Search Results (466)

The strength mobilisation framework was adopted for the first time to describe the stress–strain responses for three different types of sands, including a total of 30 published drained triaxial tests—25 for Karlsruhe Fine Sand, 2 for Ottawa sands and 3 for Fontainebleau sand, under confining pressures ranging from 50 to 400 kPa. The peak shear strength ${\tau }_{peak}$ obtained from drained triaxial shearing of these sands was used to normalise shear stress. Shear strains normalised at peak strength ${\gamma }_{peak}$ and at half peak of shear strength ${\gamma }_{M=2}$ were taken as the normalised reference strains, and the results were compared. Power–law functions were then derived when the mobilised strength was between $0.2{\tau }_{peak}$ and $0.8{\tau }_{peak}$. Exponents of the power–law functions of these sands were found to be lower than in the published undrained shearing data of clays. Using ${\gamma }_{M=2}$ as the reference strain shows a slightly better power–law correlation than using ${\gamma }_{peak}$. Linear relationships between the reference strains and variables, such as relative density, relative dilatancy index, and dilatancy, are identified. Full article

The impact mechanism of long-term creep in gas-containing coal on coal and gas outbursts has not been fully elucidated and remains insufficiently understood for the purpose of disaster engineering control. This investigation conducted triaxial creep experiments on raw coal specimens under controlled confining pressures, axial stresses, and gas pressures. Through systematic analysis of coal’s physical responses across different loading conditions, we developed and validated a novel creep damage constitutive model for gas-saturated coal through laboratory data calibration. The key findings reveal three characteristic creep regimes: (1) a decelerating phase dominates under low stress conditions, (2) progressive transitions to combined decelerating–steady-state creep with increasing stress, and (3) triphasic decelerating–steady–accelerating behavior at critical stress levels. Comparative analysis shows that gas-free specimens exhibit lower cumulative strain than the 0.5 MPa gas-saturated counterparts, with gas presence accelerating creep progression and reducing the time to failure. Measured creep rates demonstrate stress-dependent behavior: primary creep progresses at 0.002–0.011%/min, decaying exponentially to secondary creep rates below 0.001%/min. Steady-state creep rates follow a power law relationship when subject to deviatoric stress (R² = 0.96). Through the integration of Burgers viscoelastic model with the effective stress principle for porous media, we propose an enhanced constitutive model, incorporating gas adsorption-induced dilatational stresses. This advancement provides a theoretical foundation for predicting time-dependent deformation in deep coal reservoirs and informs monitoring strategies concerning gas-bearing strata stability. This study contributes to the theoretical understanding and engineering monitoring of creep behavior in deep coal rocks. Full article

Because artificially cemented granular (ACG) materials employ diverse combinations of aggregates and binders—including cemented soil, low-cement-content cemented sand and gravel (LCSG), and concrete—their stress–strain responses vary widely. In LCSG, the binder dosage is typically limited to 40–80 kg/m³ and the sand–gravel skeleton is often obtained directly from on-site or nearby excavation spoil, endowing the material with a markedly lower embodied carbon footprint and strong alignment with current low-carbon, green-construction objectives. Yet, such heterogeneity makes a single material-specific constitutive model inadequate for predicting the mechanical behavior of other ACG variants, thereby constraining broader applications in dam construction and foundation reinforcement. This study systematically summarizes and analyzes the stress–strain and volumetric strain–axial strain characteristics of ACG materials under conventional triaxial conditions. Generalized hyperbolic and parabolic equations are employed to describe these two families of curves, and closed-form expressions are proposed for key mechanical indices—peak strength, elastic modulus, and shear dilation behavior. Building on generalized plasticity theory, we derive the plastic flow direction vector, loading direction vector, and plastic modulus, and develop a concise, transferable elastoplastic model suitable for the full spectrum of ACG materials. Validation against triaxial data for rock-fill materials, LCSG, and cemented coal–gangue backfill shows that the model reproduces the stress and deformation paths of each material class with high accuracy. Quantitative evaluation of the peak values indicates that the proposed constitutive model predicts peak deviatoric stress with an error of 1.36% and peak volumetric strain with an error of 3.78%. The corresponding coefficients of determination R² between the predicted and measured values are 0.997 for peak stress and 0.987 for peak volumetric strain, demonstrating the excellent engineering accuracy of the proposed model. The results provide a unified theoretical basis for deploying ACG—particularly its low-cement, locally sourced variants—in low-carbon dam construction, foundation rehabilitation, and other sustainable civil engineering projects. Full article

