Search Results (2,049,148)

This study examined whether direct pre-ozonation changes inhibition-zone diameters and selected chemical properties of endodontic irrigants. Sodium hypochlorite (NaOCl; 5.25%), chlorhexidine digluconate (CHX; 2%), ethylenediaminetetraacetic acid (EDTA; 17%), and saline underwent a fixed procedure (gas-phase ozone, 80 µg/mL; 30 L/h; 5 min; 200 mL). Disk diffusion against Candida albicans, Staphylococcus aureus, and Enterococcus faecalis was evaluated in eight independent paired runs. pH was measured, and available chlorine in NaOCl was determined in three independent paired batches. Mean inhibition-zone diameters were smaller after ozonation in all nine comparisons, and eight comparisons were statistically significant after Holm correction; the EDTA comparison against C. albicans was not statistically significant. CHX showed the largest pH change (9.05 to 6.34; −2.71 units). Available chlorine decreased from 5.10 ± 0.06% to 2.84 ± 0.04%, a paired reduction of 2.26 percentage points (95% CI, 2.02–2.50). Under this protocol, pre-ozonation did not increase inhibition-zone diameters. These findings cannot distinguish changes in intrinsic antimicrobial activity from altered agar diffusion and do not establish a clinical effect. Dissolved ozone was not measured, and chemical transformation products were not characterized. Full article

Follicular lymphoma (FL) is an indolent B-cell malignancy typically associated with favourable outcomes and prolonged survival. However, histological transformation (HT) occurs in a subset of patients and significantly worsens survival outcomes, markedly altering the disease course. Currently, no clinical or molecular predictors of HT are available. We sought to evaluate the potential of Serpin family E member 1 (PAI-1) as a prognostic biomarker of HT in FL, with expression levels assessed by immunohistochemistry and quantified using digital image analysis. PAI-1 expression was evaluated in diagnostic lymphoma biopsies from 30 FL patients with no record of subsequent HT with a minimum follow-up of 10 years, ranging from 10.1 to 24.8 years (non-transforming FL, nt-FL), and 18 patients with subsequent HT occurring 0.7 to 14.6 years after diagnosis (subsequently transforming FL, st-FL); furthermore, the paired high-grade biopsy from the time of HT (transformed FL, tFL) was included. No significant differential expression patterns were identified comparing nt-FL, st-FL and tFL samples. However, high intrafollicular PAI-1 expression at FL diagnosis correlated with no transformation events observed. We believe high intrafollicular PAI-1 expression at presentation might define a minor subgroup of FL patients with reduced risk of HT. Full article

Background: Programmed cell death protein 1 (PD-1) inhibitor-based immunochemotherapy is a standard treatment for advanced esophageal squamous cell carcinoma (ESCC), but accessible blood-based biomarkers associated with both treatment efficacy and the risk of immune-related adverse events (irAEs) remain limited. The presence of antinuclear antibody (ANA) in the pretreatment period may reflect host immune status; however, its clinical relevance in ESCC and its relationship with programmed death-ligand 1 (PD-L1) expression have not been fully characterized. Methods: We retrospectively enrolled 180 patients with ESCC who received PD-1 inhibitor-based immunochemotherapy. Baseline characteristics, tumor responses, survival outcomes, and irAEs were evaluated according to pretreatment ANA status. An additional sensitivity analysis was conducted among 103 patients with available PD-L1 results. Cox regression models with time-varying coefficients were applied when the proportional hazards assumption was not satisfied. Results: The ANA-positive rate was 36.67% (66/180). Compared to patients who were ANA-negative, those who were ANA-positive demonstrated superior objective response rates (71.21% vs. 46.49%, p = 0.002), longer median progression-free survival (PFS; 11.93 vs. 5.93 months) and longer median overall survival (OS; 25.20 vs. 14.77 months, both p < 0.01). In addition, they had a higher rate of all-grade irAEs (60.61% vs. 35.96%, p = 0.001), especially thyroid dysfunction (28.79% vs. 8.77%, p < 0.001). Multivariable time-varying Cox models linked ANA positivity to favorable PFS (hazard ratio [HR] = 0.14, 95% confidence interval [CI]: 0.04–0.46, p = 0.001) and OS (HR = 0.06, 95% CI: 0.01–0.52, p = 0.011). In the sensitivity cohort, ANA remained predictive for both survival endpoints, while PD-L1 did not. Conclusions: Pretreatment ANA positivity was associated with higher response rates, longer survival, and a higher incidence of irAEs in patients with ESCC receiving PD-1 inhibitor-based immunochemotherapy. These exploratory findings require prospective validation before ANA can be used to guide treatment decisions or assess individual irAE risk. Full article

This study examines how the Galápagos Islands can better meet the needs of the rapidly expanding senior travel market. Using a sequential exploratory mixed-method design, the study combined qualitative input from senior tourists and tourism companies with quantitative survey data from 877 senior tourists and 30 tourism firms. PLS-SEM and MGA identify accessibility as the system’s primary structural catalyst, associated with safety perceptions, experiential engagement, and overall destination attractiveness. Results highlight a cognitive disconnect: seniors prioritize emotional reassurance, social connection, and low-effort experiences, while companies focus on infrastructure and operations. The study calls for accessibility-driven redesign that integrates emotional and social factors. Future research should explore how digital navigability and trust cues are associated with senior decision-making in remote island contexts. Full article

