Search Results (2,120)

Cellular senescence is closely connected with cancer progression, recurrence, and metastasis. Senotherapy aims to soothe the harmful effects of senescent cells either by inducing their apoptosis (senolytic) or by suppressing the senescence-associated secretory phenotype (SASP) (senomorphic). Fisetin, a well-studied senotherapeutic drug, was selected for this study to evaluate its efficiency when delivered in a liposomal formulation. The experiment evaluated the impact of liposome-encapsulated fisetin on senescent cells induced by doxorubicin (DOX) from two cell lines: WI-38 (normal lung fibroblasts) and A549 (lung carcinoma). Senescence was characterized by SA-β-galactosidase (SA-β-gal) activity, proliferation, morphology, and secretion of pro-inflammatory interleukin 6 (IL-6) and interleukin 8 (IL-8). Due to fisetin’s hydrophobic nature, it was encapsulated in liposomes to enhance cellular delivery. Cellular uptake studies confirmed that the liposomes were effectively internalized by both senescent cell types. Treatment with fisetin-loaded liposomes revealed a lack of senolytic effects but showed senomorphic activity, as evidenced by a significant reduction in IL-6 and IL-8 secretion in senescent cells. The liposomal formulation enhanced fisetin’s therapeutic efficacy, showing comparable results even at the lowest tested concentration. Full article

Greenhouses have positively impacted plant production by allowing the cultivation of different crops per year. However, the accumulation of agricultural plastics, potentially contaminated with agrochemicals, raises environmental concerns. This work evaluates the combined effect of Bordeaux mixture and low-density polyethylene (LDPE) microplastics (<5 mm) on the growth of lettuce (Lactuca sativa L.) and soil microbial communities. Different levels of Bordeaux mixture (0, 100 and 500 mg kg⁻¹), equivalent to Cu(II) concentrations (0, 17 and 83 mg kg⁻¹), LDPE microplastics (0, 1% and 5%) and their combination were selected. After 28 days of growth, biometric and photosynthetic parameters, Cu uptake, and soil microbial responses were evaluated. Plant germination and growth were not significantly affected by the combination of Cu and plastics. However, individual Cu treatments influenced root and shoot length and biomass. Chlorophyll and carotenoid concentrations increased with Cu addition, although the differences were not statistically significant. Phospholipid fatty acid (PLFA) analysis revealed a reduction in microbial biomass at the highest Cu dose, whereas LDPE alone showed limited effects and may reduce Cu bioavailability. These results suggest that even at the highest concentration added, Cu can act as a plant nutrient, while the combination of Cu–plastics showed varying effects on plant growth and soil microbial communities. Full article

Background/Objectives: Gastrin-releasing peptide receptor (GRPR) is overexpressed in breast cancer and might be used as a theranostics target. The expression of GRPR strongly correlates with estrogen receptor (ER) expression. Visualization of GRPR-expressing breast tumors might help to select the optimal treatment. Developing GRPR-specific probes for SPECT would permit imaging-guided therapy in regions with restricted access to PET facilities. In this first-in-human study, we evaluated the safety, biodistribution, and dosimetry of the [^99mTc]Tc-DB8 GRPR-antagonistic peptide. We also addressed the important issue of finding the optimal injected peptide mass. Methods: Fifteen female patients with ER-positive primary breast cancer were enrolled and divided into three cohorts receiving [^99mTc]Tc-DB8 (corresponding to three distinct doses of 40, 80, or 120 µg DB8) comprising five patients each. Additionally, four patients with ER-negative primary tumors were injected with 80 µg [^99mTc]Tc-DB8. The injected activity was 360 ± 70 MBq. Planar scintigraphy was performed after 2, 4, 6, and 24 h, and SPECT/CT scans followed planar imaging 2, 4, and 6 h after injection. Results: No adverse events were associated with [^99mTc]Tc-DB8 injections. The effective dose was 0.009–0.014 mSv/MBq. Primary tumors and all known lymph node metastases were visualized irrespective of injected peptide mass. The highest uptake in the ER-positive tumors was 2 h after injection of [^99mTc]Tc-DB8 at a 80 µg DB8 dose (SUV_max 5.3 ± 1.2). Injection of [^99mTc]Tc-DB8 with 80 µg DB8 provided significantly (p < 0.01) higher uptake in primary ER-positive breast cancer lesions than injection with 40 µg DB8 (SUV_max 2.0 ± 0.3) or 120 µg (SUV_max 3.2 ± 1.4). Tumor-to-contralateral breast ratio after injection of 80 μg was also significantly (p < 0.01, ANOVA test) higher than ratios after injection of other peptide masses. The uptake in ER-negative lesions was significantly lower (SUV_max 2.0 ± 0.3) than in ER-positive tumors. Conclusions: Imaging using [^99mTc]Tc-DB8 is safe, tolerable, and associated with low absorbed doses. The tumor uptake is dependent on the injected peptide mass. The injection of an optimal mass (80 µg) provides the highest uptake in ER-positive tumors. At optimal dosing, the uptake was significantly higher in ER-positive than in ER-negative lesions. Full article

