Search Results (4,716)

This study introduces xylitol, a natural compound, as a multifunctional additive to enhance the performance of alkali-activated slag/fly ash materials (AASFMs). A systematic investigation was conducted to elucidate xylitol’s mechanism in modifying AASFM properties, including fresh behavior, hydration kinetics, compressive strength, and autogenous shrinkage. The experimental findings demonstrated that xylitol significantly delayed early-age hydration while promoting more extensive hydration at later stages. Specifically, the initial and final setting times of AASFM pastes were extended by 640% and 370%, respectively, and paste flowability increased by 30%. At a 0.2% dosage, xylitol markedly reduced porosity and refined the microstructure of AASFMs, leading to improved mechanical properties. The 3-day and 28-day compressive strengths were enhanced by 39.8% and 39.7%, respectively, while autogenous shrinkage was suppressed by 61.4%. These results demonstrate the multifunctional potential of xylitol in AASFMs, serving as an effective retarder, plasticizer, strength enhancer, and shrinkage reducer. Notably, the refined pore structure induced by xylitol may also mitigate the risks of the alkali–silica reaction, though further durability validation is warranted. Full article

Recent studies have demonstrated that the coumarin derivative 4-Methylumbelliferone (4MU) has an antidiabetic effect in rodent models. 4MU is known to decrease the availability of hyaluronan (HA) substrates and inhibit the activity of different HA synthases. Nevertheless, it has been observed that 4MU may also affect cellular metabolism. In this study, we utilize the rat insulinoma beta cell line (INS-1E) cultured in both two-dimensional (2D) and three-dimensional (3D) experimental settings (pseudo islets), as an in vitro model to study beta cell functionality. For the first time, we observed that treating INS1E cells with 4MU results in improved insulin secretion. Additionally, we discovered that 4MU treatment elicited morphological changes from multilayer to monolayer conditions, along with a varied distribution of insulin granules and cell adhesion properties. Notably, we found that insulin secretion is not correlated with HA production. The same result was observed in co-culture experiments involving INS-1E cells and stromal vascular fraction (SVF) from adipose tissue. These experiments aim to investigate the effects of 4MU on beta cells in the context of its potential use in early-stage type 1 diabetes and in enhancing islet transplantation outcomes. Full article

We present the results of a detailed spectroscopic analysis of the double-lined spectroscopic binary system $\alpha$ Equulei. High-resolution spectra obtained with the SOPHIE spectrograph at various orbital phases were used to disentangle the composite spectra into individual components using the spectral line deconvolution (SLD) iterative technique. The atmospheric parameters of each component were refined with the SME (spectroscopy made easy) package and further validated by following methods: SED (spectral energy distribution), the independence of the abundance of individual Fe i–ii lines on the reduced equivalent width and ionisation potential, and fitting with the hydrogen line profiles. Our accurate abundance analysis uses a hybrid technique for spectrum synthesis. This is based on classical model atmospheres that are calculated under the assumption of local thermodynamic equilibrium (LTE), together with non-LTE (NLTE) line formation. This is used for 15 out of the 25 species from C to Nd that were investigated. The primary giant component (G7-type) exhibits a typical abundance pattern for normal stars, with elements from He to Fe matching solar values and neutron-capture elements showing overabundances up to 0.5 dex. In contrast, the secondary dwarf component displays characteristics of an early stage Am star. The observed abundance differences imply distinct diffusion processes in their atmospheres. Our results support the scenario in which chemical peculiarities in Am stars develop during the main sequence and may decrease as the stars evolve toward the subgiant branch. Full article

