Role of Bushen Huoxue Formula and transplanted endothelial progenitor cells play in promoting endplate microcirculation and attenuating intervertebral disc degeneration.

Objective: To explore whether Bushen Huoxue Formula (BSHXF) improves the angiogenesis ability of transplanted endothelial progenitor cells (EPCs) in endplate and its potential mechanism in delaying intervertebral disc degeneration (IDD). Methods: BSHXF was analyzed via Ultra-High Performance Liquid Chromatography (UPLC). Rabbit axial compression lumbar IDD models were constructed and the effects of BSHXF, EPCs, and their combination in IDD were determined by MRI, histological evaluation, TUNEL, and immunofluorescence assays. Additionally, CCK-8 assay, flow cytometry, and tube formation assay were used to evaluate EPCs viability, proliferation, cell cycle and the angiogenesis ability of EPCs between groups. Results: BSHXF and transplanted EPCs both attenuate the process of IDD in the rabbit model assessed by MRI, HE staining and Masson staining. TUNEL-positive NP cells were significantly reduced in the BSHXF group, EPCs group, and EPC + BSHXF group compared to the model group (P < 0.05), with the EPC + BSHXF group showing the most significant therapeutic effect. Immunofluorescence detection showed that VEGF, CD34 expression and quantity of microvessels in the endplate significantly increased in the EPC + BSHXF group compared to all the other groups (P < 0.05). Besides, the CCK-8 assay showed an upregulation of EPC viability and the tube formation assay demonstrated a significant increase in tube length and branching in EPCs cultured with BSHXF-containing serum (P < 0.05). Furthermore, BSHXF-containing serum increased VEGF expression in EPCs cultured in vitro (P < 0.05). Conclusions: Both BSHXF and EPCs transplantation play an important role in increasing endplate angiogenesis and attenuating IDD. BSHXF can enhance the viability and tube-forming ability of EPCs and endplate microcirculation.

Network Pharmacology with Metabolomics Study to Reveal the Mechanisms of Bushen Huoxue Formula in Intervertebral Disc Degeneration Treatment.

Background: Intervertebral disc degeneration (IVDD) is a pathophysiological process that leads to severe back pain or neurological deficits. The Bushen Huoxue Formula (BSHXF) is a traditional herbal remedy widely used to treat diseases related to IVDD. However, its pharmacological mechanism needs further exploration. Objective: This study aimed to elucidate the mechanisms through which BSHXF treats IVDD-related diseases by integrating metabolomics with network pharmacology. Methods: Network pharmacology was utilized to identify potential targets of BSHXF against IVDD. Additionally, an animal model of needle puncture-induced disc degeneration was established to assess the effect of BSHXF. Mice were randomly assigned to the sham group, model group, and BSHXF group. Various techniques, including PCR, CCK-8 assay, MRI, histological examinations, and immunohistochemical analyses, were employed to evaluate degenerative and oxidative stress conditions in mouse disc tissue and cultured nucleus pulposus (NP) cells. UHPLC-HRMS/MS was used to differential distinct metabolites in the disc tissue from different groups, and MetaboAnalyst 5.0 was employed to enrich the metabolic pathways. Results: Through network pharmacology, 15 core proteins were identified through protein-protein interaction (PPI) network construction. Functional enrichment analysis highlighted the critical role of BSHXF in addressing IVDD by influencing the response to oxidative stress. Furthermore, experimental evidence demonstrated that BSHXF significantly improved the pathological progression of IVDD and increased oxidative stress markers SOD-1 and GPX1, both in the disc degeneration model and cultured NP cells. Metabolomics identified differential metabolites among the three groups, revealing 15 metabolic pathways between the sham and model groups, and 13 metabolic pathways enriched between the model and BSHXF groups. Conclusion: This study, integrating network pharmacology and metabolomics, suggests that BSHXF can alleviate IVDD progression by modulating oxidative stress. Key metabolic pathways associated with BSHXF-mediated reduction of oxidative stress include the citrate cycle, cysteine and methionine metabolism, alanine, aspartate and glutamate metabolism, glycine, serine and threonine metabolism, D-glutamine and D-glutamate metabolism, glutathione metabolism, and tryptophan metabolism. While this research demonstrates the therapeutic potential of BSHXF in reducing oxidative stress levels in IVDD, further research is needed to thoroughly understand its underlying mechanisms.

A randomized controlled trial: The efficacy and safety of Bushen Huoxue formula in the management of lower back pain from lumbar disc herniation.