The aviation industry is under increasing pressure to reduce its environmental impact while maintaining safety and performance standards. One promising area for improvement lies in the use of sustainable materials in airport infrastructure. One of the issues preventing uptake of emerging sustainable technologies is the lack of guidance relating to the opportunities, potential benefits, associated risks and an implementation plan specific to airport pavements. This research reviewed opportunities to incorporate waste materials into rigid airport pavements, focusing on concrete base slabs. Commonly used supplementary cementitious materials (SCMs), such as fly ash and ground granulated blast furnace slag (GGBFS) were considered, as well as recycled aggregates, including recycled concrete aggregate (RCA), recycled crushed glass (RCG), and blast furnace slag (BFS). Environmental Product Declarations (EPDs) were also used to quantify the potential for environmental benefit associated with various concrete mixtures, with findings showing 23% to 50% reductions in embodied carbon are possible for selected theoretical concrete mixtures that incorporate waste materials. With considered evaluation and structured implementation, the integration of waste materials into rigid airport pavements offers a practical and effective route to improve environmental outcomes in aviation infrastructure. It was concluded that a Triple Bottom Line (TBL) framework—assessing financial, environmental, and social factors—guides material selection and can support sustainable decision-making, as does performance-based specifications that enable sustainable technologies to be incorporated into airport pavement. The study also proposed a consequence-based implementation hierarchy to facilitate responsible adoption of waste materials in airside pavements. The outcomes of this review will assist airport managers and pavement designers to implement practical changes to achieve more sustainable rigid airport pavements in the future. Full article

The demand for anion exchange membranes (AEMs) is growing due to their applications in water electrolysis, CO₂ reduction conversion and fuel cells, as well as water treatment, driven by the increasing energy demand and the need for a sustainable future. However, current AEMs still face challenges, such as insufficient permeability and stability in strongly acidic or alkaline media, which limit their durability and the sustainability of membrane fabrication. In this study, polyvinyl alcohol (PVA) and chitosan (CS) biopolymers are selected for membrane preparation. Zinc oxide (ZnO) and porous organic polymer (POP) nanoparticles are also introduced within the PVA-CS polymer blends to make mixed-matrix membranes (MMMs) with increased OH⁻ transport sites. The membranes are characterized based on typical properties for AEM applications, such as thickness, water uptake, KOH uptake, Cl⁻ and OH⁻ permeability and ion exchange capacity (IEC). The OH⁻ transport of the PVA-CS blend is increased by at least 94.2% compared with commercial membranes. The incorporation of non-porous ZnO and porous POP nanoparticles into the polymer blend does not compromise the OH⁻ transport properties. On the contrary, ZnO nanoparticles enhance the membrane’s water retention capacity, provide basic surface sites that facilitate hydroxide ion conduction and reinforce the mechanical and thermal stability. In parallel, POPs introduce a highly porous architecture that increases the internal surface area and promotes the formation of continuous hydrated pathways, essential to efficient OH⁻ mobility. Furthermore, the presence of POPs also contributes to reinforcing the mechanical integrity of the membrane. Thus, PVA-CS bio-based membranes are a promising alternative to conventional ion exchange membranes for various applications. Full article