Background: Cerebral aneurysm (CA) is a focal or diffuse pathological dilation of the cerebral arterial wall that arises due to various etiological factors. It represents a serious vascular condition, particularly affecting the elderly, and carries a high risk of rupture and neurological morbidity. Clonidine (CL), an α2-adrenergic receptor agonist, has been reported to suppress aneurysm progression; however, its underlying molecular mechanisms, especially in relation to cerebral endothelial dysfunction, remain unclear. This study aimed to investigate the potential of CL to mitigate CA development by modulating apoptosis, inflammation, and oxidative stress in an Angiotensin II (Ang II)-induced endothelial injury model. Methods: Human brain microvascular endothelial cells (HBMECs) were used to establish an in vitro model of endothelial dysfunction by treating cells with 1 µM Ang II for 48 h. CL was administered 2 h prior to Ang II exposure at concentrations of 0.1, 1, and 10 µM. Cell viability was assessed using the MTT assay. Oxidative stress markers, including reactive oxygen species (ROS) and Nitric Oxide (NO), were measured using 2′,7′–dichlorofluorescin diacetate (DCFDA). Gene expression levels of vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP-2 and MMP-9), high mobility group box 1 (HMGB1), and nuclear factor kappa B (NF-κB) were quantified using RT-qPCR. Levels of proinflammatory cytokines; tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and interferon-gamma (IFN-γ); were measured using commercial ELISA kits. Results: Ang II significantly increased ROS production and reduced NO levels, accompanied by heightened proinflammatory cytokine release and endothelial dysfunction. MTT assay revealed a marked decrease in cell viability following Ang II treatment (34.18%), whereas CL preserved cell viability in a concentration-dependent manner: 44.24% at 0.1 µM, 66.56% at 1 µM, and 81.74% at 10 µM. CL treatment also significantly attenuated ROS generation and inflammatory cytokine levels (p < 0.05). Furthermore, the expression of VEGF, HMGB1, NF-κB, MMP-2, and MMP-9 was significantly downregulated in response to CL. Conclusions: CL exerts a protective effect on endothelial cells by reducing oxidative stress and suppressing proinflammatory signaling pathways in Ang II-induced injury. These results support the potential of CL to mitigate endothelial injury in vitro, though further in vivo studies are required to confirm its translational relevance. Full article

Autonomic imbalance is one of the major pathological disturbances in chronic heart failure (CHF). Additionally, enhanced oxidative stress and inflammation are considered to be the main contributors to the disease progression. A growing body of evidence suggests cholinergic stimulation as a potential therapeutic approach in CHF, since it corrects the autonomic imbalance and alters the inflammatory response via the cholinergic anti-inflammatory pathway. Although previous research has provided some insights into the potential mechanisms behind these effects, there is a gap in knowledge regarding different cholinergic stimulation methods and their specific mechanisms of action. In the present study, an isoprenaline model (5 mg/kg/day s.c. for 7 days, followed by 4 weeks of CHF development) was used. Afterwards, rats received pyridostigmine (22 mg/kg/day in tap water for 14 days) or no treatment. Pyridostigmine treatment prevented the progression of CHF, decreasing chamber wall thinning (↑ PWDd, ↑ PWDs) and left ventricle dilatation (↓ LVIDd, ↓ LVIDs), thus improving cardiac contractile function (↑ EF). Additionally, pyridostigmine improved antioxidative status (↓ TBARS, ↓ NO₂⁻; ↑ CAT, ↑ GSH) and significantly reduced cardiac fibrosis development, confirmed by pathohistological findings and biochemical marker reduction (↓ MMP2, ↓ MMP9). However, further investigations are needed to fully understand the exact cellular mechanisms involved in the CHF attenuation via pyridostigmine. Full article

Background: Varicocele is a common condition involving the dilation of veins in the scrotum, often linked to male infertility and testicular dysfunction. This study aimed to elucidate the molecular effects of successful varicocele treatment on sperm proteomes following percutaneous sclero-embolization. Methods: High-resolution tandem mass spectrometry was performed for proteomic profiling of pooled sperm lysates from five patients exhibiting improved semen parameters before and after (3 and 6 months) varicocele sclero-embolization. Data were validated by Western blot analysis. Results: Seven proteins were found exclusively in varicocele patients before surgery—such as stathmin, IFT20, selenide, and ADAM21—linked to inflammation and oxidative stress. After sclero-embolization, 55 new proteins emerged, including antioxidant enzymes like selenoprotein P and GPX3. Thioredoxin (TXN) and peroxiredoxin (PRDX3) were upregulated, indicating restoration of key antioxidant pathways. Additionally, the downregulation of some histones and the autophagy-related protein ATG9A suggests a shift toward an improved chromatin organization and a healthier cellular environment post-treatment. Conclusions: Varicocele treatment that improves sperm quality and fertility parameters leads to significant proteome modulation. These changes include reduced oxidative stress and broadly restored sperm maturation. Despite the limited patient cohort analyzed, these preliminary findings provide valuable insights into how varicocele treatment might enhance male fertility and suggest potential biomarkers for improved male infertility treatment strategies. Full article

