Neuroimmune modulating and energy supporting nanozyme-mimic scaffold synergistically promotes axon regeneration after spinal cord injury.

Spinal cord injury (SCI) represents a profound central nervous system affliction, resulting in irreversibly compromised daily activities and disabilities. SCI involves excessive inflammatory responses, which are characterized by the existence of high levels of proinflammatory M1 macrophages, and neuronal mitochondrial energy deficit, exacerbating secondary damage and impeding axon regeneration. This study delves into the mechanistic intricacies of SCI, offering insights from the perspectives of neuroimmune regulation and mitochondrial function, leading to a pro-fibrotic macrophage phenotype and energy-supplying deficit. To address these challenges, we developed a smart scaffold incorporating enzyme mimicry nanoparticle-ceriumoxide (COPs) into nanofibers (NS@COP), which aims to pioneer a targeted neuroimmune repair strategy, rescuing CGRP receptor on macrophage and concurrently remodeling mitochondrial function. Our findings indicate that the integrated COPs restore the responsiveness of pro-inflammatory macrophages to calcitonin gene-related peptide (CGRP) signal by up-regulating receptor activity modifying protein 1 (RAMP1), a vital component of the CGRP receptor. This promotes macrophage fate commitment to an anti-inflammatory pro-resolution M2 phenotype, then alleviating glial scar formation. In addition, NS@COP implantation also protected neuronal mitochondrial function. Collectively, our results suggest that the strategy of integrating nanozyme COP nanoparticles into a nanofiber scaffold provides a promising therapeutic candidate for spinal cord trauma via rational regulation of neuroimmune communication and mitochondrial function.

Constitutive Modeling of Annealed OFHC with Wide Strain-Rate and Temperature Effects: Incorporating Dislocation Dynamics and Normalized Microstructural Size Evolution.

The flow stress of face-centered cubic (FCC) metals exhibits a rapid increase near a strain rate of 104 s-1 under fixed-strain conditions. However, many existing constitutive models either fail to capture the mechanical characteristics of this plastic deformation or use piecewise strain-rate hardening models to describe this phenomenon. Unfortunately, these piecewise models may suffer from issues such as discontinuity of physical quantities and difficulties in determining segment markers, and struggle to reflect the underlying physical mechanisms that give rise to this mutation phenomenon. In light of this, this paper proposes that the abrupt change in flow stress sensitivity to strain rate in FCC metals can be attributed to microstructural evolution characteristics. To address this, a continuous semiempirical physical constitutive model for FCC metals is established based on the microstructural size evolution proposed by Molinari and Ravichandran and the dislocation motion slip mechanism. This model effectively describes the mutation behavior of strain-rate sensitivity under fixed strain, particularly evident in an annealed OFHC. The predicted results of the model across a wide range of strain rates (10-4-106 s-1) and temperatures (77-1096 K) demonstrate relative errors generally within ±10% of the experimental values. Furthermore, the model is compared with five other models, including the mechanical threshold stress (MTS), Nemat-Nasser-Li (NNL), Preston-Tonks-Wallace (PTW), Johnson-Cook (JC), and Molinari-Ravichandran (MR) models. A comprehensive illustration of errors reveals that the proposed model outperforms the other five models in describing the plastic deformation behavior of OFHC. The error results offer valuable insights for selecting appropriate models for engineering applications and provide significant contributions to the field.

Application of TVD-Net for sagittal alignment and instability measurements in cervical spine radiographs.

