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Neuromuscular junction (NMJ) degeneration is one of pathological factors of sarcopenia. Low‐magnitude high‐frequency vibration (LMHFV) was reported effective in alleviating the sarcopenia progress. However, no previous study has investigated treatment effects of LMHFV targeting NMJ degeneration in sarcopenia. We first compared morphological differences of NMJ between sarcopenic and non‐sarcopenic subjects, as well as young and old C57BL/6 mice. We then systematically characterized the age‐related degeneration of NMJ in SAMP8 against its control strain, SAMR1 mice, from 3 to 12 months old. We also investigated effects of LMHFV in SAMP8 on the maintenance of NMJ during the onset of sarcopenia with respect to the Agrin‐LRP4‐MuSK‐Dok7 pathway and investigated the mechanism related to ERK1/2 signaling. We observed sarcopenic/old NMJ presented increased acetylcholine receptors (AChRs) cluster fragmentation and discontinuity than non‐sarcopenic/young NMJ. In SAMP8, NMJ degeneration (morphologically at 6 months and functionally at 8 months) was observed associated with the sarcopenia onset (10 months). SAMR1 showed improved NMJ morphology and function compared with SAMP8 at 10 months. Skeletal muscle performance was improved at Month 4 post‐LMHFV treatment. Vibration group presented improved NMJ function at Months 2 and 6 posttreatment, accompanied with alleviated morphological degeneration at Month 4 posttreatment. LMHFV increased Dok7 expression at Month 4 posttreatment. In vitro, LMHFV could promote AChRs clustering in myotubes by increasing Dok7 expression through suppressing ERK1/2 phosphorylation. In conclusion, NMJ degeneration was observed associated with the sarcopenia onset in SAMP8. LMHFV may attenuate NMJ degeneration and sarcopenia progression by increasing Dok7 expression through suppressing ERK1/2 phosphorylation. [ABSTRACT FROM AUTHOR]

This paper proposes a novel hybrid algorithm, named Multi-Strategy Hybrid Harris Hawks Tunicate Swarm Optimization Algorithm (MSHHOTSA). The primary objective of MSHHOTSA is to address the limitations of the tunicate swarm algorithm, which include slow optimization speed, low accuracy, and premature convergence when dealing with complex problems. Firstly, inspired by the idea of the neighborhood and thermal distribution map, the hyperbolic tangent domain is introduced to modify the position of new tunicate individuals, which can not only effectively enhance the convergence performance of the algorithm but also ensure that the data generated between the unknown parameters and the old parameters have a similar distribution. Secondly, the nonlinear convergence factor is constructed to replace the original random factor c1 to coordinate the algorithm's local exploitation and global exploration performance, which effectively improves the ability of the algorithm to escape extreme values and fast convergence. Finally, the swarm update mechanism of the HHO algorithm is introduced into the position update of the TSA algorithm, which further balances the local exploitation and global exploration performance of the MSHHOTSA. The proposed algorithm was evaluated on eight standard benchmark functions, CEC2019 benchmark functions, four engineering design problems, and a PID parameter optimization problem. It was compared with seven recently proposed metaheuristic algorithms, including HHO and TSA. The results were analyzed and discussed using statistical indicators such as mean, standard deviation, Wilcoxon's rank sum test, and average running time. Experimental results demonstrate that the improved algorithm (MSHHOTSA) exhibits higher local convergence, global exploration, robustness, and universality than BOA, GWO, MVO, HHO, TSA, ASO, and WOA algorithms under the same experimental conditions. [ABSTRACT FROM AUTHOR]

Reasonable production capacity is related to the economic benefits of an open-pit coal mine. This study analyzes the relationship between the working face length, the annual advancing speed and the production capacity. It constructs a production capacity function relationship model. Take the Baorixile open-pit coal mine as an example. The remaining unmined parts are divided into four regions, and the range of production capacity in each region is analyzed by the established model and the determined respectively. On this basis, three mining district division plans are proposed. By analyzing and comparing the stripping ratio, mining life of the district, fault influence, difficulty of transition connection in the mining districts, the convenience of transportation system layout and other indexes of each plan, Plan 3 is determined to be the optimal plan. The production capacity planning results of each mining district in this plan are as follows: the production capacity of the 3rd mining district is 30–35 Mt/a; the production capacity of the 4th mining district in Region 1 is 20–31 Mt/a, and the production capacity in Region 2 is 24–33 Mt/a; the production capacity of the 5th mining district is 20–27 Mt/a. [ABSTRACT FROM AUTHOR]

