Search Results (592)

Plant flowers are recognized as a rich source of bioactive phenolic compounds. In this study, for the first time, the recovery of antioxidant phenolic compounds from Cytisus striatus flowers (CF) was optimized using microwave-assisted extraction (MAE). The variables (% of ethanol, temperature, and time) were studied using a response surface methodology (RSM). Extraction efficiency was assessed by total phenol content, total flavonoid content, and the antioxidant capacity through DPPH, ABTS, FRAP, and CUPRAC assays. Additionally, cytotoxicity and anti-inflammatory properties were evaluated in different cell lines. The optimal extraction conditions (87.6% ethanol, 160.8 °C and 8.76 min) yielded extracts rich in phenolics (85.9 mg GAE/g CF) and flavonoids (120.3 mg RE/g CF), with strong antioxidant capacity. LC-MS/MS analysis identified 27 phenolic compounds, including chrysin, apigenin, and quercetin derivatives. Cytotoxicity tests showed that CF extract maintained high viability (>80%) in human embryonic kidney (HEK293T) and human lung adenocarcinoma (A549) cells up to 2000 µg/mL, indicating low cytotoxicity. The anti-inflammatory potential was evidenced by a decrease in IL-1β levels and an increase in IL-10 cytokine production in LPS-stimulated macrophages. These results highlight the great potential of CF as a promising bioresource to obtain value-added compounds for the development of functional foods, nutraceuticals, and cosmetic products. Full article

Chagas disease, caused by Trypanosoma cruzi, poses a significant public health challenge due to its widespread prevalence, limited therapeutic options, and adverse effects associated with available medications. In this study, we developed 13 novel pyrazole-imidazoline derivatives, inspired by a previously identified cysteine protease inhibitor, and evaluated their antiparasitic activity. Our in silico analyses predicted favorable physicochemical profiles and promising oral bioavailability for these derivatives. Upon phenotypic screening, we observed that these new derivatives exhibited low cytotoxicity (CC₅₀ > 100 µM) and marked efficacy against intracellular amastigotes. Derivative 1k showed high activity (IC₅₀ = 3.3 ± 0.2 µM), selectivity (SI = 73.9), and potency (pIC₅₀ = 5.4). In a 3D cardiac microtissue model, 1k significantly reduced parasite load, matching the efficacy of benznidazole (Bz) even at lower concentrations. Both 1k and Bz effectively prevented parasite recrudescence; however, neither resulted in parasite sterility under the experimental conditions employed. The combination of 1k–Bz yielded an additive interaction, highlighting its potential for in vivo combination therapy. While structural changes abolished cysteine protease inhibition, incorporating a CF₃ substituent at the para position and excluding the amino group enhanced antiparasitic activity. These findings reinforce the promise of the pyrazole-imidazoline scaffold and support further structural optimizations to develop innovative candidates for treating Chagas disease. Full article

Background: People with cystic fibrosis (pwCF) frequently suffer from chronic lung infections, with Pseudomonas aeruginosa being the predominant pathogen contributing to disease progression and morbidity. The increasing prevalence of multi-drug-resistant (MDR) P. aeruginosa has diminished treatment options. Antimicrobial peptides (AMPs) have emerged as promising alternatives to conventional antibiotics due to their unique membrane-targeting mechanisms. OMN51, a novel bioengineered AMP derived from capitellacin, was evaluated for antimicrobial activity against P. aeruginosa in sputum samples from pwCF. This study aimed to compare the bactericidal effects of OMN51 with those of a range of conventional antibiotics known to have activity against P. aeruginosa clinical isolates derived from pwCF. Methods:P. aeruginosa clinical isolates were obtained from fifty-six unique sputum cultures of pwCF at a tertiary-university-affiliated hospital. Minimum inhibitory concentrations (MICs) of OMN51 and comparator antibiotics were determined using broth microdilution. Antimicrobial susceptibility was evaluated using the Kirby–Bauer disc diffusion method. Results: OMN51 demonstrated in vitro bactericidal activity across all P. aeruginosa isolates, including MDR strains. MIC values for OMN51 ranged from 4 to 16 µg/mL, with no observed resistance or cross-resistance. Comparative analysis revealed the superior efficacy of OMN51 compared with conventional antibiotics. Conclusions: OMN51 exhibits robust in vitro activity against MDR P. aeruginosa, supporting its candidacy as a therapeutic agent for MDR P. aeruginosa- associated infections. Further studies are warranted to assess pharmacokinetics and in vivo safety and efficacy. OMN51 represents a first-in-class, membrane-targeting therapeutic showing promise against MDR P. aeruginosa. Full article