BACKGROUND: Lower back pain (LBP) arising from lumbar disc herniation (LDH) poses a challenging health issue, often necessitating therapeutic interventions. Bushen Huoxue formula (BSHXF) has proved as a potential treatment option with great clinical effect. However, comprehensive investigations into its efficacy and safety in conjunction with celecoxib for managing LBP from LDH are lacking. The objective of this article is to investigate the efficacy and safety of BSHXF in the management of patients with LBP from LDH. METHODS: This single center, randomized clinical trial was conducted from March 2023 to September 2023 and all patients suffered from LBP of LDH. Participants were randomly assigned to the BSHXF group (celecoxib and BSHXF) or the control group (celecoxib and placebo). The patients received treatment for 2 weeks. Assessment was conducted before treatment, the last day of the treatment, 4 weeks and 8 weeks after the treatment. Oswestry Disability Index (ODI), Visual Analog Scale (VAS), Roland-Morris Disability Questionnaire (RMDQ), Timed up and go test (TUGT), trunk range of movement (Trunk ROM), Hospital Anxiety and Depression Scale (HADS) were used for the evaluation. RESULTS: A total of 206 subjects completed treatment, among whom 104 participants were randomized to the BSHXF group and 102 participants were randomized to the control group. There were no significant differences between groups in terms of the observed indicators (P > .05). After treatment, patients in BSHXF group obtained significant lower scores at 2-week, 4-week, 8-week of VAS, ODI, RMDQ, TUGT, Trunk ROM and HADS than the baseline data (P < .05). The ODI score was significantly lower than the control group at 2-week, 4-week, 8-week (2w: 11.30 ±â€…5.80 vs 14.23 ±â€…6.33, P < .001; 4w: 10.95 ±â€…4.93 vs 13.54 ±â€…6.35, P < .001; 8w: 10.27 ±â€…5.25 vs 12.84 ±â€…6.57, P = .002). Similarly, the scores of VAS, RMDQ, TUGT, Trunk ROM scores of the BSHXF group markedly decreased at 2, 4, and 8-week when compared to their control group (P < .05). Furthermore, no significant difference showed up in the score of HADS between the between the BSHXF and the control group after treatment (P > .05). CONCLUSION: This randomized clinical trial found that BSXHF can help significantly improve the clinical outcomes of celecoxib including pain intensity reduction and lumbar function improvement in LBP patients.

Experimental investigation of thermal performance of vertical multitube cylindrical latent heat thermal energy storage systems.

The multitube design in the shell-and-tube type latent heat thermal energy storage (LHTES) system has received intensive attention due to its promising benefits in enhancing heat storage efficiency. In this paper, single and multi-tube shell LHTES systems were experimentally investigated. First, this study experimentally compared the thermal characteristics between a multiple-tube heat exchanger (MTHX) and a single-tube heat exchanger (STHX). The STHX's geometrical parameters coincided with a virtual cylindrical domain in the MTHX, being similar to the single-tube model formulated by simplifying the numerical solution to investigate the MTHX. The experimental data was then used to validate the simplified numerical model commonly used in the literature that converted the multi-tube problem to a single-tube model by formulating a virtual cylindrical domain for each tube in the MTHX system. The results showed that there was a noticeable difference in the thermal characteristics between the actual STHX and the virtual cylindrical STHX domain in the MTHX system. The comparison indicated that the simplified numerical model could not accurately reflect the thermal performance of the MTHX system. An experimental study or three-dimensional numerical modelling was required for the thermal analysis of the multi-tube problems. Second, the effect of tube number in the MTHX was experimentally investigated. It was found that an increase in tube number boosted both charging and discharging rates without inhibiting the natural convection. The five-tube configuration decreased the total charging and discharging duration by 50% compared to the two-tube one. Finally, the effect of heat transfer fluid (HTF) operating parameters on the system performance was evaluated on the five-tube MTHX system. The results revealed that the adoption of higher HTF temperature considerably improved the charging performance. The charging time decreased by up to 41% with the HTF temperature increasing from 70 to 80 °C. Meanwhile, a variation in the HTF flow rate from 5 to 20 L/min showed a more pronounced influence on charging than on discharging due to the different dominant heat transfer mechanisms.

A lumbar disc degeneration model established through an external compressive device for the study of microcirculation changes in bony endplates.

