Search Results (862)

Background/Objectives: Wound healing proceeds in a timely and sequential manner through four well-defined phases: hemostasis, inflammation, proliferation, and remodeling. To explore the therapeutic efficacy and underlying mechanism of a novel monoacylglycerol lipase (MAGL) inhibitor (designated as MAGL11), a diabetic mouse model of skin wounds was established. Methods: Wound healing progression was assessed via gross observation, while histological analyses (including HE staining and Masson staining) were conducted to evaluate tissue repair. Additionally, proteomic analysis and in vitro experiments were employed to validate the therapeutic effects and clarify the molecular mechanism of MAGL11. Results: In vivo studies revealed that treatment with MAGL11 significantly accelerated wound closure in diabetic mice. Compared with the control group, MAGL11-treated wounds exhibited notably increased granulation tissue formation and collagen deposition, which was accompanied by a distinct anti-inflammatory effect. Results from proteomic profiling and in vitro experiments further demonstrated that MAGL11 exerted its pro-healing effects by promoting the activation of the Rap1/PI3K/Akt signaling pathway. Specifically, MAGL11 enhanced the migration and chemotaxis of fibroblasts (NIH3T3), human umbilical vein endothelial cells (HUVECs), and keratinocytes (HaCaT) while simultaneously inhibiting cellular apoptosis—all of which collectively contributed to improved wound healing. Conclusions: These findings suggest that MAGL11 holds promise as a potential candidate for diabetic wound therapy, primarily through its ability to promote angiogenesis, fibroblast activation, and epithelial regeneration. Full article

Temperature homogeneity assumes a crucial role in the manufacture of asphalt mixtures due to its impact on mechanical formation and mixing homogeneity. The existence of reclaimed asphalt pavement (RAP) exacerbates its impact on temperature inhomogeneity. To address this, the RAP contents of 20%, 40%, and 60%, combined with RAP preheated temperatures of 353 K, 373 K, and 393 K, were taken into consideration to examine the thermal transition and evolution of temperature for the recycled asphalt mixtures in the mixing. Thermal images captured within the range of 30 s to 120 s were used to monitor the temperature evolution of the recycled asphalt mixtures during the mixing. To quantitatively assess the level of thermal non-uniformity, a Relative Thermal Equilibrium Temperature Index (RETI) was introduced. This index reflects the degree of deviation from ideal thermal equilibrium within the recycled mixtures. Based on the RETI calculation, complete temperature homogeneity cannot be attained until the end of the mixing of hot recycled asphalt mixtures. However, a prolongation of the mixing time or an elevation in the RAP preheated temperature can expedite the thermal equilibrium process of recycled asphalt mixtures. Additionally, the RAP contents also exerted a crucial influence on the thermal equilibrium process of the recycled asphalt mixtures. Full article

This study assesses how satellite clock products affect Precise Point Positioning (PPP) for GPS, Galileo, and GPS+Galileo. Multi-GNSS data at 30 s were processed for 12 global IGS stations over one week in 2025, with each day split into eight independent three-hour sessions. SP3 clocks (ORB, 5 min) were compared with dedicated CLKs (CLO, 5 s, 30 s, 5 min) across final (FIN), rapid (RAP), and ultra-rapid (ULT; observed/predicted) product lines from multiple analysis centers. Two timing strategies were tested: nearest-epoch sampling (CLOCK0) and linear interpolation (CLOCK1). CLO consistently delivered the lowest 2D/3D errors and the fastest convergence. ORB degraded accuracy by a few millimeters and extended convergence by ~5–10 min, most notably for GPS. With 5 min clocks, CLOCK1 yielded small gains for Galileo but often hurt GPS; with 30 s clocks, interpolation was immaterial; 5 s clocks offered no measurable benefit. FIN outperformed RAP; OPS slightly outperformed MGEX; ESA/GFZ ranked highest. ULT solutions were weaker, especially in the predicted half. Zenith tropospheric delay (ZTD) biases were negligible; variance was smallest for GPS+Galileo with CLO (~7–10 mm), increased by ~1–2 mm with ORB, and was largest in ULT. Dense, high-quality clock products remain essential for reliable PPP. Full article

