Search Results (5,663)

Tendinopathy is a common musculoskeletal disorder that increases the risk of tendon rupture if not properly treated. Current local injection therapies require frequent administration, and no fully effective drug is yet available. Curcumin (Cur) exhibits excellent anti-inflammatory and antioxidant effects, but its poor water solubility and low stability limit its clinical application. To overcome these challenges, this study encapsulated Cur into pluronic F127-based nanomicelles (Cur-F127) to improve its aqueous solubility and stability. Subsequently, the micelles were incorporated into a hydrogel network (Cur-F127&gel) formed by oxidized hyaluronic acid (oxi-HA) and adipic acid dihydrazide (ADH) to achieve sustained release. The resulting Cur-F127 micelles had a particle size of 20.14 ± 0.287 nm, an encapsulation efficiency (EE%) of 89.95 ± 0.60%, and a drug loading (DL%) of 5.57 ± 0.05%. The composite hydrogel possessed a loose, porous three-dimensional network, excellent biocompatibility, and favorable degradation behavior. The system enabled sustained release of Cur for over 20 days without an initial burst. In a rat model of tendinopathy, Cur-F127&gel significantly promoted tendon repair, as evidenced by reduced inflammatory cell infiltration, improved collagen fiber alignment, restored expression of key mitochondrial-related proteins (Ndufs3, Uqcrq, Uqcr10, Atp5mc3), and alleviated oxidative stress damage demonstrated by increased SOD activity and decreased MDA content in tendon tissue, thereby suppressing disease progression. This injectable sustained-release hydrogel system for poorly soluble drugs provides an effective approach for the local, long-acting delivery of Cur and long-term repair of tendinopathy, highlighting its potential value for clinical application. Full article

To examine how grain-size distribution affects the mechanical response and fracture behavior of Lac du Bonnet (LdB) granite under uniaxial compression, numerical simulations were conducted using the particle flow code (PFC) with a grain-based model. By displacing grain centroids in different directions along the y-axis, four LdB granite models with distinct grain sizes were generated, with grains delineated by Voronoi tessellation. The main findings are as follows: (1) The flat-jointed constitutive model reproduces the experimental response well, and introducing unbonded contacts (micrometer-scale gaps) improves the simulation of crack-closure behavior during loading. (2) Secondary cracks initiate predominantly at grain boundaries, and the yield stress is strongly associated with the evolution of intragranular tensile cracks. (3) Grain size governs the sequence of crack accumulation (tensile vs. shear), the growth rate and spatial correlation of damage, and the distribution and intensity of local failures; smaller grains hinder macroscopic damage, whereas larger grains are more readily penetrated and filled by microcracks. (4) Mechanical cutting tests show that grain-size combinations produce several dominant secondary-failure modes; the failure thickness is controlled by the penetration depth of the subsequent cutting head, and the stress concentration near the cutting head is sensitive to grain size. Full article

Traditional macroscopic test methods (e.g., uniaxial compression and indirect tensile strength tests) cannot accurately describe the internal microstructure and its influence on the mechanical properties of asphalt mixtures from a microscopic perspective. With the advancement of digital image processing (DIP) techniques and numerical simulation methods, relatively complete workflows for microstructure characterization and mesostructural evaluation of composite materials have been established. In this study, a three-dimensional finite element model incorporating voids was developed using the Monte Carlo method and ABAQUS software to investigate the relationships between void morphology, distribution, and the mechanical properties of porous asphalt mixtures. By varying void size and shape in the model, correlations between mesostructural stress–strain characteristics and void morphology were derived. The stress distribution around aggregates and damage initiation trends in the mesostructure were summarized. The relationship between the anticipated strength (numerically assessed) of porous asphalt mixture and the void ratio was established through simulations of models with varying void ratios. Finally, a micromechanical model for porous asphalt mixture with optimized mechanical performance is proposed, featuring an icosahedral void shape, a void diameter range of 3–4 mm, and a void ratio of 18%. Full article