BACKGROUND: Cervical spinal malalignment and instability are frequently occurring pathological conditions involving neck pain, radiculopathy, and myelopathy, often requiring surgical intervention. Accurate assessment of cervical alignment and instability are essential in surgical planning and evaluating postoperative outcomes. PURPOSE: To automatically measure the sagittal alignment and instability of the cervical spine, we develop a novel deep-learning model by detecting landmarks on cervical radiographs. METHODS: We introduce the transformer-embedded residual network (ResNet) as the network's core to automatically identify vertebral landmarks on digital and film-transformed cervical radiographs, and simultaneously measure the segmental Cobb angle and horizontal displacement. A Transformer Module was embedded into the latent space to extract the relationship between different vertebrae. Then a Rotating Attention Module was integrated between the encoder-decoder pairs to highlight the key points and maintain more details. Finally, a Vector Loss Module was proposed to restrain the orientation of the adjacent vertebra to reduce misdetection. All images were obtained from local hospital. Digital images were split into training, validation, and test subsets (896, 225, and 353 images, respectively). Likewise, film-transformed images were split into 404, 115, and 150 images, respectively. The results of the model were compared with manual measurements. RESULTS: Our deep learning algorithm achieved mean absolute difference (MAD) at a level of 2.20° and 2.33°, symmetric mean absolute error(SMAPE)at 16.63% and 19.35%, respectively, when measuring Cobb angle on digital images and films. On evaluating cervical instability, the diagnostic accuracy, sensitivity, specificity, precision, and F1-score evaluation metrics were calculated. The corresponding values were 89.80%, 86.49%, 90.68%, 71.11%, and 78.05% on digital images, and 90.00%, 83.78%, 91.15%, 75.61%, and 79.49% on film-transformed images, which were comparable to experienced surgeons. Visualization results demonstrated robust effectiveness in subjects with severe osteophytes or artifacts. CONCLUSION: This study presents a novel and efficient deep-learning model to assist landmarks identification and angulation and displacement calculation on lateral cervical spine radiographs, and demonstrates excellent accuracy in measuring cervical alignment and sound sensitivity and specificity in cervical instability diagnosis. It should be helpful for future research and clinical applications.

Low-dose celecoxib-loaded PCL fibers reverse intervertebral disc degeneration by up-regulating CHSY3 expression.

Intervertebral disc degeneration (IDD) has been identified as one of the predominant factors leading to persistent low back pain and disability in middle-aged and elderly people. Dysregulation of Prostaglandin E2 (PGE2) can cause IDD, while low-dose celecoxib can maintain PGE2 at the physiological level and activate the skeletal interoception. Here, as nano fibers have been extensively used in the treatment of IDD, novel polycaprolactone (PCL) nano fibers loaded with low-dose celecoxib were fabricated for IDD treatment. In vitro studies demonstrated that the nano fibers had the ability of releasing low-dose celecoxib slowly and sustainably and maintain PGE2. Meanwhile, in a puncture-induced rabbit IDD model, the nano fibers reversed IDD. Furthermore, low-dose celecoxib released from the nano fibers was firstly proved to promote CHSY3 expression. In a lumbar spine instability-induced mouse IDD model, low-dose celecoxib inhibited IDD in CHSY3wt mice rather than CHSY3-/- mice. This model indicated that CHSY3 was indispensable for low-dose celecoxib to alleviate IDD. In conclusion, this study developed a novel low-dose celecoxib-loaded PCL nano fibers to reverse IDD by maintaining PGE2 at the physiological level and promoting CHSY3 expression.

Research on non-cohesive jet formed by Zr-based amorphous alloys.

The shaped charge jet formation of a Zr-based amorphous alloy and the applicability of different numerical algorithms to describe the jet formed were experimentally and numerically investigated. X-ray experiments were performed to study jet characteristics. The numerical results for the Zr-based amorphous alloy jet formed via the Euler and smooth particle hydrodynamics (SPH) algorithms were compared and analyzed using the Autodyn hydrocode. Particle motion was examined based on material properties. The Zr-based amorphous alloy formed a noncohesive jet driven by an 8701 explosive. Both the Euler and SPH algorithms achieved high accuracy for the determination of jet velocity. When the improved Johnson-Holmquist constitutive model (JH-2) was used, numerical results confirmed the model's suitability for the Zr-based amorphous alloy. The Euler algorithm effectively reflected jet shape within a short computing time, whereas the SPH algorithm was highly suitable for showing the shape of the jet tail within a long computing time. In the 3D Euler model, the flared jet mouth indicated radial particle dispersion; however, in the 2D model, particle dispersion in the head was directly observed by using the JH-2 material model. The brittle fracture of the material reduced the proportion of particles near the liner apex forming a jet. Furthermore, a new method in which stagnation pressure was used to predict jet formation and its coherence was proposed since the collapse angle was difficult to obtain.