Objective: To establish a new animal model of intervertebral disc degeneration (IDD) by axial compression on lumbar spine of rabbits and to investigate the changes of microcirculation in bony endplates during the progress of IDD. Methods: 32 New Zealand white rabbits were equally divided into 4 groups as follows: Control group with no operation and compression, Sham operation group with apparatus placement only, 2-week compression group and 4-week compression group with the devices installed and compressed for their preset duration. All groups of rabbits underwent MRI, histological evaluation, disc height index measurement and Microfil contrast agent perfusions to examine the ratio of endplate microvascular channels. Results: The new animal model of IDD was successfully established after axial compression for 4 weeks. The MRI grades for the 4-week compression group was 4.63 ± 0.52 and significantly different to the sham operation group (P < 0.05). Histologically, decrease of normal NP cells and extracellular matrix and disorganization of the architecture of the annulus fibrosus apparently occurred in 4-week compression group, which was different to the sham operation group (P < 0.05). There was no statistically difference between the 2-week compression and sham operation group no matter in the histology and MRI assessment. The disc height index slowly decreased as the compression duration rose. The ratio of microvascular channel volume within the bony endplate in 2-week and 4-week compression group were both reduced whereas the 4-week compression group obtained significantly less vascularization volume (6.34 ± 1.52 vs. 19.52 ± 4.63, P < 0.05). Conclusion: A new model of lumbar IDD was successfully established by axial compression and the volume of microvascular channels in the bony endplate gradually decreased as the grade of IDD increased. This model provides a new choice for etiological studies on IDD and investigation of nutrient supply disturbance.

Magnetic biochar based on furfural residue as an excellent candidate for efficient adsorption of Tetracycline, Bisphenol A, Congo red, and Cr6.

Magnetic porous adsorbent materials are widely favored for their large specific surface area, good adsorption performance, and ease of separation. This work provided a magnetic biochar derived from furfural residue (M-FRAC) with excellent adsorption properties for various pollutants, including Congo red (CR), Tetracycline (TC), Bisphenol A (BPA), and Cr6+. The influence of experimental parameters, such as pollutant concentration, contact time, and pH, on the adsorption properties of M-FRAC was studied in detail. The adsorption process was highly dependent on pH and initial contaminant concentration. All pollutant adsorption was favorable under acidic conditions. The optimal pH of the CR, TC, and Cr6+ adsorption was 5, 4, and 2, respectively, while that of BPA was in the range of 2-5. The experimental equilibrium adsorption amount of CR, TC, BPA, and Cr6+ by M-FRAC was 110.89, 602.81, 157.76, and 265.31 mg/g, respectively. The adsorption processes of pollutants on M-FRAC were in accordance with the Langmuir isotherm model. The adsorption kinetics fitted the pseudo-second-order (PSO) kinetics model. In addition, M-FRAC could be readily separated from solution by applying an external magnetic field. Therefore, the M-FRAC has a good application prospect in practical industrial wastewater treatment.

Analysis and Correction of Measurement Error of Spherical Capacitive Sensor Caused by Assembly Error of the Inner Frame in the Aeronautical Optoelectronic Pod.

The ball joint is a multi-degree-of-freedom transmission pair, if it can replace the inner frame in the aviation photoelectric pod to carry the optical load, which will greatly simplify the system structure of the photoelectric pod and reduce the space occupied by the inner frame. However, installation errors in ball joint siting introduce nonlinear errors that are difficult to correct and two degree of freedom angular displacement of the ball joint is difficult to detect, which limits application in the precision control of two degrees of freedom systems. Studies of spherical capacitive sensors to date have not tested sensors for use in an inner frame stabilisation mechanism nor have they analysed the influence of installation error on sensor output. A two-axis angular experimental device was designed to measure the performance of a ball joint capacitive sensor in a frame stabilisation mechanism in an aeronautical optoelectronic pod, and a mathematical model to compensate for ball joint capacitive sensor installation error was created and tested. The experimental results show that the resolution of the capacitive sensor was 0.02° in the operating range ±4°, the repeatability factor was 0.86%, and the pulse response time was 39 µs. The designed capacitive sensor has a simple structure, high measurement accuracy, and strong robustness, and it can be integrated into ball joint applications in the frames of aeronautical photoelectric pods.

A Novel Method for Detecting the Two-Degrees-of-Freedom Angular Displacement of a Spherical Pair, Based on a Capacitive Sensor.

The spherical pair has an important role in the inner frame of the stabilization mechanism of the aviation optoelectronic pod. However, its two-degrees-of-freedom (2-DOF) angular displacement signal is difficult to detect, seriously restricting its application in aviation optoelectronic pods. Therefore, this study proposes a new method to measure a spherical pair's 2-DOF angular displacement using a spherical capacitive sensor. The capacitive sensor presented by this method realizes the measurement of the 2-DOF angular displacement of the spherical pair by integrating the spherical electrode groups in the ball head and the ball socket of the spherical pair. First, based on the geometric structure of the spherical pair, the structure of the capacitive sensor is designed, and the mathematical model for the capacitive sensor is deduced. Then, the sensor's output capacitance, in different directions, is simulated by Ansoft Maxwell software. Finally, an experiment device is built for the measurement experiments. The simulation analysis and experimental results show that the spherical capacitive sensor has an approximately linear output in different directions, and the measured output capacitance is as high as 89.7% of the theoretical value. Compared with the existing sensors that measure the 2-DOF angular displacement signal of the ball pair, the sensor proposed in this study has an integrated structure, which can be integrated into the spherical pair. That makes it possible to apply the spherical pair to the inner frame of the aviation optoelectronic pod.