Fiber-reinforced polymer (FRP) pipes are increasingly used in pressure piping systems due to their corrosion resistance and favorable mechanical performance; however, the direct experimental validation of design assumptions adopted in international standards remains limited. The objective of this study is to experimentally validate the mechanical response and stress distribution of filament-wound GFRP pipes under representative loading conditions and to assess the consistency of the measured behavior with the allowable-stress design framework of ISO 14692 and complementary ASME and BS codes. In this study, the mechanical behavior of filament-wound glass fiber-reinforced polymer (GFRP) pipes is investigated through a combined experimental program including tensile, bending, and full-scale internal pressure tests. Electrical resistance strain gauges were applied in axial and circumferential directions to directly measure deformation under internal pressure up to 31 bar, allowing experimental stresses to be derived using orthotropic laminate relationships. The results demonstrate a predominantly linear elastic response within the service range, followed by progressive damage initiation at higher load levels, with circumferential stresses consistently exceeding axial stresses, confirming a hoop-dominated response. At the maximum applied pressure of 31 bar, axial and circumferential strains reached approximately ε_a ≈ 1.30 × 10⁻³ and ε_h ≈ 1.60 × 10⁻³, corresponding to experimentally derived stresses of σ_a^exp ≈ 15.3 MPa and σ_h^exp ≈ 18.8 MPa, without catastrophic failure. The novelty of this work lies in the direct integration of full-scale strain gauge measurements with standardized allowable-stress design assumptions, enabling an experimental validation of ISO 14692 that is rarely addressed in existing studies. The experimentally derived stress–strain data show good agreement with theoretical models and provide a direct link between measured behavior and the allowable stress philosophy and design equations defined in ISO 14692 and complementary ASME and BS design codes. The findings validate the applicability of standardized design approaches and provide experimentally grounded support for engineering design decisions in FRP piping systems. Full article

The periodic thermal loads to which electronic devices are exposed during operation induce alternating thermal stresses due to the mismatched coefficients of thermal expansion (CTE) between the solder joints and the surrounding materials. This leads to cyclic thermal strain, ultimately causing crack initiation, propagation, and failure of interconnect structures. This study investigates thermal fatigue failure of Sn3.5Ag solder joints induced by cyclic thermal stresses from CTE mismatch. Numerical simulations and experiments reveal that alternating shear strain concentrates at the joint–pad interface, serving as the crack initiation site. This study proposes a hypothesis: extracting the equivalent viscoplastic strain range from the steady-state hysteretic response after cyclic stabilization and applying it to the Coffin–Manson model can mitigate the strain overestimation inherent to methods based on the initial transient impact, thereby providing a more reasonable physical basis for thermal fatigue life evaluation. Based on this, the thermal fatigue life of the solder joint is predicted to be 18,930 cycles. Analysis confirms significantly higher viscoplastic strain energy density at this critical point, indicating energy dissipation drives damage. This study addresses the above hypothesis from three aspects: deformation mechanism, cyclic response, and energy dissipation, providing a key basis for developing a highly reliable method for assessing solder joint life. Full article

To reduce water consumption and potential formation damage associated with conventional water-based fracturing fluids while improving the proppant-carrying and flow adaptability of CO₂-based systems without relying on specialized CO₂ thickeners, a CO₂–water polymer hybrid fracturing fluid was developed using an AM/AA copolymer (poly(acrylamide-co-acrylic acid), P(AM-co-AA)) as the thickening agent for the aqueous phase. Systematic experimental investigations were conducted under high-temperature and high-pressure conditions. Fluid-loss tests at different CO₂ volume fractions show that the CO₂–water polymer hybrid fracturing fluid system achieves a favorable balance between low fluid loss and structural continuity within the range of 30–50% CO₂, with the most stable fluid-loss behavior observed at 40% CO₂. Based on this ratio window, static proppant-carrying experiments indicate controllable settling behavior over a temperature range of 20–80 °C, leading to the selection of 60% polymer-based aqueous phase + 40% CO₂ as the optimal mixing ratio. Rheological results demonstrate pronounced shear-thinning behavior across a wide thermo-pressure range, with viscosity decreasing systematically with increasing shear rate and temperature while maintaining continuous and reproducible flow responses. Pipe-flow tests further reveal that flow resistance decreases monotonically with increasing flow velocity and temperature, indicating stable transport characteristics. Phase visualization observations show that the CO₂–water polymer hybrid fracturing fluid system exhibits a uniform milky dispersed appearance under moderate temperature or elevated pressure, whereas bubble-dominated structures and spatial phase separation gradually emerge under high-temperature and relatively low-pressure static conditions, highlighting the sensitivity of phase stability to thermo-pressure conditions. True triaxial hydraulic fracturing experiments confirm that the CO₂–water polymer hybrid fracturing fluid enables stable fracture initiation and sustained propagation under complex stress conditions. Overall, the results demonstrate that the AM/AA copolymer-based aqueous phase can provide effective viscosity support, proppant-carrying capacity, and flow adaptability for CO₂–water polymer hybrid fracturing fluid over a wide thermo-pressure range, confirming the feasibility of this approach without the use of specialized CO₂ thickeners. Full article