Sensory Nerve Maintains Intervertebral Disc Extracellular Matrix Homeostasis Via CGRP/CHSY1 Axis.

Sensory nerves are long being recognized as collecting units of various outer stimuli; recent advances indicate that the sensory nerve also plays pivotal roles in maintaining organ homeostasis. Here, this study shows that sensory nerve orchestrates intervertebral disc (IVD) homeostasis by regulating its extracellular matrix (ECM) metabolism. Specifically, genetical sensory denervation of IVD results in loss of IVD water preserve molecule chondroitin sulfate (CS), the reduction of CS bio-synthesis gene chondroitin sulfate synthase 1 (CHSY1) expression, and dysregulated ECM homeostasis of IVD. Particularly, knockdown of sensory neuros calcitonin gene-related peptide (CGRP) expression induces similar ECM metabolic disorder compared to sensory nerve denervation model, and this effect is abolished in CHSY1 knockout mice. Furthermore, in vitro evidence shows that CGRP regulates nucleus pulposus cell CHSY1 expression and CS synthesis via CGRP receptor component receptor activity-modifying protein 1 (RAMP1) and cyclic AMP response element-binding protein (CREB) signaling. Therapeutically, local injection of forskolin significantly attenuates IVD degeneration progression in mouse annulus fibrosus puncture model. Overall, these results indicate that sensory nerve maintains IVD ECM homeostasis via CGRP/CHSY1 axis and promotes IVD repair, and this expands the understanding concerning how IVD links to sensory nerve system, thus shedding light on future development of novel therapeutical strategy to IVD degeneration.

Influence Mechanism of Foamed Concrete Coating Thickness on the Blast Resistance of RC Walls.

How to effectively reduce the damage of frequent accidental explosions and explosion attacks to existing walls is an important concern of the blast resistance field. In the present study, the influence of the foamed concrete (density 820 kg/m3, water-cement ratio 0.4) coating thickness on the blast resistance of a 120 mm RC (reinforced concrete) wall was studied through blast experiments, numerical simulations, and shock wave theory. Results show that the influences of foamed concrete on the blast resistance of RC walls are jointly decided by the stress drop caused by impedance effect and exponential attenuation and the stress rise caused by high-speed impact compression. The coating thickness mainly affects the foam concrete's fragmentation degree and stress attenuation. A lower critical coating thickness exists in foamed concrete-coated RC walls. The blast resistance of the RC wall will decrease when the coating thickness is less than that value. The lower critical coating thickness is related to the intensity of blast load and the energy absorption capacity of foamed concrete, and it can be predicted by monitoring the explosive stress and energy incident to the RC wall.

W-Transformer: Accurate Cobb angles estimation by using a transformer-based hybrid structure.