Sporadic colorectal cancer (CRC), the third leading cause of cancer-related death globally, arises through a continuum from normal tissue to adenomas, progressing from low-grade (LGD) to high-grade dysplasia (HGD); yet, the early epigenetic drivers of this transition remain unclear. To investigate these events, we profiled LGD and HGD adenomas using EM-seq, and identified a consensus differential methylation signature (DMS) of 626 regions through two independent bioinformatics pipelines. This signature effectively distinguished LGD from HGD in both tissue and plasma-derived cell-free DNA (cfDNA), highlighting specific methylation patterns. Functional annotation indicated enrichment for regulatory elements associated with transcription factor activity and cell signaling. Applying the DMS to the TCGA CRC dataset revealed three tumor subtypes with increasing hypermethylation and one normal cluster. The most hypermethylated subtype exhibited poor survival, high mutation burden, and disrupted transcriptional networks. While overlapping with classical CpG Island Methylator Phenotype (CIMP) categories, the DMS captured a broader spectrum of methylation alterations. These findings suggest that the DMS captures functionally relevant, antecedent epigenetic alterations in CRC progression, enabling the robust stratification of dysplasia severity and tumor subtypes. This signature holds promise for enhancing preclinical detection and molecular classification, and warrants further evaluation in larger prospective cohorts. Full article

The challenge of achieving high-precision direction-of-arrival (DOA) estimation with enhanced degrees of freedom (DOFs) under a limited number of physical array elements remains a critical issue in array signal processing. To address this limitation, this paper makes the following three key contributions: (1) a novel moving sparse array synthesis model incorporating time-frequency-spatial joint processing for coprime frequencies signal sources; (2) an optimized coprime frequencies-based unmanned aerial vehicle array (CF-UAVA) configuration with derived closed-form expressions for the distribution of synthesized array; and (3) two DOA estimation methods: a group sparsity-based approach universally applicable to the proposed aperture synthesis model and a joint group sparsity and virtual array interpolation tailored for the proposed CF-UAVA configuration. Comprehensive simulation results demonstrate the superior DOA estimation accuracy and increased DOFs achieved by our proposed aperture synthesis model and DOA estimation algorithms compared to conventional approaches. Full article

Objectives: Shoulder injury prevalence appears to be the highest among all injuries in CrossFit (CF) athletes. Nevertheless, there is no evidence deriving from prospective studies to explain this phenomenon. The purpose of this study was to document shoulder injury incidence in CF participants over a 12-month period and prospectively investigate the risk factors associated with their demographic, epidemiological, and functional characteristics. Methods: The sample comprised 109 CF athletes in various levels. Participants’ data were collected during the baseline assessment, using a specially designed questionnaire, as well as active range of motion, muscle strength, muscle endurance, and sport-specific tests. Non-parametric statistical tests and inferential statistics were employed, and in addition, linear and regression models were created. Logistic regression models incorporating the study’s continuous predictors to classify injury occurrence in CF athletes were developed and evaluated using the Area Under the ROC Curve (AUC) as the performance metric. Results: A shoulder injury incidence rate of 0.79 per 1000 training hours was recorded. Olympic weightlifting (45%) and gymnastics (35%) exercises were associated with shoulder injury occurrence. The most frequent injury concerned rotator cuff tendons (45%), including lesions and tendinopathies, exhibiting various severity levels. None of the examined variables individually showed a statistically significant correlation with shoulder injuries. Conclusions: This is the first study that has investigated prospectively shoulder injuries in CrossFit, creating a realistic profile of these athletes. Despite the broad spectrum of collected data, the traditional statistical approach failed to identify shoulder injury predictors. This indicates the necessity to explore this topic using more sophisticated techniques, such as advanced machine learning approaches. Full article