This paper addresses a special truck routing optimization problem in open-pit mines based on the minimization of time-varying transport energy consumption. A mixed-integer programming model is formulated to clearly describe the engineering problem, and a series of constraints are deduced to strengthen the model. To ensure that the model has time-varying characteristics, a method to estimate time-varying parameters is proposed by using pattern recognition and trend surface estimation. This time-varying resistance coefficient is mainly used to describe the process of road damage caused by frequent rolling of heavy trucks on the road surface. At the same time, in order to make the truck routing converge to the optimal energy consumption solution quickly, some definitions and properties are then provided based on stochastic theory, and a strategy to improve the computational efficiency of the model is proposed using these properties. Finally, an improved genetic algorithm is designed to solve the model. The results of experiments show that the proposed algorithm is effective and efficient. [ABSTRACT FROM AUTHOR]

In this work, the biological polysaccharide-based antioxidant polyglucose-sorbitol-carboxymethyl ether (PSC) was used as the precursor to synthesize Fe 2 O 3 @PSC nanoparticles, which are expected to scavenge excess reactive oxygen species (ROS) to inhibit osteogenesis and promote osteoclast differentiation in iron accumulation (IA)-related osteoporosis. The Fe 2 O 3 @PSC nanoparticles obtained were of a uniform particle size of 7.3 nm with elemental O/Fe/Cl/C at a ratio of 190:7:2:88. In addition, the Fe 2 O 3 @PSC nanoparticles showed the ability to supply equivalent amounts of iron as the typical iron agent ferric ammonium citrate (FAC) in vitro and in vivo. Importantly, the Fe 2 O 3 @PSC nanoparticles not only induced antioxidative MC3T3-E1 and Raw 264.7 cells to scavenge ROS but also promoted osteogenic differentiation by activating Akt-GSK-3β-β-catenin and inhibiting osteoclast differentiation by inhibiting the MAPK and NF-κB pathways in vitro. In vivo , no IA-related osteoporosis was induced in a mouse model when enough iron was supplied by the Fe 2 O 3 @PSC nanoparticles. Overall, the biological polysaccharide-based antioxidant PSC can supply iron and prevent IA-related osteoporosis, indicating that it is a promising novel iron agent for applications to treat iron deficiency diseases. • PSC macro-molecule could scavenge ROS by activating cellular antioxidant pathways. • Fe 2 O 3 @PSC prevented iron-accumulation related osteoporosis by PSC's ROS scavenging effect in vitro and vivo. • Fe 2 O 3 @PSC supplied enough iron as conventional iron agent in vitro and vivo. [ABSTRACT FROM AUTHOR]

Background: Deep Vein Thrombosis (DVT) is a common disease, frequently afflicting the lower limb veins of bedridden patients. Intermittent Pneumatic Compression (IPC) is often employed as an effective solution for this problem. In our study, a random selection of 264 patients underwent IPC treatment for either one or 8 hours daily. The rate of severe venous thrombosis was substantially reduced in the IPC-treated group compared to the control group. However, real-time monitoring of blood flow during IPC operation periods remains a challenge, leading to rare awareness of IPC working mechanism on thrombosis prevention. Methods: Here, microfluidic chip methodology is used to create an in vitro vein-mimicking platform integrating venous valves in a deformable channel. Whole blood of patients after knee surgery was perfused into the venous channel at a controlled flow rate obtained from patients with IPC treatment clinically. Results: According to the numerical simulations results, both of an increase in compressive pressure and a decrease in time interval of IPC device can accelarete blood flow rate and the shear stress within the vein. The vein chip experiments also reveal that the fibrin accumulation can be greatly lowered in IPC treated group, indicating less thrombosis formation in future. A time interval of 24 seconds and a maximum contraction pressure of 40 mmHg were proved to be the most effective parameters for the IPC device adopted in our clinical trail. Conclusion: This vein chip presents a novel method for observing the functional mechanisms of IPC device for DVT prevention. It provides crucial data for further standardization and optimization of IPC devices in clinical usage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dai, Chai, Yao, Tang, Shi, Jiang and Zhu.)

