Search Results (28,401)

Polymer-based superplasticizers represent an emerging class of additives in cement and concrete production with demonstrated effects on zeta potential, ion exchange, turbidity and rheological behavior during hydration. This study examines the influence of polymer-based grinding aids focusing on the dosage of A2 on the grinding performance of Portland cement. Among the tested additives, A2 exhibited superior dispersing ability and agglomeration-preventing activity, yielding a zeta potential of −8.98 mV. Correspondingly, the release of the ion concentration of Ca²⁺ decreased to 190 mg/L, while SO₄²⁻ increased to 400 mg/L, indicating enhanced ionic interaction at the optimal A2 dosage of 2.5 g. The turbidity tests further revealed that cement samples ground with 2.5 g of A2 remained homogeneously suspended for longer periods compared to other additives. Overall, the analysis of cement surface properties confirmed that polymer-based grinding aids, particularly A2, significantly improve the dispersion stability of cement particles during grinding. Full article

Background: Using natural substances for cancer therapy has attracted considerable interest due to their safety and reduced systemic toxicity. Nigella sativa (NS) oil, a traditional natural oil rich in bioactive compounds, possesses significant therapeutic potential. Brucine (BR), an alkaloid, exhibits potent cytotoxicity against various cancer cell lines; however, its poor selectivity and high systemic toxicity limit its clinical application. Objective: To overcome these challenges, this study aimed to enhance drug delivery and improve therapeutic efficacy. Method: A PEGylated nanoemulsion (NE) incorporating NS and BR was developed and characterized for particle size, size distribution, zeta potential, viscosity, and drug content. The in vitro release of BR was evaluated both with and without serum incubation. A quantitative amount of serum protein associated with the surface of the NE was estimated, and a hemolytic safety assay was carried out. Finally, an in vitro cytotoxicity study was conducted, and the in vivo anti-tumor effect of the developed PEGylated BR-loaded NE was evaluated and compared with its naked counterpart. Result: The developed PEGylated BR-loaded NE possessed favorable characteristics as a nanocarrier for parenteral administration, with a particle size of 188.5 nm, a zeta potential of −1.61, a viscosity of 3.4 cP, and 99% drug content uniformity. It released up to 60.4% of BR over 12 h, while only 18.4 µg/µmol of the total lipids were adsorbed on the surface of the formulation, compared with 54.5 µg/µmol for the naked counterpart. The PEGylated NE was safe, inducing less than 5% of hemolysis, and displayed substantial inhibition of MDA cell growth. Conclusions: The PEGylated NE achieved a significant reduction in tumor volume, suggesting that PEGylated NE may serve as a promising platform for enhancing anti-tumor activity. Full article

Background: Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), remain major causes of morbidity and mortality, yet no targeted pharmacological therapy is available. Excessive neutrophil and macrophage infiltration drives reactive oxygen species (ROS) production and cytokine release, leading to alveolar–capillary barrier disruption and fatal respiratory failure. Methods: We applied an integrative multi-omics strategy combining single-cell transcriptomics, peripheral blood proteomics, and lung tissue proteomics in a lipopolysaccharide (LPS, 10 mg/kg)-induced mouse ALI model to identify key signaling pathways. Harpagide, an iridoid glycoside identified from our natural compound screen, was evaluated in vivo (40 and 80 mg/kg) and in vitro (0.1–1 mg/mL). Histopathology, oxidative stress markers (SOD, GSH, and MDA), cytokine levels (IL-6 and IL-1β), and signaling proteins (HIF-1α, p-PI3K, p-AKT, Nrf2, and HO-1) were quantitatively assessed. Direct target engagement was probed using surface plasmon resonance (SPR), the cellular thermal shift assay (CETSA), and 100 ns molecular dynamics (MD) simulations. Results: Multi-omics profiling revealed robust activation of HIF-1, PI3K/AKT, and glutathione-metabolism pathways following the LPS challenge, with HIF-1α, VEGFA, and AKT as core regulators. Harpagide treatment significantly reduced lung injury scores by ~45% (p < 0.01), collagen deposition by ~50%, and ROS accumulation by >60% relative to LPS (n = 6). The pro-inflammatory cytokines IL-6 and IL-1β were reduced by 55–70% at the protein level (p < 0.01). Harpagide dose-dependently suppressed HIF-1α and p-AKT expression while enhancing Nrf2 and HO-1 levels (p < 0.05). SPR confirmed direct binding of Harpagide to HIF-1α (KD = 8.73 µM), and the CETSA demonstrated enhanced thermal stability of HIF-1α. MD simulations revealed a stable binding conformation within the inhibitory/C-TAD region after 50 ns. Conclusions: This study reveals convergent immune–microenvironmental regulatory mechanisms across cellular and tissue levels in ALI and demonstrates the protective effects of Harpagide through multi-pathway modulation. These findings offer new insights into the pathogenesis of ALI and support the development of “one-drug, multilayer co-regulation” strategies for systemic inflammatory diseases. Full article