Diabetic sensorimotor polyneuropathy (DSPN) is the most prevalent complication of diabetes, affecting nearly half of all persons with diabetes. It is characterized by nerve degeneration, progressive sensory loss and pain, with increased risk of ulceration and amputation. Despite its high prevalence, disease-modifying treatments for DSPN do not exist. Mitochondrial dysfunction and Ca²⁺ dyshomeostasis are key contributors to the pathophysiology of DSPN, disrupting neuronal energy homeostasis and initiating axonal degeneration. Recent findings have demonstrated that antagonism of the muscarinic acetylcholine type 1 receptor (M₁R) promotes restoration of mitochondrial function and axon repair in various neuropathies, including DSPN, chemotherapy-induced peripheral neuropathy (CIPN) and HIV-associated neuropathy. Pirenzepine, a selective M₁R antagonist with a well-established safety profile, is currently under clinical investigation for its potential to reverse neuropathy. The transient receptor potential melastatin-3 (TRPM3) channel, a Ca²⁺-permeable ion channel, has recently emerged as a downstream effector of G protein-coupled receptor (GPCR) pathways, including M₁R. TRPM3 activation enhanced mitochondrial Ca²⁺ uptake and bioenergetics, promoting axonal sprouting. This review highlights mitochondrial and Ca²⁺ signaling imbalances in DSPN and presents M₁R antagonism and TRPM3 activation as promising neuro-regenerative strategies that shift treatment from symptom control to nerve restoration in diabetic and other peripheral neuropathies. Full article

Urban metabolism frameworks offer insight into flows of energy, materials, and services in cities, yet tree species selection is seldom treated as a metabolic indicator. In Amman, Jordan, we integrate spatial metabolic metrics to critique monocultural greening policies and demonstrate how species choices forecast long-term urban metabolic performance. Using ENVI-met 5.61 simulations, we compare Melia azedarach, Olea europaea, and Ceratonia siliqua, mainly assessing urban flow related elements like air temperature reduction, CO₂ sequestration, and evapotranspiration alongside rooting depth, isoprene emissions, and biodiversity support. Melia delivers rapid cooling but shows other negatives like a low biodiversity value; Olea offers average cooling and sequestration but has allergenic pollen issues in people as a flow; Ceratonia provides scalable cooling, increased carbon uptake, and has a high ecological value. We propose a metabolic reframing of green infrastructure planning to choose urban species, guided by system feedback rather than aesthetics, to ensure long-term resilience in arid urban climates. Full article

Introduction: Breast density is a well-recognized factor in breast cancer risk assessment, with higher density linked to increased malignancy risk and reduced sensitivity of conventional mammography. Background parenchymal enhancement (BPE), observed in contrast-enhanced imaging, reflects physiological contrast uptake in non-pathologic breast tissue. While extensively characterized in breast MRI, the role of BPE in contrast-enhanced mammography (CEM) remains uncertain due to inconsistent findings regarding its correlation with breast density and cancer risk. Unlike breast density—standardized through the ACR BI-RADS lexicon—BPE lacks a uniform classification system in CEM, leading to variability in clinical interpretation and research outcomes. To address this gap, we introduce the BPE-CEM Standard Scale (BCSS), a structured four-tiered classification system specifically tailored to the two-dimensional characteristics of CEM, aiming to improve consistency and diagnostic alignment in BPE evaluation. Materials and Methods: In this retrospective single-center study, 213 patients who underwent mammography (MG), ultrasound (US), and contrast-enhanced mammography (CEM) between May 2022 and June 2023 at the “A. Perrino” Hospital in Brindisi were included. Breast density was classified according to ACR BI-RADS (categories A–D). BPE was categorized into four levels: Minimal (< 10% enhancement), Light (10–25%), Moderate (25–50%), and Marked (> 50%). Three radiologists independently assessed BPE in a subset of 50 randomly selected cases to evaluate inter-observer agreement using Cohen’s kappa. Correlations between BPE, breast density, and age were examined through regression analysis. Results: BPE was Minimal in 57% of patients, Light in 31%, Moderate in 10%, and Marked in 2%. A significant positive association was found between higher breast density (BI-RADS C–D) and increased BPE (p < 0.05), whereas lower-density breasts (A–B) were predominantly associated with minimal or light BPE. Regression analysis confirmed a modest but statistically significant association between breast density and BPE (R² = 0.144), while age showed no significant effect. Inter-observer agreement for BPE categorization using the BCSS was excellent (κ = 0.85; 95% CI: 0.78–0.92), supporting its reproducibility. Conclusions: Our findings indicate that breast density is a key determinant of BPE in CEM. The proposed BCSS offers a reproducible, four-level framework for standardized BPE assessment tailored to the imaging characteristics of CEM. By reducing variability in interpretation, the BCSS has the potential to improve diagnostic consistency and facilitate integration of BPE into personalized breast cancer risk models. Further prospective multicenter studies are needed to validate this classification and assess its clinical impact. Full article