Injectable hydrogels offer a new therapy option for irregular bone deformities. Based on gelatin methacryloyl (GelMA), bone marrow mesenchymal stem cells (BMSCs), and bone morphogenetic protein 2 (BMP2), we created a photo-crosslinked composite bioactive scaffold. The composite scaffolds had appropriate mechanical properties for stem cells adhesion and proliferation, as well as good biocompatibility and the ability to stimulate BMSCs osteogenic differentiation in vitro . The synergistic effect of BMSCs and BMP2 enabled the composite bioactive scaffold to exhibit higher osteogenic potential in vivo than scaffolds loaded alone with BMSCs or BMP2, according to imaging and histology studies. In conclusion, by promoting the osteogenic differentiation of BMSCs, the composite bioactive scaffold based on BMSCs-BMP2-GelMA has demonstrated remarkable application potential in bone regeneration and bone defects repair., Competing Interests: CX was employed by the Hangzhou Lancet Robotics Company Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chai, Huang, Mahmut, Wang, Yao, Zhang, Zhuang, Xie, Xu and Jiang.)

Mesenchymal stem cells (MSCs) can be effective in alleviating the progression of osteoarthritis (OA). However, low MSC retention and survival at the injection site frequently require high doses of cells and/or repeated injections, which are not economically viable and create additional risks of complications. In this study, we produced MSC-laden microcarriers in spinner flask culture as cell delivery vehicles. These microcarriers containing a low initial dose of MSCs administered through a single injection in a rat anterior cruciate ligament (ACL) transection model of OA achieved similar reparative effects as repeated high doses of MSCs, as evaluated through imaging and histological analyses. Mechanistic investigations were conducted using a co-culture model involving human primary chondrocytes grown in monolayer, together with MSCs grown either within 3D constructs or as a monolayer. Co-culture supernatants subjected to secretome analysis showed significant decrease of inflammatory factors in the 3D group. RNA-seq of co-cultured MSCs and chondrocytes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed processes relating to early chondrogenesis and increased extracellular matrix interactions in MSCs of the 3D group, as well as phenotypic maintenance in the co-cultured chondrocytes. The cell delivery platform we investigated may be effective in reducing the cell dose and injection frequency required for therapeutic applications., Competing Interests: Wei Liu is employed by Beijing CytoNiche Biotechnology Co. Ltd. The other authors declare no financial and personal relationships with other people or organizations that can inappropriately influence our work., (© 2021 The Authors.)

The aim of this study was to investigate the effects of melatonin on oxidative stress, the expression of transient receptor potential melastatin-2 (TRPM2) in guinea pig brains, and the influence of melatonin on oxidative stress in lungs and airway inflammation induced by particulate matter 2.5 (PM2.5). A particle suspension (0.1 g/ml) was nasally administered to the guinea pigs to prepare a PM2.5 exposure model. Cough frequency and cough incubation period were determined through RM6240B biological signal collection and disposal system. Oxidative stress markers, including malondialdehyde (MDA), total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px), in the medulla oblongata were examined through spectrophotometer. Reactive oxygen species (ROS) were detected in the hypoglossal nucleus, cuneate nucleus, Botzinger complex, dorsal vagal complex, and airway through dihydroethidium fluorescence. Hematoxylin-eosin (HE) staining and substance P expression via immunohistochemistry revealed the inflammatory levels in the airway. TRPM2 was observed in the medulla oblongata through immunofluorescence and Western blot. The ultrastructure of the blood-brain barrier and neuronal mitochondria was determined by using a transmission electron microscope. Our study suggests that melatonin treatment decreased PM2.5-induced oxidative stress level in the brains and lungs and relieved airway inflammation and chronic cough. TRPM2 might participate in oxidative stress in the cough center by regulating cough.