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Since accidents such as roof caving, rock fragmentation, and severe deformation are particularly likely to occur during roadway excavation in soft and thick coal seams, grasping the range and distribution of deformation and fracturing of surrounding rock is of crucial for evaluating roadway stability and optimizing support design in such coal seams. In this study, based on the stress paths encountered during roadway excavation, true triaxial loading and unloading tests were carried out on soft coal, and the deformation and strength evolutions of soft coal under different intermediate principal stress conditions were analyzed. The test results show that the stress–strain relationship in the pre-peak plasticity-strengthening and post-peak plasticity-weakening stages follows a quadratic function, and the strengeth evolution conforms to the Mogi–Coulomb criterion. Moreover, analytical solutions for the displacement of surrounding rock, the radius of the broken zone, and the radius of the plastic zone of soft-coal roadways under excavation stress paths were derived after taking the nonlinear hardening and softening characteristics of the strain of soft coal, the Mogi–Coulomb criterion, the intermediate principal stress, and the dilatancy characteristics of surrounding rock into comprehensive consideration. Finally, in accordance with a practical engineering case, the influences of the intermediate principal stress coefficient, the lateral pressure coefficient, and the support force on the deformation and failure characteristics of the soft-coal roadway were analyzed. The analysis reveals that an increase in intermediate principal stress aggravates the deformation of surrounding rock and enlarges the plastic and broken zones; variations in the lateral pressure coefficient alter the shape of the broken zone and the distribution of surface displacement; and an increase in the support force effectively reduces the plastic zone, broken zone, and surface displacement of the roadway. The research results can provide valuable theoretical basis for the stability evaluation and support design of soft-coal roadways. [ABSTRACT FROM AUTHOR]

Chondroitin sulfate proteoglycans (CSPGs) inhibit sympathetic reinnervation in rodent hearts post-myocardial infarction (MI), causing regional hypoinnervation that is associated with supersensitivity of β-adrenergic receptors and increased arrhythmia susceptibility. To investigate the role of CSPGs and hypoinnervation in the heart of larger mammals, we used a rabbit model of reperfused MI and tested electrophysiological responses to sympathetic nerve stimulation (SNS). Innervated hearts from MI and sham rabbits were optically mapped using voltage and Ca2+-sensitive dyes. SNS was performed with electrical stimulation of the spinal cord, and β-adrenergic responsiveness was tested using isoproterenol. Sympathetic nerve density and CSPG expression were evaluated using immunohistochemistry. CSPGs were robustly expressed in the infarct region of all MI hearts, and the presence of CSPGs was associated with reduced sympathetic nerve density in the infarct versus remote region. Action potential duration (APD) dispersion and tendency for induction of ventricular tachycardia/fibrillation (VT/VF) were increased with SNS in MI but not sham hearts. SNS decreased APD at 80% repolarization (APD80) in MI but not sham hearts, whereas isoproterenol decreased APD80 in both groups. Isoproterenol also shortened Ca2+ transient duration at 80% repolarization in both groups but to a greater extent in MI hearts. Our data suggest that sympathetic remodeling post-MI is similar between rodents and rabbits, with CSPGs associated with sympathetic hypoinnervation. Despite a reduction in sympathetic nerve density, the infarct region of MI hearts remained responsive to both physiological SNS and isoproterenol, potentially through preserved or elevated β-adrenergic responsiveness, which may underlie increased APD dispersion and tendency for VT/VF. NEW & NOTEWORTHY: Here, we show that CSPGs are present in the infarcts of rabbit hearts with reperfused MI, where they are associated with reduced sympathetic nerve density. Despite hypoinnervation, sympathetic responsiveness is maintained or enhanced in MI rabbit hearts, which also demonstrate increased APD dispersion and tendency for arrhythmias following sympathetic modulation. Together, this study indicates that the mechanisms of sympathetic remodeling post-MI are similar between rodents and rabbits, with hypoinnervation likely associated with enhanced β-adrenergic sensitivity. [ABSTRACT FROM AUTHOR]

Poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) are versatile drug nanocarriers with a wide spectrum of applications owing to their extensive advantages, including biodegradability, non-toxic side effects, and low immunogenicity. Among the numerous nanoparticle preparation methods available for PLGA NPs (the hydrophobic polymer), one of the most extensively utilized preparations is the sonicated-emulsified solvent evaporation method, owing to its simplicity, speed, convenience, and cost-effectiveness. Nevertheless, several factors can influence the outcomes, such as the types of concentration of the surfactants and organic solvents, as well as the volume of the aqueous phase. The objective of this article is to explore the influence of these factors on the properties of PLGA NPs and their drug release behavior following encapsulation. Herein, PLGA NPs were fabricated using bovine serum albumin (BSA) as a surfactant to investigate the impact of influencing factors, including different water-soluble organic solvents such as propylene carbonate (PC), ethyl acetate (PA), and dichloromethane (DCM). Notably, the size of PLGA NPs was smaller in the EA group compared to that in the DCM group. Moreover, PLGA NPs showed excellent stability, ascribed to the presence of the BSA surfactant. Furthermore, PLGA NPs were co-loaded with varying concentrations of hydrophilic drugs (doxorubicin hydrochloride) and hydrophobic drugs (celecoxib), and exhibited pH-sensitive drug release behavior in PBS with pH 7.4 and pH 5.5. [ABSTRACT FROM AUTHOR]