Background: Immunization is a highly effective intervention for controlling over 20 life-threatening infectious diseases, significantly reducing both morbidity and mortality rates. One notable achievement in vaccination efforts was the global eradication of smallpox, which the World Health Assembly declared on 8 May 1980. Additionally, there has been a remarkable 99.9% reduction in wild poliovirus cases since 1988, decreasing from more than 350,000 cases that year to just 30 cases in 2022. Objectives: The objective of this review was to assess the effects of various interventions designed to increase vaccination uptake among adults. Search Methods: A thorough search was conducted in the CENTRAL, Embase Ovid, Medline Ovid, PubMed, Web of Science, and Global Index Medicus databases for primary studies. This search was conducted in August 2021 and updated in November 2024. Selection Criteria: Randomized trials were eligible for inclusion in this review, regardless of publication status or language. Data Analysis: Two authors independently screened the search outputs to select potentially eligible studies. Risk ratios (RR) with 95% confidence intervals (CI) were calculated for each randomized controlled trial (RCT). A meta-analysis was conducted using a random-effects model, and the quality of the evidence was assessed using the GRADE approach. Main Results: A total of 35 randomized controlled trials met the inclusion criteria and were included in this review, with the majority conducted in the United States. The interventions targeted adults aged 18 and older who were eligible for vaccination, involving a total of 403,709 participants. The overall pooled results for interventions aimed at increasing influenza vaccination showed a risk ratio of 1.41 (95% CI: 1.15, 1.73). Most studies focused on influenza vaccination (18 studies), while the remaining studies examined various other vaccines, including those for hepatitis A, COVID-19, hepatitis B, pneumococcal disease, tetanus, diphtheria, pertussis (Tdap), herpes zoster, and human papillomavirus (HPV). The results indicate that letter reminders were slightly effective in increasing influenza vaccination uptake compared to the control group (RR: 1.75, 95% CI: 0.97, 1.16; 6 studies; 161,495 participants; low-certainty evidence). Additionally, participants who received education interventions showed increased levels of influenza vaccination uptake compared to those in the control group (RR: 1.88, 95% CI: 0.61, 5.76; 3 studies; 1318 participants; low-certainty evidence). Furthermore, tracking and outreach interventions also led to an increase in influenza vaccination uptake (RR: 1.87, 95% CI: 0.78, 4.46; 2 studies; 33,752 participants; low-certainty evidence). Conclusions: Letter reminders and educational interventions targeted at recipients are effective in increasing vaccination uptake compared to control groups. Full article

Background and Objectives: Metabolic tumor volume (MTV) and inflammation-based indices have recently gained attention as potential prognostic markers of diffuse large B-cell lymphoma (DLBCL). We aimed to evaluate the prognostic significance of metabolic and systemic inflammatory parameters in predicting treatment response, relapse, and overall survival (OS) in patients with DLBCL. Materials and Methods: This retrospective cohort study included 70 patients with DLBCL. Clinical characteristics, laboratory values, and metabolic parameters, including maximum standardized uptake value (SUVmax^liver and SUVmax), heterogeneity indices HI1 and HI2, and MTV were analyzed. Survival outcomes were assessed using Kaplan–Meier and log-rank tests. Receiver operating characteristic analyses helped evaluate the diagnostic performance of the selected biomarkers in predicting relapse and mortality. Univariate and multivariate logistic regression analyses were conducted to identify the independent predictors. Results: The mean OS and mean relapse-free survival (RFS) were 71.6 ± 7.4 and 38.7 ± 2.9 months, respectively. SUVmax^liver ≤ 22 and HI2 > 62.3 were associated with a significantly shorter OS. High lactate dehydrogenase (LDH) levels and HI2 > 87.9 were significantly associated with a reduced RFS. LDH, SUVmax^liver, and HI2 had a significant predictive value for relapse. SUVmax^liver and HI2 levels were also predictive of mortality; SUVmax^liver ≤ 22 and HI2 > 62.3 independently predicted mortality, while HI2 > 87.9 independently predicted relapse. MTV was not significantly associated with survival. Conclusions: Metabolic tumor burden and inflammation-based markers, particularly SUVmax^liver and HI2, are significant prognostic indicators of DLBCL and may enhance risk stratification and aid in identifying patients with an increased risk of relapse or mortality, potentially guiding personalized therapy. Full article

