Search Results (113)

L-type Ca²⁺ channels, particularly Ca_V1.2, play a crucial role in cardiac excitation-contraction coupling and are known to exhibit mechanosensitivity. However, the mechanisms regulating their response to mechanical stress remain poorly understood. To investigate the mechanosensitivity and nitric oxide (NO)-dependent regulation of L-type Ca²⁺ channels in rat ventricular cardiomyocytes, we used RNA sequencing to assess isoform expression and whole-cell patch-clamp recordings to measure L-type Ca²⁺ current (I_Ca,L) under controlled mechanical and pharmacological conditions. RNA sequencing revealed predominant expression of Ca_V1.2 (TPM: 0.1170 ± 0.0075) compared to Ca_V1.3 (0.0021 ± 0.0002) and Ca_V1.1 (0.0002 ± 0.0002). Local axial stretch (6–10 μm) consistently reduced I_Ca,L in proportion to stretch magnitude. The NO donor SNAP (200 μM) had variable effects on basal I_Ca,L in unstretched cells (stimulatory, inhibitory, or biphasic) but consistently restored stretch-reduced I_Ca,L to control levels. Ascorbic acid (10 μM), which reduces S-nitrosylation, increased basal I_Ca,L and partially restored the reduction caused by stretch, implicating S-nitrosylation in channel regulation. The sGC inhibitor ODQ (5 μM) decreased I_Ca,L in both stretched and unstretched cells, indicating involvement of the NO–cGMP pathway. Mechanical stress modulates L-type Ca²⁺ channels through a complex interplay between S-nitrosylation and NO–cGMP signaling, with S-nitrosylation playing a predominant role in stretch-induced effects. This mechanism may represent a key component of cardiac mechanotransduction and could be relevant for therapeutic targeting in cardiac pathologies involving mechanically induced dysfunction. Full article

The Southern Lhasa Terrane, as the southernmost tectonic unit of the Eurasian continent, has long been a focal area in global geoscientific research due to its complex evolutionary history. The Yeba Formation exposed in this terrane comprises an Early–Middle Jurassic volcanic–sedimentary sequence that records multiphase tectonic deformation. This study applies structural analysis to identify three distinct phases of tectonic deformation in the Yeba Formation of the Southern Lhasa Terrane. The D₁ deformation is characterized by brittle–ductile shearing, as evidenced by the development of E-W-trending regional shear foliation (S₁). S₁ planes dip northward at angles of 27–87°, accompanied by steeply plunging stretching lineations (85–105°). Both south- and north-directed shear-rotated porphyroclasts are observed in the hanging wall. ⁴⁰Ar-³⁹Ar dating results suggest that the D₁ deformation occurred at ~79 Ma and may represent an extrusion-related structure formed under a back-arc compressional regime induced by the low-angle subduction of the Neo-Tethys Ocean plate. The D₂ deformation is marked by the folding of the pre-existing shear foliation (S₁), generating an axial planar cleavage (S₂). S₂ planes dip north or south with angles of 40–70° and fold hinges plunge westward or NWW. Based on regional tectonic evolution, it is inferred that the deformation may have resulted from sustained north–south compressional stress during the Late Cretaceous (79–70 Ma), which caused the overall upward extrusion of the southern Gangdese back-arc basin, leading to upper crustal shortening and thickening and subsequently initiating folding. The D₃ deformation is dominated by E-W-striking ductile shear zones. The regional shear foliation (S₃) exhibits a preferred orientation of 347°∠75°. Outcrop-scale ductile deformation indicators reveal a top-to-the-NW shear sense. Combined with regional tectonic evolution, the third-phase (D3) deformation is interpreted as a combined product of the transition from compression to lateral extension within the Lhasa terrane, associated with the activation of the Gangdese Central Thrust (GCT) and the uplift of the Gangdese batholith since ~25 Ma. Full article

This study presents an analytical solution to examine the mechanical behavior of an incompressible, functionally graded hyperelastic cylinder under combined extension and torsion. The exp-exp strain energy density function characterizes the hyperelastic material, with parameters varying exponentially along the radial direction. To validate the solution, finite element simulations using a custom UHYPER in ABAQUS are performed. The analytical and numerical results show strong agreement across different stretch and twist levels. The stress distribution and maximum stress are significantly influenced by the exponential parameter governing material gradients. Unlike axial stretch, torsion induces a more intricate longitudinal stress distribution, with large twisting producing two extrema that shift toward the cylinder’s center and outer surface. Longitudinal stress primarily governs von Mises stress and strain energy density variations across the radial direction. A critical axial stretch is identified, below which torsion-induced axial force transitions to compression, elongating the cylinder during twisting. Beyond this stretch, the axial force shifts from tensile to compressive with increasing twist, causing initial shortening before further elongation. Full article

