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Vascular smooth muscle cells (SMCs) are heterogeneous, and their differential responses to vascular injury are not well understood. To address this question, we performed single-cell analysis of vascular cells to a ligation injury in mouse carotid arteries after 3 days. While endothelial cells had a homogeneous activation of mesenchymal genes, less than 30% of SMCs responded to the injury and generated 2 distinct clusters - i.e., proinflammatory SMCs and stress-responsive SMCs. Proinflammatory SMCs were enriched with high levels of inflammatory markers such as vascular cell adhesion molecule-1 while stress-responsive SMCs overexpressed heat shock proteins. Trajectory analysis suggested that proinflammatory SMCs were potentially derived from a specific subpopulation of SMCs. Ligand-receptor pair analysis showed that the interaction between macrophages and proinflammatory SMCs was the major cell-cell communication among all cell types in the injured arteries. In vitro coculture demonstrated that VCAM1+ SMCs had a stronger chemotactic effect on macrophage recruitment than VCAM1- SMCs. Consistently, the number of VCAM1+ SMCs significantly increased in injured arteries and atherosclerotic lesions of ApoE-/- mice and human arteries. These findings provide insights at the single-cell level on the distinct patterns of endothelial cells and SMC responses to vascular injury.

Cell reprogramming has wide applications in tissue regeneration, disease modelling and personalized medicine. In addition to biochemical cues, mechanical forces also contribute to the modulation of the epigenetic state and a variety of cell functions through distinct mechanisms that are not fully understood. Here we show that millisecond deformation of the cell nucleus caused by confinement into microfluidic channels results in wrinkling and transient disassembly of the nuclear lamina, local detachment of lamina-associated domains in chromatin and a decrease of histone methylation (histone H3 lysine 9 trimethylation) and DNA methylation. These global changes in chromatin at the early stage of cell reprogramming boost the conversion of fibroblasts into neurons and can be partially reproduced by inhibition of histone H3 lysine 9 and DNA methylation. This mechanopriming approach also triggers macrophage reprogramming into neurons and fibroblast conversion into induced pluripotent stem cells, being thus a promising mechanically based epigenetic state modulation method for cell engineering.

BackgroundMuscle denervation from trauma and motor neuron disease causes disabling morbidities. A limiting step in functional recovery is the regeneration of neuromuscular junctions (NMJs) for reinnervation. Stem cells have the potential to promote these regenerative processes, but current approaches have limited success, and the optimal types of stem cells remain to be determined. Neural crest stem cells (NCSCs), as the developmental precursors of the peripheral nervous system, are uniquely advantageous, but the role of NCSCs in neuromuscular regeneration is not clear. Furthermore, a cell delivery approach that can maintain NCSC survival upon transplantation is critical.MethodsWe established a streamlined protocol to derive, isolate, and characterize functional p75+ NCSCs from human iPSCs without genome integration of reprogramming factors. To enhance survival rate upon delivery in vivo, NCSCs were centrifuged in microwell plates to form spheroids of desirable size by controlling suspension cell density. Human bone marrow mesenchymal stem cells (MSCs) were also studied for comparison. NCSC or MSC spheroids were injected into the gastrocnemius muscle with denervation injury, and the effects on NMJ formation and functional recovery were investigated. The spheroids were also co-cultured with engineered neuromuscular tissue to assess effects on NMJ formation in vitro.ResultsNCSCs cultured in spheroids displayed enhanced secretion of soluble factors involved in neuromuscular regeneration. Intramuscular transplantation of spheroids enabled long-term survival and retention of NCSCs, in contrast to the transplantation of single-cell suspensions. Furthermore, NCSC spheroids significantly improved functional recovery after four weeks as shown by gait analysis, electrophysiology, and the rate of NMJ innervation. MSC spheroids, on the other hand, had insignificant effect. In vitro co-culture of NCSC or MSC spheroids with engineered myotubes and motor neurons further evidenced improved innervated NMJ formation with NCSC spheroids.ConclusionsWe demonstrate that stem cell type is critical for neuromuscular regeneration and that NCSCs have a distinct advantage and therapeutic potential to promote reinnervation following peripheral nerve injury. Biophysical effects of spheroidal culture, in particular, enable long-term NCSC survival following in vivo delivery. Furthermore, synthetic neuromuscular tissue, or "tissues-on-a-chip," may offer a platform to evaluate stem cells for neuromuscular regeneration.