Tumor necrosis factor alpha (TNF-α) serves as a major regulator of inflammatory responses. The initial, critical release and activation of TNF-α in acute pancreatitis (AP) is primarily triggered within the pancreatic acinar cells through intracellular mechanisms in response to initial injury. This local, acinar cell-derived TNF-α recruits immune cells into the pancreas, which then produce more TNF-α, leading to the amplification of the inflammatory cascade. This opinion emphasises the role of TNF-α-mediated dysfunction of pancreatic β-cells and apoptosis induction through the Bax/Bcl-2/caspase-3 pathway. AP is often diagnosed by autodigestive pancreatic damage and systemic inflammatory response with transient or persistent hyperglycaemia. TNF-α signalling takes place through TNFR1, which initiates apoptotic events that weaken mitochondrial integrity leading to β-cell disruption and diminished insulin secretion. Studies reported TNF-α-mediated increases in Bax expression, anti-apoptotic Bcl-2 suppression and activation of caspase-3. Therapeutic strategies such as TNFR1 inhibitors, Bax/Bcl-2 modulators and BH3 mimetics possess great potential to preserve β-cell integrity. However, TNF-α inhibition requires a careful approach in order to avoid compromising immune defence in AP patients. TNF-α-driven β-cell apoptosis represents a strong link between inflammation and metabolic dysfunction that makes it a suitable target for AP. Future directions should prioritise translational research in human cohorts and developing receptor-specific interventions to balance immune modulation with β-cell preservation. Full article

Research has shown that diet significantly influences the chance of developing chronic inflammatory diseases including inflammatory bowel disease, cardiovascular disease, obesity, type 2 diabetes and several types of cancer. Dietary components modulate the immune system by either promoting or mitigating inflammatory pathways. One such pathway is the activation of the NLRP3 inflammasome—a multiprotein complex that is involved in the innate immune response. The NLRP3 inflammasome is triggered by various stimuli including ionic flux, mitochondrial dysfunction, lysosomal damage and ROS. Upon activation through a two-signal process, an immune response is initiated that protects the body against pathogens and cellular stress. In a healthy body, this pathway is closely regulated to maintain homeostasis and prevent excessive inflammation that can result in tissue damage or chronic inflammatory diseases. Several components present in a human diet can activate or inhibit the NLRP3 inflammasome. To support a balanced diet, organizations like the WHO have developed dietary recommendations. These promote the consumption of fruits, vegetables, whole grains, lean proteins and healthy fats. These foods contain a variety of nutrients and bioactive compounds, including saturated fatty acids, cholesterol, omega-6 fatty acids and natural sugars, which are pro-inflammatory. At the same time, they also supply anti-inflammatory compounds such as monounsaturated fatty acids, antioxidants and probiotics. While current literature highlights the NLRP3 inflammasome as a critical regulator of inflammation, it lacks detailed insights into how the specific dietary components of a healthy diet influence its modulation. Therefore, this literature review elucidates the various mechanisms through which these dietary compounds modulate the NLRP3 inflammasome. The significance of maintaining a balance between pro- and anti-inflammatory components in the diet is highlighted by its role as a regulator of inflammatory diseases, for example, through mechanisms such as epigenetic pathways. Full article

This extensive work was carried out to demonstrate the variations in inelastic displacement ratios (IDR) of degrading concrete structures under repeated earthquakes. While the development of sophisticated methods for assessing the seismic demands under repeated earthquakes has been ongoing, these methods are still based on simple material models. None of these models consider the degradation effect. Similarly, the seismic provisions currently in use do not consider repeated earthquakes. They assume that the structure resists the main shock only. The stiffness and strength of the structure is reduced as a result of initial loading, and likewise, the retrofitting of the structure cannot be provided in a brief time; hence, the successive shocks cause more structural damage or failure. Material deterioration effects are evident in structures that experience repeated earthquakes. Even though they survive under the main shock, they collapse under smaller aftershocks. This study comprises the simulation of repeated earthquakes, running simulations with degradation taking into account, preparing IDR curves, and comparing the results that show repeated earthquakes have a profound impact on the IDR of concrete structures compared to single earthquakes, and degradation provides significantly lower IDR values for both single and repeated earthquakes. Full article