We recently found that myometrial distension stimulates maternal uterine vascular remodeling, and hypothesized that this may be a previously unrecognized mechanism for inducing arterial growth during pregnancy. The aim of this study was to further characterize a recently developed surgical model in which medical-grade silicone was infused into one uterine horn of a non-gravid rat to induce acute myometrial stretch, followed by an additional, gradual distension due to the secretion of an exudate into the uterine lumen. Our objectives were to better understand the effects of stretch on the myometrium and to look for the expression of proangiogenic and proinflammatory factors that may stimulate uterine vascular remodeling. Morphometric analysis showed hypertrophy of the uterine corpus that was primarily due to axial growth since the myometrial cross-sectional area was unchanged due to a thinning of the uterine wall secondary to stretch. This finding was supported by significantly increased myometrial smooth muscle cell mitosis. There was also an increase in the concentration of myometrial elastin but not collagen. The analysis showed modest increases in neutrophils, activated and unactivated macrophages, and the proinflammatory cytokines RANTES, MIP-3α, GRO-KC, and TNFα. The most dramatic change was the extremely high level of VEGF in the exudate, which was increased >900× above circulating levels. Full article

Damage mechanisms are a key factor in materials science and are essential for understanding and predicting the behavior of materials under complex loading conditions. In this paper, the influence of different directions, different rates and different model parameters on the mechanical behavior of AZ31 magnesium alloy during the tensile process is investigated based on the secondary development of the VUMAT user subroutine based on the GTN damage model and verified by the tensile experiments at different loading rates and in different directions. The results show that AZ31 magnesium alloy exhibits significant differences in mechanical properties in radial and axial stretching, where the yield strength is lower in the radial direction than in the axial direction, and the elongation is the opposite. Moreover, the maximum stress and elongation of the material decreased with the increasing tensile rate, revealing the importance of the loading rate on the material properties. Compared with the existing studies, this paper determines the GTN model parameters of the AZ31 magnesium alloy extruded state bar by theresponse surface method combined with the optimization algorithm and obtains the parameter set that can accurately describe the damage behavior of this material. The study also found that the nucleation-averaged plastic strain (${\epsilon }_N$) has the most significant effect on the maximum stress and fracture point of the stress–strain curve by the sensitivity analysis of six key parameters of the GTN model, while the other parameters change the shape of the curve and the local features to different degrees. Further analysis shows that the differences in yield strength and elongation can be attributed to the differences in basal slip, twinning behavior and dynamic recrystallization in the microstructure, which provides an important guidance for the optimization of the microstructure of AZ31 magnesium alloy. This study not only reveals the influence law of loading conditions on the mechanical properties of AZ31 magnesium alloy but also provides a theoretical basis and reference for understanding the damage mechanism of magnesium alloy and optimizing its mechanical properties. Full article

Myopic eye growth induces mechanical stretch, which can lead to structural and functional retinal alterations. Here, we investigated the effect of lens-induced myopic growth on the distribution of retinal ganglion cells (RGCs), glial fibrillary acidic protein (GFAP) expression and intensity, and peripapillary retinal nerve fiber layer (ppRNFL) thickness in common marmosets (Callithrix jacchus) induced with myopia continuously for six months, using immunohistochemistry and spectral-domain optical coherence tomography. We also explored the relationship between cellular structural parameters and the photopic negative response (PhNR) using full-field electroretinography. Marmosets induced with myopia for six months developed axial myopia, had a thinner ppRNFL, reduced peripapillary ganglion cell (≈20%) and astrocyte density (≈42%), increased panretinal GFAP expression (≈42%) and nasal mid-periphery staining intensity (≈81%) compared to age-matched controls. Greater degrees of myopia and vitreous elongation were associated with reduced peripapillary RGCs and astrocyte density, and increased GFAP expression and intensity. These cellular structural changes did not show a significant relationship with the features of the PhNR, which remained unchanged. The outcomes of this study suggest that myopia induces a reorganization of the peripapillary inner retina at the cellular level that may not result in measurable functional repercussions at this stage of myopia development. Full article

