Search Results (5,250)

Background: Ursolic acid (UA) is a natural pentacyclic triterpenoid with notable antitumor activity, yet its poor water solubility and insufficient targeting restrict clinical translation. Methods: Forty novel ursolic acid-phosphine derivatives bearing seven distinct lipophilic cationic moieties were synthesized via C28 modification and structurally characterized by ¹H NMR and ¹³C NMR. Their antitumor activities in PC3-M cells were evaluated via in vitro assays. Mechanistic investigations were performed using transcriptomic analysis and Western blot. Molecular docking was performed to predict the binding profile of Compound 25 with FGFR1. In vivo antitumor efficacy and biosafety were assessed in RM-1 xenograft models in C57BL/6 mice. Results: Compound 25 (bearing a tris(3,5-dimethylphenyl)phosphine group at the C28 position with an alkyl chain length of five methylene units) exhibited the most potent activity against PC3-M cells, dose-dependently inhibiting proliferation, migration, and invasion and inducing apoptosis. It triggered mitochondrial apoptosis via ROS accumulation and disrupted cytoskeletal homeostasis by suppressing the FGFR1/KRAS/RAC1/PIP4K2 axis. Molecular docking results suggested its strong binding affinity and specificity. In vivo studies confirmed its significant antitumor effect and favorable safety. Conclusions: These results highlight the potential of Compound 25 as a promising lead compound and provide valuable insights for further medicinal chemistry optimization and the development of novel anticancer drugs derived from ursolic acid. Full article

Concrete building systems require decisions at both the member and the building level, because locally efficient cross sections do not necessarily lead to a favorable whole-building response. This study presents a two-level comparative framework comprising (i) a member-level parametric assessment of nine reinforced-concrete and composite cross-section families across six concrete grades (54 scenarios) and (ii) a building-level ETABS assessment of seven structural configurations (Models A–G) derived from a residential reinforced-concrete frame benchmark. At the member level, the alternatives were evaluated based on axial resistance, along with simplified screening-level CO${}_2$ and cost proxies. At the member level, axial resistance increased with concrete grade, although the marginal benefit diminished at higher grades for steel-dominant layouts. Balanced composite sections showed the most favorable normalized strength-to-material-proxy trends, whereas steel-heavy alternatives provided high absolute resistance but lower overall efficiency. The comparison between the member-level hybrid-section screening and the building-level composite configuration further showed that promising local section behavior does not automatically translate into superior whole-building performance. At the building level, the compared configurations were assessed through vertical base reactions, modal properties, and top-level lateral displacement response. Replacing solid beams and columns with hollow members of identical outer dimensions reduced the self-weight-related base reaction from 9591 to 8832 kN (7.9%) but slightly increased the top-level displacement response, indicating a mass–stiffness trade-off. Larger improvements were obtained when the global lateral-force-resisting mechanism was modified directly: the braced configuration produced the shortest fundamental period ($T_1=0.433$ s) and the lowest displacement response, while the core-wall configuration also reduced both period and displacement substantially. By contrast, the height-extended configuration produced the most flexible response among Models A–F. An additional exploratory variant with semi-rigid beam-to-column connections (Model G) confirmed that connection-level flexibility produces a measurable but moderate increase in period and displacement relative to the reference frame, without altering the global load-resisting mechanism. Overall, the results confirm that member-level and building-level assessments should be treated as complementary decision levels in early-stage structural design. Full article

