miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells.

JOURNAL/nrgr/04.03/01300535-202501000-00035/figure1/v/2024-05-14T021156Z/r/image-tiff Our previous study found that rat bone marrow-derived neural crest cells (acting as Schwann cell progenitors) have the potential to promote long-distance nerve repair. Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication. Nevertheless, the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear. To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves, we collected conditioned culture medium from hypoxia-pretreated neural crest cells, and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation. The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells. We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells. Subsequently, to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons, we used a microfluidic axonal dissociation model of sensory neurons in vitro, and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons, which was greatly dependent on loaded miR-21-5p. Finally, we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb, as well as muscle tissue morphology of the hind limbs, were obviously restored. These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p. miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome. This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in repairing damaged peripheral nerves, and also promotes the application of miR-21-5p in tissue engineering regeneration medicine.

Promotive effect of skin precursor-derived Schwann cells on brachial plexus neurotomy and motor neuron damage repair through milieu-regulating secretome.

Brachial plexus injury (BPI) with motor neurons (MNs) damage still remain poor recovery in preclinical research and clinical therapy, while cell-based therapy approaches emerged as novel strategies. Previous work of rat skin precursor-derived Schwann cells (SKP-SCs) provided substantial foundation for repairing peripheral nerve injury (PNI). Given that, our present work focused on exploring the repair efficacy and possible mechanisms of SKP-SCs implantation on rat BPI combined with neurorrhaphy post-neurotomy. Results indicated the significant locomotive and sensory function recovery, with improved morphological remodeling of regenerated nerves and angiogenesis, as well as amelioration of target muscles atrophy and motor endplate degeneration. Besides, MNs could restore from oxygen-glucose-deprivation (OGD) injury upon SKP-SCs-sourced secretome treatment, implying the underlying paracrine mechanisms. Moreover, rat cytokine array assay detected 67 cytokines from SKP-SC-secretome, and bioinformatic analyses of screened 32 cytokines presented multiple functional clusters covering diverse cell types, including inflammatory cells, Schwann cells, vascular endothelial cells (VECs), neurons, and SKP-SCs themselves, relating distinct biological processes to nerve regeneration. Especially, a panel of hypoxia-responsive cytokines (HRCK), can participate into multicellular biological process regulation for permissive regeneration milieu, which underscored the benefits of SKP-SCs and sourced secretome, facilitating the chorus of nerve regenerative microenvironment. Furthermore, platelet-derived growth factor-AA (PDGF-AA) and vascular endothelial growth factor-A (VEGF-A) were outstanding cytokines involved with nerve regenerative microenvironment regulating, with significantly elevated mRNA expression level in hypoxia-responsive SKP-SCs. Altogether, through recapitulating the implanted SKP-SCs and derived secretome as niche sensor and paracrine transmitters respectively, HRCK would be further excavated as molecular underpinning of the neural recuperative mechanizations for efficient cell therapy; meanwhile, the analysis paradigm in this study validated and anticipated the actions and mechanisms of SKP-SCs on traumatic BPI repair, and was beneficial to identify promising bioactive molecule cocktail and signaling targets for cell-free therapy strategy on neural repair and regeneration.

Application value of intraoperative electrophysiological monitoring in cerebral eloquent area glioma surgery: a retrospective cohort study.

INTRODUCTION: Surgery for gliomas involving eloquent areas is a very challenging microsurgical procedure. Maximizing both the extent of resection (EOR) and preservation of neurological function have always been the focus of attention. Intraoperative neurophysiological monitoring (IONM) is widely used in this kind of surgery. The purpose of this study was to evaluate the efficacy of IONM in eloquent area glioma surgery. METHODS: Sixty-eight glioma patients who underwent surgical treatment from 2014 to 2019 were included in this retrospective cohort study, which focused on eloquent areas. Clinical indicators and IONM data were analysed preoperatively, two weeks after surgery, and at the final follow-up. Logistic regression, Cox regression, and Kaplan‒Meier analyses were performed, and nomograms were then established for predicting prognosis. The diagnostic value of the IONM indicator was evaluated by the receiver operating characteristic (ROC) curve. RESULTS: IONM had no effect on the postoperative outcomes, including EOR, intraoperative bleeding volume, duration of surgery, length of hospital stay, and neurological function status. However, at the three-month follow-up, the percentage of patients who had deteriorated function in the monitored group was significantly lower than that in the unmonitored group (23.3% vs. 52.6%; P < 0.05). Logistic regression analysis showed that IONM was a significant factor in long-term neurological function (OR = 0.23, 95% CI (0.07-0.70). In the survival analysis, long-term neurological deterioration indicated worsened overall survival (OS) and progression-free survival (PFS). A prognostic nomogram was established through Cox regression model analysis, which could predict the probability 3-year survival rate. The concordance index was 0.761 (95% CI 0.734-0.788). The sensitivity and specificity of IONM evoked potential (SSEP and TCeMEP) were 0.875 and 0.909, respectively. In the ROC curve analysis, the area under the curve (AUC) for the SSEP and TCeMEP curves was 0.892 (P < 0.05). CONCLUSIONS: The application of IONM could improve long-term neurological function, which is closely related to prognosis and can be used as an independent prognostic factor. IONM is practical and widely available for predicting postoperative functional deficits in patients with eloquent area glioma.

An enhanced multi-attribute crowd evacuation model incorporating the effects of environmental impact factors.