Nitrogen (N) and phosphorus (P) play vital roles in crop growth. However, conventional fertilizers exhibit low utilization efficiency, making them prone to causing resource wastage and water eutrophication. Although metal–organic frameworks (MOFs) have shown great potential for application in controlled-release fertilizers (CRFs), currently reported MOF-based CRFs suffer from low nutrient content, which limits their further application. To address this issue, this study synthesized a series of hierarchically porous MOFs, denoted as MIL-156(X), using sodium acetate as a modulator under hydrothermal conditions. These materials were subsequently loaded with urea and phosphate from aqueous solution to form MOFs-based CRFs (N-P-MIL-156(X)). Results indicate that MIL-156(X) retain microporous integrity while incorporating abundant mesopores. Increasing modulator content reduced particle size and average pore diameter but increased specific surface area and adsorption capacity for urea and phosphate. MIL-156-H (with a high modulator content addition) exhibited the highest adsorption capacity, conforming to Langmuir isotherm and pseudo-second-order kinetics. The adsorption mechanisms of urea and phosphate involved hydrogen bonding and the formation of Ca intra-spherical complexes, respectively. N-P-MIL-156-H contained 10.8% N and 16.3% P₂O₅, with sustained release durations exceeding 42 days (N) and 56 days (P₂O₅) in an aqueous solution. Pot trials demonstrated significantly higher nutrient use efficiency (N-44.8%, P₂O₅-16.56%) and a 12.22% yield increase compared to conventional fertilization (N-35.6%, P₂O₅-13.32%). Thus, N-P-MIL-156-H-based fertilization significantly promotes rice growth and N/P utilization efficiency, offering a promising strategy for developing controlled-release fertilizers and improving nutrient management. Full article

Introduction: Fluoride varnishes are widely used in caries prevention, but the rate and duration of fluoride ion release differ depending on material composition and environmental factors. Objectives: This systematic review synthesized evidence from in vitro studies on human teeth to identify key factors influencing fluoride release. Methods: A systematic literature search was conducted in July 2025 in PubMed, Scopus, Web of Science, Embase, and the Cochrane Library using the terms “fluoride release” AND “varnish” in titles and abstracts. Study selection followed PRISMA 2020 guidelines, predefined eligibility criteria, and was structured according to the PICO framework. Of 484 retrieved records, 15 studies met the inclusion criteria and were analyzed qualitatively. Results: The primary outcome was the magnitude and duration of fluoride release from varnishes. Most studies reported peak release within the first 24 h, followed by a marked decline, although some formulations (e.g., Clinpro XT and Duraphat) maintained more stable long-term release. Substantial methodological heterogeneity was observed across studies, including differences in sample type, storage medium, pH, temperature, and measurement protocols, which influenced fluoride release dynamics. Reported secondary outcomes included enamel remineralization, changes in surface properties, and antibacterial activity, with bioactive additives such as CPP–ACP and TCP enhancing preventive effects. Acidic conditions consistently increased fluoride release. Conclusions: The magnitude and persistence of fluoride release from varnishes depend on both intrinsic material properties and external environmental conditions. Bioactive additives may prolong fluoride availability and provide additional preventive benefits. Full article

Hydrogels are crosslinked polymer chains that form a three-dimensional network, widely used for wound dressing due to their ability to absorb significant amounts of fluid. This study aimed to develop a hydrogel patch for wound dressing with self-healing properties, particularly for joints and stretchable body parts, providing a physical barrier while maintaining an optimal environment for wound healing. Polyvinyl alcohol (PVA) and sodium carboxymethyl cellulose (Na CMC) were crosslinked with borax, which reacts with the active hydroxyl groups in both polymers to form a hydrogel. The patches were loaded with ciprofloxacin HCl (CIP), a broad-spectrum antibiotic used to prevent and treat various types of wound infections. Hydrogels were subjected to rheological, morphological, antimicrobial, self-healing, ex vivo release, swelling, cytotoxicity, wound healing, and stability studies. The hydrogels exhibited shear-thinning, thixotropic, and viscoelastic properties. Microscopic images of the CIP hydrogel patch showed a porous, crosslinked matrix. The antimicrobial activity of the patch revealed antibacterial effectiveness against five types of Gram-positive and Gram-negative bacteria, demonstrating a minimum inhibitory concentration of 0.05 μg/mL against E. coli. The swelling percentage was found to be 337.4 ± 12.7%. The cumulative CIP release percentage reached 103.7 ± 3.7% after 3 h, followed by zero-order release kinetics. The stability studies revealed that the crossover point shifted toward higher frequencies after 3 months of storage at room temperature, suggesting a relaxation in the hydrogel bonds. The cytotoxicity study revealed that the CIP hydrogel patch is non-cytotoxic. Additionally, the in vivo study demonstrated that the CIP hydrogel patch possesses wound-healing ability. Therefore, the CIP PVA/Na CMC/Borax patch could be used in wound dressing. Full article