Background: Post-approval manufacturing changes for biologics require rigorous comparability assessments to ensure uninterrupted quality and clinical performance. CMAB007 (Aomaishu^®), a China-approved (2023) omalizumab biosimilar, underwent process enhancements—including media optimization and anion-exchange chromatography substitution—yielding a 5-fold increase in production without altering the host cell line. Methods: A novel three-arm tiered strategy was adopted to compare post-change CMAB007, pre-change CMAB007, and reference (Xolair^®) products. Critical quality attributes (CQAs) were classified into tiers based on risk impact, with tier-specific acceptance criteria. Comprehensive analytics assessed structure, post-translational modifications, purity/impurities, activity, and Fc-mediated functions. Forced degradation (lyophilized/reconstituted states) and accelerated stability studies were evaluated. Based on the high degree of CMC similarity and to prevent “biological drift”, the pharmacokinetic (PK) and safety comparability of the post-change CMAB007 versus the reference product (Xolair^®) was confirmed in a randomized, double-blind, two-arm study in healthy males (N = 114; single 150 mg subcutaneous administration). The pre-change product was not included in this clinical PK study. Results: Post-change CMAB007 exhibited analytical similarity within tiered acceptance criteria for all CQAs. Stability studies confirmed enhanced robustness under stress conditions. PK equivalence was demonstrated for AUC_0–inf (GMR: 99.82%; 90% CI: 91.46~108.94%), AUC_0–t (99.54%; 91.40~108.41%), and C_max (101.88%; 95.21~109.01%). Immunogenicity (ADA incidence: 10.5% vs. 12.5%, p = 0.742) and safety profiles were comparable. Conclusions: This study pioneers a tiered three-arm comparability strategy for post-approval changes, integrating advanced analytics, risk-based quality assessment, and clinical validation. The approach mitigates “biological drift” risks, ensuring biosimilar quality, efficacy, and safety while enabling sustainable production scalability. Full article

The cosmetic industry represents a major sector of the global economy and is expected to significantly grow in the coming years. To enhance consumer acceptance and address increasing sustainability concerns, cosmetic companies are actively seeking innovative solutions to mitigate their environmental, economic, and social impacts. In accordance with this, several scientific studies focus on the development, scale-up, and life cycle assessment of sustainable cosmetic products, especially those derived from side streams in accordance with circular economy principles. Various reviews have addressed this topic; however, they typically cover one or two of these dimensions, providing only a partial perspective. In particular, existing studies mainly analyze the types of side streams used and the resulting products, often lacking a comprehensive framework that can effectively support the translation of these approaches into industrial-scale production. The aim of the present review is to address this gap by providing a comprehensive analysis of the maturity level of development, scale-up processes, and life cycle assessment of cosmetic products based on agro-industrial side streams. This analysis is intended to support companies in the transition towards more sustainable practices by reducing carbon footprint and limiting the intensive extraction of virgin raw materials. The different approaches and methodologies proposed for the development and scale-up of sustainable cosmetic products from agro-industrial side streams are also analyzed, considering whether life cycle assessment has been performed. Furthermore, the most suitable business models will be selected as innovative and sustainable value chains capable of generating economic benefits, fostering local development, and enhancing resource efficiency and supply security. Full article

Purpose: Oral squamous cell carcinoma (OSCC) carries a substantial burden in low- and middle-income countries as well as underserved subpopulations within high-income settings, where structural barriers contribute to worse outcomes. While evidence supports targeted screening of high-risk groups, practical guidance for designing organized, quality-assured programs remains limited. This review proposes a framework to translate contemporary cancer-screening principles into operational criteria for OSCC. Methods: A review following the Scale for the Assessment of Narrative Review Articles principles was conducted. Conceptual papers, international evaluations, implementation studies, and programmatic guidance were included. The evidence was synthesized narratively, with emphasis on contemporary cancer-screening principles, implementation frameworks, and their applicability to OSCC. Results: Clinical oral examination can improve the detection of OSCC in early stages and reduce mortality among high-risk groups when embedded in coordinated care pathways. Effective programs require governance structures, screening policies, risk-stratified approaches, and robust information systems capable of call-recall, referral tracking, and quality monitoring. Dental schools and academic clinics may serve as feasible regional hubs for programs within mixed health systems. Conclusions: Aligning core OSCC-screening principles with operational enablers offers a practical pathway to develop context-appropriate programs that strengthen capacity, promote equity, and generate evidence for responsible scale-up. Full article