Calcium Spark Detection and Event-Based Classification of Single Cardiomyocyte Using Deep Learning.

Ca2+ sparks are the elementary Ca2+ release events in cardiomyocytes, altered properties of which lead to impaired Ca2+ handling and finally contribute to cardiac pathology under various diseases. Despite increasing use of machine-learning algorithms in deciphering the content of biological and medical data, Ca2+ spark images and data are yet to be deeply learnt and analyzed. In the present study, we developed a deep residual convolutional neural network method to detect Ca2+ sparks. Compared to traditional detection methods with arbitrarily defined thresholds to distinguish signals from noises, our new method detected more Ca2+ sparks with lower amplitudes but similar spatiotemporal distributions, thereby indicating that our new algorithm detected many very weak events that are usually omitted when using traditional detection methods. Furthermore, we proposed an event-based logistic regression and binary classification model to classify single cardiomyocytes using Ca2+ spark characteristics, which to date have generally been used only for simple statistical analyses and comparison between normal and diseased groups. Using this new detection algorithm and classification model, we succeeded in distinguishing wild type (WT) vs RyR2-R2474S± cardiomyocytes with 100% accuracy, and vehicle vs isoprenaline-insulted WT cardiomyocytes with 95.6% accuracy. The model can be extended to judge whether a small number of cardiomyocytes (and so the whole heart) are under a specific cardiac disease. Thus, this study provides a novel and powerful approach for the research and application of calcium signaling in cardiac diseases.

Creep and permeability evolution behavior of red sandstone containing a single fissure under a confining pressure of 30 MPa.

The long-term deformation and permeability evolution with time are key issues for geo-engineering applications such as radioactive waste disposal. Rock permeability concurrent with deformation is significantly influenced by cracking. This study investigated the creep-permeability evolution behavior of red sandstone specimens containing a single fissure under a confining pressure of 30 MPa. First, the effects of stress ratio (SR) and fissure dip angle on the creep behavior of rock were investigated. The more loading/unloading cyclic numbers, the larger the irrecoverable axial deformation. The instant elastic strains and visco-elastic strains linearly increased with SR for both the intact and fissured specimens, whereas the instant plastic strains showed different results. The visco-plastic strains nonlinearly increased. For fissured and intact specimens, the creep strains and the steady-state creep rates nonlinearly increased as SR increased. The instantaneous strains, instant elastic strains, and visco-elastic strains slightly varied when the fissure dip angle was less than 45° but notably decreased with increasing fissure dip angle beyond 45°. However, the fissure dip angle had no obvious effects on the plastic and creep strains. Damage (D) was defined using the ratio of non-elastic strains to the total strain. D increased approximately linearly with SR, but the fissure dip angle had no obvious influences. Subsequently, the long-term strength (LTS) of the red sandstone was determined using two different methods. The LTS first decreased when the fissure dip angle increased from 0 to 45° but increased with increasing dip angle. The triaxial and creep failure modes were mainly shear along anti-wing cracks for the fissured specimens but shear failure occurred for the intact specimen. Moreover, the permeability of the fissured red sandstone was governed by SR and deformation or time. During the multi-step loading/unloading creep process, the permeability first decreased and then had a sudden rise when tertiary creep occurred.

Numerical simulation of particle migration from crushed sandstones during groundwater inrush.

Groundwater inrush through fault fracture zones is caused by small particle migration from fractured rocks of the faults. To investigate particle migration with the water flow, a 3D model was established for the solid-water two-phase flow. First, the simulated crushed sandstone was represented by certain different-sized particles with a novel cohesive force. The discrete element method (DEM) was applied for particles considering the cohesive force, the collisions, the friction, and other conventional forces. Second, the process of particle migrating from the crushed sandstone was simulated under multiple effects accompanied by some experiments. The results indicate that the migration characteristics vary with different-sized particles, and the mass loss for different-sized particles are high at the beginning leading to stabilized conditions at different times. It can be also found that the total mass loss rate and the final mass loss all increase with the increases of initial water velocity, while the final mass loss decrease with the increases of the axial force. Moreover, selected stimulation results were compared with the experimental results and the previous simulated results, and reasonable agreements could be obtained, which would provide consults for particle migration during groundwater inrush through fault fracture zones in underground engineering.