Importance: Understanding trends in the use of hormonal therapy (HT) for prostate cancer (PCa) is crucial to optimize treatment strategies, particularly for older men with locally advanced and metastatic disease. Objective: To evaluate changes in the patterns of adjuvant and primary HT use over time in older U.S. men diagnosed with locally advanced and metastatic prostate cancer. Design, Setting, and Participants: This cohort study utilized SEER-Medicare data, which covers approximately 48% of the U.S. population and links cancer registry data with Medicare claims, including 149,515 men aged ≥66 years diagnosed with PCa between 2010 and 2019. We analyzed trends in the use of adjuvant HT for higher-risk and primary HT for lower-risk PCa. Multivariable logistic regression models were used to adjust for clinical and demographic factors. Main Outcomes and Measures: The primary outcome was the proportion of men receiving any form of HT within 6 months of PCa diagnosis. HT included injectable Gonadotropin-releasing hormone (GnRH) agonists and antagonists, orchiectomy, and anti-androgens agents. Results: The rate of adjuvant HT in higher-risk PCa patients increased significantly from 53.6% in 2010 to 68.1% in 2019 (p < 0.0001), with a steady rise in the last four years. In contrast, the rate of men with lower-risk disease receiving primary HT declined from 25% in 2010 to 16.9% in 2013, then peaked at 28.2% in 2015, and stabilized between 25% and 27.3% from 2017 to 2019. The overall HT usage increased from 33.5% in 2010 to 45.2% in 2019, showing a consistent increase over the years. These patterns persisted after adjusting for clinical and demographic factors. Conclusions and Relevance: The increasing use of adjuvant HT in higher-risk PCa patients aligns with evolving treatment guidelines, while the stable rate of primary HT in lower-risk patients represents persistent inappropriate use and highlights the need for further efforts to optimize treatment choices. While previous studies focused on men with intermediate-risk PCa receiving radiation therapy, our study broadens the scope to include men who did not undergo radiation therapy, providing a more inclusive view of HT trends. Future research should focus on refining strategies to reduce inappropriate primary HT use and improve adjuvant HT administration. Full article

Identifying the activation status of advanced driver assistance systems (ADAS) in real-world driving environments is crucial for safety, responsibility attribution, and accident forensics. Unlike prior studies that primarily rely on simulation-based settings or unsynchronized data, we collected a multimodal dataset comprising synchronized controller area network (CAN)-bus and smartphone-based inertial measurement unit (IMU) signals from drivers on consistent highway sections under both ADAS-enabled and manual modes. Using these data, we developed lightweight classification pipelines based on statistical and deep learning approaches to explore the feasibility of distinguishing ADAS operation. Our analyses revealed systematic behavioral differences between modes, particularly in speed regulation and steering stability, highlighting how ADAS reduces steering variability and stabilizes speed control. Although classification accuracy was moderate, this study provides one of the first data-driven demonstrations of ADAS status detection under naturalistic conditions. Beyond classification, the released dataset enables systematic behavioral analysis and offers a valuable resource for advancing research on driver monitoring, adaptive ADAS algorithms, and accident forensics. Full article

This study reports the development of electrospun poly(methyl methacrylate) (PMMA) fiber mats incorporating ibuprofen (IBU)-intercalated layered double hydroxides (LDH) for enhanced transdermal drug delivery systems (TDDS). IBU, in its anionic form, was successfully intercalated into LDH, which possesses anion exchange capabilities, and subsequently embedded into PMMA fibers via electrospinning. In vitro drug release experiments demonstrated that UPMMA–LDH–IBU fibers exhibited significantly higher IBU release than PMMA–IBU controls. This enhancement was attributed to the improved hydrophilicity and water absorption imparted by the LDH, as confirmed by contact angle and water uptake measurements. Furthermore, artificial skin permeation tests revealed that the UPMMA–LDH–IBU fibers maintained comparable release rates to those observed during buffer immersion, indicating that the rate-limiting step was the diffusion of IBU within the fiber matrix rather than the interface with the skin or buffer. These findings highlight the critical role of LDH in modulating drug release behavior and suggest that UPMMA–LDH–IBU electrospun fiber mats offer a promising and efficient platform for advanced TDDS applications. Full article