Bioresorbable electronic stimulators are of rapidly growing interest as unusual therapeutic platforms, i.e., bioelectronic medicines, for treating disease states, accelerating wound healing processes and eliminating infections. Here, we present advanced materials that support operation in these systems over clinically relevant timeframes, ultimately bioresorbing harmlessly to benign products without residues, to eliminate the need for surgical extraction. Our findings overcome key challenges of bioresorbable electronic devices by realizing lifetimes that match clinical needs. The devices exploit a bioresorbable dynamic covalent polymer that facilitates tight bonding to itself and other surfaces, as a soft, elastic substrate and encapsulation coating for wireless electronic components. We describe the underlying features and chemical design considerations for this polymer, and the biocompatibility of its constituent materials. In devices with optimized, wireless designs, these polymers enable stable, long-lived operation as distal stimulators in a rat model of peripheral nerve injuries, thereby demonstrating the potential of programmable long-term electrical stimulation for maintaining muscle receptivity and enhancing functional recovery.

Rapid urbanization has made road construction and maintenance imperative, but detecting road diseases has been time-consuming with limited accuracy. To overcome these challenges, we propose an efficient YOLOv7 road disease detection model. Our approach involves integrating MobilieNetV3 as the backbone feature extraction network to reduce the network's parameters and computational requirements. Additionally, we introduce the BRA attention module into the spatial pyramid pooling module to eliminate redundant information and enhance the network's feature representation capability. Moreover, we utilize the F-ReLU activation function in the backbone network, expanding the convolutional layers' receptive field range. To optimize the model's boundary loss, we employ the Wise-IoU loss function, which places more emphasis on the quality of ordinary samples and enhances the overall performance and generalization ability of the network. Experimental results demonstrate that our improved detection algorithm achieves a higher recall rate and mean average precision (mAP) on the public dataset (RDD) and the NJdata dataset in Nanjing's urban area. Specifically, compared to YOLOv7, our model increases the recall rate and mAP on RDD by 3.3% and 2.6%, respectively. On the NJdata dataset, our model improves the recall rate and mAP by 1.9% and 1.3%, respectively. Furthermore, our model reduces parameter and computational requirements by 30% and 22.5%, respectively, striking a balance between detection accuracy and speed. In conclusion, our road disease detection model presents an effective solution to address the challenges associated with road disease detection in urban areas. It offers improved accuracy, efficiency, and generalization capabilities compared to existing models. [ABSTRACT FROM AUTHOR]

Rationally adjusting the interface between SnO2 electron transport layer (ETL) and the perovskite (PVK) buried surface plays a key role in achieving efficient and stable PVK solar cells (PSCs). Herein, a cost‐effective organic salt, 5‐bromo‐6‐chloro‐3‐indolyl sulfate potassium salt (SPS), used as an interface modifier is deposited on the SnO2 ETL. SPS has played a multifunctional role in ETL and PVK layer: 1) the highly electronegative SO4− group of SPS can be adsorbed on the surface of SnO2 films, resulting in the energy levels of the PVK layer and SnO2 ETL becomes more compatible. 2) The lower contact angle of the modified SnO2 film is conducive to the formation of pinhole‐free PVK films. 3) The functional groups in SPS are helpful for the decrease of defect density in the PVK films. As a consequence, the defect density reduces from 8.17 × 1015 to 5.57 × 1015 cm−3. The power conversion efficiency (PCE) of modified PSCs increases from 19.82% to 21.33%. Furthermore, the unencapsulated modified devices retain 91.7% of the initial PCE after 624 h. These results indicate that using SPS as a multifunctional interface modifier is a promising strategy to achieve efficient and stable PSCs. [ABSTRACT FROM AUTHOR]