Search Results (1,662)

Background: Estrogen deficiency and glucocorticoid exposure are major contributors to osteoporosis. Although menaquinone-7 (MK-7) exhibits osteoprotective effects, whether low-dose supplementation is comparable to high-dose treatment remains unclear. Methods: Female Sprague–Dawley rats were assigned to sham control (SC), ovariectomy plus dexamethasone (OVX+Dex), and OVX+Dex treated with low-dose MK-7 (100 μg/kg) or high-dose MK-7 (20 mg/kg). Bone microarchitecture, histopathology, and serum bone turnover markers were evaluated. Results: OVX+Dex induced marked deterioration of trabecular bone microarchitecture, characterized by reduced bone volume and structural disruption. These changes were accompanied by increased osteoclast activity (cathepsin K), decreased osteogenic and extracellular matrix–related markers (cbfa-1, osteonectin, and biglycan), and downregulation of osteoprotegerin, indicating a pronounced imbalance in bone remodeling. Serum analysis further revealed reduced estradiol levels and alterations in circulating bone turnover markers, consistent with a dysregulated high-turnover state. Both low- and high-dose MK-7 significantly improved bone microarchitecture, restored remodeling-related protein expression, and partially normalized serum calcium-regulating hormones and bone turnover markers (all p < 0.05), with no significant differences observed between doses. Conclusions: MK-7 attenuates osteoporosis by restoring the balance between bone resorption and formation. Notably, low-dose MK-7 provides protective effects comparable to high-dose treatment, supporting its potential clinical utility. Full article

This study develops a ternary Fe-based geopolymer system composed of metakaolin (MK), red mud (RM), and fly ash (FA) for the preparation of sustainable water-retaining subgrade materials for sponge-city roadbed applications. Unlike conventional formulations primarily designed for structural strength or rapid permeability, the proposed MK–FA–RM system was designed to improve water-storage capacity while maintaining adequate mechanical support and environmental compatibility. In this ternary system, MK provides highly reactive aluminosilicate species for geopolymer network formation, RM introduces Fe-bearing phases and enhances industrial solid-waste utilization, and FA contributes to particle packing, workability, and resource efficiency. A constrained ternary mixture design implemented using Design-Expert software was adopted to optimize precursor proportions. Within the investigated compositional range, the fitted first-order mixture model showed acceptable statistical adequacy for preliminary composition screening (R² = 0.86). The optimal blend (60% MK, 30% RM, and 10% FA) achieved a 7-day compressive strength of 8.37 MPa and a water retention rate of 35.3% under ambient curing conditions, satisfying the strength requirement considered for the target subgrade/base-layer application. Microstructural and phase analyses suggest that the synergistic interaction of the three precursors promoted Fe-modified aluminosilicate gel formation together with conventional geopolymer gel products, while improving matrix continuity and preserving interconnected pore space for water storage. This multiscale structural effect helps explain how the material achieved a balance between water retention capacity and mechanical support. Under the tested conditions, the material maintained acceptable residual strength after short-term exposure to water, acid, and sulfate-containing solutions. Life-cycle assessment indicated a 70% reduction in CO₂ emissions compared with ordinary Portland cement, while pilot-scale cost analysis showed a 39% lower production cost than MetaMax-based geopolymer materials. Pilot-scale application further demonstrated the constructability and water-regulation potential of the material in practical environments. Overall, the proposed ternary Fe-based geopolymer demonstrates that Fe-rich industrial wastes can be engineered into low-carbon and economically viable water-retaining subgrade materials that balance hydraulic regulation, structural adequacy, and sustainability. Nevertheless, long-term durability, cyclic loading performance, and direct nanoscale characterization of Fe-bearing gel evolution still require further investigation. Full article

MK-2048 is a potent second-generation HIV integrase inhibitor that has demonstrated acceptable safety and pharmacokinetics (PKs) in clinical trials of vaginal formulations. The substrate-type interactions between MK-2048 and the transporters/metabolizing enzymes that are highly expressed in the human female reproductive tract (FRT) were evaluated. The interactions between MK-2048 and P-gp/BCRP were investigated using a cellular bidirectional permeability assay, while those between MK-2048 and MRP4 were assessed using a vesicular uptake assay. Reaction phenotyping was performed to characterize the interactions between MK-2048 and CYP1A1 and CYP1B1. Using human cervicovaginal fluids (CVFs), MK-2048’s solubility was determined using a thermodynamic solubility method and its protein binding was determined using a rapid equilibrium dialysis method. Our study shows an efflux of MK-2048 in P-gp/BCRP-overexpressing MDCKII cells, which was reduced by a P-gp/BCRP inhibitor. Uptake of MK-2048 in MRP4/control vesicles was found to be ATP-independent. MK-2048 was metabolized by the CYP1A1 enzyme but not by CYP1B1. These data confirm that MK-2048 is a substrate of P-gp, BCRP, and CYP1A1, but is not a substrate of MRP4 or CYP1B1. MK-2048 displays low solubility and high protein binding in human CVF. This data suggests that MK-2048 may potentially interact with drugs that modulate the activity of P-gp, BCRP, and CYP1A1. Full article