Background: Tramadol binds to opioid receptors and inhibits norepinephrine and serotonin reuptake, causing serotonin syndrome. Tianeptine stimulates serotonin reuptake and reduces serotonin levels. The aim of this study was to investigate whether tianeptine is effective against serotonin syndrome that may occur with serotoninergic drugs such as tramadol and citalopram. Methods: Rats were divided into eight groups (n = 6) that received tramadol (50 mg/kg), citalopram (10 mg/kg), or tianeptine (5 mg/kg) alone or a combination of tramadol + citalopram, tramadol + tianeptine, citalopram + tianeptine or tramadol + citalopram + tianeptine at the same doses administered to the stomach by oral gavage for 3 weeks. The healthy control group was given saline. Malondialdehyde, total glutathione, superoxide dismutase, and catalase levels were measured in removed brain tissues. The tissues were also examined histopathologically. Results: In the tramadol, tramadol + citalopram, and tramadol + citalopram + tianeptine groups, malondialdehyde levels were found to be higher compared to the control group, while glutathione, superoxide dismutase, and catalase levels were found to be lower. In other groups, values close to the control group were measured. Morphological degeneration was observed in neurons in the tramadol + citalopram group. The swelling of astrocytes and pericellular edema in oligodendrocytes were also observed. A significant population increase was noted in microglial cells. Blood vessels belonging to the tissue were observed to be severely dilated and congested. Histopathological damage was partially resolved in the group given tramadol + citalopram + tianeptine. Conclusions: The tramadol + citalopram combination caused severe oxidative stress in brain tissue. Tramadol alone caused mild damage in brain tissue, whereas tianeptine prevented the brain damage caused by tramadol. Full article

The South Shetland Islands and Antarctic Peninsula (SHETPENANT region) constitute a geodynamically active area shaped by the interaction of major tectonic plates and active magmatic systems. This study analyzes GNSS time series spanning from 2017 to 2024 to investigate surface deformation associated with the 2020–2021 seismic swarm near the Orca submarine volcano. Horizontal and vertical displacement velocities were estimated for the preseismic, coseismic, and postseismic phases using the CATS method. Results reveal significant coseismic displacements exceeding 20 mm in the horizontal components near Orca, associated with rapid magmatic pressure release and dike intrusion. Postseismic velocities indicate continued, though slower, deformation attributed to crustal relaxation. Stations located near the Orca exhibit nonlinear, transient behavior, whereas more distant stations display stable, linear trends, highlighting the spatial heterogeneity of crustal deformation. Stress and strain fields derived from the velocity models identify zones of extensional dilatation in the central Bransfield Basin and localized compression near magmatic intrusions. Maximum strain rates during the coseismic phase exceeded 200 $\mathrm{\nu }$strain/year, supporting a scenario of crustal thinning and fault reactivation. These patterns align with the known structural framework of the region. The integration of GNSS-based displacement and strain modeling proves essential for resolving active volcano-tectonic interactions. The findings enhance our understanding of back-arc deformation processes in polar regions and support the development of more effective geohazard monitoring strategies. Full article

Background: The MiBlend Study investigated the effect of consuming different combinations of fruits and vegetables (F&Vs) blends on markers of chronic disease risk and gene expression changes in healthy human subjects. Overall, the increase in F&Vs led to reduced susceptibility to the induction of DNA damage ex vivo, higher antioxidant capacity of plasma, and improved microvasculature as reflected by retinal analysis. As with most dietary intervention studies, inter-individual variability was observed in the responses, which might be the consequence of genetic differences. Therefore, this study aims to identify if genetic variants in relevant genes affect outcomes and responses to the dietary interventions. Methods: The literature review identified 15 polymorphic genes related to phytochemical metabolism, oxidative stress, and detoxification, which were tested in 146 participant samples using TaqMan and PCR analysis. The effect of genotypes on study outcomes was determined via analysis of variance. Results: XRCC1 wildtype carriers were more protected from ex vivo-induced DNA damage after consuming flavanol-rich F&Vs than other variants. XRCC1 is involved in DNA repair, particularly oxidative damage, and its wildtype allele enhances repair efficiency. GSTP1 wildtype carriers had a larger improvement in microvasculature after all F&V blends, especially those rich in polyphenols. GSTP1 polymorphisms likely affect microvascular responses to polyphenol-rich F&V intake by modulating detoxification and fiber-derived butyrate that can influence arterial dilation and endothelial function. Conclusions: Stratifying participants by relevant genetic polymorphisms can reveal predisposed responses to nutrients and guide efforts to personalize disease prevention strategies. Full article