High gravity (high-g) combustion can significantly increase flame propagation speed, thereby potentially shortening the axial length of aero-engines and increasing their thrust-to-weight ratio. In this study, we utilized the large eddy simulation model to investigate the combustion characteristics and flame morphology evolution of premixed propane–air flames in a channel with a backward-facing step. The study reveals that both the increase in centrifugal force and flow velocity can enhance pressure fluctuations during combustion and increase the turbulence intensity. The presence of centrifugal force promotes the occurrence of Rayleigh–Taylor instability (RTI) between hot and cold fluids. The combined effects of RTI and Kelvin–Helmholtz instability (KHI) enhance the disturbance between hot and cold fluids, shorten the fuel combustion time, and intensify the dissipation of large-scale vortices. The increase in fluid flow velocity can raise the flame front’s hydrodynamic stretch rate, thereby enhancing the turbulence level during combustion to a certain extent and increasing the fuel consumption rate. When a strong centrifugal force is applied, the global flame propagation speed can be more than doubled. Within a certain range, the increase in high-g field strength can enhance the intensity of RTI and accelerate the transition of RTI to the nonlinear stage. Full article

In response to an investigation on the paths of changes in the crystallization and radial differences during the forming process of nascent fibers, in this study, we conducted numerical simulation and analyzed the changes in crystallization mechanical parameters and tensile properties through a fluid dynamics two-phase model. The model was based on the melt-spinning method focusing on melt spinning, the environment of POLYFLOW, and the method of joint simulation, coupled with Nakamura crystallization kinetics, including the development of process collaborative parameters, stretch-induced crystallization, viscoelasticity, filament cooling, gravity term, inertia, and air resistance. Finally, for nylon 6 BHS and CN9987 resin spinning, the model successfully predicted the distribution changes in temperature, velocity, strain rate tensor, birefringence, and stress tensor along the axial and radial fibers and obtained the variation pattern of fibers’ crystallinity along the entire spinning process under different stretching rates. Furthermore, we also explored the effects of spinning conditions, including inlet flow rate, winding speeds, and the extrusion temperature, on the fibers’ crystallization process and obtained the influence rules of different spinning conditions on fiber crystallization. Knowing the paths of changes in mechanical performance can provide important guidance and optimization strategies for the future industrial preparation of high-performance fibers. Full article

As a special type of clay, expansive clay is widely distributed in China. Its characteristics of swelling and softening when meeting water and shrinking and cracking when losing water bring many hidden dangers to engineering construction. Expansive clay is known as “engineering cancer”, and in-depth research on the unloading mechanical response characteristics and the unloading constitutive relationships of expansive clay is a prerequisite for conducting geotechnical engineering design and safety analysis in expansive-soil areas. In order to obtain the unloading mechanical response characteristics and the expression of the unloading tangent modulus of expansive clay, typical expansive clay in the Hefei area was taken as the research object, and triaxial unloading stress path tests were conducted. The stress–strain properties, microstructures, macro failure modes, and strength indexes of the expansive clay were analyzed under unloading stress paths. Through an applicability analysis of several classical soil strength criteria, an unloading constitutive model and the unloading tangent modulus expression of the expansive clay were constructed based on the Mohr–Coulomb (hereinafter referred to as “M-C”) criterion, the Drucker–Prager (hereinafter referred to as “D-P”) criterion, and the extended Spatial Mobilized Plane (hereinafter referred to as “SMP”) criterion theoretical frameworks. The following research results were obtained: (1) The stress–strain curves of the three stress paths of the expansive clay were hyperbolic. The expansive clay showed typical strain-hardening characteristics and belonged to work-hardening soil. (2) Under the unloading stress paths, the soil particles were involved in the unloading process of stress release, and the failure samples showed obvious stretching, curling, and slipping phenomena in their soil sheet elements. (3) Under both unloading stress paths, the strength of the expansive clay was significantly weakened and reduced. Under the lateral unloading paths, the cohesive force (c) of the expansive clay was reduced by 32.7% and the internal friction angle (φ) was increased by 19% compared with those under conventional loading, while under the axial unloading path, c was reduced by 63.5% and φ was reduced by 28.7%. (4) For typical expansive clay in Hefei, the conventional triaxial compression (hereinafter referred to as “CTC”) test, the reduced triaxial compression (hereinafter referred to as “RTC”) test, and the reduced triaxial extension (hereinafter referred to as “RTE”) test stress paths were suitable for characterization and deformation prediction using the M-C strength criterion, D-P strength criterion, and extended SMP strength criterion, respectively. (5) The derived unloading constitutive model and the unified tangent modulus formula of the expansive clay could accurately predict the deformation characteristics of the unloading stress path of the expansive clay. These research results will provide an important reference for future engineering construction in expansive-clay areas. Full article