Current industry standards for evaluating concrete durability in wastewater environments, such as ASTM C267, rely almost exclusively on mass loss as the primary performance indicator. This study demonstrates that mass change alone can be an ambiguous metric that does not fully characterize the structural degradation of advanced cementitious binders. Through a comprehensive physical, chemical, and mechanical evaluation of 27 binary and ternary mixtures (totalling 486 specimens), we identify four limitations of mass-based standards: (1) The Slag Anomaly, where excellent surface mass preservation masks a significant loss of internal structural capacity, indicating potential internal structural softening. (2) The Sewage Anomaly, where specimens in active biogenic environments exhibit mass gain (up to +1.21%) despite continuous chemical attack. (3) Non-Linear Scaling, where 5% “accelerated” acid tests fundamentally alter degradation kinetics compared to realistic 1% environments. (4) The Maturation Conflict, where extended curing (56 days) significantly improves the physical resistance of slow-reacting pozzolans (cyment) while increasing the mass loss of high-performance ternary blends (MK/SF), likely linked to the exhaustion of their chemical buffering capacity. Current standards relying solely on mass loss may not capture internal degradation in slag-based cements that remain geometrically intact. We propose residual flexural strength as a necessary complementary metric. Full article

Vision-based fire detection is highly sensitive to domain shifts between indoor and outdoor scenes, which often degrades the generalization of supervised models trained on a single domain. To study this problem, the Fire Detection Dataset is curated from multiple public sources as a large-scale benchmark for cross-domain fire and smoke recognition. Cross-domain deployment faces two main challenges: substantial appearance variations in fire and smoke, and highly diverse negative classes that can easily trigger false alarms. To address these issues, a tailored cross-domain framework is studied by combining adversarial alignment and discrepancy-based statistical alignment to learn more domain-invariant features and mitigate negative transfer. Experimental results show that domain adaptation substantially improves target-domain generalization over weak alignment baselines. In particular, Domain-Adversarial Neural Networks (DANN) achieve 89.44% accuracy on Indoor → Outdoor and 79.10% on Outdoor → Indoor, while Multi-Kernel Maximum Mean Discrepancy (MK-MMD) attains the best fire-class F1-score of 78.04% on Outdoor → Indoor. These results highlight the value of domain alignment for improving robust fire detection across heterogeneous deployment environments. Full article

Vegetation cover plays a fundamental role in maintaining ecosystem structure and function. Understanding its spatial and temporal variability, along with its driving factors, is critical for advancing environmental studies. This research targets the subtropical Zhejiang region in southeastern China, utilizing MODIS-derived NDVI data covering 2001 to 2020. By integrating Sen’s slope estimator, Mann–Kendall trend analysis, spatial autocorrelation (Moran’s I), and the Geodetector framework, we assessed trends, patterns, and primary influencing factors of vegetation change. Our findings include: (1) a statistically significant upward trend in NDVI across 59.4% of the study area (Sen’s slope = 0.0025, p < 0.01), corresponding to an approximate annual increase of 0.44%; (2) notable spatial clustering of NDVI values, with high NDVI zones located in southwestern forested areas and low NDVI zones in expanding urban regions, indicating a clear spatial differentiation between natural and human-dominated landscapes; (3) elevation (Q = 0.64), nighttime lights (Q = 0.63), and slope (Q = 0.57) showed relatively higher explanatory power, and the interaction between nighttime lights and land use (NTL × LULC) exhibited the strongest explanatory power (Q = 0.72); (4) high-risk zones, associated with dense populations and intense urban development, coincided with lower NDVI values. These results deepen our understanding of vegetation dynamics in subtropical zones and provide insights for sustainable ecosystem and land management. Full article