The gastrointestinal tract mediates the absorption of nutrients from the diet, which is increasingly contaminated with toxic metal(loid) species (TMs) and thus threatens food safety. Evidence in support of the influx of TMs into the bloodstream of the general and vulnerable populations (babies, children, pregnant women, and industrial workers) has been obtained by accurately quantifying their blood concentrations. The interpretation of these TM blood concentrations, however, is problematic, as we cannot distinguish between those that are tolerable from those that may cause the onset of environmental diseases. Since TMs that have invaded the bloodstream may perturb biochemical processes therein that will eventually cause organ damage it is crucial to better understand their bioinorganic chemistry as these processes collectively determine their organ availability. Thus, bioinorganic processes of TMs in the bloodstream represent selectivity filters which protect organs from their influx and ultimately determine the corresponding exposure-response relationships. The need to better understand selectivity filters prompted us to mechanistically disentangle them into the major bioinorganic chemistry processes. It is argued that the detoxification of TMs in the bloodstream and the biomolecular mechanisms, which mediate their uptake into target organs, represent critical knowledge gaps to revise regulatory frameworks to reduce the disease burden. Full article

Background/Objectives: The extensive use of computed tomography (CT) has led to a significant increase in the detection of small and non-palpable pulmonary nodules, necessitating the use of invasive methods for definitive diagnosis. Video-assisted thoracoscopic surgery (VATS) has become the preferred procedure for nodule resections; however, intraoperative localization remains challenging, especially for deep or subsolid lesions. This study explores whether SPECT/CT improves the technical and clinical outcomes of radio-guided occult lesion localization (ROLL) before uniportal video-assisted thoracoscopic surgery (u-VATS). Methods: This is a retrospective study involving consecutive patients referred for the resection of pulmonary nodules who underwent CT-guided ROLL followed by u-VATS between September 2017 and December 2024. From January 2023, SPECT/CT was systematically added after planar imaging. The cohort was divided into a planar group and a planar + SPECT/CT group. The inclusion criteria involved nodules sized ≤ 2 cm, with ground glass or solid characteristics, located at a depth of <6 cm from the pleural surface. ^99mTc-MAA injected activity, timing, the classification of planar and SPECT/CT image findings (focal uptake, multisite with focal uptake, multisite without focal uptake), spillage, and post-procedure complications were evaluated. Statistical analysis was performed, with continuous data expressed as the median and categorical data as the number. Comparisons were made using chi-square tests for categorical variables and the Mann–Whitney U test for procedural duration. Cohen’s kappa coefficient was calculated to assess agreement between imaging modalities. Results: In total, 125 patients were selected for CT-guided radiotracer injection followed by uniportal-VATS. The planar group and planar + SPECT/CT group comprised 60 and 65 patients, respectively. Focal uptake was detected in 68 (54%), multisite with focal uptake in 46 (36.8%), and multisite without focal uptake in 11 patients (8.8%). In comparative analyses between planar and SPECT/CT imaging in 65 patients, 91% exhibited focal uptake, revealing significant differences in classification for 40% of the patients. SPECT/CT corrected the classification of 23 patients initially categorized as multisite with focal uptake to focal uptake, improving localization accuracy. The mean procedure duration was 39 min with SPECT/CT. Pneumothorax was more frequently detected with SPECT/CT (43% vs. 1.6%). The intraoperative localization success rate was 96%. Conclusions: SPECT/CT imaging in the ROLL procedure for detecting pulmonary nodules before u-VATs demonstrates a significant advantage in reclassifying radiotracer positioning compared to planar imaging. Considering its limited impact on surgical success rates and additional procedural time, SPECT/CT should be reserved for technically challenging cases. Larger sample sizes, multicentric and prospective randomized studies, and formal cost–utility analyses are warranted. Full article