The flow and heat transfer of a steady, viscous biomagnetic fluid containing magnetic particles caused by the swirling and stretching motion of a three-dimensional cylinder has been investigated numerically in this study. Because fluid and particle rotation are different, a magnetic field is applied in both radial and tangential directions to counteract the effects of rotational viscosity in the flow domain. Partial differential equations are used to represent the governing three-dimensional modeled equations. With the aid of customary similarity transformations, this system of partial differential equations is transformed into a set of ordinary differential equations. They are then numerically resolved utilizing a common finite differences technique that includes iterative processing and the manipulation of tridiagonal matrices. Graphs are used to depict the physical effects of imperative parameters on the swirling velocity, temperature distributions, skin friction coefficient, and the rate of heat transfer. For higher values of the ferromagnetic interaction parameter, it is discovered that the axial velocity increases, whereas temperature and tangential velocity drop. With rising levels of the ferromagnetic interaction parameter, the size of the axial skin friction coefficient and the rate of heat transfer are both accelerated. In some limited circumstances, a comparison with previously published work is also handled and found to be acceptably accurate. Full article

Background: Grade 2–3 diffuse gliomas (DGs) show extensive infiltration through white matter (WM) tracts. Along-tract analysis of WM tracts based on diffusion tensor tractography (DTI) can been performed to assess the microstructural integrity of WM tracts. The clinical implication of these DTI-related findings is still under debate, especially in tumor patients. The aim of this study was to analyze and compare diffusion-based parameters along WM tracts and variables specific to WM -tumor interactions in DGs and correlate them with preoperative neuropsychological assessment. Methods: Fourteen patients with IDH-mutated grade 2–3 DGs were included. Tumor volumes were manually segmented on 3D-FLAIR images after spatial normalisation to MNI space. DTI was acquired using a single-shot echo-planar sequence on a 3T with 48 sampling directions. DTI data were reconstructed within the MNI space using q-space diffeomorphic reconstruction (QSDR) in DSI studio. Five bilateral sets of WM tracts were reconstructed based on the HCP-1065 template. All WM tracts were stretched to the same length of 100 indices, and for each index diffusion-based parameters fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), mean diffusivity (MD) and quantitative anisotropy (QA) were sampled. Tumor-related parameters (TRP); tumor volume (Tv), maximum tumor presence (MTP) and the number of sequential indices in which a tumor is present (Te) were derived based on the along-tract analysis. Normal data were constructed by calculating the average and standard deviations of contralateral and not-affected WM tracts for each diffusion-based parameter, respectively. Affected WM tracts were individually compared to normal data using a z-test. Preoperative neuropsychological assessment was performed in all subjects and correlated to results from the along-tract analysis using correlation and logistic regression models. Results: Abnormalities in diffusion-based parameters were detected in WM tracts. Topographical and quantitative information were presented within the same graph. AD and MD displayed the highest linear correlation with the TRPs. Abnormal QA showed a linear correlation with Tv per WM tract. Neuropsychological impairment was correlated with all the TRPs and with abnormal FA (p < 0.05) and abnormal QA (p < 0.01). Abnormal QA was the only independent variable able to predict the presence of neuropsychological impairment in the patients based on the linear regression analysis. Conclusions: Graphical presentation of the along-tract analysis presented in this study shows that it may be a sensitive and robust method to acquire and display topographical and qualitative information regarding WM tracts in close proximity to DGs. Further studies and refinements to the methods presented herein may advance current clinical methods for evaluating displacement and infiltrations and further aid the efforts of pre-planning surgical interventions with the goal to maximise EOR and tailor oncological treatment. Full article

Theories of myopia etiology based on near work and lack of outdoor exposure have had inconsistent support and have not prevented the rising prevalence of global myopia. New scientific theories in the cause and prevention of myopia are needed. Myopia prevalence is low in native people consuming traditional diets lacking in sodium chloride, and nutritional epidemiological evidence supports the association of rising myopia prevalence with dietary sodium intake. East Asian populations have among the highest rates of myopia associated with high dietary sodium. Similar associations of sodium and rising myopia prevalence were observed in the United States in the late 20th century. The present perspective synthesizes nutritional epidemiology evidence with pathophysiological concepts and proposes that axial myopia occurs from increased fluid retention in the vitreous of the eye, induced by dietary sodium chloride intake. Salt disturbs ionic permeability of retinal membranes, increases the osmotic gradient flow of fluid into the vitreous, and stretches ocular tissue during axial elongation. Based on the present nutritional epidemiology evidence, experimental research should investigate the effect of sodium chloride as the cause of myopia, and clinical research should test a very low-salt diet in myopia correction and prevention. Full article