This study extends beyond traditional single-binder assessments by developing a mechanistic framework for interpreting the behavior of multi-component geopolymer systems. It systematically examines the roles of industrial by-products (granulated blast-furnace slag), agricultural residues (barley straw ash), and construction-derived materials (recycled granite powder) when integrated into a metakaolin-based matrix, with particular emphasis on their influence on gel formation pathways, microstructural refinement, and macroscopic performance. A sustainable geopolymer concrete (SGC) system was formulated using multi-binder combinations at replacement levels ranging from 5% to 30%. Comprehensive evaluations were conducted, including fresh properties, mechanical performance, durability characteristics, thermal resistance, and microstructural features. The results demonstrate that the 70Mk–30GBFS composition facilitates the development of a dense hybrid C–(A)–S–H/N–A–S–H gel network, resulting in a 26.8% enhancement in compressive strength and a 32.0% decrease in chloride ion penetration. Rather than depending on empirical relationships, the study establishes a mechanistically grounded link between precursor chemistry, interfacial transition zone (ITZ) refinement, and performance limits. These findings contribute to a deeper understanding of multi-component geopolymer design and support the development of high-performance, sustainable concrete materials for structural applications. Full article

Background: Osteoporosis is a major skeletal disorder, particularly affecting postmenopausal women. Young ovariectomized rat models are commonly used to investigate estrogen deficiency-related skeletal changes, although they do not fully reproduce osteoporosis in a mature postmenopausal skeleton. Established pharmacological therapies remain the cornerstone of osteoporosis management, while nutritional factors continue to be investigated for their potential supportive role in bone metabolism. Menaquinone-7 (MK-7), a form of vitamin K2, has been investigated for potential skeletal effects through vitamin k-dependent mechanisms, particularly osteocalcin carboxylation. The aim of this study was to evaluate the dose-dependent effects of MK-7 on bone turnover markers, femoral mechanical resistance, qualitative histological findings, and hepatic safety in a young ovariectomized rat model. Methods: Forty female Wistar rats that were 8 weeks old, and thus still undergoing skeletal maturation, were assigned to four groups: sham-operated controls, ovariectomized controls, ovariectomized rats treated with low-dose MK-7, and ovariectomized rats treated with high-dose MK-7. Treatment was administered every 48 h for 12 weeks. At study completion, 35 rats survived; standardized analysis included eight animals per group. Plasma bone turnover markers (BTMs) and alanine aminotransferase were measured, femoral strength was assessed by the three-point bending test, and bone and liver histology was analyzed. Results: Biomechanical testing showed that high-dose MK-7 was associated with greater femoral mechanical resistance compared with untreated ovariectomized rats, while qualitative histology suggested differences in cortical architecture among groups. Biochemically, MK-7 treatment reduced undercarboxylated osteocalcin, suggesting vitamin K-dependent target engagement, whereas conventional turnover markers showed discordant findings. Overall, hepatic architecture was preserved, although mild hepatocellular apoptosis was observed. Conclusions: In this young OVX rat model, high-dose MK-7 was associated with improved femoral mechanical resistance compared with untreated OVX controls. However, because ovariectomy was performed during skeletal maturation, these findings should be interpreted as preliminary and cannot be directly extrapolated to established postmenopausal osteoporosis in a mature skeleton, and further studies are needed to clarify its activity pathways and safety profile. Full article

This study presents a sustainable strategy to address the inherent limitations of metakaolin (MK)-based geopolymers—specifically their water sensitivity, high permeability, efflorescence, and susceptibility to corrosion—arising from their calcium-deficient composition. To mitigate these issues, calcium hydroxide (Ca(OH)₂ or CH) was incorporated into MK mixtures at dosages ranging from 1% to 15%. The influence of CH on mechanical and durability performance was evaluated under both air and water curing conditions. The results show that although a higher CH content reduced flowability and accelerated setting, it markedly enhanced compressive strength, water resistance, and corrosion protection. CH addition also effectively suppressed efflorescence and refined the transport properties of the geopolymer matrix. These improvements are attributed to the formation of C-(A)-S-H gel, which densified the microstructure and strengthened the overall matrix. Electrochemical assessments further confirmed the enhanced corrosion resistance of embedded steel reinforcement. Collectively, the findings demonstrate that CH supplementation is an effective approach for improving the performance and long-term durability of MK-based geopolymers, broadening their potential for structural and environmental applications. Full article