The objectives of the present work were as follows: (i) the detection of cathelicidin biomolecules in the milk of individual goats during the early stages of mastitis and their potential use for the diagnosis of mastitis at its early stage and (ii) the evaluation of the presence of cathelicidin proteins in the bulk-tank milk from goat and sheep farms. In an experimental study, after inoculation of Staphylococcus simulans into a mammary gland of goats, bacteriological and cytological examinations of milk samples, as well as proteomics examinations [two-dimensional gel electrophoresis analysis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS) analysis] were performed sequentially, from 4 to 48 h post-challenge. Cathelicidin-1 and cathelicidin-2 were detected consistently in milk samples obtained throughout the study, and spot optical densities obtained from PDQuest v.8.0 were recorded. Associations were calculated between the presence of mastitis in a mammary gland at a given timepoint and the detection of cathelicidin proteins in the respective milk sample. All inoculated mammary glands developed mastitis, confirmed by the consistent bacterial isolation from milk samples and the increased somatic cell content therein. Spot optical density of cathelicidin proteins was higher than in samples from contralateral mammary glands. There was a significant association between the presence of mastitis in a mammary gland and the detection of cathelicidin biomolecules in the respective milk sample; the overall accuracy was 81.8% (95% confidence interval: 70.4–90.2%). In a field investigation, the presence of cathelicidin proteins was evaluated in the bulk-tank milk of 32 dairy goat and 57 dairy sheep farms. In this part of the work, no cathelicidin proteins were detected in any bulk-tank milk sample of goat, 0.0% (95% confidence interval: 0.0–10.7%), or sheep, 0.0% (95% confidence interval: 0.0–6.3%), farms. Full article

Machining chromium–nickel alloy steel is challenging due to its material properties, such as high strength and toughness. These properties often lead to tool damage and degradation of tool life, which overall impacts the production time, cost, and quality of the product. Therefore, it is essential to investigate early signs of tool damage to determine the effective machining conditions for chromium–nickel alloy steel, thereby increasing tool life and improving product quality. In this study, the early signs of tool wear were observed in a physical vapor deposition (PVD) carbide-coated tool (Seco Tools, Björnbacksvägen, Sweden) during the machining of X5CrNi18-10 steel under both dry and wet conditions. A finish turning operation was performed on the outer diameter (OD) of the workpiece with a 0.4 mm nose radius tool. At the early stage, the tool was examined from the functional side (f–side) and the passive side (p–side). The results indicate that dry machining leads to increased coating removal, more heat generation, and visible damage, such as pits and surface scratches. By comparison, wet machining helps reduce heat and wear, thereby improving tool life and machining quality. These findings suggest that a coolant must be used when machining chromium–nickel alloy steel with a PVD carbide-coated tool. Full article

The kinetics of insulin aggregation and fibril formation were studied in vitro using Scanning Electron Microscopy (SEM) and Fourier Transform Infrared (FTIR) spectroscopy. Our investigation centered on the protein’s morphological and structural changes to better understand the transient molecular configurations that occur during the lag phase. SEM images showed that, already at early incubation stages, a network of disordered pseudo-filaments, ranging in length between 200 and 500 nanometers, develops on the surface of large aggregates. At later stages, fibrils catalyzed by protein aggregates were observed. Principal Component Analysis (PCA) of the FTIR data identified signatures of intramolecular β-sheet secondary structures forming during the lag phase and at the onset of the exponential growth phase. These absorption bands are linked to secondary nucleation mechanisms due to their transient nature. This interpretation is further supported by a chemical equilibrium model, which yielded a reliable secondary nucleation rate constant, K₂, on the order of 10⁴ M⁻² s⁻¹. Full article

Ischemic stroke is a primary cause of cerebrovascular diseases and continues to be one of the leading causes of death and disability among patients worldwide. Pathological processes caused by vascular damage due to stroke occur in a time-dependent manner and are classified into three categories: acute, subacute, and chronic. Current treatments for ischemic stroke are limited to effectiveness in the early stages. In this study, we investigated the therapeutic effect of an oriental medicine, Gosha-jinki-gan (TJ107), on improving chronic ischemic stroke using the mouse model with middle cerebral artery occlusion (MCAO). The changes in the intracerebral inflammatory response (macrophages (F4/80), TLR2•4, IL-23, IL-17, TNF-α, and IL-1β) were examined using real-time RT-PCR. The MCAO mice showed the increased expression of glial fibrillary acidic protein (GFAP) and of F4/80, TLR2, TLR4, IL-1β, TNF-α, and IL-17 in the brain tissue from the MCAO region. This suggests that they contribute to the expansion of the ischemic stroke infarct area and to the worsening of the neurological symptoms of the MCAO mice in the chronic phase. On the other hand, the administration of TJ107 was proven to reduce the infarct area, with decreased GFAP expression, suppressed macrophage infiltration in the brain, and reduced TNF-α, IL-1β, and IL-17 production compared with the MCAO mice. This study first demonstrated Gosha-jinki-gan’s therapeutic effects on the chronic ischemic stroke. Full article