Cardiac iron overload is a rare but important adverse consequence of systemic iron overload, marked by the abnormal accumulation of iron in the myocardium. It is most typically caused by hereditary hemochromatosis (mutations in the HFE gene) or secondary iron overload conditions, such as transfusion-dependent anemias. Excess iron in the myocardium causes oxidative stress, cardiomyocyte damage, and progressive fibrosis, ultimately leading to cardiomyopathy. Clinical manifestations are diverse and may include heart failure, arrhythmias, and restrictive or dilated cardiomyopathy. Given the worsened prognosis with cardiac involvement, timely diagnosis and management are essential to improve clinical outcomes. This review provides a contemporary overview of the cardiovascular complications associated with iron overload, including clinical manifestations, diagnostic approaches, and treatment options. Full article

Nitric oxide (NO), the first gaseous molecule identified as a signaling mediator, plays a pivotal role in numerous physiological processes including cardiovascular regulation, immune response, and neurotransmission. Synthesized from L-arginine by nitric oxide synthase (NOS), NO exerts both protective and cytotoxic effects depending on its local concentration. At low levels, NO supports tumor growth by mitigating oxidative stress, while at high concentrations, it induces apoptosis through mechanisms such as p53 activation, cytochrome c release, and peroxynitrite formation. These dual properties position NO as a complex but promising agent in cancer therapy. Recent studies have highlighted the potential of NO in enhancing the efficacy of photodynamic therapy (PDT), where it synergizes with reactive oxygen species (ROS) to induce cytotoxic effects in tumor cells. Despite its promise, challenges such as rapid diffusion and limited tumor accumulation hinder NO’s therapeutic utility. This has spurred the development of NO donors and nanotechnology-based delivery systems to enable controlled, site-specific release. Moreover, NO has been shown to counteract multidrug resistance, improve tumor perfusion by dilating vasculature, and potentiate ROS-based therapies like PDT and radiotherapy. However, an emerging concern is NO’s role in promoting proliferation and migration of non-targeted “bystander” tumor cells following PDT-induced stress, primarily through iNOS upregulation. This feedback loop can contribute to tumor aggressiveness and metastasis, underscoring the need for a deeper understanding of NO’s molecular actions. While iNOS inhibitors show preclinical promise in various inflammatory and neoplastic conditions, no such agents have reached clinical approval, due to the complexity and context-dependent effects of NO. Future research should focus on refining NO delivery systems, developing selective iNOS inhibitors, and elucidating NO’s dual role in cancer biology to fully harness its therapeutic potential in PDT and beyond. Full article

Coral sand is characterized by unique particle morphology and pore structure, which result in pronounced dilatancy and a high internal friction angle during shear. The dilatancy angle is a critical parameter for finite element analyses of sand foundation bearing capacity; the inappropriate selection of this parameter can lead to significant computational errors. In this research, a series of consolidated drained triaxial tests were conducted on coral sand samples from the South China Sea to investigate the dilatancy behavior and its effect on shear strength parameters. A dilatancy equation for coral sand was proposed, incorporating the dilatancy index, relative density, and mean effective stress. The results indicate the following: (1) Within the confining pressure range of 25–400 kPa, the stress–strain curves exhibit varying degrees of strain softening. When the effective confining pressure reaches 400 kPa, the dilatant behavior is nearly suppressed, resulting in a transition from dilatancy to contraction; (2) The peak internal friction angle decreases significantly with increasing effective confining pressure. However, the sensitivity to confining pressure varies for samples with different relative densities (Dr = 30–90%), with denser samples showing a more rapid reduction in peak friction angle; (3) At a confining pressure of 25 kPa, the maximum dilatancy angle of coral sand samples reaches 44.2°, significantly exceeding the typical range observed in terrestrial quartz sands. This difference may be attributed to the irregular and angular characteristics of the coral sand particles; (4) Based on Bolton’s dilatancy theory, a dilatancy equation applicable to coral sand was developed, demonstrating a strong linear relationship among the dilatancy index (I_R), relative density (Dr), and peak mean effective stress (p′_f). These findings provide valuable guidance for the selection of strength parameters for engineering applications involving coral sand. Full article