Atherosclerotic cardiovascular disease treatment is being reevaluated, since a residual cardiovascular risk (RCR) persists even in patients who achieve optimal LDL-C values. Underlying causes are metabolic dysfunction, lipoprotein(a), inflammation, and triglyceride-rich lipoproteins and their remnants. Dietary treatment options like time-restricted eating (TRE) are becoming more widely acknowledged for their potential advantages in metabolic health and weight control, as a treatment of atherosclerosis expanding beyond LDL-C medication. Beyond weight loss, TRE (which restricts meals to a window of 6 to 8 h) appears as the most accessible treatment, and has been shown to improve blood pressure, lipid profiles, and glucose regulation through mechanisms like metabolic switching and circadian synchronization. We hypothesize, and will present our arguments, that a key mechanism underlying the cardiovascular and weight-related benefits of TRE is its impact on the circadian regulation of angiopoietin-like protein 4 (ANGPTL4) activity within adipose tissue. Additionally, lipolysis is accelerated by ANGPTL4 activation. TRE, via its actions on ANGPTL4, therefore not only inhibits adipose fatty acid uptake but stimulates their release as well. Additionally, TRE may increase intravascular very low-density lipoprotein (VLDL) catabolism by muscle due to the reduced exposure of lipoprotein lipase (LPL) to competing chylomicrons, known to slow the rate of VLDL catabolism. During the prolonged fasting, VLDL residence time is thus shortened, limiting the exposure to endothelium and hepatic lipases and thus reducing the amount of atherogenic remnant particles. Larger, longer-term randomized controlled studies in a variety of groups are required to further clarify TRE’s function in RCR prevention and therapy. As knowledge of triglyceride lipoprotein (TRL) metabolism expands, a comprehensive strategy for the management of RCR emerges, and a broader spectrum of LPL regulator-based therapeutics is created. Consequently, it is advisable to prioritize further research into the influence of TRE on LPL modulation via ANGPTL4 and ANGPTL8, which provides a natural, accessible, and low-cost alternative. Full article

Phosphorus-based compounds play a crucial role in agricultural productivity. However, excessive phosphorus discharge into water bodies contributes to eutrophication. This study proposes a circular approach for phosphorus recovery and reuse through the thermal valorization of Posidonia oceanica residues, an abundant marine biomass along Mediterranean coasts. After energy recovery from this waste (12.3 MJ kg⁻¹), the resulting ash was assessed as an effective adsorbent for aqueous phosphorus removal. Batch experiments were conducted to evaluate adsorption kinetics and equilibrium, considering the influence of key operational variables, such as temperature, pH, and adsorbent dosage. Under optimal conditions, the material achieved a maximum retention of approximately 55–60 mgP g⁻¹. The Freundlich model successfully describes the equilibrium isotherm data, indicating a heterogeneous adsorbent and an overall endothermic process. Phosphorus removal was favored at basic pH values (9.5–10.5), where the monohydrogen phosphate predominates. Leaching tests further revealed that saturated material releases phosphorus and other minerals in a manner clearly dependent on the final pH, with higher phosphorus release under more acidic conditions. These results suggest that Posidonia ash could serve as a low-cost adsorbent while also acting as a potential phosphorus source in soils. Full article

The increasing threat of terrorism involving Radiological Dispersal Devices (RDDs) necessitates comprehensive evaluation and preparedness strategies, especially in densely populated public areas. This study aims to assess the potential consequences of RDD detonation, focusing on the effective doses received by individuals and the ground deposition of radioactive materials in a hypothetical urban environment. Utilizing the HotSpot code, simulations were performed to model the dispersion patterns of ¹³⁷Cs and ²⁴¹Am under varying meteorological conditions, mirroring the complexities of real-world scenarios as outlined in recent literature. The results demonstrate that ¹³⁷Cs dispersal produces a wider contamination footprint, with effective doses exceeding the public exposure limit of 1 mSv at distances up to 1 km, necessitating broad protective actions. In contrast, ²⁴¹Am generates higher localized contamination, with deposition levels surpassing cleanup thresholds near the release point, creating long-term remediation challenges. Dose estimates for first responders highlight the importance of adhering to operational dose limits, with scenarios approaching 100 mSv under urgent rescue conditions. Overall, the findings underscore the need for rapid dose assessment, early shelter-in-place orders, and targeted decontamination to reduce population exposure. These insights provide actionable guidance for emergency planners and first responders, enhancing preparedness protocols for RDD incidents in major urban centers. Full article