This study presents an integrated design methodology for earthquake demolition rescue robots by combining UXMs, Kano, and QFD to improve design rationality and performance in extreme rescue scenarios. It addresses key gaps in existing approaches, particularly the lack of systematic experiential data acquisition, quantitative requirement analysis, and effective design translation. UXMs are applied to reconstruct critical task scenarios and identify high-load nodes and user experience variations. The Kano model is used to prioritise and classify user requirements, which are then translated into engineering characteristics through QFD. Based on this framework, a conceptual robot design is developed using the FBS model and evaluated through process-level simulation and usability assessment. The results demonstrate that the proposed method enables structured requirement transformation and supports traceable design decisions. Simulation indicates the consistency of task workflows and coordination among functional modules at the process level. A System Usability Scale score of 80.22 indicates a relatively high level of perceived usability at the conceptual evaluation stage. The proposed methodology provides a structured and traceable conceptual design framework for earthquake rescue robots. While the current validation is based on conceptual-level evaluation, the methodology offers a traceable design pathway that may be extended to other high-risk emergency equipment with further empirical testing. Full article

Staphylococcus aureus biofilms formed on titanium surfaces are highly relevant to orthopedic implant-associated infection and remain difficult to control after maturation. This study aimed to evaluate whether ultraviolet A (UVA, 365 nm) combined with cinnamaldehyde (CA) could improve antibiofilm activity against titanium-associated S. aureus biofilms in a stage-resolved in vitro model and to examine whether the observed responses were associated with reactive oxygen species (ROS). Early stage (8 h) and 24 h biofilm models were established on total hip arthroplasty (THA)-derived titanium discs. After condition screening, 0.5 mM CA combined with 5 min UVA exposure was selected for subsequent experiments. Biofilm biomass was assessed by crystal violet staining, bacterial viability by live/dead staining and colony-forming unit (CFU) enumeration, ROS-associated fluorescence by dihydroethidium (DHE) imaging, and biofilm-associated gene expression by quantitative real-time PCR (qRT-PCR). Chondrocyte viability was also evaluated under the selected antibiofilm-effective conditions. The combined treatment showed stage-dependent antibiofilm effects, with greater biomass reduction in the 8 h biofilm model and marked impairment of bacterial viability and culturability in both models. ROS-associated fluorescence increased under combined exposure and was partially attenuated by N-acetyl-L-cysteine (NAC) in the 24 h biofilm model. In parallel, CA + UVA was associated with lower expression levels of clfA, icaA, and icaD in the 8 h biofilm model and of icaA, icaB, and icaD in the 24 h biofilm model, with partial NAC attenuation in the latter. Chondrocyte viability was lower in all treatment groups than in the untreated control, although the combined treatment did not show an obvious additional decrease compared with the single-treatment groups. These findings indicate that UVA combined with CA exerts stage-dependent antibiofilm effects in an in vitro titanium-associated S. aureus biofilm model. The observed ROS-associated responses were consistent with, but do not establish, mechanistic involvement. The current treatment setting also requires further optimization before translational applicability can be more confidently considered. Full article

The Teachers’ Beliefs and Intentions Questionnaire (TBIQ) assesses educators’ beliefs and intentions regarding the importance of sensitive interactions with young children. Understanding these beliefs is particularly relevant in contemporary educational contexts where teacher–child interactions are viewed as central to children’s learning and development. Despite its use in several countries, there is no validated Spanish version available. This study aimed to translate, culturally adapt, and psychometrically validate a Spanish version of the TBIQ for early childhood education settings in Chile. Following international guidelines for cross-cultural adaptation, the questionnaire was translated into Spanish and administered to early childhood teachers and assistant teachers working in public early childhood education centers. The original two-factor structure (Beliefs and Intentions) was tested using confirmatory factor analyses with robust estimators for ordinal data. Results supported the two-factor model after removing six items with low factor loadings and indicated excellent model fit. Both scales demonstrated high internal consistency. However, measurement invariance across educator roles could not be established, and cross-group comparisons should be interpreted with caution. Despite this limitation, the Spanish version of the TBIQ demonstrates adequate validity and reliability and offers a brief and accessible instrument for research and for the assessment of educators’ beliefs and intentions regarding interaction quality in early childhood education. Full article