This paper reviews constitutive models used to predict concrete spalling under elevated temperatures, with emphasis on fire exposure and concrete linings in deep geological repositories for spent fuel and nuclear waste. The review synthesizes (1) how material composition (ordinary Portland cement concrete, geopolymer concrete, and fiber-reinforced systems using polypropylene and steel fibers) affects spalling resistance; (2) how coupled environmental and mechanical actions (temperature, moisture, stress state, chloride ingress, and radiation) drive damage initiation and spalling; and (3) how constituent-scale characteristics (microstructure, porosity, permeability, elastic modulus, and water content) govern thermal–hydro–mechanical–chemical (THMC) transport and damage evolution. We compare major constitutive modeling frameworks, including plasticity–damage models (e.g., concrete damage plasticity), statistical damage approaches, and fully coupled THM/THMC formulations, and highlight how key parameters (e.g., water-to-binder ratio, temperature-driven pore-pressure gradients, and crack evolution laws) control predicted spalling onset, depth, and timing. Several overarching challenges emerge: lack of standardized experimental protocols for spalling tests and assessments, which limits cross-study benchmarking; continued debate on whether spalling is dominated by pore pressure, thermo-mechanical stress, or their interaction; limited integration of multiscale and constituent-level material characteristics; and high data and computational demands associated with advanced multi-physics models. The paper concludes with targeted research directions to improve model calibration, validation, and performance-based design of concrete systems for high-temperature and repository applications. Full article

Hypo-peritectic steels are susceptible to interfacial cracking during thin-slab continuous casting, in which non-metallic inclusions play a critical role. This study systematically investigates the effects of inclusion type and morphology on interface cracking behavior in the steel matrix, with the aim of improving billet shell quality. Hot tensile experiments were conducted using a Gleeble 3800 thermal simulator, and a finite element–based cohesive zone model was developed to simulate inclusion-induced crack nucleation and propagation. The results demonstrate that inclusions markedly influence interfacial stress distribution and damage evolution. The maximum interfacial stresses associated with MnS, Al₂O₃, and composite inclusions are 20.7, 23.4, and 30.5 MPa, respectively. Owing to severe stress concentration at sharp corners, composite inclusions exhibit the earliest crack nucleation at an applied stress of 11.3 MPa and the highest energy dissipation. In all cases, cracks initially nucleate at the location of maximum tensile stress (α = 90°), propagate along the interface, and subsequently penetrate into the matrix, ultimately leading to failure. The strong agreement between numerical simulations and experimental results confirms that angular inclusions accelerate damage by disrupting matrix continuity. These findings provide theoretical guidance for improving hypo-peritectic steel quality through inclusion morphology control during continuous casting. Full article

Aircraft structures are highly susceptible to fatigue damage, particularly in thin-walled aluminum alloy components such as skin panels. Damage in the form of holes or material loss drastically reduces fatigue life and compromises structural safety, which makes effective repair strategies essential. This study presents an experimental investigation into the fatigue performance of EN AW-2024-T3 aluminum alloy plates with central openings subjected to uniform shear. Repair nodes were applied using two approaches: conventional riveted metal patches and adhesively bonded composite patches. Variants of patch geometry, thickness, and diameter were evaluated to determine their influence on load transfer, buckling response, and fatigue life. The results show that central holes significantly shorten fatigue life, with a 20 mm hole causing a 67% reduction and a 50 mm hole causing a 95% reduction when compared with undamaged plates. Riveted metal patches restored only part of the lost performance, as stress concentrators introduced by fastener holes initiated new fatigue cracks. In contrast, adhesively bonded composite patches provided a substantial improvement, extending fatigue life beyond that of the riveted solutions, improving buckling shape, and delaying crack initiation. Larger patches, particularly those combined with metallic inserts, proved most effective in restoring structural functionality. The findings confirm the effectiveness of bonded composite repairs as a lightweight and reliable method for extending fatigue life and enhancing the safety of damaged aircraft structures. The study highlights the importance of patch geometry and stiffness in the design of repair nodes. Full article

The reliability of solid rocket motors depends primarily on the structural integrity of their propellants. Internal cavity defects in the widely used hydroxyl-terminated polybutadiene (HTPB) propellant, formed during manufacturing and service, significantly degrade its mechanical properties and compromise motor safety. This study developed a constitutive model for HTPB propellant based on the generalized incremental stress–strain damage model (GISSMO). The validity of the constitutive model was verified through uniaxial tensile tests conducted at various tensile rates. Based on this constitutive model, numerical simulations were performed to examine the effects of initial modulus, impact rate, and cavity confining pressure on the failure modes of propellants containing cavities with radii from 40 to 100 mm. The results show that the simulation’s force–displacement curve agrees well with the test. The simulation accurately captures the propellant’s transition from elastic–plastic plateau at low rates to elastic response at high rates. The prediction error for the maximum tensile force is less than 5%. For cavities of 80 mm and 100 mm, local stress concentration causes damage to the inner wall, followed by rapid cavity extrusion, collapse, and possible cross-shaped matrix fracture. However, cavities of 40 mm and 60 mm show greater stability, experiencing only volume compression, which rarely causes overall damage. When the propellant’s initial modulus is higher than 24 MPa, damage propagation in large cavities over 80 mm is suppressed. A low modulus worsens structural deformation. At low impact velocity, cavity compression is significant, and the structure remains conformal. At high impact velocity (4000 MPa/s), the cavity stays conformal, the matrix collapses, and the damage value decreases. For 60 mm cavities, damage is localized, and the overall structure is most stable within a confining pressure of 5 to 9.5 MPa. This study clarifies the interaction between engineering parameters and cavity size, providing a basis for optimizing the safety of the propellant structure. Full article