We investigate whether a belief in trend continuation, often associated with the so-called “hot-hand effect,” can be endogenously triggered by personal performance feedback in a controlled financial experiment. Participants allocated funds across assets with randomly generated prices, under conditions of known probabilities and varying levels of risk. In a two-stage setup, participants were first exposed to random price sequences to learn the task and potentially develop perceptions of personal success. They then faced additional price paths under incentivized conditions. Our findings show that participants initially increased purchases following gains—consistent with a feedback-driven belief in momentum—but this pattern faded over time. When facing sustained losses, loss aversion dominated decision-making, overriding early optimism. These results highlight how cognitive heuristics and emotional biases interact dynamically, suggesting that belief in trend continuation is context-sensitive and constrained by the reluctance to realize losses. Full article

Kidney transplantation is the treatment of choice for patients with end-stage kidney disease. Despite significant advances in graft survival, rejection continues to pose a major clinical challenge. Conventional monitoring tools, such as serum creatinine, donor-specific antibodies, and proteinuria, lack sensitivity and specificity for early detection of graft injury. Moreover, while biopsy remains the current gold standard for diagnosing rejection, it is prone to confounders, invasive, and associated with procedural risks. However, non-invasive novel biomarkers have emerged as promising alternatives for earlier rejection detection and improved immunosuppression management. This review focuses on the leading candidate biomarkers currently under clinical investigation, with an emphasis on their diagnostic performance, prognostic value, and potential to support personalised immunosuppressive strategies in kidney transplantation. Full article

Diabetic retinopathy (DR) is a progressive, multifactorial complication of diabetes and one of the major global causes of visual impairment. Its pathogenesis involves chronic hyperglycaemia-induced oxidative stress, inflammation, mitochondrial dysfunction, neurodegeneration, and pathological angiogenesis, as well as emerging systemic contributors such as gut microbiota dysregulation. While current treatments, including anti-vascular endothelial growth factor (anti-VEGF) agents, corticosteroids, and laser photocoagulation, have shown clinical efficacy, they are largely limited to advanced stages of DR, require repeated invasive procedures, and do not adequately address early neurovascular and metabolic abnormalities. Resveratrol (RSV), a naturally occurring polyphenol, has emerged as a promising candidate due to its potent antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic properties. This review provides a comprehensive analysis of the molecular mechanisms by which RSV exerts protective effects in DR, including modulation of oxidative stress pathways, suppression of inflammatory cytokines, enhancement of mitochondrial function, promotion of autophagy, and inhibition of pathological neovascularisation. Despite its promising pharmacological profile, the clinical application of RSV is limited by poor aqueous solubility, rapid systemic metabolism, and low ocular bioavailability. Various routes of administration, including intravitreal injection, topical instillation, and oral and sublingual delivery, have been investigated to enhance its therapeutic potential. Recent advances in drug delivery systems, including nanoformulations, liposomal carriers, and sustained-release intravitreal implants, offer potential strategies to address these challenges. This review also explores RSV’s role in combination therapies, its potential as a disease-modifying agent in early-stage DR, and the relevance of personalised medicine approaches guided by metabolic and genetic factors. Overall, the review highlights the therapeutic potential and the key translational challenges in positioning RSV as a multi-targeted treatment strategy for DR. Full article

