Fetal dermal mesenchymal stem cells (FDMSCs), isolated from fetal skin, are serving as a novel MSC candidate with great potential in regenerative medicine. More recently, the paracrine actions, especially MSC-derived exosomes, are being focused on the vital role in MSC-based cellular therapy. This study was to evaluate the therapeutic potential of exosomes secreted by FDMSCs in normal wound healing. First, the in vivo study indicated that FDMSC exosomes could accelerate wound closure in a mouse full-thickness skin wound model. Then, we investigated the role of FDMSC-derived exosomes on adult dermal fibroblast (ADFs). The results demonstrated that FDMSC exosomes could induce the proliferation, migration, and secretion of ADFs. We discovered that after treatment of exosomes, the Notch signaling pathway was activated. Then, we found that in FDMSC exosomes, the ligands of the Notch pathway were undetectable expect for Jagged 1, and the results of Jagged 1 mimic by peptide and knockdown by siRNA suggested that Jagged 1 may lead the activation of the Notch signal in ADFs. Collectively, our findings indicated that the FDMSC exosomes may promote wound healing by activating the ADF cell motility and secretion ability via the Notch signaling pathway, providing new aspects for the therapeutic strategy of FDMSC-derived exosomes for the treatment of skin wounds.

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As a crucial part of the Intelligent Transportation System, traffic forecasting is of great help for traffic management and guidance. However, predicting short-term traffic conditions on a large-scale road network is challenging due to the complex spatio-temporal dependencies found in traffic data. Previous studies used Euclidean proximity or topological adjacency to explore the spatial correlation of traffic flows, but did not consider the higher-order connectivity patterns exhibited in a road network, which have a significant influence on traffic propagation. Meanwhile, traffic sequences display distinct multiple timefrequency properties, yet few researchers have made full use of this resource. To fill this gap, we propose a novel hybrid framework-Wavelet-based Higher-order Spatial-Temporal method (Wavelet-HST) to accurately predict network-scale traffic speeds. Wavelet-HST first uses discrete wavelet transform (DWT) to decompose raw traffic data into several components with different frequency sub-bands. Then a motifbased graph convolutional recurrent neural network (Motif-GCRNN) is proposed to learn the higherorder spatio-temporal dependencies of traffic speeds from low-frequency components, and auto-regressive moving average (ARMA) models are employed to simulate random fluctuations from the high-frequency components. We evaluate the framework on a traffic dataset collected in Chengdu, China, and experimental results demonstrate that Wavelet-HST outperforms six state-of-art prediction methods by an improvement of 7.8% ∼10.5% in the root mean square error. INDEX TERMS Traffic prediction, graph convolutional network (GCN), spatio-temporal modeling, higherorder connectivity patterns, wavelet transform, time-frequency properties.

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The regenerative repair of deep-degree (second degree) burned skin remains a notable challenge in the treatment of burn injury, despite improvements being made with regards to treatment modality and the emergence of novel therapies. Fetal skin constitutes an attractive target for investigating scarless healing of burned skin. To investigate the inflammatory response during scarless healing of burned fetal skin, the present study developed a nude mouse model, which was implanted with normal human fetal skin and burned fetal skin. Subsequently, human peripheral blood mononuclear cells (PBMCs) were used to treat the nude mouse model carrying the burned fetal skin. The expression levels of matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinases (TIMP)-1 were investigated during this process. In the present study, fetal skin was subcutaneously implanted into the nude mice to establish the murine model. Hematoxylin and eosin staining was used to detect alterations in the skin during the development of fetal skin and during the healing process of deep-degree burned fetal skin. The expression levels of MMP-9 and TIMP-1 were determined using immunochemical staining, and their staining intensity was evaluated by mean optical density. The results demonstrated that fetal skin subcutaneously implanted into the dorsal skin flap of nude mice developed similarly to the normal growth process in the womb. In addition, the scarless healing process was clearly observed in the mice carrying the burned fetal skin. A total of 2 weeks was required to complete scarless healing. Following treatment with PBMCs, the burned fetal skin generated inflammatory factors and enhanced the inflammatory response, which consequently resulted in a reduction in the speed of healing and in the formation of scars. Therefore, exogenous PBMCs may alter the lowered immune response environment, which is required for scarless healing, resulting in scar formation. In conclusion, the present study indicated that the involvement of inflammatory cells is important during the healing process of deep-degree burned skin, and MMP-9 and TIMP-1 may serve important roles in the process of scar formation.

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