The PI3K plays a crucial role in cancer progression, and the development of PI3K inhibitors has always been a hot research direction in oncology. Through virtual screening and docking, potential lead compounds were identified. ADMET prediction revealed that KTC101 possesses superior pharmacokinetic profile. Molecular dynamics simulations indicated that compound KTC101 could stably bind to PI3Kδ, with a binding free energy of −374.627 kJ/mol. Analysis of the metabolism of KTC101 revealed that this compound could undergo diverse phase I metabolic reactions catalyzed by hepatic CYP450 enzymes to form highly polar metabolites, indicating its strong metabolic potential and easy metabolic clearance in vivo. Then it was synthesized and evaluated for kinase inhibitory activity and antiproliferative effects in HNSCC cell lines. KTC101 was first reported as a PI3K inhibitor, with IC₅₀ values of 191.23 ± 40.84 nM, 23.30 ± 5.68 nM, and 146.20 ± 21.82 nM for PI3Kα, PI3Kδ and PI3Kγ, respectively, and demonstrated dose-dependent inhibition of cancer cell growth in vitro, with IC₅₀ values of 4.1 ± 0.73 μM for HSC3 cells and 2.2 ± 0.11 μM for HSC4 cells. It exhibited inhibitory activity against PI3K, showing greater inhibitory potency toward PI3Kδ. This study demonstrates the anti-tumor potential of KTC101. Full article

Aging populations worldwide face increasing burdens from physiological deterioration. Bioactive peptides derived from milk proteins have attracted interest for their biological activities, yet systematic evidence against aging remains limited. Here, we investigated casein hydrolysates in a D-galactose-induced murine aging model. Following eight weeks of oral administration at graded doses, we quantified systemic oxidative stress markers, inflammatory cytokine profiles, hepatic and cerebral histopathology, and multiple immune competence parameters. Our data demonstrate that casein peptides dose-dependently suppressed lipid peroxidation, elevated endogenous antioxidant enzyme activities, and rebalanced cytokine networks toward an anti-inflammatory state. Concurrently, peptide treatment attenuated tissue lesions in both liver and brain, while restoring thymus and spleen indices, normalizing T-cell subset distributions, and recovering serum immunoglobulin levels. These findings indicate that oral administration of the casein hydrolysate peptide preparation was associated with improvements in redox homeostasis, inflammatory status, tissue integrity, and immune function in D-galactose-induced aging mice. This work provides mechanistic insights into casein peptides as a multi-target protective agent against age-associated physiological decline, supporting further exploration of their therapeutic potential in aging biology. Full article

Segmental bone loss after fracture-related infection (FRI) may require biological reconstruction, endoprosthetic replacement, or amputation. This narrative review examines antimicrobial management, surgical selection, and outcomes of megaprosthetic reconstruction, with emphasis on adult lower-limb periarticular defects. Evidence is distinguished as direct FRI evidence, mixed clinical evidence, or indirect evidence from oncological reconstruction and periprosthetic joint infection (PJI). Megaprostheses provide immediate structural stability and may facilitate early weight-bearing in selected patients with extensive joint involvement, limited capacity for prolonged rehabilitation, or failed biological reconstruction. However, infection, soft-tissue failure, and mechanical complications remain substantial concerns. The frequently cited PJI incidence of 15–43% comes from heterogeneous megaprosthesis populations and is not an estimate specific to reconstruction after post-traumatic FRI. Small FRI series report encouraging short-term infection control, whereas mixed and megaprosthesis PJI cohorts demonstrate recurrent infection and further salvage surgery. Staged reconstruction is commonly reported, but comparisons between surgical strategies are vulnerable to selection bias, small samples, and inconsistent outcome definitions. Biological reconstruction outcomes provide contextual benchmarks rather than evidence of comparative superiority. Overall, megaprosthetic reconstruction is a reasonable salvage option when the expected benefit of immediate stability and preservation of joint motion outweighs the risks of infection and later implant failure. Treatment should integrate adequate debridement, appropriate systemic and local antimicrobial therapy, viable soft-tissue coverage, host optimization, and shared decision-making; the available evidence does not establish a universally preferred reconstruction algorithm. Full article

Connection of a storage installation to the distribution system can result in a reduction in power line losses. However, the effect of the operation of an identical energy storage within different system nodes will be varied. This is particularly noticeable in the case of branched distribution systems, where, depending on the current transmitted loads, the highest power line losses may occur in other areas of the system. This paper presents a method for selecting the nodes with the greatest potential for reducing power line losses based on the correlation between the energy storage capacity at a given node and the value of losses. Spearman’s rank correlation was used to determine the set of nodes, assuming that the results of power flow calculations for different variants of energy storage deployment in the system will be regarded as input data. Full article