Aim: Pacifiers play a critical role in the early stages of craniofacial and palate development during infancy. While they provide comfort and aid in soothing, their use can also have significant impacts on the growth and function of the oral cavity. This study aimed to simulate and predict the behavior of six different types of pacifiers and their functional interaction with the tongue and palate, with the goal of understanding their potential effects on orofacial growth and development. Materials and Methods: Biomechanical analysis using Finite Element Analysis (FEA) mathematical models was employed to evaluate the behavior of six different commercial pacifiers in contact with the palate and tongue. Three-dimensional solid models of the palate and tongue were based on the mathematical framework from a 2007 publication. This allowed for a detailed investigation into how various pacifier designs interact with soft and hard oral tissues, particularly the implications on dental and skeletal development. Results: The findings of this study demonstrate that pacifiers exhibit different interactions with the oral cavity depending on their geometry. Anatomical–functional pacifiers, for instance, tend to exert lateral compressions near the palatine vault, which can influence the hard palate and contribute to changes in craniofacial growth. In contrast, other pacifiers apply compressive forces primarily in the anterior region of the palate, particularly in the premaxilla area. Furthermore, the deformation of the tongue varied significantly across different pacifier types: while some pacifiers caused the tongue to flatten, others allowed it to adapt more favorably by assuming a concave shape. These variations highlight the importance of selecting a pacifier that aligns with the natural development of both soft and hard oral tissues. Conclusions: The results of this study underscore the crucial role of pacifier geometry in shaping both the palate and the tongue. These findings suggest that pacifiers have a significant influence not only on facial bone growth but also on the stimulation of oral functions such as suction and feeding. The geometry of the pacifier affects the soft tissues (tongue and muscles) and hard tissues (palate and jaw) differently, which emphasizes the need for careful selection of pacifiers during infancy. Choosing the right pacifier is essential to avoid potential negative effects on craniofacial development and to ensure that the benefits of proper oral function are maintained. Therefore, healthcare professionals and parents should consider these biomechanical factors when introducing pacifiers to newborns. Full article

Background/Objective: Pharmacological interventions often exert systemic effects beyond their primary targets, underscoring the need for a comprehensive evaluation of their metabolic impact. Etodolac is a nonsteroidal anti-inflammatory drug (NSAID) that alleviates pain, fever, and inflammation by inhibiting cyclooxygenase-2 (COX-2), thereby reducing prostaglandin synthesis. While its pharmacological effects are well known, the broader metabolic impact and potential mechanisms underlying improved clinical outcomes remain underexplored. Untargeted metabolomics, which profiles the metabolome without prior selection, is an emerging tool in clinical pharmacology for elucidating drug-induced metabolic changes. In this study, untargeted metabolomics was applied to investigate metabolic changes following a single oral dose of etodolac in healthy male volunteers. By analyzing serial blood samples over time, we identified endogenous metabolites whose concentrations were positively or inversely associated with the drug’s plasma levels. This approach provides a window into both therapeutic pathways and potential off-target effects, offering a promising strategy for early-stage drug evaluation and multi-target discovery using minimal human exposure. Methods: Thirty healthy participants received a 400 mg dose of Etodolac. Plasma samples were collected at five time points: pre-dose, before Cmax, at Cmax, after Cmax, and 36 h post-dose (n = 150). Samples underwent LC/MS-based untargeted metabolomics profiling and pharmacokinetic analysis. A total of 997 metabolites were significantly dysregulated between the pre-dose and Cmax time points, with 875 upregulated and 122 downregulated. Among these, 80 human endogenous metabolites were identified as being influenced by Etodolac. Results: A total of 17 metabolites exhibited time-dependent changes closely aligned with Etodolac’s pharmacokinetic profile, while 27 displayed inverse trends. Conclusions: Etodolac influences various metabolic pathways, including arachidonic acid metabolism, sphingolipid metabolism, and the biosynthesis of unsaturated fatty acids. These selective metabolic alterations complement its COX-2 inhibition and may contribute to its anti-inflammatory effects. This study provides new insights into Etodolac’s metabolic impact under healthy conditions and may inform future therapeutic strategies targeting inflammation. Full article