p-Cresyl sulfate (PCS), a gut-derived uremic toxin with proinflammatory and cytotoxic effects, has been implicated in cardiovascular injuries among patients with chronic kidney disease (CKD). Aortic stiffness (AS), assessed by carotid–femoral pulse wave velocity (cfPWV), is a recognized predictor of cardiovascular risk. This study investigated the association between serum PCS levels and AS in patients with nondialysis-dependent CKD. In total, 165 patients with nondialysis-dependent CKD were enrolled. Clinical data and fasting blood samples were collected. Arterial stiffness (AS) was assessed bilaterally by measuring carotid–femoral pulse wave velocity (cfPWV) on both the left and right sides. A value above 10 m/s was considered indicative of increased stiffness. Serum PCS levels were quantified using high-performance liquid chromatography–mass spectrometry. Fifty patients (30.3%) had AS. The AS group was significantly older and had higher diabetes prevalence, systolic blood pressure, fasting glucose, urinary protein-creatinine ratio, and PCS levels than the control group. In the multivariate analysis, both PCS (odds ratio [OR]: 1.097; 95% confidence interval [CI]: 1.024–1.175; p = 0.008) and age (OR: 1.057; 95% CI: 1.025–1.090; p < 0.001) were independently associated with AS. In conclusion, elevated serum PCS and older age were independently associated with AS. Thus, PCS is a potential early marker of vascular damage in CKD. Full article

To assess the association between known (PlGF, sFlt-1, betaHCG, PAPPA) and novel (cell-free DNA, cfDNA, and total endothelial and platelet microvesicles, MVs) maternal blood biomarkers measured at the first trimester with the later development of preeclampsia (PE) and PE-related severe adverse events (SAE), we conducted a retrospective case–control study including women with an established diagnosis of preeclampsia (cases) and healthy pregnant women (controls). Biomarkers were measured from first-trimester blood samples stored in a hospital biobank. A total of 89 women, 54 women with PE and 35 controls were included. PlGF showed good performance for diagnosing overall preeclampsia (AUC: 0.71; 95% CI 0.59–0.82), early-onset preeclampsia (AUC 0.80; 95% CI 0.68–0.9) and fetal-neonatal SAEs (AUC: 0.73; 95% CI 0.63–0.84). Multivariate models including clinical variables, PlGF and other biomarkers showed good to very good discrimination for the development of PE, early-onset PE and fetal-neonatal SAEs (AUCs of 0.87, 0.89 and 0.79, respectively). Platelet-derived MVs were the best isolated biomarker for late-onset PE and, combined with systolic blood pressure, showed good discrimination (AUC: 0.81; 95% CI 0.71–0.92). For maternal SAEs, a model incorporating cfDNA and sFlt-1 provided excellent discrimination (AUC 0.92; 95% CI 0.82–1.00). Our findings suggest that multivariate models incorporating both clinical variables and first-trimester biomarkers may improve risk stratification for PE, especially for late-onset PE and for identifying women at risk of severe maternal or fetal complications. Notably, the inclusion of novel biomarkers such as cfDNA and MVs added value in clinical scenarios where the predictive performance of existing tools remains suboptimal. Full article

