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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]

In order to analyze the temporal and spatial changes of natural grassland vegetation coverage in different months of the growing season in Northern Xinjiang and its relationship with meteorological factors, the pixel dichotomy model, change rate analysis and correlation analysis were used to explore the temporal and spatial changes of natural grassland vegetation coverage and its relationship with meteorological factors in Northern Xinjiang in June, July, August and September from 1998 to 2018. The results showed that the vegetation coverages of natural grassland in Northern Xinjiang were lower in the middle and east with less precipitation and higher temperature, higher in the north, west and south with higher altitude, more precipitation and higher relative humidity, which increased from the middle and east to the north, west and south. In June, July, August and September, the natural grassland vegetation coverage in Northern Xinjiang showed no significant decreasing trend, in which the monthly average natural grassland coverage was June>July> September>August. The normalized difference vegetation index of natural grassland in Northern Xinjiang showed an increasing trend in July and decreasing trend in June, August and September. The monthly average natural grassland vegetation coverages in Northern Xinjiang were mainly positively correlated with precipitation and relative humidity in June, July and August, and were mainly positively correlated with temperature and sunshine hours in September. [ABSTRACT FROM AUTHOR]

The sliding electrical contact (SEC) between rails and armature is a focus in electromagnetic rail launchers. The extreme conditions, such as high current density, high temperature, and high contact pressure, influence SEC performance. In this article, the segmented rails were used to study the effects of launch mass on SEC. Two groups of experiments, armatures with and without launch mass, were carried out. The mass difference of rail parts was measured, the macro- and micromorphology of rails surface were observed, and the driving current and muzzle voltage were obtained. Three conclusions are obtained: 1) the mass difference of rail parts in shooting with launch mass is greater than that without launch mass, due to the high temperature of armature contact surfaces; 2) because of the electron migration, the mass difference of the cathode rail is larger than the anode rail; and 3) the contact resistance between rails and armature without launch mass is lower than that with launch mass, result from the large contact area. Moreover, the current density and the temperature of the armature and rails were calculated. Results show that the temperature of surface of armature with launch mass is higher than that without launch mass. In a word, based on the results from experiments and simulations, the launch mass improves the sliding electric contact performance. [ABSTRACT FROM AUTHOR]

Change of biophysical factors in tissue microenvironment is an important step in a chronic disease development process. A mechanical and biochemical factor from cell living microniche can regulate cell epigenetic decoration and, therefore, further induce change of gene expression. In this review, we will emphasize the mechanism that biophysical microenvironment manipulates cell behavior including gene expression and protein decoration, through modifying histone amino acid residue modification. The influence given by different mechanical forces, including mechanical stretch, substrate surface stiffness, and shear stress, on cell fate and behavior during chronic disease development including tumorigenesis will also be teased out. Overall, the recent work summarized in this review culminates on the hypothesis that a mechanical factor stimulates the modification on histone which could facilitate disease detection and potential therapeutic target. [ABSTRACT FROM AUTHOR]

The [Ca24Al28O64]4+:4e− (C12A7:e−) electride is a conductive oxide ceramic with high injected electron concentration and low work function, but its brittleness leads to difficulty in mechanical processing and low production yield. The present work aimed at improving the mechanical properties of C12A7:e− by introducing monoclinic ZrO2. When the ZrO2 content was 5 wt%, the fracture toughness increased 133% from 1.819 to 4.214 MPa m1/2 and the flexural strength increased 116% from 15.916 to 34.469 MPa for C12A7:e−-5 wt% ZrO2, indicating that ZrO2 can effectively improve the mechanical properties of C12A7:e−. The microstructure and phase analysis showed that the toughening mechanisms of ZrO2 composite C12A7:e− contain both stress-induced phase transformation toughening and dispersion toughening of ZrO2 particles. When the content of ZrO2 is between 0 and 5 wt%, the injected electron concentration of C12A7:e−-ZrO2 was maintained in the range of 2.05–2.10 × 1021 cm−3 and illustrate excellent electrical transport properties. The study indicated that adding ZrO2 in C12A7:e− effectively solves the problem of brittle fracture, improves the finished product rate during processing, and maintains its excellent electrical transport properties. [ABSTRACT FROM AUTHOR]