This analysis examines long-term changes in water levels of the Mead and Glen Canyon reservoirs on the Colorado River. Both reservoirs display clear declining trends in water levels, particularly after 2003. The causes include a combination of climate change, megadrought, increased water consumption, and alterations in the hydrological regime. Lake Mead exhibits a stronger and more concerning decline than Lake Powell, including extreme drought conditions over the past three years. The Rescaled Adjusted Partial Sums (RAPS) analysis identifies three statistically distinct subperiods, with an unambiguous decline in the most recent period. The day-to-day (DTD) method indicates reduced day-to-day water level variability in Lake Mead following the commissioning of the Powell reservoir, confirming its regulating influence. The Standardized Hydrological Index (SHI) indicates an accelerating intensification of drought conditions over the past 20 years. Regression analysis confirms a strong relationship between the water levels of the two reservoirs, along with significantly increased water losses in the more recent period. The literature suggests that climate projections are highly unfavorable, with further reductions in Colorado River discharge expected. The study underscores the urgent need to adapt water-management policies and align consumption with the new hydrological realities. Full article

The circular economy represents a significant opportunity to enhance the mechanical properties of bituminous mixtures, thereby contributing to sustainable development. This research compares the behaviour of traditional bituminous mixtures with sustainable ones that reuse recycled materials, industrial waste products, or additives that improve mechanical or rheological properties. The methodology employed comprised the acquisition of fatigue resistance laws from 4-point bending tests on prismatic specimens. This facilitated the analytical determination of the number of axles of 13 tons that the section of pavement with sustainable material can support for comparison with the axles supported in the conventional mix. The findings corroborate the utilization of sustainable bituminous mixtures in pavement sections, employing the maximum circularity criterion. The fatigue laws calculated must permit the use of different calculation methods or other applications in green infrastructures, such as cycling lanes or pedestrian areas. On sections with an AADT of between 800 and 25 HV/day, all of the analyzed bituminous mixtures with sustainable materials prolong the service life of the road. There were increases in service life of between 25.5% and 6.6%, respectively, which satisfactorily achieved an increase in pavement service life based on the criterion of maximum circularity. Full article

To enhance the ductility of coal mine filling materials using recycled asphalt pavement (RAP) and address the limitations in RAP recycling and utilization, this study processed RAP into crushed materials (CMs) and ball-milled materials (BMs). Supplementary with fly ash (FA) and cement, RAP-fly ash cement paste backfill (RFCPB) was prepared. For 1000 g of RFCPB slurry, the composition was 365 g CM, 73 g cement, 270 g water, and a total of 292 g of FA and BM, with an F/B ratio ranging from 1:7 to 7:1. A systematic test program was carried out, including rheological property tests, unconfined compressive strength (UCS) tests combined with deformation monitoring, microstructure analysis, and leaching toxicity tests. Based on these tests, the influence of F/B ratio on the action mechanism, workability, mechanical properties, ductility and environmental compatibility of RFCPB was comprehensively explored. The results show that the rheological behavior of RFCPB slurry conforms to the Herschel–Bulkley (H-B) model; with the decrease in F/B ratio, the yield stress and apparent viscosity of the slurry increase significantly, while the slump and slump flow decrease correspondingly, which is closely related to the particle gradation optimization by BM. For mechanical properties and ductility, the 28-day UCS of RFCPB first increases and then decreases with the decrease in F/B ratio, all meeting the mine backfilling strength requirements; notably, the increase in BM proportion regulates the failure mode from brittle to ductile, which is the key to improving ductility. Microstructural analysis indicates that Dolomite and Albite in BM participate in hydration reactions to generate N-A-S-H and C-A-S-H gels, which fill internal pores, optimize pore structure, and thus synergistically improve UCS and ductility. Additionally, the leaching concentration of toxic ions in RFCPB complies with the environmental protection standards for solid waste. This study provides a theoretical basis for enhancing backfill ductility and advancing the coordinated disposal of RAP and fly ash solid wastes. Full article

Unmanned aerial vehicle (UAV) swarms offer an efficient solution for data collection from widely distributed ground users (GUs). However, incomplete environment information and frequent changes make it challenging for standard centralized planning or pure reinforcement learning approaches to simultaneously maintain global solution quality and local flexibility. We propose a hierarchical data collection framework for heterogeneous UAV-assisted wireless sensor networks (WSNs). A small set of high-capability UAVs (H-UAVs), equipped with substantial computational and communication resources, coordinate regional coverage, trajectory planning, and uplink transmission control for numerous resource-constrained low-capability UAVs (L-UAVs) across power-Voronoi-partitioned areas using multi-agent deep reinforcement learning (MADRL). Specifically, we employ Multi-Agent Deep Deterministic Policy Gradient (MADDPG) to enhance H-UAVs’ decision-making capabilities and enable coordinated actions. The partitions are dynamically updated based on GUs’ data generation rates and L-UAV density to balance workload and adapt to environmental dynamics. Concurrently, a large number of L-UAVs with limited onboard resources perform self-organized data collection from GUs and execute opportunistic relaying to a remote access point (RAP) via H-UAVs. Within each Voronoi cell, L-UAV motion follows a weighted Vicsek model that incorporates GUs’ age of information (AoI), link quality, and congestion avoidance. This spatial decomposition combined with decentralized weak-swarm control enables scalability to large-scale L-UAV deployments. Experiments demonstrate that the proposed strong and weak agent MADDPG (SW-MADDPG) scheme reduces AoI by 30% and 21% compared to No-Voronoi and Heuristic-HUAV baselines, respectively. Full article