Traditional expansion joints in bridge structures are prone to durability problems, such as leakage, corrosion, and high maintenance demands, which can significantly reduce service life. To overcome these limitations, ultra-high-performance concrete (UHPC) link slabs have emerged as an effective jointless solution; however, their mechanical performance and sensitivity to key design and modeling parameters are not yet fully understood. This study presents a nonlinear finite element investigation of UHPC link slabs using the Concrete Damaged Plasticity (CDP) model in ABAQUS. A baseline model, validated against the experimental results, was established with a link slab length of 1100 mm and representative material and detailing properties. A systematic sensitivity analysis was then performed by varying five geometrical parameters (link slab length and thickness, debonding length, reinforcement diameter, and reinforcement spacing) and five numerical/material parameters (non-debonding and debonding interface friction coefficient, UHPC and normal concrete compressive strength, and steel yield strength). For each case, the load–displacement response was examined through initial stiffness (K₀), yield and peak load–deformation values (P_y, Δ_y and P_u, Δ_u), and ductility ratio (μ). The results highlight the dominant role of reinforcement detailing; larger bar diameters and closer spacing substantially increased stiffness and strength while maintaining ductility. Debonding length emerged as a critical tuning parameter, with longer debonding improving ductility but slightly reducing strength. Slab thickness primarily influenced stiffness, whereas overall length showed minor effects on peak capacity. On the numerical side, steel yield strength proved to be the most influential input, affecting all response measures, while the non-debonding interface friction coefficient strongly governed yield capacity. Variations in the debonding friction coefficient, UHPC compressive strength, and normal concrete strength exhibited secondary influence within the tested ranges. Overall, the findings provide practical guidance for both the designing and detailing of UHPC link slabs and the calibration of FEM (finite element modeling) models. By clarifying which parameters most strongly govern stiffness, strength, and ductility, this study supports more reliable structural design and efficient numerical modeling of UHPC link slabs in accelerated bridge construction applications. Full article

Genomic instability not only drives tumor initiation and progression but also cooperates with apoptosis resistance to promote therapeutic evasion in hepatocellular carcinoma (HCC). Activation of MDM2, a negative regulator of p53, together with XIAP overexpression, represents a critical axis underlying this resistance. Simultaneous targeting of MDM2 and XIAP by MX69, a small molecule inhibitor, may therefore offer a potent interventional strategy to suppress cell proliferation and enhance pro-apoptotic signaling in HCC in vitro models. To evaluate the effects of MX69, cell viability was assessed via CVDK-8, colony formation, and real-time cell analysis. Oxidative stress levels and DNA damage were examined using fluorescence imaging and comet assays, respectively, while mitochondrial membrane potential was monitored through JC-1 staining. Furthermore, flow cytometry was employed to quantify apoptotic cell death and cell cycle distribution, while Western blot analysis was used to characterize the expression of apoptosis-related proteins. In vitro cytotoxicity assays revealed that MX69 reduced the viability of HUH7 and Hep3B cells in a dose-dependent manner, suppressed colony formation, and exerted anti-proliferative effects in real-time proliferation assays. Cell viability and IC50 values were evaluated using CVDK-8 and RTCA assays. Furthermore, MX69 induced oxidative stress and mitochondrial dysfunction, as evidenced by elevated ROS levels and loss of mitochondrial membrane potential. This was accompanied by significant DNA damage, detected by comet assay and γ-H2AX immunofluorescence, and G0–G1 cell cycle arrest. Moreover, MX69 triggered apoptotic cell death, demonstrating potent anticancer activity. Collectively, our findings identify MDM2/XIAP dual inhibition by MX69 as a promising therapeutic approach in HCC, with potential to overcome apoptosis resistance linked to genomic instability. Full article