Understanding the structural behaviour of flat plate systems during fire exposure is critical for ensuring the safety of occupants and emergency personnel. Flat slabs, a widely used structural system, undergo significant thermal deformations in fire, which increase demands on supporting columns and reduce the stiffness and strength of concrete and steel. While experimental fire tests have provided valuable data to understand the behaviour of isolated components of flat slabs, numerical analysis is the only route to comprehending the structural behaviour of full-scale flat plate structures during fire exposure. ABAQUS is commonly used for modelling reinforced concrete (RC) structures under fire, with two prevailing techniques: (1) solid element modelling for concrete and truss reinforcement and (2) shell element modelling with embedded steel layers and line-column elements. However, uncertainties remain regarding the influence of modelling parameters such as dilation angle and concrete tensile stress, and the impact of surface fire exposure has not been comprehensively studied. This study presents a novel contribution by conducting a detailed numerical investigation of a full-scale flat plate structure exposed to fire using both modelling approaches. The shell-element model was validated against experimental data and used to evaluate the effect of dilation angle and tensile strength assumptions. A unique aspect of this work is the assessment of fire exposure on different slab surfaces, including bottom, top, and both, which provides insights into slab deflections and column displacements under different surface fire exposure scenarios. The structure was then modelled using solid elements to systematically compare modelling techniques. The results highlight key differences between approaches and guide for selecting the most suitable modelling strategies for fire-exposed flat plate systems. Full article

This study proposes an advanced thermodynamic energy equation to accurately simulate the stress–dilatancy relationship in granular soils for both uncrushed and crushed sands. Traditional energy formulations primarily consider dissipation energy and often neglect the role of free energy. Recent developments have introduced free energy components to account for plastic energy contributions from dilation and particle crushing. However, significant discrepancies between theoretical predictions and experimental observations remain, largely due to the omission of complex mechanisms such as contact network rearrangement, force-chain buckling, grain rolling, rotation without slip, and particle crushing. To address these gaps, the proposed model incorporates dual exponential decay functions into the free energy framework. Rather than explicitly modeling each mechanism, this formulation aims to phenomenologically capture the interplay between fundamentally opposing thermodynamic forces arising from complex mechanisms during granular microstructure evolution. The model’s applicability is validated using the experimental results from both uncrushed silica sand and crushed calcareous sand. Through extensive comparison with over 100 drained triaxial tests on various sands, the proposed model shows substantial improvement in reproducing stress–dilatancy behavior. The average discrepancy between predicted and measured $\eta –D$ relationships is reduced to below 15%, compared to over 60% using conventional models. This enhanced energy equation provides a robust and practical tool for predicting granular soil behavior, supporting a wide range of geotechnical engineering applications. Full article

Background/Objectives: Sentence stress as part of linguistic prosody plays an important role for verbal communication. It emphasizes particularly important words in a phrase and is reflected by acoustic cues such as the voice fundamental frequency. However, visual cues, especially facial movements, are also important for sentence stress perception. Since cochlear implant (CI) recipients are limited in their use of acoustic prosody cues, the question arises as to what extent they are able to exploit visual features. Methods: Virtual characters were used to provide highly realistic but controllable stimuli for investigating sentence stress in groups of experienced CI recipients and typical-hearing (TH) peers. In addition to the proportion of correctly identified stressed words, task load was assessed via reaction times (RTs) and task-evoked pupil dilation (TEPD), and visual attention was estimated via eye tracking. Experiment 1 considered congruent combinations of auditory and visual cues, while Experiment 2 presented incongruent stimuli. Results: In Experiment 1, CI users and TH participants performed similarly in the congruent audiovisual condition, while the former were better at using visual cues. RTs were generally faster in the AV condition, whereas TEPD revealed a more detailed picture, with TH subjects showing greater pupil dilation in the visual condition. The incongruent stimuli in Experiment 2 showed that modality use varied individually among CI recipients, while TH participants relied primarily on auditory cues. Conclusions: Visual cues are generally useful for perceiving sentence stress. As a group, CI users are better at using facial cues than their TH peers. However, CI users show individual differences in the reliability of the various cues. Full article