Background: Cartilage defects account for substantial economic and humanistic burdens and pose a significant clinical problem. The efficacy of clinical approaches to cartilage repair is often inadequate, in part, owing to the restricted proliferative capacity of chondrocytes. Molecules have the capacity to promote the differentiation of multipotent mesenchymal stem cells into chondrocytes and may also gain the ability to repair the damaged cartilage.Objective: This study aimed to investigate the role of Atsttrin (progranulin-derived engineered protein) in cartilage repair as well as the signaling pathway involved.Methods: Primary and mesenchymal stem cell lines were used for the micromass culture. A murine cartilage defect model was used to determine the role of Atsttrin in cartilage repair in vivo. Real-time polymerase chain reaction and Western blot analysis were used to monitor the effect of Atsttrin on the transcriptional and protein levels, respectively, of key anabolic and catabolic signaling molecules.Results: Atsttrin stimulated chondrogenesis in vitro and accelerated cartilage repair in vivo. In addition, Atsttrin-mediated cartilage repair occurred primarily through tumor necrosis factor receptor 2-initiated Akt signaling and downstream JunB transcription factor. Conclusion:Atsttrin might serve as a promising therapeutic modality for cartilage regeneration.

ObjectivesDysregulated chondrocyte metabolism is closely associated with the pathogenesis of osteoarthritis (OA). Suppressing chondrocyte catabolism to restore cartilage homeostasis has been extensively explored, whereas far less effort has been invested toward enhancing chondrocyte anabolism. This study aimed to repurpose clinically approved drugs as potential stimulators of chondrocyte anabolism in treating OA.MethodsScreening of a Food and Drug Administration-approved drug library; Assays for examining the chondroprotective effects of digoxin in vitro; Assays for defining the therapeutic effects of digoxin using a surgically-induced OA model; A propensity-score matched cohort study using The Health Improvement Network to examine the relationship between digoxin use and the risk of joint OA-associated replacement among patients with atrial fibrillation; identification and characterisation of the binding of digoxin to low-density lipoprotein receptor-related protein 4 (LRP4); various assays, including use of CRISPR-Cas9 genome editing to delete LRP4 in human chondrocytes, for examining the dependence on LRP4 of digoxin regulation of chondrocytes.ResultsSerial screenings led to the identification of ouabain and digoxin as stimulators of chondrocyte differentiation and anabolism. Ouabain and digoxin protected against OA and relieved OA-associated pain. The cohort study of 56 794 patients revealed that digoxin use was associated with reduced risk of OA-associated joint replacement. LRP4 was isolated as a novel target of digoxin, and deletion of LRP4 abolished digoxin’s regulations of chondrocytes.ConclusionsThese findings not only provide new insights into the understanding of digoxin’s chondroprotective action and underlying mechanisms, but also present new evidence for repurposing digoxin for OA.

The actual combustion rate of pulverized coal in the blast furnace tuyere is hard to be measured. In this research, the combustion rate of pulverized coal injected into oxygen blast furnace was obtained by a new equipment. This equipment can simulate the actual blast furnace well, and the relationship between pulverized coal injection (PCI) ratio and AO/C was established by mathematical deduction. The experimental results show that the best combustibility of the four pulverized coals is C, and when the coal injection ratio is 350 kg/tHM, the combustion rate can be reached 79%, while the combustion rate of B in the same case is only 45.6%. With the increase of AO/C, the relative amount of oxygen to coal increases, the combustion conditions become better, and combustion rate of the pulverized coal increases. In addition, under the condition of high temperature and rapid combustion, with the increase of coal’s volatile, the combustion rate increases and the corresponding PCI ratio is also increased. By using the new equipment, the unburned coal under the oxygen blast furnace conditions can be collected for further study.

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