Covalent triazine frameworks (CTFs) have gained recognition as stable porous organic polymers, for example, for CO₂ separation. From the monomer 4,4′-(phenazine-5,10-diyl)dibenzonitrile (pBN), new pBN-CTFs were synthesized using the ionothermal method with a variation in temperature (400 and 550 °C) and the ZnCl₂-to-monomer ratio (10 and 20). N₂ adsorption yielded BET surface areas up to 1460 m²g ⁻¹. The pBN-CTFs are promising CO₂ adsorbents and are comparable to other benchmark CTFs such as CTF-1 with a CO₂ uptake of pBN-CTF-10-550 at 293 K of up to 54 cm³ g⁻¹ or 96 mg g⁻¹, with a CO₂/CH₄ IAST selectivity of 22 for a 50% mixture of CO₂/CH₄. pBN-CTF-10-400 has a very high heat of adsorption of 79 kJ mol⁻¹ for CO₂ near zero coverage in comparison to other CTFs, and it also stays well above the liquefaction heat of CO₂ due to its high microporosity of 50% of the total pore volume. Full article

Hepatocellular carcinoma (HCC) remains a therapeutic challenge due to metabolic plasticity and drug resistance. Oncolytic viruses (OVs), such as thymidine kinase-deleted vaccinia virus (oncoVV), selectively lyse tumors while stimulating antitumor immunity, however, their metabolic interplay with cancer cells is poorly understood. Here, we engineered an oncoVV-expressing Aphrocallistes vastus lectin (oncoVV-AVL) and uncovered its unique ability to exploit the ACSS2/TFEB axis, driving metabolic competition in HCC. In vitro, oncoVV-AVL triggered cell autophagy and lipid accumulation (3.4–5.7-fold upregulation of FASN and ACC1) while suppressing glucose uptake (41–63% higher extracellular glucose and 33–34% reduced lactate). Mechanistically, oncoVV-AVL upregulated acetyl-CoA synthetase 2 (ACSS2), promoting its nuclear translocation and interaction with transcription factor EB (TFEB) to concurrently activate lipogenesis and autophagic flux. The pharmacological inhibition of ACSS2 abolished these effects, confirming its central role. In vivo, oncoVV-AVL suppressed tumor growth while inducing lipid deposition (2-fold triglyceride increase), systemic hypoglycemia (42% glucose reduction), and autophagy activation (elevated LC3B-II/I ratios). This study establishes ACSS2 as a metabolic checkpoint in OV therapy, providing a rationale for combining oncolytic virotherapy with metabolic modulators in HCC. Full article

As climate change intensified water scarcity in Southern Europe, tourism-dependent regions such as Portugal’s Algarve faced growing pressure to adapt their water management systems. This study investigated how hotel groups in the Algarve have adopted and communicated water reuse technologies—specifically desalination and greywater recycling—under environmental, institutional, and reputational constraints. A comparative qualitative case study was conducted involving three hotel groups—Vila Vita Parc, Pestana Group, and Vila Galé—selected through purposive sampling based on organizational capacity and technology adoption stage. The analysis was supported by a supplementary mini-case from Mallorca, Spain. Publicly accessible documents, including sustainability reports, media coverage, and policy frameworks, were thematically coded using organizational environmental behavior theory and the OECD Principles on Water Governance. The results demonstrated that (1) higher organizational capacity was associated with greater maturity in water reuse implementation; (2) communication transparency increased alongside technological advancement; and (3) early-stage adopters encountered stronger financial, regulatory, and operational barriers. These findings culminated in the development of the Maturity–Communication–Governance (MCG) Framework, which elucidates how internal resources, stakeholder signaling, and institutional alignment influence sustainable infrastructure uptake. This research offered policy recommendations to scale water reuse in tourism through financial incentives, regulatory simplification, and public–private partnerships. The study contributed to the literature on sustainable tourism and decentralized climate adaptation, aligning with UN Sustainable Development Goals 6.4, 12.6, and 13. Full article