We investigated the effects of a Tankyrase (TNKS-1/2) inhibitor on mechanical stress-induced gene expression in human chondrocytes and examined TNKS-1/2 expression in human osteoarthritis (OA) cartilage. Cells were seeded onto stretch chambers and incubated with or without a TNKS-1/2 inhibitor (XAV939) for 12 h. Uni-axial cyclic tensile strain (CTS) (0.5 Hz, 8% elongation, 30 min) was applied and the gene expression of type II collagen a1 chain (COL2A1), aggrecan (ACAN), SRY-box9 (SOX9), TNKS-1/2, a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), and matrix metalloproteinase-13 (MMP-13) were examined by real-time PCR. The expression of ADAMTS-5, MMP-13, nuclear translocation of nuclear factor-κB (NF-κB), and β-catenin were examined by immunocytochemistry and Western blotting. The concentration of IL-1β in the supernatant was examined by enzyme-linked immunosorbent assay (ELISA). TNKS-1/2 expression was assessed by immunohistochemistry in human OA cartilage obtained at the total knee arthroplasty. TNKS-1/2 expression was increased after CTS. The expression of anabolic factors were decreased by CTS, however, these declines were abrogated by XAV939. XAV939 suppressed the CTS-induced expression of catabolic factors, the release of IL-1β, as well as the nuclear translocation of NF-κB and β-catenin. TNKS-1/2 expression increased in mild and moderate OA cartilage. Our results demonstrated that XAV939 suppressed mechanical stress-induced expression of catabolic proteases by the inhibition of NF-κB and activation of β-catenin, indicating that TNKS-1/2 expression might be associated with OA pathogenesis. Full article

The mechanical response of articular cartilage (AC) under compression is anisotropic and depth-dependent. AC is osmotically active, and its intrinsic osmotic swelling pressure is balanced by its collagen fibril network. This mechanism requires the collagen fibers to be under a state of tensile pre-strain. A simple mathematical model is used to explain the depth-dependent strain calculations observed in articular cartilage under 1D axial compression (perpendicular to the articular surface). The collagen fibers are under pre-strain, influenced by proteoglycan concentration (fixed charged density, FCD) and collagen stiffness against swelling stress. The stiffness is introduced in our model as an anisotropic modulus that varies with fibril orientation through tissue depth. The collagen fibers are stiffer to stretching parallel to their length than perpendicular to it; when combined with depth-varying FCD, the model successfully predicts how tissue strains decrease with depth during compression. In summary, this model highlights that the mechanical properties of cartilage depend not only on proteoglycan concentration but also on the intrinsic properties of the pre-strained collagen network. These properties are essential for the proper functioning of articular cartilage. Full article

Background: This research explores the application of morphometric texture analysis in chest Computed Tomography (CT) scans for determining Bone Mineral Content (BMC) and its temporal changes, both crucial in diagnosing osteoporosis. The study establishes an innovative approach to osteoporosis screening by leveraging Hounsfield Units (HUs) in CT scans to evaluate BMC, offering a comparison with dual-energy X-ray absorptiometry (DXA)-based BMC. Methods: A total of 806 instances (encompassing 379 individuals) were meticulously compiled from a sole institution, during the period stretching from 6 May 2012 to 30 June 2020. In this detailed analysis, each participant was subjected to a pair of chest CT scans, sequentially pursued by a DXA scan, spread over two years. Focused records of BMC values at the inaugural lumbar vertebra (L1) were secured from both the DXA and CT axial slices across all instances. A meticulous selection process pinpointed the largest trabecular section from the L1 vertebral body, whereupon 45 distinctive texture attributes were harvested utilizing gray-level co-occurrence matrix methodologies. Utilizing these amassed 45 attributes, a regression architecture was devised, aiming to forecast the precise BMC values individually. Moreover, an alternative regression framework was engaged, leveraging 90 distinct features, to gauge the BMC fluctuations observed between the duo of scans administered to each participant. Results: The precision of the cultivated regression frameworks was scrupulously assessed, benchmarking against the correlation coefficient (CC) and the mean absolute deviation (MAE) in comparison to the DXA-established references. The regression apparatus employed for estimating BMC unveiled a CC of 0.754 and an MAE of 1.641 (g), respectively. Conversely, the regression mechanism devoted to discerning the variations in BMC manifested a CC of 0.680, coupled with an MAE of 0.528 (g), respectively. Conclusion: The innovative methodology utilizing morphometric texture analysis in CT HUs offers an indirect, yet promising, approach for osteoporosis screening by providing estimations of BMC and its temporal changes. The estimations demonstrate moderate positive correlations with DXA measures, suggesting a potential alternative in circumstances where DXA scanning is limited. Full article