Articular cartilage has limited self-regenerative capacity and the therapeutic methods for cartilage defects are still dissatisfactory in clinic. Recent studies showed that exosomes derived from mesenchymal stem cells promoted chondrogenesis by delivering bioactive substances to the recipient cells, indicating exosomes might be a novel method for repairing cartilage defect. Herein, we investigated the role and mechanism of human umbilical cord mesenchymal stem cells derived small extracellular vesicles (hUC-MSCs-sEVs) on cartilage regeneration. In vitro results showed that hUC-MSCs-sEVs promoted the migration, proliferation and differentiation of chondrocytes and human bone marrow mesenchymal stem cells (hBMSCs). MiRNA microarray showed that miR-23a-3p was the most highly expressed among the various miRNAs contained in hUC-MSCs-sEVs. Our data revealed that hUC-MSCs-sEVs promoted cartilage regeneration by transferring miR-23a-3p to suppress the level of PTEN and elevate expression of AKT. Moreover, we fabricated Gelatin methacrylate (Gelma)/nanoclay hydrogel (Gel-nano) for sustained release of sEVs, which was biocompatible and exhibited excellent mechanical property. In vivo results showed that hUC-MSCs-sEVs containing Gelma/nanoclay hydrogel (Gel-nano-sEVs) effectively promoted cartilage regeneration. These results indicated that Gel-nano-sEVs have a promising capacity to stimulate chondrogenesis and heal cartilage defects, and also provided valuable data for understanding the role and mechanism of hUC-MSCs-sEVs in cartilage regeneration.

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Background The treatment of critical-size bone defect is a great difficulty in orthopedics. Osteogenesis and angiogenesis are critical issue during the process of bone repair and remodeling. Mesenchymal stem cells (MSCs)-derived exosomes have the same therapeutic effect to MSCs-based therapies. The effect of human umbilical cord MSCs-derived sEVs (hUC-MSCs-sEVs) on vascularized bone regeneration and the potential mechanism remains to be investigated. Herein, we aimed to explore the therapeutic effect and the mechanism of hUC-MSCs-sEVs on critical-size bone defect. Methods To investigate the potential osteogenesis and angiogenesis effects of sEVs in vitro, we extracted sEVs from hUC-MSCs, and then sEVs were co-incubated with BMSCs and HUVECs. We next investigated the effect and potential mechanism of sEVs on the effects of osteogenesis and angiogenesis. We fabricated 3D-printed bioglass scaffold with Gelma/nanoclay hydrogel coatings to load sEVs (BG-gel-sEVs) to ensure in vivo sustained efficacy of sEVs. Finally, the skull defect model was used to evaluate the capacity of vascularized bone regeneration of the composited scaffolds. Results hUC-MSCs-sEVs facilitated calcium deposition and the endothelial network formation, inducing osteogenic differentiation and angiogenesis by delivering miR-23a-3p to activate PTEN/AKT signaling pathway. Additionally, the BG-gel-sEVs composited scaffold achieved vascularized bone regeneration in vivo. Conclusion This finding illuminated that hUC-MSCs-sEVs promoted osteogenesis and angiogenesis by delivering miR-23a-3p to activate PTEN/AKT signaling pathway, achieving vascularized bone regeneration.

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To improve the concentration performance of the concentrator in the iron ore beneficiation process for iron ore tailings, a coupled simulation analysis of the concentration process was conducted using the discrete element software EDEM (Engineering Discrete Element Method) and the finite element FLUENT software. The volume concentration at the bottom flow outlet of the concentrator was used as the evaluation index. The scraper rotation speed, feed rate, and feed concentration were considered as parameters. Response surface experiments were designed using the Box-Behnken module in Design Expert11 software, and numerical simulations were performed to obtain data. Based on the numerical simulation results, a prediction model was established using the backpropagation neural network (backpropagation neural network, BP-NN) and combined with the genetic algorithm (genetic algorithm, GA) for parameter optimization of the thickener’s concentration conditions. The results showed that with a scraper rotation speed of 9.7677 rpm, feed rate of 0.2037 m/s, and feed concentration of 6.5268%, the maximum outlet volume concentration reached approximately 62.00%. The predicted optimal working conditions were validated through physical tests and numerical simulations. The average outlet volume concentration in the physical tests was 60.712% (n = 10) (“n” is the number of experiments), with an error of only 2.077% compared to the predicted value. The middle outlet volume concentration in the numerical simulation experiments was 59.951% (n = 10), with an error of only 3.304% from the expected value. These results demonstrate the feasibility of using a genetic neural network for optimizing the EDEM–FLUENT simulation parameters of the thickener, providing valuable insights for the matching optimization of the thickener’s process parameters.

Background The treatment of critical-size bone defect is a great difficulty in orthopedics. Osteogenesis and angiogenesis are critical issue during the process of bone repair and remodeling. MSCs-derived small extracellular vesicles (sEVs) show desirable therapeutic prospects in tissue regeneration due to satisfied advantages including high stability, facilitated acquisition and abundant source. However, the effect of Human umbilical cord MSCs-derived sEVs (hUC-MSCs-sEVs) on vascularized bone regeneration and the potential mechanism remains to be investigated. Herein, we aimed to explore the therapeutic effect and the mechanism of hUC-MSCs-sEVs on critical-size bone defect. Methods To investigate the potential osteogenesis and angiogenesis effects of sEVs in vitro, we extracted sEVs from hUC-MSCs, and then sEVs were co-incubated with BMSCs and HUVECs. We next investigated the potential mechanism of sEVs on the effects of osteogenesis and angiogenesis by luciferase reporter gene assay and western blot. We fabricated 3D-printed bioglass scaffold with Gelma/nanoclay hydrogel coatings to load sEVs(BG-gel-sEVs) to ensure in vivo sustained efficacy of sEVs. Finally, the skull defect model was used to evaluate the capacity of vascularized bone regeneration of the composited scaffolds. Results hUC-MSCs-sEVs facilitated calcium deposition and the endothelial network formation, inducing osteogenic differentiation and angiogenesis by delivering miR-23a-3p to activate PTEN/AKT signaling pathway. Additionally, the BG-gel-sEVs composited scaffold achieved vascularized bone regeneration in vivo. Conclusion This finds illuminated that hUC-MSCs-sEVs promoted osteogenesis and angiogenesis by delivering miR-23a-3p to activate PTEN/AKT signaling pathway, achieving vascularized bone regeneration.

The recovery of zinc from metallurgical dust sludge is a crucial component of using solid waste as a resource in the metallurgical process, and deep eutectic solvent–ultrasonic synergistic enhanced leaching is an efficient method of doing so with excellent economic effects. The leaching rate of zinc is used as the value of response in this study, along with the four process conditions of leaching temperature, leaching time, liquid–solid ratio, and ultrasonic power. By building a regression model, the relationship between the various parameter components is investigated, and a strategy for optimization is then chosen and confirmed. The findings indicate that, for the parameters of temperature 40 °C, ultrasonic power 90 W, liquid–solid ratio 7:1 g/L, stirring speed 250 rpm, and leaching duration 80 min, the prediction value of the regression model of the zinc leaching rate is 98.47%. The average zinc leaching rate obtained by the 3 parallel verification experiments was 98.49%; the deviation from the regression model’s predicted value was 0.02%. This demonstrated that the experimental results were consistent with those predicted by the regression model, the experimental results were reliable and trustworthy, and the optimization scheme was reasonable and accurate. Compared with the conventional leaching method (leaching rate: 91.61%), the method under ultrasound increased the zinc leaching rate by 6.88%.