The incorporation of reclaimed asphalt pavement (RAP) offers significant environmental benefits; however, its use is often limited by an increased susceptibility to cracking due to the insufficient elasticity of the severely aged RAP binder. This limitation is conventionally mitigated using polymers such as styrene–butadiene styrene, which, despite their effectiveness, are costly and carbon intensive. This paper introduces a low-carbon sulfur-based ternary polymer developed through TiO₂-catalyzed inverse vulcanization of elemental sulfur to be used as a modifier to address the abovementioned challenge at the asphalt mixture level. The sulfur polymer containing waste cooking oil and metal-rich biochar was incorporated into hot-mix asphalt having 25% RAP. The mixture specimens were evaluated before and after accelerated thermal and ultraviolet aging. Cracking resistance was measured using the Indirect Tensile Asphalt Cracking Test (IDEAL-CT), while resistance to rutting and moisture damage were assessed through the Hamburg Wheel Tracking Test (HWT). IDEAL-CT findings showed improved ${\mathrm{C}\mathrm{T}}_{\mathrm{I}\mathrm{n}\mathrm{d}\mathrm{e}\mathrm{x}}$ values for the modified mixture under unaged conditions and after three days of thermal aging, with smaller variations noted after prolonged thermal aging and during the combined thermal–ultraviolet aging process. Results from the HWT test revealed that the addition of the sulfur polymer did not negatively impact resistance to rutting or moisture damage; all mixtures remained significantly below rutting failure thresholds. Furthermore, a simplified environmental analysis indicated that substituting 10 wt% of petroleum binder with the sulfur polymer lowered the binder’s cradle-to-gate global warming potential by around 11%. In summary, study results showed that the newly developed sulfur polymer system has the potential to improve cracking resistance even when exposed to select accelerated aging protocols while decreasing embodied carbon, thus endorsing its viability as a sustainable modifier for asphalt mixtures. Full article

Background/Objectives: Sex-specific differences in the mechanisms of acute liver injury remain poorly understood. CDK5 regulatory subunit-associated protein 3 (CDK5RAP3) is crucial for liver development and endoplasmic reticulum (ER) homeostasis. This study aimed to investigate sex-dependent changes in CDK5RAP3 expression in a carbon tetrachloride (CCl₄)-induced acute liver injury model and to explore the mechanisms underlying differential susceptibility between males and females. Methods: Acute liver injury was induced in male and female mice by CCl₄ administration. Liver injury was evaluated by serum biochemical parameters and histopathological analysis. CDK5RAP3 expression, inflammatory cytokines, and ER stress-related apoptotic markers were assessed. Hepatocyte apoptosis was examined by TUNEL staining. In addition, CDK5RAP3 was conditionally deleted in mouse embryonic fibroblasts (MEFs) using 4-hydroxytamoxifen to assess its direct role in regulating inflammatory and apoptotic responses in vitro. Results: CCl₄ exposure caused liver injury in both sexes, with male mice showing more severe biochemical and histological damage. CDK5RAP3 expression was significantly reduced after CCl₄ treatment, particularly in males. Inflammatory mediators and ER stress-associated apoptotic markers were upregulated, accompanied by increased hepatocyte apoptosis. A similar enhancement of inflammatory and apoptotic signaling was observed in CDK5RAP3-deficient MEFs. Conclusions: Downregulation of CDK5RAP3 is associated with ER stress, inflammation, and apoptosis, contributing to increased susceptibility of male mice to acute liver injury. These findings provide insight into sex-specific mechanisms of hepatic injury and highlight CDK5RAP3 as a potential therapeutic target. Full article