The growing problem of antibiotic resistance poses one of the greatest threats to modern medicine, making the search for new, alternative strategies to treat bacterial infections a matter of priority. The aim of the study was to evaluate the antimicrobial activity of selected postbiotic substances (PS) and nisin against methicillin-susceptible (MS) and methicillin-resistant (MR) strains of coagulase-negative staphylococci (NAS) and mammaliicocci. The study was conducted on 24 strains of coagulase-negative staphylococci and mammaliicocci isolated from milk collected from Holstein-Friesian (HF) cows with subclinical mastitis. In vitro, PS/EMo (100–400 AU/mL) and PS/Eas (100–200 AU/mL) were the most effective, inhibiting the growth of all MS and MR strains of NAS and Mammaliicoccus spp. (100.0%). A high percentage of strains were also sensitive to postbiotic substances produced by Lactococcus lactis subsp. lactis PS/MK2/8 (400–1600 AU/mL), PS/MK1/3 (100–400 AU/mL), and nisin (100–25,600 AU/mL), both in MR strains (94.1%, 82.4%, 88.2%, respectively) and in MS strains (100.0%, 85.7% and 100%, respectively). PS/Esach (100–25,600 AU/mL) inhibited the growth of all strains, including the mecA gene-positive mammaliicocci strains (100.0%), but was slightly less effective against the MS strains (64.7%). The lowest activity was observed with postbiotic substances produced by Enterococcus faecium, PS/4231 (100–1600 AU/mL) and PS/9296 (100–6400 AU/mL), which inhibited the growth of 3 out of 17 MR strains (17.65%). Among the Mammaliicoccus strains with the mecA gene, postbiotic substances derived from strains PS/4231 and PS/9296 inhibited the growth of 42.9% and 28.6% of the strains, respectively. Four tested strains were sensitive to all postbiotic substances (MSC9, MSC11, MSC12 and SCH3). This study confirms that postbiotic substances and nisin inhibit the growth of staphylococci isolated from the milk of cows with subclinical mastitis, including methicillin-resistant strains. Full article

Intracellular calcium (Ca²⁺) signaling is a central regulator of corticogenesis, governing haveneural stem cell behavior, fate transitions, neuronal migration, and circuit assembly. Beyond its canonical role as a second messenger, Ca²⁺ shapes cytoskeletal organization by modulating microtubule dynamics essential for mitotic spindle function, radial glial scaffold, nucleokinesis, and neurite extension. This review synthesizes evidence from in vivo, ex vivo, and in vitro studies to delineate Ca²⁺-dependent pathways and Ca²⁺-binding proteins that couple, within restricted Ca²⁺ microdomains in space and time, to microtubule regulation during mammalian cortical development. We highlight mechanistic nodes involving calmodulin, Ca²⁺/calmodulin-dependent kinases (CaMKs), S100 proteins, cadherins/protocadherins, centrins (CENs), and Ca²⁺ sensors such as STIM1 and calneurons, which collectively coordinate spindle orientation, progenitor division modes, radial migration, and neurite outgrowth. Finally, we discuss how perturbations in Ca²⁺-controlled cytoskeletal programs may contribute to abnormal cortical cytoarchitecture and neurodevelopmental disease. By integrating Ca²⁺ microdomain transients with microtubule control modules, this review provides a unified framework for understanding how Ca²⁺ orchestrates key cellular events during mammalian corticogenesis and propose that Ca²⁺ oscillatory codes are translated into direct or indirect microtubule/cytoskeletal remodeling transitions that determine neural stem cell fate, migration, and maturation, to accurately establish cortical architecture and function. Full article

Quantifying vegetation dynamics has become a critical scientific imperative in the context of global ecosystem restoration initiatives targeting degraded forests. Previous studies have explored vegetation-cover change trends at different spatial scales worldwide using the Theil–Sen (TS) estimator and Mann–Kendall (MK) test, yet few have accounted for the uncertainty in resulting trends across time-series datasets of varying lengths. Taking the coastal zone of Fujian Province in Southeast China as a case study, we investigated the uncertainty of vegetation-cover change trends using normalized difference vegetation index (NDVI) datasets of different lengths (e.g., 20-year, 15-year, and 10-year) via the TS estimator and MK test. Additionally, piece-wise regression was employed to detect turning points and shifts in vegetation trends between 2001 and 2020. The results indicate significant discrepancies in trend estimation across datasets of different lengths, with consistency ratios ranging from 46.1% to 64.7% among the 20-year, 15-year, and 10-year series. The MK test is more sensitive to time-series length than the TS estimator, with areas of significant change decreasing by over 50% when transitioning from a 20-year to a 10-year dataset. The spatial distribution of trend shifts exhibits a distinct “coastal–inland” polarization pattern, with 2010 as the turning point. Eight modes of vegetation trend shifts were identified based on pre- and post-turning point dynamics. Furthermore, piece-wise regression improved trend accuracy by approximately 15%. This research advances the mechanistic understanding of spatiotemporal vegetation dynamics and supports adaptive ecosystem management strategies. Full article