Automated micromanipulation enables precise, repeatable interaction with single cells and subcellular structures. This review examines four platform archetypes defined by their dominant interaction mechanism: field-mediated optical tweezers, flow-mediated automated microfluidics, mobile microrobots, and fixed-probe micropipette/microneedle systems. Rather than treating them as equivalent robot classes, the review compares their working principles, sensing and control architectures, application fit, quantitative performance evidence, and biological trade-offs. Recent advances in closed-loop operation, intelligent perception, multimodal sensing, and hybrid workflows are analyzed, and a standardized set of reporting metrics is proposed to support objective comparison and translation. Full article

Hepatitis B virus (HBV) infection remains a major global public health burden, primarily due to the persistence of covalently closed circular DNA (cccDNA) in infected hepatocytes. Toll-like receptor 3 (TLR3) has been suggested to be a promising therapeutic target, as its activation stimulates innate immune responses that facilitate cccDNA clearance. In this study, a structure-based computational approach was employed to identify novel small-molecule TLR3 agonists. A human TLR3 ectodomain (ECD) homodimer model was constructed using homology modeling, revealing a critical cavity at the C-terminal interface, which is responsible for the ligand-binding-induced ECD dimerization. Subsequently, three compounds, ZINC3991624 (Vilanterol) and ZINC95564694 (Naloxegol) from the FDA-approved drug database along with TCM10752 from the Traditional Chinese Medicine (TCM) database, were identified as potential candidates through docking-based virtual screening, rigorous ADMET evaluation and molecular dynamics simulations. These candidates outperformed CU-CPT17e, the only known TLR3 agonist, by maintaining lower backbone RMSD values, preserving key inter-subunit distances and protein–protein interface area and sustaining C-terminal hydrogen-bonding networks. In conclusion, our study provides a structural basis for the further development of novel TLR3 agonists, offering a promising computational framework for future host-directed immunotherapeutics aimed at HBV cccDNA clearance. Full article

Conventional lime mortars are commonly described as composite systems based on the functional separation between binder and aggregate. However, some historical mortars show microstructural features suggesting that both functions may derive from a single heterogeneous raw material. The experimental contribution of this study is the controlled production and testing of a reference mortar in which Panchina calcarenite is the sole solid precursor, supplying both the lime-forming and granular fractions without externally added aggregate. The calcarenite was investigated as a single natural source of both binder-forming and granular constituents: its carbonate fraction provides the precursor for lime formation, whereas its pre-existing siliciclastic fraction is retained as an internally derived granular component. A reference mortar was prepared exclusively from the calcarenite-derived material, while additional formulations contained 5–15 wt.% diatomaceous earth as a reactive siliceous addition. Mineralogical evolution, carbonation behaviour, hardened-state physical properties, and mechanical performance of the mortars were investigated after 12 months of curing. Compressive strengths of 2.0–3.3 MPa were obtained, depending on composition, supporting the technological feasibility of producing mechanically viable mortars without the separate addition of an external aggregate. The results support the feasibility of calcarenite-derived mortar systems in which the same heterogeneous raw material supplies both the binder-forming and internally derived granular fractions, and provide an experimental basis for discussing analogous technological solutions in historical construction. Full article

Background: Pregnancy and the postpartum period are unique stages in a woman’s life, characterised by profound physiological, psychological, and social changes that require continuous adaptation. During these periods, women frequently seek reliable health information to support healthy behaviours and informed decision-making. Advances in information and communication technologies have facilitated rapid and convenient access to health-related information through smartphones, tablets, and other digital devices, making mHealth applications increasingly popular as tools to support maternal health. Objective: This systematic review aimed to analyse the effectiveness of mHealth applications in promoting healthy and active lifestyles during pregnancy and the postpartum period. A secondary objective was to identify the key characteristics and functionalities associated with effective mHealth applications. Methods: A comprehensive literature search was conducted in three electronic databases (PubMed, Web of Science, and EBSCO) covering publications from 2016 to 2025. Studies were eligible if they included pregnant or postpartum women, evaluated mHealth applications designed to promote healthy and active lifestyles, and compared women using these applications with those receiving usual care, traditional information resources, or no intervention. Outcomes included improvements in physical activity, healthy eating behaviours, sleep quality, and stress management. Only registered or protocol-based randomised controlled trials (RCTs) were included. Methodological quality was assessed using the Downs and Black checklist. Results: Twenty RCTs met the inclusion criteria. The mean methodological quality score was 20.00 ± 1.45. Eighteen perinatal mHealth applications were identified, of which 16 demonstrated effectiveness according to the predefined clinical and/or behavioural outcomes evaluated in the respective interventions. Among the effective applications, the most frequently reported functionalities were health education, followed by personalisation, self-monitoring, feedback, and interaction with healthcare professionals. Regarding app characteristics, information quality was the most frequently identified feature, followed by clinical appropriateness, usability, accessibility, and data security and privacy. Conclusions: Among the applications classified as effective, high-quality health information, clinical appropriateness, data security and privacy, and functionalities such as health education, interaction with healthcare professionals, self-monitoring, personalized feedback, and personalization were frequently observed. Nevertheless, further improvements are needed in the quality of health information, data security and privacy, and the integration of communication with healthcare professionals to maximise the effectiveness of mHealth applications designed for pregnancy and the postpartum period. Full article