An investigation of rock fracture characteristics subjected to the true triaxial intermediate principal stress is crucial for understanding the failure mechanism of surrounding rock in an actual underground engineering project and guiding the project's implementation. In this study, a series of different true triaxial stress path tests were conducted to investigate the distribution of macroscopic rock fractures and internal cracks under various stress paths using a true triaxial servo test system and combining it with CT scanning technology. The results indicated that, due to the intermediate principal stress with constant direction, the true triaxial stress path has obvious directionality compared to the regular triaxial rock macroscopic and internal fracture distribution law and the fracture planes are aligned along the σ2 direction. Once the direction of the intermediate principal stress changes, the corresponding crack propagation direction immediately reverses and expands along the new intermediate principal stress direction. The direction of rock fracture is strongly dependent on the state (direction) of the intermediate principal stress, i.e., the direction of σ2 plays a decisive role in the macroscopic rock fracture characteristics. Accordingly, the "effect of intermediate principal stress-induced rock fracture" was proposed in this study. Based on the results of the CT scans in which the fracture dip angle within the rock is approximately parallel to the σ2 direction under different true triaxial paths, the intermediate principal stress plays a vital role in rock rupture. Combined with experimental and theoretical analyses, the rationality of this effect was verified. In addition, a numerical calculation method for the true triaxial rupture evolution of rocks with random fractures was proposed using ABAQUS software (version 2020), and a numerical calculation model for typical roadway excavation was developed. The rupture growth of the roadway surrounding rock was characterized by stratified evolution along the σ2 direction corresponding to the actual engineering. In addition, the numerical analysis of a typical roadway excavation with two different intermediate principal stress orientations indicated that the fracture of the surrounding rock in both kinds of roadways is roughly along the σ2 direction, which further supports the rationality of the "effect of intermediate principal stress-induced rock fracture." [ABSTRACT FROM AUTHOR]

Chondroitin sulfate proteoglycans (CSPGs) inhibit sympathetic reinnervation in rodent hearts post myocardial infarction (MI), causing regional hypo-innervation that is associated with supersensitivity of β-adrenergic receptors and increased arrhythmia susceptibility. To investigate the role of CSPGs and hypo-innervation in the heart of larger mammals, we used a rabbit model of reperfused MI and tested electrophysiological responses to sympathetic nerve stimulation (SNS). Innervated hearts from MI and sham rabbits were optically mapped using voltage and Ca 2+ -sensitive dyes. SNS was performed with electrical stimulation of the spinal cord and β-adrenergic responsiveness was tested using isoproterenol. Sympathetic nerve density and CSPG expression were evaluated using immunohistochemistry. CSPGs were robustly expressed in the infarct and border zone of all MI hearts, and the presence of CSPGs was associated with reduced sympathetic nerve density in the infarct vs. remote region. Action potential duration (APD) dispersion and susceptibility to ventricular tachycardia/fibrillation (VT/VF) were increased with SNS in MI hearts but not in sham. SNS decreased APD 80 in MI but not sham hearts, while isoproterenol decreased APD 80 in both groups. Isoproterenol also shortened Ca 2+ transient duration (CaTD 80 ) in both groups but to a greater extent in MI hearts. Our data suggest sympathetic remodeling post-MI is similar between species, with CSPGs associated with sympathetic hypo-innervation. Despite a reduction in sympathetic nerve density, the infarct region of MI hearts remained responsive to both physiological SNS and isoproterenol, potentially through preserved or elevated β-adrenergic responsiveness, which may underly increased APD dispersion and susceptibility for VT/VF., New & Noteworthy: Here we show that CSPGs are present in the infarcts of rabbit hearts with reperfused MI, where they are associated with reduced sympathetic nerve density. Despite hypo-innervation, sympathetic responsiveness is maintained or enhanced in MI rabbit hearts, which also demonstrate increased APD dispersion and tendency for arrhythmias following sympathetic modulation. Together, this study indicates that the mechanisms of sympathetic remodeling post-MI are similar between species, with hypo-innervation likely associated with enhanced β-adrenergic sensitivity.

Nicotine is the primary addictive component of tobacco products. Through its actions on the heart and autonomic nervous system, nicotine exposure is associated with electrophysiological changes and increased arrhythmia susceptibility. To assess the underlying mechanisms, we treated rabbits with transdermal nicotine (NIC, 21 mg/day) or control (CT) patches for 28 days before performing dual optical mapping of transmembrane potential (RH237) and intracellular Ca 2+ (Rhod-2 AM) in isolated hearts with intact sympathetic innervation. Sympathetic nerve stimulation (SNS) was performed at the first to third thoracic vertebrae, and β-adrenergic responsiveness was additionally evaluated following norepinephrine (NE) perfusion. Baseline ex vivo heart rate (HR) and SNS stimulation threshold were higher in NIC versus CT ( P = 0.004 and P = 0.003, respectively). Action potential duration alternans emerged at longer pacing cycle lengths (PCL) in NIC versus CT at baseline ( P = 0.002) and during SNS ( P = 0.0003), with similar results obtained for Ca 2+ transient alternans. SNS shortened the PCL at which alternans emerged in CT but not in NIC hearts. NIC-exposed hearts tended to have slower and reduced HR responses to NE perfusion, but ventricular responses to NE were comparable between groups. Although fibrosis was unaltered, NIC hearts had lower sympathetic nerve density ( P = 0.03) but no difference in NE content versus CT. These results suggest both sympathetic hypoinnervation of the myocardium and regional differences in β-adrenergic responsiveness with NIC. This autonomic remodeling may contribute to the increased risk of arrhythmias associated with nicotine exposure, which may be further exacerbated with long-term use. NEW & NOTEWORTHY Here, we show that chronic nicotine exposure was associated with increased heart rate, increased susceptibility to alternans, and reduced sympathetic electrophysiological responses in the intact rabbit heart. We suggest that this was due to sympathetic hypoinnervation of the myocardium and diminished β-adrenergic responsiveness of the sinoatrial node following nicotine treatment. Though these differences did not result in increased arrhythmia propensity in our study, we hypothesize that prolonged nicotine exposure may exacerbate this proarrhythmic remodeling.