Armature ejecta, which erodes the insulator and reduces surface dielectric strength, has been considered as a threat to solid-armature launchers. Two series of experiments were carried out in a small caliber launcher (SCL) to investigate the sources of armature ejecta and degradation mechanisms of the insulator. In first series of experiment, the ejection of armature was imaged by a high-speed camera. The influence of linear current density on ejection was studied in second series of experiment. Mass difference of insulator samples was used to evaluate the output of armature ejecta. Insulation performance was judged from the surface flashover voltage. And the degradation mechanism resulted from armature ejecta was analyzed based on the process of surface flashover. Results show that the local breakdown at armature–rail interfaces is one of the sources of armature ejecta. The amount of ejecta on samples increased with linear current density. Average flashover voltages decreased when ejecta increased in Zone A (0–200 mm) and Zone B (200–600 mm). And there was little difference of average flashover voltages in Zone C (600–900 mm). The discharge channel of the post-shot sample was composed of arcs and ejecta. The distortion of the surface electric field and the shorten of creepage distance are degradation mechanisms of bore insulators in solid-armature launchers. [ABSTRACT FROM AUTHOR]

Muzzle arc is a general phenomenon when the armature leaves the muzzle, and it is also a reason for the complexity of intermediate ballistic of electromagnetic launchers. In this article, a 3-D model has been developed to investigate muzzle arc flow field in a smaller caliber launcher. The coupled interaction of electromagnetic, flow, and thermal fields is realized by the magnetohydrodynamic (MHD) theory in conjunction with a renormalization group (RNG) $k$ - $\varepsilon $ turbulence model. The arc boundary conditions, arc root radius, and time-dependent current density are reasonably set on the basis of the experimental data and physical process. Simulation results reveal the relationship between muzzle arc and muzzle voltage. The rising edge of muzzle voltage corresponds to the arc expansion stage. The falling edge corresponds to the muzzle breakdown stage. And the turning point from rising edge to falling edge is the moment of muzzle breakdown. The flat section corresponds to the arc extinguishing stage. The muzzle blowback is the consequence of the arc expansion which produces a compression wave moving toward the breech. The velocity of blowback flow decreases from 670 to 270 m/s during the arc expansion stage. Then, it increases to about 350 m/s and tends to be stable due to the muzzle breakdown. [ABSTRACT FROM AUTHOR]

For reconstructive surgeons, critically skeletal damage represents a major challenge. Growing evidence indicate that bone repair is dynamically regulated by the mesenchymal stem cell (MSC)‐macrophage interaction. Mechanical strain plays a fundamental role in bone repair and regeneration by influencing MSCs differentiation. Recently, a few findings indicate that macrophages may be mechanically sensitive and their phenotype can be regulated, in part, by mechanical cues. However, how macrophages subjected mechanical stretch influence the osteogenic differentiation of MSCs remain unclear. Thus, the purpose of this study is to explore the effect of macrophages stimulated with mechanical stretch on MSCs osteogenesis. By using a coculture system, we discover that macrophages efficiently induce osteogenic differentiation of MSCs under specific stretch conditions. A synergy mechanism between M2 polarization and YAP/BMP2 axis are identified through molecular and genetic analyses. Macrophages are activated by cyclic stretch and polarized to M2 phenotype that produce anti‐inflammatory cytokines such as IL‐10 and TGF‐β to regulate the local inflammatory microenvironment. Furthermore, mechanical stretch induces YAP activation and nuclear translocation, subsequently regulates downstream BMP2 expression to facilitate MSCs osteogenesis. These findings not only advance our understanding of the complex influence among the mechanical strain, macrophage inflammatory response as well as the osteogenic differentiation of MSCs, but also reveal a control system from mechanical signals to chemical response then to cell behaviors during bone repair and regeneration. [ABSTRACT FROM AUTHOR]