The central cholinergic system is an important player in the control of motor function, appetite, the reward system, attention, memory and learning. Its participation in neurological diseases (e.g., Alzheimer’s and Parkinson’s disease, epilepsy) and in psychiatric diseases (e.g., schizophrenia, depression) makes it a preferred study subject for drug development. The present review summarizes salient features of the central cholinergic synapses that will guide future studies. Cholinergic synapses are defined by the presence of choline acetyltransferase (ChAT), the vesicular ACh transporter (VAChT), the high-affinity choline transporter CHT-1 and the presence of PRiMA-coupled acetylcholinesterase (AChE). The firing frequency of cholinergic fibers is reflected in high-affinity choline uptake activity, which also responds to variations in ChAT, VAChT and AChE activities conferring considerable plasticity to cholinergic responses. The availability of glucose and choline can limit ACh synthesis and release under conditions of high ACh turnover. Future studies will focus on rapid methods to measure ACh release and a deeper understanding of cholinergic plasticity during development, aging and dementia. Full article

Legionella pneumophila (L. pneumophila) infection is characterized by a wide spectrum of manifestations, from influenza-like illness to life-threatening atypical pneumonia with multiorgan failure. The aim of our study was the assessment of in vitro and ex vivo neutrophil activation in L. pneumophila infections, as well as the role of neutrophils’ peptides such as LL-37 in infection. The ability of neutrophils to form ex vivo extracellular traps (NETs) in response to bacterial infection was examined by immunofluorescence. In parallel, patients’ sera, as well as opsonized standard L. pneumophila strains, were used for in vitro activation of neutrophils from healthy individuals. The serum levels of interleukins were assessed using the LEGENDplexTM Multi-Analyte Flow Assay Kit. Furthermore, citrullinated cf-DNA as a marker of neutrophil extracellular traps (NETs) was detected in the serum of patients with acute infection. It was demonstrated that neutrophils released NETs in vitro and ex vivo upon L. pneumophila (interaction in an autophagy-independent manner. Notably, IL-1b was detected on NETs, but an antimicrobial peptide LL-37 was absent. The lack of antimicrobial activity failed to inhibit bacterial proliferation. In addition, in vitro and ex vivo NETs formation was observed during the Clarithromycin treatment. Those NETs were decorated with bioactive antimicrobial peptide LL-37, which inhibits bacterial proliferation. The findings provide evidence that neutrophils release NETs in vitro and ex vivo by expressing the IL1β protein in them. The lack of expression of the antimicrobial peptide LL-37 on the NETs demonstrates the inability of the cells to inhibit proliferation, and consequently the elimination of L. pneumophila. Clarithromycin plays a dual role in the elimination. Full article

A polyamidoamine-based hydrogel (H-M-GLY) and its montmorillonite-based composite (H-M-GLY/MMT) were studied as selective cleaning materials for cultural heritage conservation. H-M-GLY was synthesized from a glycine-based polyamidoamine oligomer with acrylamide terminals (M-GLY) through radical polymerization at pH 7.3 and had a basic character. The M-GLY oligomer was in turn synthesized from N,N′-methylenebisacrylamide and glycine in a 1:0.85 molar ratio. H-M-GLY/MMT was obtained by cross-linking a 1:0.1—weight ratio—M-GLY/MMT mixture at pH 4.0, to promote polyamidoamine-MMT interaction. The composite hydrogel absorbed less water than the plain hydrogel and proved tougher, due to montmorillonite’s electrostatic interactions with the positively charged M-GLY units. Scanning electron microscopic analysis showed that MMT was uniformly dispersed throughout the hydrogel. Both hydrogels were subjected to ink bleeding tests on papers written with either iron gall or India ink. Microscopic observation revealed neither bleeding nor release of hydrogel fragments. Being basic, H-M-GLY successfully deacidified the surface of aged paper. H-M-GLY/MMT, swollen in a 1:9 ethanol/water solution, was found to be effective in removing wax, known to trap carbonaceous particles and form dark stains on artistic artifacts. This study demonstrates the great potential of polyamidoamine-based hydrogels as versatile selective cleaning systems for cellulosic and other cultural heritage materials. Full article