Background: Patients with resected stage IIB and IIC melanoma are at high risk of recurrence and distant metastasis, despite surgical treatment. The recent emergence of immune checkpoint inhibitors (ICIs) has led to their evaluation in the adjuvant setting for early-stage disease. This review aims to synthesize current evidence regarding adjuvant immunotherapy for stage IIB/IIC melanoma, explore emerging strategies, and highlight key challenges and future directions. Methods: We conducted a comprehensive literature review of randomized clinical trials, observational studies, and relevant mechanistic and biomarker research on adjuvant therapy in stage IIB/IIC melanoma. Particular focus was placed on pivotal trials evaluating PD-1 inhibitors (KEYNOTE-716 and CheckMate 76K), novel vaccine and targeted therapy trials, mechanisms of resistance, immune-related toxicity, and biomarker development. Results: KEYNOTE-716 and CheckMate 76K demonstrated significant improvements in recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) with pembrolizumab and nivolumab, respectively, compared to placebo. However, no definitive overall survival benefit has yet been shown. Adjuvant immunotherapy is linked to immune-related adverse events, including permanent endocrinopathies. Emerging personalized approaches, such as circulating tumor DNA monitoring and gene expression profiling, may enhance patient selection, but remain investigational. Conclusions: Adjuvant PD-1 blockade offers clear RFS benefits in high-risk stage II melanoma, but optimal patient selection remains challenging, due to uncertain overall survival benefit and toxicity concerns. Future trials should integrate biomarker-driven approaches to refine therapeutic decisions and minimize overtreatment. Full article

Spawning diversity plays an essential role in fish survival and reproduction, which contributes to the exceptional diversity of teleosts among vertebrates. Different zona radiata structures reflect the adaptability of fish to the environment of spawning and early embryonic development. The morphological and transcriptional characteristics of fish follicle development between different spawning habits, particularly the zona radiata variations, have been poorly documented. In this study, we integrated histology and transcriptomics to investigate the differences in the zona radiata structure and gene expression profiles among follicles from different spawning habits of Culter alburnus. Our results revealed that stage Ⅲ was the crucial period for zona radiata thickening and structure differentiation. Transcriptomic analyses of adhesive and semi-buoyant eggs at stage Ⅲ revealed a significant upregulation of genes involved in glycoprotein synthesis, extracellular matrix formation, and regulation of protease activity in adhesive eggs, such as the wfdc and a2ml gene family. This upregulation likely underpins the thicker zona radiata in adhesive eggs, facilitating their attachment to substrates. This study represents the first elucidation of the ultrastructure of the zona radiata and gene expression patterns in different developmental stages of adhesive and semi-buoyant eggs of Culter alburnus, offering new perspectives for aquaculture research in understanding fish reproductive adaptations. Full article

Bone-related defects present a key challenge in orthopaedics. The current gold standard, autografts, poses significant limitations, such as donor site morbidity, limited supply, and poor morphological adaptability. This study investigates the potential of scaffold geometry to induce osteogenic differentiation of human adipose-derived stem cells (hADSCs) through mechanotransduction, without the use of chemical inducers. Four distinct poly-(L)-lactic acid (PLA) scaffold architectures—Traditional Cross (Tc), Triangle (T), Diamond (D), and Gyroid (G)—were fabricated using fused filament fabrication (FFF) 3D printing. hADSCs were cultured on these scaffolds, and their response was evaluated utilising an alkaline phosphatase (ALP) assay, immunofluorescence, and extensive proteomic analyses. The results showed the D scaffold to have the highest ALP activity, followed by Tc. Proteomics results showed that more than 1200 proteins were identified in each scaffold with unique proteins expressed in each scaffold, respectively Tc—204, T—194, D—244, and G—216. Bioinformatics analysis revealed structures with complex curvature to have an increased expression of proteins involved in mid- to late-stage osteogenesis signalling and differentiation pathways, while the Tc scaffold induced an increased expression of signalling and differentiation pathways pertaining to angiogenesis and early osteogenesis. Full article