Background/Objectives: Both adiposity and nutritional–inflammatory status influence glucose metabolism; however, their longitudinal associations with glycemic changes in non-diabetic populations remain unclear. We examined the independent, interactive, and joint associations of body mass index (BMI) and prognostic nutritional index (PNI) with the 3-year change in HbA1c (ΔHbA1c). PNI, a composite marker of serum albumin and peripheral lymphocyte count, reflects both protein nutritional status and systemic immune competence. We hypothesized that BMI and PNI would each independently predict ΔHbA1c and that their joint profiling would identify higher-risk subgroups. Methods: A total of 9414 non-diabetic adults from the Shanghai Suburban Adult Cohort were included. Participants with diabetes at baseline (defined as fasting plasma glucose ≥ 7.0 mmol/L, 2-h post-load glucose ≥ 11.1 mmol/L, HbA1c ≥ 6.5%, or self-reported physician diagnosis of diabetes or use of glucose-lowering medications) were excluded. BMI was measured, and PNI was calculated as serum albumin + 5 × lymphocyte count. ΔHbA1c was assessed over a 3-year period. Multivariable linear regression, interaction testing, and joint stratification were performed. Covariate selection was guided by prior biological plausibility, and model adequacy was evaluated using the Akaike Information Criterion (AIC). Results: Both BMI (β = 0.013% per kg/m², 95% CI: 0.011–0.016, p < 0.001) and PNI (β = 0.002% per unit, 95% CI: 0.000–0.004, p = 0.019) were independently and positively associated with ΔHbA1c. No significant interaction was observed (p = 0.431). High BMI (≥24 kg/m²) was associated with glycemic worsening irrespective of PNI level (β ≈ 0.075%, p < 0.001). Among normal-weight individuals, higher PNI was associated with a modest increase in ΔHbA1c (β = 0.031%, p = 0.007). Conclusions: Although the absolute effect sizes were modest at the individual level, BMI was consistently and independently associated with glycemic deterioration therefore, even small per-unit increases may translate into meaningful risk at the population level given the high prevalence of overweight and obesity. PNI showed a small positive association, suggesting that in relatively healthy populations a higher PNI may partly capture subtle pro-glycemic factors—such as low-grade inflammation or higher protein intake—rather than representing unambiguous nutritional benefit. The absence of interaction suggests that BMI and PNI act through largely independent pathways. These findings extend prior evidence by demonstrating that PNI provides modest additional glycemic information beyond BMI in non-diabetic community-dwelling adults, particularly among those of normal weight. Full article

Background: Denture stomatitis is strongly associated with Candida biofilms on prosthetic surfaces and remains difficult to manage due to biofilm persistence and antifungal resistance. Selenium-based nanomaterials, particularly biogenic selenium nanoparticles (SeNPs) functionalized with natural polymers or phytochemicals, have emerged as potential material-centered strategies for biofilm control. Objective: To systematically evaluate the antifungal and antibiofilm effects of selenium-based nanomaterials on Candida biofilms in the context of denture materials. Methods: A systematic review was conducted in accordance with the PRISMA guidelines and registered in PROSPERO. Multiple databases were searched from inception without language restrictions. Eligible studies included experimental investigations of biogenic or functionalized SeNPs or organoselenium compounds targeting Candida biofilms on denture materials or in relevant in vitro models. A qualitative synthesis was performed due to anticipated heterogeneity. Results: Eleven studies met the inclusion criteria. Of these, four studies directly evaluated selenium-based interventions on denture materials, while seven provided supporting mechanistic evidence using in vitro models on non-denture substrates. Across denture-related studies, selenium-based modifications reduced fungal adhesion, biofilm biomass, and colony-forming units, without detrimental effects on material properties. Functionalization with polymers or phytochemicals was associated with enhanced antifungal activity and nanoparticle stability. Mechanistic studies suggested multimodal antifungal effects, including membrane disruption, inhibition of virulence factors, and modulation of biofilm-related pathways. Methodological quality was moderate, with common limitations in reporting and experimental standardization. Conclusions: Functionalized biogenic SeNPs show promising antifungal and antibiofilm activity against Candida in preclinical denture-related models. However, all available evidence is in vitro, with no in vivo or clinical studies identified. Substantial heterogeneity and limited long-term safety data preclude clinical recommendations. Further research should focus on standardized methodologies, clinically relevant in vivo models, and controlled clinical trials to assess translational potential. Full article