Testosterone (T) produced by Leydig cells (LCs) is essential for male reproduction; yet, the regulatory mechanisms underlying steroidogenesis remain incompletely understood. Here, we investigated the role of cyclin-dependent kinase 5 regulatory subunit-associated protein 3 (CDK5RAP3) in Leydig cell development and steroidogenesis, based on its identification by immunoprecipitation-mass spectrometry (IP-MS) as a protein associated with steroidogenesis and cholesterol metabolism in mouse testicular tissue. Using human samples, we found that CDK5RAP3 expression was significantly reduced in Leydig cells from patients with spermatogenic failure (T < 10.4 nmol/L). Notably, CDK5RAP3 expression increased during mouse postnatal Leydig cell maturation and regeneration in an ethane dimethanesulfonate (EDS)-induced rat model. Functional analyses in primary LCs and MLTC-1 cells showed that hCG stimulation triggered CDK5RAP3 nuclear translocation without altering its overall expression, while CDK5RAP3 knockdown markedly impaired hCG-induced testosterone production and reduced the expression of the steroidogenic regulator steroidogenic acute regulatory (STAR) protein, as well as key steroidgenic enzymes, including cytochrome P450 family 11 subfamily A member 1 (CYP11A1), 17a-hydroxylase (CYP17A1), and 3β-hydroxysteroid dehydrogenase (HSD3B). Conversely, CDK5RAP3 overexpression enhanced testosterone production in the absence of hCG. In vivo, AAV2/9-mediated CDK5RAP3 silencing in adult mouse testes resulted in a significant reduction in serum testosterone levels compared with controls (3.60 ± 0.38 ng/mL vs. 1.83 ± 0.37 ng/mL). Mechanistically, CDK5RAP3 interacted with SMAD4 and CEBPB, and BMP pathway inhibition by Noggin rescued the testosterone deficit caused by CDK5RAP3 loss. Together, these findings identify CDK5RAP3 as an essential regulator of Leydig cell steroidogenesis and provide insight into its potential relevance to male infertility associated with low testosterone. Full article

Pyroptosis is a type of programmed cell death (PCD) with pro-inflammatory properties, which is characterized by the swelling with bubbles and the release of LDH and inflammatory cell cytokines. Polyphyllin II (PPII) is the main active ingredient of the Chinese herb Rhizoma Paridis and has been proven to exert high efficacy against a variety of malignant tumors. At present, the anti-tumor research on PPII mainly focuses on apoptosis that is an anti-inflammatory type of PCD, but other potential modes of death cell death and mechanisms of PPII remain to be discovered. Here, we first found that PPII could effectively inhibit the growth of hepatocellular carcinoma (HCC) cells via pyroptosis. After treatment with PPII, the morphology of swelling with bubbles and the formation of pores in the cell membrane in HCC cells were observed, and LDH and cell cytokines (IL-1β, IL-18, IL-6, TNF-α, IFN-β, and IFN-γ) were released. Furthermore, the flow cytometry results showed that PPII could activate oxidative stress by increasing Ca²⁺ influx, thereby promoting the production of ROS to exert anti-tumor effects. RNA sequencing revealed that pyroptosis is closely linked to several signaling pathways, including the MAPK, TNF, Rap1, mTOR, and FoxO pathways, as well as the PD-L1 expression and PD-1 checkpoint pathway. An in vivo study demonstrated that PPII treatment suppressed liver tumor growth in mice by pyroptosis in a dose-dependent manner, and it showed no obvious side effects within a certain range. The Western blot results of tumor tissues revealed that the pyroptosis effect of PPII on liver cancer was associated with the activation of the NLRP3/Caspase1/GSDMD pathway, which upregulates the expression of NLRP3, Cleaved-Caspase 1, GSDMD-N, IL-1β, and IL-18 proteins and downregulates the expression of pro-Caspase 1 and GSDMD proteins. In summary, our findings revealed the pyroptosis effect and mechanism of PPII in HCC cells in vitro and in vivo, suggesting that PPII may be used as a potential pyroptosis inducer for HCC treatment in the future. Full article

To limit reflective cracking in asphalt pavements with cold-recycled base courses, cold recycling mixtures (CRMs) are designed to provide predominantly bituminous bonding, making their viscoelastic behaviour of paramount importance. This study presents an experimental evaluation of the viscoelasticity of CRMs containing 0–90% RAP, 5.5–7.4% bitumen emulsion, and 1% cement. The dynamic modulus and phase angle were determined according to AASHTO T 378-22 across temperatures of 5–40 °C and loading frequencies of 0.1–25 Hz. To assess the applicability of the time–temperature superposition principle (TTSP) for describing the CRMs’ mechanical behaviour, master curves were constructed and the statistical analysis of the model fit quality was performed. The research findings demonstrate that CRMs’ mechanical behaviour can be effectively modelled using TTSP, with their viscoelastic response being influenced by RAP and bitumen emulsion content. CRMs showed lower temperature sensitivity than HMA, yet changes in dynamic modulus and phase angle remained statistically significant. This study advances the performance-based design of CRMs and points to the potential of rheological modelling for their constitutive characterization. Full article