Artisanal fisheries in Mexico frequently operate with limited data, lacking historical catch and effort series. In this context, the population status of the dogfish (Rhizoprionodon terraenovae) was evaluated for the first time in Priority Marine Regions 45–46 and the area of influence of the Wetland of International Importance Playa Tortuguera Rancho Nuevo, Tamaulipas, using methods based on size frequencies. Between November 2018 and February 2020, 541 artisanal fishing organisms were analyzed in La Barra del Tordo using FISAT II. The von Bertalanffy growth parameters for combined sexes were: L∞ = 105 cm, k = 0.59 years⁻¹, t₀ = −0.195 years. Total (Z), natural (M) and fishing (F) mortalities were 4.13, 0.467 and 3.22 years⁻¹, respectively. The average exploitation rate (E = F/Z) was 0.78 (95% CI: 0.745–0.805), exceeding the reference point of 0.5 (G) indicating severe overexploitation. The parameters showed biological consistency (Ø′ = 3.81; M/k = 0.79), and natural mortality was within the range reported for the species. This finding, in a priority region for conservation under the regime of the Conservation Sector of the Marine Ecological Management Program, shows the urgent need to implement fisheries management with an ecosystem approach that guarantees the sustainability of the fishery and the integrity of the coastal ecosystem. The study demonstrates that, even with limited data, it is possible to obtain robust estimates to inform management decisions in natural protected areas Full article

To enhance the utilization of industrial coal gangue, response surface methodology was used to optimize the concrete mix proportions based on three key factors: the mass ratio of fly ash (FA) to metakaolin (MK) (A), the combined dosage of FA and MK (B), and the water-to-binder ratio (C). A quadratic regression model was established, and the optimal mixture was characterized using FT-IR, XRD, and SEM. The model exhibited high statistical significance (p < 0.001) and an excellent fit (R² > 0.95), confirming its predictive reliability. Single-factor analysis revealed that the order of influence on 28 d compressive strength was C > A > B, indicating that the water-to-binder ratio had the most significant effect on later-age strength. The optimal mix proportions were determined as follows: fly ash-to-MK ratio of 0.65, admixture dosage of 20% by mass of total binder, and C of 0.475. Under these conditions, the measured 28 d compressive strength reached 35.9 MPa, which was within 5% of the model-predicted value, thereby validating the model’s accuracy. Microstructural analysis demonstrated that the appropriate incorporation of FA and MK promoted the formation of C-S-H gel, refined the pore structure, and improved the quality of the interfacial transition zone, which collectively enhanced the mechanical performance. A systematic understanding of the strength and microstructural mechanisms of concrete incorporating coal gangue, fly ash, and metakaolin is currently lacking, which hinders the design of more robust and durable structures. This study addresses this gap by systematically clarifying the individual and combined effects of the key variables on the strength of coal gangue concrete. The findings reveal the underlying mechanisms, providing a scientific basis for the sustainable, large-scale application of coal gangue concrete in construction. Full article

Toxoplasma gondii, the causative agent of toxoplasmosis, a disease widely distributed, is an intracellular parasite that invades host cells of different tissues using specialized endocytic activity. Recent studies suggest that tunneling nanotubes (TNTs), thin cell-surface projections, may participate in the parasite–host cell interaction. Here we report results that suggest the involvement of host-cell TNTs in the adhesion of T. gondii tachyzoites to epithelial LLC-MK² cells. Microscopy analysis showed that incubating cells in a medium containing 0.45 M sucrose induces reversible assembly of TNTs without affecting cell viability. The presence of extended TNTs correlated with increased parasite adhesion and reduced parasite entry, thus suggesting a structural or signaling role in mediating adhesion. TNTs assembled following sucrose incubation contain both actin and tubulin components as determined by immunofluorescence microscopy. These results highlight a possible functional relevance of TNTs in T. gondii host cell interaction, especially in parasite adhesion, opening new perspectives for understanding T. gondii-host cell interaction. Full article