We propose an enhanced floor field model (FFM) to analyze the behavioral characteristics of crowds with varying attributes proportions during evacuation. This model governs pedestrian movement through the Dynamic Floor Field (DFF) and the Static Floor Field (SFF). The DFF takes into account individual factors such as the gender, familiarity with the environment, and social relationships of evacuees, which influence safe evacuation. Concurrently, the SFF encapsulates the impact of environmental factors like obstacles, exits, and guidance effects. Subsequently, this refined FFM was applied and validated using a sports center evacuation scenario. The results demonstrated that the enhanced FFM accurately replicated evacuees' asymmetric behavior and queuing, and aligned well with other models when the number of evacuees fluctuated over time. In the absence of guidance, both environmental familiarity and gender emerged as primary factors influencing partial evacuation. Additionally, the gender of pedestrians significantly affected the overall evacuation. Notably, compared to pre-existing environmental information available to evacuees, the implementation of guidance to augment pedestrians' environmental familiarity resulted in a more efficient evacuation. The FFM model and these findings could be instrumental in simulating personnel evacuation and formulating emergency management strategies in crowded areas.

Anisotropic microtopography surface of chitosan scaffold regulating skin precursor-derived Schwann cells towards repair phenotype promotes neural regeneration.

For repairing peripheral nerve and spinal cord defects, biomaterial scaffold-based cell-therapy was emerged as an effective strategy, requiring the positive response of seed cells to biomaterial substrate and environment signals. Previous work highlighted that the imposed surface properties of scaffold could provide important guidance cues to adhered cells for polarization. However, the insufficiency of native Schwann cells and unclear cellular response mechanisms remained to be addressed. Given that, this study aimed to illuminate the micropatterned chitosan-film action on the rat skin precursor-derived Schwann cells (SKP-SCs). Chitosan-film with different ridge/groove size was fabricated and applied for the SKP-SCs induction. Results indicated that SKP-SCs cultured on 30 µm size microgroove surface showed better oriented alignment phenotype. Induced SKP-SCs presented similar genic phenotype as repair Schwann cells, increasing expression of c-Jun, neural cell adhesion molecule, and neurotrophic receptor p75. Moreover, SKP-SC-secretome was subjected to cytokine array GS67 assay, data indicated the regulation of paracrine phenotype, a panel of cytokines was verified up-regulated at secreted level and gene expression level in induced SKP-SCs. These up-regulated cytokines exhibit a series of promotive neural regeneration functions, including cell survival, cell migration, cell proliferation, angiogenesis, axon growth, and cellular organization etc. through bioinformatics analysis. Furthermore, the effectively polarized SKP-SCs-sourced secretome, promoted the proliferation and migration capacity of the primarily cultured native rat Schwann cells, and augmented neurites growth of the cultured motoneurons, as well as boosted axonal regrowth of the axotomy-injured motoneurons. Taken together, SKP-SCs obtained pro-neuroregeneration phenotype in adaptive response to the anisotropic topography surface of chitosan-film, displayed the oriented parallel growth, the transition towards repair Schwann cell genic phenotype, and the enhanced paracrine effect on neural regeneration. This study provided novel insights into the potency of anisotropic microtopography surface to Schwann-like cells phenotype regulation, that facilitating to provide promising engineered cell-scaffold in neural injury therapies.

Urban Scene LOD Vectorized Modeling From Photogrammetry Meshes.

Urban scene modeling is a challenging task for the photogrammetry and computer vision community due to its large scale, structural complexity, and topological delicacy. This paper presents an efficient multistep modeling framework for large-scale urban scenes from aerial images. It takes aerial images and a textured 3D mesh model generated by an image-based modeling system as the input and outputs compact polygon models with semantics at different levels of detail (LODs). Based on the key observation that urban buildings usually have piecewise planar rooftops and vertical walls, we propose a segment-based modeling method, which consists of three major stages: scene segmentation, roof contour extraction, and building modeling. By combining the deep neural network predictions with geometric constraints of the 3D mesh, the scene is first segmented into three classes. Then, for each building mesh, the 2D line segments are detected and used to slice the ground into polygon cells, followed by assigning each cell a roof plane via a MRF optimization. Finally, the LOD model is obtained by extruding cells to their corresponding planes. Compared with direct modeling in 3D space, we transform the mesh into a uniform 2D image grid representation and most of the modeling work is performed in 2D space, which has the advantages of low computational complexity and high robustness. In addition, our method doesn't require any global prior, such as the Manhattan or Atlanta world assumption, making it flexible to model scenes with different characteristics and complexity. Experiments on both single buildings and large-scale urban scenes demonstrate that by combining 2D photometric with 3D geometric information, the proposed algorithm is robust and efficient in urban scene LOD vectorized modeling compared with the state-of-the-art approaches.

Tuned Local Surface Potential of Epoxy Resin Composites by Inorganic Core-Shell Microspheres: Key Roles of the Interface.

Designing and controlling the interface interaction between polymer and filler is a challenge for nanocomposite insulation materials with the enhanced insulating and thermal conductive properties simultaneously. Meanwhile, the roles of the interface in the charge distribution of the composite on the macroscale are well studied. However, the effects of the interface on the nanoscale are not clear. In this work, first, we have demonstrated a method to modify the dielectric constant of composites by introduced air into the core-shell-structured M-SiO2@Al2O3 particles. To clarify the electric interfacial region, we use Kelvin probe force microscopy (KPFM) to image with high spatial resolution of the surface charge distribution around an individual M-SiO2@Al2O3 particle embedded in the epoxy matrix. We find that the KPFM results of the distinct electric interfacial region are consistent with the finite element simulation. Moreover, the charge accumulation is much easier in the presence of the M-SiO2@Al2O3 particles because of the increasing concentration of traps. This work provides significant insight into understanding the intrinsic interfacial behavior in insulating polymeric composites.