Smart hydrogel systems with stimuli-responsive properties are increasingly being investigated in combination with advanced additive manufacturing techniques for targeted drug delivery and wound healing in regenerative medicine; however, their clinical translation remains limited by challenges related to material performance, design complexity, and manufacturing scalability. This review analyzes recent developments in smart hydrogel design and 4D-printed scaffolds, with emphasis on programmable and stimuli-responsive architectures. The literature is selectively evaluated based on relevance to (i) hydrogel structure–property relationships, (ii) 3D/4D printing strategies, and (iii) demonstrated performance in drug delivery and wound healing applications. The analysis highlights design approaches enabling spatiotemporal control of drug release and dynamic scaffold behavior, while also examining how fabrication methods influence functional outcomes. Major limitations are critically assessed, including issues of reproducibility, mechanical stability, long-term performance, and the gap between experimental studies and clinical application. Challenges in defining and implementing 4D printing in biomedical contexts are discussed as well. Overall, this review identifies current design trade-offs, outlines priorities for improving reliability and translational potential, and synthesizes emerging trends in 3D and 4D printed hydrogel scaffolds for precision drug delivery and regenerative wound therapy. Full article

Background/Objectives: Silver nanoparticles (AgNPs) are highly valuable nanomaterials due to their unique optical and physicochemical properties. AgNPs have a lot of promise as contrast-enhancing and diagnostic agents in image-guided treatment. With a focus on their incorporation into image-guided and theranostic approaches, this narrative review attempts to assess the current function of AgNPs in imaging diagnostics. Methods: Using major scientific databases, such as PubMed, Web of Science, and Scopus, a narrative literature review has been conducted with an emphasis on recent preclinical and experimental research examining AgNP-based systems for diagnostic imaging applications. The design of the NPs, surface functionalization, imaging modality, and diagnostic performance of the evaluated studies were analyzed. Results: Due to their surface plasmon resonance and tunable physicochemical properties, AgNPs show great promise in a variety of imaging techniques, such as optical imaging, computed tomography (CT), and multimodal platforms, according to the reviewed literature. Functionalized AgNPs emerged as agents in image-guided therapy due to their improved target selectivity, enhanced imaging contrast, and signal amplification in tissues. Conclusions: AgNPs are appealing nanoscale platforms for image-guided methods and imaging diagnostics. Despite their encouraging preclinical results, some key issues, such as toxicity, biocompatibility, and clinical translation, remain critical. AgNP-based therapeutic and diagnostic systems will need to overcome these constraints in the future. Full article

