atrophy is an increasingly global health problem affecting millions, there is a lack of clinical drugs or effective therapy. Excessive loss of muscle mass is the typical characteristic of muscle atrophy, manifesting as muscle weakness accompanied by impaired metabolism of protein and nucleotide. (D)-3-hydroxybutyrate (3HB), one of the main components of the ketone body, has been reported to be effective for the obvious hemodynamic effects in atrophic cardiomyocytes and exerts beneficial metabolic reprogramming effects in healthy muscle. This study aims to exploit how the 3HB exerts therapeutic effects for treating muscle atrophy induced by hindlimb unloaded mice. Results: Anabolism/catabolism balance of muscle protein was maintained with 3HB via the Akt/FoxO3a and the mTOR/4E-BP1 pathways; protein homeostasis of 3HB regulation includes pathways of ubiquitin–proteasomal, autophagic-lysosomal, responses of unfolded-proteins, heat shock and anti-oxidation. Metabolomic analysis revealed the effect of 3HB decreased purine degradation and reduced the uric acid in atrophied muscles; enhanced utilization from glutamine to glutamate also provides evidence for the promotion of 3HB during the synthesis of proteins and nucleotides. Conclusions: 3HB significantly inhibits the loss of muscle weights, myofiber sizes and myofiber diameters in hindlimb unloaded mouse model; it facilitates positive balance of proteins and nucleotides with enhanced accumulation of glutamate and decreased uric acid in wasting muscles, revealing effectiveness for treating muscle atrophy. Graphical

Background: Muscle atrophy resulting wholly or partially from disuse represents a serious medical complication that decreases quality of life and increases morbidity and mortality. The accumulation of misfolded/unfolded proteins disrupts endoplasmic reticulum (ER) homeostasis and thus causes ER stress. Growing evidence indicates that ER stress plays an essential role in skeletal muscle remodeling under various physiological or pathophysiological conditions. However, whether ER stress is involved in disuse-induced muscle atrophy remains unclear. Methods: To induce muscle atrophy, 8-week-old C57BL/6JNifdc male mice were subjected to 3, 7, or 14 days of hindlimb unloading (HU), and rhesus macaques (Macaca mulatta) were subjected to 10∘ head-down tilted bed rest (HDBR) for 6 weeks. Tauroursodeoxycholic acid (TUDCA) (500 mg/kg/d) was orally administered to mice during HU to inhibit ER stress. Quantitative PCR, Western blotting, and immunohistochemistry were conducted to evaluate gene, protein, and structural changes, respectively. Results: ER stress marker genes were rapidly induced by HU in a similar trend to that observed with atrophy-related genes such as Atrogin-1, muscle RING finger 1 (MuRF1), and muscle ubiquitin ligase of SCF complex in atrophy-1 (MUSA1). Inhibition of ER stress with TUDCA, a pan-ER stress inhibitor, attenuated HU-induced muscle atrophy and the upregulation of ubiquitin ligases via the AKT/forkhead box O3a pathway. In addition, the oxidative-to-glycolytic myofiber type transition caused by HU was also inhibited by TUDCA treatment. ER stress activation was also confirmed in HDBR-induced rhesus soleus muscle atrophy. Conclusions: The strong positive correlation between ER stress activation and both HU- and HDBR-induced muscle atrophy indicates that ER stress activation is ubiquitously involved in disuse-induced muscle atrophy, regardless of species. Thus, inhibiting ER stress may be an effective therapeutic strategy to prevent muscle atrophy during disuse.

Background: Long non-coding RNA (lncRNA) H19 is one of the most highly expressed and conserved transcripts in mammalian development, and its functions have been fully discussed in many contexts including tumorigenesis and skeletal muscle development. However, its exact role in muscle atrophy remains largely unknown. This study investigated the effect of lncRNA H19 on muscle atrophy and the potential underlying mechanism. Methods: Hindlimb suspension (HS) of C57BL/6 mice and starvation of C2C12 cells with PBS were conducted to induce atrophy. Real-time PCR and Western blotting were used to measure the expression of RNAs and proteins. LncRNA H19 and its encoded miR-675 were overexpressed or inhibited in different models of muscle atrophy. Immunofluorescence was carried out to examine the cross-sectional area (CSA) and minimal Feret’s diameter (MFD) of myofibers and myotube diameter. Results: The expression levels of lncRNA H19 and miR-675 were significantly reduced in both the soleus and gastrocnemius muscles in response to HS. Overexpression of lncRNA H19 led to an increase in Atrogin-1 mRNA expression, and this effect was reversed by inhibiting miR-675. The overexpression of miR-675 aggravated both HS- and starving-induced muscle atrophy by inhibiting the IGF1R/Akt signaling pathway and promoting FoxO/Atrogin-1 expression. Conversely, miR-675 inhibition had the opposite effects. Conclusion: The lncRNA H19/miR-675 axis can induce muscle atrophy, and its downregulation in mice with HS-induced muscle atrophy may act as a protective mechanism against this condition.

Skeletal muscle atrophy, characterized by the loss of muscle mass and function, can result from disuse, aging, disease, drug. Exercise preconditioning—a form of exercise training performed before these harmful threats—induces notable remodeling and extensive biochemical adaptations in skeletal muscle, creating a protective phenotype in muscle fibers, and thus serving as an effective intervention for preventing skeletal muscle atrophy. Here, we review the current understanding relating to how exercise preconditioning protects skeletal muscle from damage caused by inactivity, sarcopenia, disease, or pharmacological intervention, with an emphasis on the cellular mechanisms involved. Key mechanisms highlighted as making a significant contribution to the protective effects of exercise on skeletal muscle fibers include mitochondria; the expression of cytoprotective proteins such as HSP72, SOD2, SESN2, PGC-1α and AMPK; and the regulation of oxidative stress. These findings underscore the potential of exercise preconditioning as a non-pharmacological intervention for preserving muscle mass and function, as well as preventing muscular atrophy, ultimately improving the quality of life for at-risk populations.

We report on the fabrication and photovoltaic characteristics of vertical arrays of silicon axial p-i-n junction nanowire (NW) solar cells grown by vapor-liquid-solid (VLS) epitaxy. NW surface passivation with silicon dioxide shell is shown to enhance carrier recombination time, open-circuit voltage (V_OC), short-circuit current density (J_SC), and fill factor (FF). The photovoltaic performance of passivated individual NW and NW arrays was compared under 532 nm laser illumination with power density of ∼10 W/cm². Higher values of V_OC and FF in the NW arrays are explained by enhanced light trapping. In order to verify the effect of NW density on light absorption and hence on the photovoltaic performance of NW arrays, dense Si NW arrays were fabricated using nanoimprint lithography to periodically arrange the gold seed particles prior to epitaxial growth. Compared to sparse NW arrays fabricated using VLS growth from randomly distributed gold seeds, the nanoimprinted NW array solar cells show a greatly increased peak external quantum efficiency of ∼8% and internal quantum efficiency of ∼90% in the visible spectral range. Three-dimensional finite-difference time-domain simulations of Si NW periodic arrays with varying pitch (P) confirm the importance of high NW density. Specifically, due to diffractive scattering and light trapping, absorption efficiency close to 100% in the 400–650 nm spectral range is calculated for a Si NW array with P = 250 nm, significantly outperforming a blanket Si film of the same thickness.