Autophagy is an evolutionarily conserved cellular process that maintains homeostasis by degrading intracellular materials. Numerous studies have investigated the role of autophagy-related genes (ATGs) in plant adaptation to abiotic stresses. In plants, hypoxia (e.g., flooding events, oxygen supply during growth) rapidly activates the autophagy pathway as a protective mechanism for cell survival. Considering the moisture-loving yet waterlogging-sensitive nature of tea plants, this study explored the role of CsATG8f in the tea plant’s response to submergence. We found that overexpression of CsATG8f formed more autophagosomes than controls under submergence. Furthermore, CsATG8f was confirmed to physically interact with CsRAP2.12. Co-overexpression of both genes partially suppressed transcription of hypoxia-response genes while activating the antioxidant system, thereby enhancing tea plants’ resistance to submergence. Consistent with this, the opposite trend was observed in silenced plants, which attempted to mitigate stress damage by increasing GABA levels in vivo. In conclusion, our study reveals the crucial roles of CsATG8f and CsRAP2.12 in tea plant tolerance to submergence and provides new insights into potential regulatory networks governing tea plant adaptation to flooding. Full article

Modernizing municipal roads requires rehabilitation strategies that ensure adequate structural performance while reducing environmental and economic burdens. Although cold in-place recycling with foamed bitumen (CIR-FB) has been widely investigated, integrated assessments combining mechanistic–empirical modeling with LCA and LCCA remain limited—particularly for municipal roads in Central and Eastern Europe, where reclaimed asphalt pavement (RAP) quality, climatic conditions and budget constraints differ from commonly studied regions. This study compares two reconstruction variants for a 1 km road section: a conventional design using virgin materials (V₁-N) and a recycling-based alternative (V2-Rc) incorporating RAP from the existing wearing and binder layers and reclaimed aggregate (RA) from the existing base. CIR-FB mixture testing (stiffness ≈ 5.25 GPa; foamed bitumen = 2.5%, cement = 2.0%) was integrated into mechanistic–empirical fatigue analysis, material-flow quantification, LCA and LCCA. The V₂-Rc variant achieved a 3–21-fold increase in fatigue life compared to V₁-N at equal thickness. Material demand decreased by approximately 27%, demolition waste by approximately 39%, and approximately 92% of the existing pavement was reused in situ. Transport work was reduced five-fold (veh-km) and more than six-fold (t-km). LCA showed a 15.9% reduction in CO₂-eq emissions, while LCCA indicated approximately 19% lower construction cost, with advantages remaining robust under ±20% sensitivity. The results demonstrate that CIR-FB, when supported by proper RAP/RA characterization, can substantially improve structural, environmental and economic performance in municipal road rehabilitation. Full article

The growing use of reclaimed asphalt pavement (RAP) in warm-mix asphalt (WMA) presents significant challenges when RAP originates from aged polymer-modified binder (PMB) pavements, where severe oxidation and polymer degradation lead to excessive stiffness and poor cracking resistance. This study presents a multi-scale evaluation of a hybrid modification strategy combining recycled engine oil waste (REOW, 3 wt.%) and styrene–butadiene–styrene (SBS, 1–4 wt.%) to restore aged PMB-containing RAP systems under controlled binder conditions. Three binders (control, REOW-modified, and REOW–SBS hybrid) were prepared using a fixed 70/30 virgin-to-RAP binder blend and characterized through rheological analysis, and multiple stress creep recovery (MSCR). The findings show that REOW softened the binder but reduced elastic recovery, whereas SBS modification restored elastic response. Corresponding WMA mixtures with 30 wt.% RAP and 5.0 wt.% total binder content were evaluated for moisture damage, raveling, rutting, and cracking resistance. At the mixture scale, the hybrid system achieved a TSR of 83%, reduced Hamburg rut depth by ~20%, and increased SCB fracture energy by ~30% compared with the control. These findings demonstrate that combined rejuvenation–reinforcement effectively re-mobilizes aged PMB chemistry and restores polymer elasticity, enabling high-performance WMA production with RAP derived from polymer-modified pavements. Full article