Background: Rheumatic diseases (RDs) are associated with increased cardiovascular morbidity, including a 40% higher risk of atrial fibrillation (AF). While ablation has become the cornerstone of rhythm control, its safety in patients with rheumatic diseases remains poorly defined. Methods: Adults with a primary admission diagnosis of AF catheter ablation from 2016 to 2022 were identified using the National Inpatient Sample. We excluded patients with other forms of supraventricular tachycardia, pacemaker/defibrillator procedures, and atrioventricular junction ablations. Sociodemographic, clinical characteristics, and outcomes were compared between groups. Multivariate logistic regression adjusted for age, race, sex, and potential comorbid confounders was used to assess for independent associations. Results: A weighted total of 48,855 patients were included, 2.5% of which had RD. These patients were predominantly female, older, and had higher rates of renal dysfunction, hypertension, heart failure, history of stroke, ischemic heart disease, heart failure, and obstructive sleep apnea (all p < 0.001). Patients with RD had higher complication rates (12.9% vs. 8.8%, p < 0.001); specifically, bleeding (p < 0.001), infection (p = 0.008), pericardial (p = 0.003), and respiratory complications (p < 0.001). RDs were not found to be an independent predictor of complications, though there was a trend towards more complications (odds ratio 1.43, 95% confidence interval 0.97–2.11, p = 0.070). Conclusions: Patients with RD undergoing AF ablation were older, female, and had higher rates of comorbidities. This translated to higher unadjusted periprocedural complications in patients with rheumatic diseases. While RDs were not independently associated with adverse outcomes, a trend towards increased complications was observed. Full article

Magnesium oxychloride cement (MOC), produced from reactive MgO and MgCl₂, has re-emerged as a promising low-carbon binder due to its rapid setting and high early-age strength. Yet its limited resistance to moisture and immersion remains the principal barrier to broader construction deployment. This review synthesizes the MOC evidence base using a structured approach that combines PRISMA-informed study identification and screening with bibliometric mapping to contextualize research evolution and thematic development. The review follows a structured data extraction of mix design, curing conditions, characterization methods, and performance outcomes. The synthesis confirms that MOC performance is strongly system-dependent. MgO reactivity, MgCl₂ concentration, mixture ratios, and curing regime govern hydration products, microstructure, and durability, accounting for the apparent variation across studies. Comparative assessment shows that improvements in water resistance are most consistently reported for phosphate-based modification, SCM incorporation, and polymer/hybrid strategies. However, benefits are frequently accompanied by trade-offs in workability, setting, strength development, and cost, and reinforcement compatibility and corrosion risk remain insufficiently resolved for structural applications. The review highlights gaps in reporting and durability testing that currently limit cross-study comparability and translation, and it consolidates priority research directions toward standardized protocols, mechanism-based durability design, scale-up validation, and robust sustainability assessment. Full article

Single-species hedges can help mitigate a range of urban and climate change-related issues, such as slowing stormwater flow and reducing rainfall runoff, particularly during the growing season. There is, however, little information on the service delivery of mixed hedges and their comparison to single-species, year-round, as well as on the practicality of functional rather than ornamental plant mixing. Here, we report on an initial case study to address this. Chosen hedge taxa (Crataegus monogyna, Elaeagnus × submacrophylla ‘Gilt Edge’, Ligustrum ovalifolium, Thuja plicata ‘Atrovirens’) represented a range of plant characteristics. These were trialled outdoors in Reading (SE England, UK) as treatment groupings of either single-species or mixed-species (‘evergreen’ and ‘broadleaf’ mix), along with a bare soil control, in 110 L troughs. We applied 5 min simulated rainfall onto each treatment twice in every meteorological season and assessed canopy throughfall. We also monitored substrate moisture content change as a proxy for evapotranspiration and substrate storage capacity of subsequent rainfall. During summer, the deciduous taxa and mixed hedges had the highest evapotranspiration rates, suggesting their potential to influence soil water storage, but in our experimental setup, that did not translate into significant differences in substrate moisture between treatments. During autumn and winter, the single-species Thuja treatment had the highest rainfall interception rate, followed by both mixed species treatments. In winter, canopy and leaf characteristics rather than physiological activity correlated with increased rainfall attenuation. However, by the end of the experiment (spring 2023), Crataegus, Thuja and both mixed hedge treatments had significantly lower throughfall (higher interception) compared to bare soil. We are continuing to test these treatments in a longer-term field experiment. Management of mixed-species hedges for rainfall attenuation is practically achievable, despite some differences in individual species’ growth rates and plant habits. Full article