BACKGROUND: Scoliosis is a type of spinal deformity, which is harmful to a person's health. In severe cases, it can trigger paralysis or death. The measurement of Cobb angle plays an essential role in assessing the severity of scoliosis. PURPOSE: The aim of this paper is to propose an automatic system for landmark detection and Cobb angle estimation, which can effectively help clinicians diagnose and treat scoliosis. METHODS: A novel hybrid framework was proposed to measure Cobb angle precisely for clinical diagnosis, which was referred as W-Transformer due to its w-shaped architecture. First, a convolutional neural network of cascade residual blocks as our backbone was designed. Then a transformer was fused to learn the dependency information between spine and landmarks. In addition, a reinforcement branch was designed to improve the overlap of landmarks, and an improved prediction module was proposed to fine-tune the final coordinates of landmarks in Cobb angles estimation. Besides, the public Accurate Automated Spinal Curvature Estimation (AASCE) MICCAI 2019 challenge was served as data set. It supplies 609 manually labeled spine anterior-posterior (AP) X-ray images, each of which contains a total of 68 landmark labels and three Cobb Angles tags. RESULTS: From the perspective of the AASCE MICCAI 2019 challenge, we achieved a lower symmetric mean absolute percentage error (SMAPE) of 8.26% for all Cobb angles and the lowest averaged detection error of 50.89 in terms of landmark detection, compared with many state-of-the-art methods. We also provided the SMAPEs for the Cobb angles of the proximal-thoracic (PT), the main-thoracic (MT), and the thoracic-lumbar (TL) area, which are 5.27%, 14.59%, and 20.97% respectively, however, these data were not covered in most previous studies. Statistical analysis demonstrates that our model has obtained a high level of Pearson correlation coefficient of 0.9398 ( p < 0.001 $p<0.001$ ), which shows excellent reliability of our model. Our model can yield 0.9489 ( p < 0.001 $p<0.001$ ), 0.8817 ( p < 0.001 $p<0.001$ ), and 0.9149 ( p < 0.001 $p<0.001$ ) for PT, MT, and TL, respectively. The overall variability of Cobb angle measurement is less than 4 ∘ $^\circ$ , implying clinical value. And the mean absolute deviation (standard deviation) for three regions is 3.64 ∘ $^\circ$ (4.13 ∘ $^\circ$ ), 3.84 ∘ $^\circ$ (4.66 ∘ $^\circ$ ), and 3.80 ∘ $^\circ$ (4.19 ∘ $^\circ$ ). The results of Student paired t $t$ -test indicate that no statistically significant differences are observed between manual measurement and our automatic approach ( p $p$ -value is always > $>$ 0.05). Regarding the diagnosis of scoliosis (Cobb angle > $>$ 10 ∘ $^\circ$ ), the proposed method achieves a high sensitivity of 0.9577 and a specificity of 0.8475 for all spinal regions. CONCLUSIONS: This study offers a brand-new automatic approach that is potentially of great benefit of the complex task of landmark detection and Cobb angle evaluation, which can provide helpful navigation information about the early diagnosis of scoliosis.

Hydrophobicity of Polyacrylate Emulsion Film Enhanced by Introduction of Nano-SiO2 and Fluorine.

This study proposes to utilize modified Nano-SiO2/fluorinated polyacrylate emulsion that was synthesized with a semi-continuous starved seed emulsion polymerization to improve the hydrophobicity, thermal stability, and UV-Vis absorption of polyacrylate emulsion film. To verify the proposed method, a series inspection had been conducted to investigate the features of the emulsion film. The morphological analysis indicated that Nano-SiO2 was surrounded by a silane molecule after modification, which can efficiently prevent silica nanoparticles from aggregating. Fourier transform infrared spectra confirmed that modified SiO2 and dodecafluoroheptyl methacrylate (DFMA) were successfully introduced to the copolymer latex. The particle size of latex increased with the introduction of modified Nano-SiO2 and DFMA. UV-Vis absorption spectra revealed that modified silicon nanoparticles can improve the ultraviolet shielding effect obviously. X-ray photoelectron spectroscopy illustrated that the film⁻air interface was richer in fluorine than film section and the glass side. The contact angle of modified Nano-SiO2/fluorinated polyacrylate emulsion containing 3 wt % DFMA was 112°, slightly lower than double that of polyacrylate emulsion, indicating composite emulsion films possess better hydrophobicity. These results suggest that introducing modified Nano-SiO2 and fluorine into polyacrylate emulsion can significantly enhance the thermal stability of emulsion films.