Cystic Fibrosis Screen Positive Inconclusive Diagnosis/CFTR-related Metabolic Syndrome (CFSPID/CRMS) presents a significant clinical challenge due to its variable diagnostic outcomes and uncertain disease progression. Current diagnostic strategies, including sweat chloride testing and genetic analysis fall short in delivering clear guidance for clinical decision-making and risk assessment. Here, we comment on the potential of CFTR functional tests in patient-derived intestinal organoids (PDIOs) to enhance early risk stratification in CFSPID/CRMS cases. Using four hypothetical cases based on real-world data, we illustrate diverse clinical trajectories: diagnosis of cystic fibrosis (CF), reclassification as a CFTR-related disorder (CFTR-RD), non-CF designation, and persistent diagnostic uncertainty. Organoid-based assays—such as forskolin-induced swelling (FIS), steady-state lumen area (SLA) analysis, and rectal organoid morphology analysis (ROMA)—offer functional insights into CFTR activity and drug responsiveness. Compared to existing CFTR functional tests, such as Intestinal Current Measurement (ICM) and Nasal Potential Difference (NPD), these assays are more accessible, highly reproducible, and when needed support personalized medicine approaches. PDIO-based assays could help identify infants at high risk of disease progression, facilitating earlier interventions while minimizing unnecessary follow-ups for those unlikely to develop CF-related symptoms. Although not yet widely implemented, these assays hold promise for refining CFSPID diagnostics and management. Future research should focus on establishing standardized protocols allowing validation of clinical utility. Full article

Background: The gut microbiome is a key modulator of the gut–brain axis and may contribute to the pathophysiology of both gastrointestinal and systemic disorders. This study aimed to evaluate gut microbiota composition and tryptophan/phenylalanine metabolism in women with unclassified irritable bowel syndrome (IBS-U), with or without coexisting chronic fatigue syndrome (CFS). Methods: Eighty women were enrolled and divided into two groups: IBS-U without CFS (Group I, n = 40) and IBS-U with coexisting CFS (Group II, n = 40). Microbial composition and diversity were assessed using the GA-map™ Dysbiosis Test, including the dysbiosis index (DI) and Shannon Diversity Index (SDI). Hydrogen and methane levels were measured in breath samples. Urinary concentrations of selected microbial and neuroactive metabolites—homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA), xanthurenic acid (XA), quinolinic acid (QA), hydroxyphenylacetic acid (HPA), and 3-indoxyl sulfate (3-IS)—were quantified using LC-MS/MS. Fatigue severity was assessed using the Chalder Fatigue Questionnaire (CFQ-11) and the fatigue severity scale (FSS). Results: Compared to Group I, patients with IBS-CFS showed significantly greater microbial diversity, higher breath methane levels, and elevated urinary concentrations of QA, XA, 3-IS, and HVA, alongside lower concentrations of 5-HIAA and KYN. Fatigue severity was positively correlated with urinary XA and QA levels. Conclusions: Women with IBS and coexisting CFS exhibit distinct gut microbiota and tryptophan metabolite profiles compared to those without fatigue. The observed metabolite–symptom associations, particularly involving neuroactive kynurenine derivatives, warrant further investigation. These preliminary findings should be interpreted as hypothesis-generating and require validation through high-resolution microbiome analyses, functional pathway profiling, and longitudinal or interventional studies to clarify causality and clinical significance. Full article

The time-dependent dielectric breakdown (TDDB) degradation mechanism, governed by the synergistic interaction of multiphysics fields, plays a pivotal role in the performance degradation and eventual failure of semiconductor devices and advanced packaging back-end-of-line (BEOL) structures. This work specifically focuses on the dielectric breakdown mechanism driven by metal ion migration within inter-metal dielectric layers, a primary contributor to TDDB degradation. A SPICE-compatible modeling approach is developed to accurately capture the dynamics of this ion migration-induced degradation. The proposed model is rooted in the fundamental physics of metal ion migration and the evolution of conductive filaments (CFs) within the dielectric layer under operational stress conditions. By precisely characterizing the degradation behavior induced by TDDB, a SPICE-compatible degradation model is developed. This model facilitates accurate predictions of resistance changes across a range of operational conditions and lifetime, encompassing variations in stress voltages, temperatures, and structural parameters. The predictive capability and accuracy of the model are validated by comparing its calculated results with numerical ones, thereby confirming its applicability. Furthermore, building upon the established degradation model, the impact of line-edge roughness (LER) is incorporated through a process variation model based on the power spectral density (PSD) function. This PSD-derived model provides a quantitative characterization of LER-induced fluctuations in critical device dimensions, enabling a more realistic representation of process-related variability. By integrating this stochastic variability model into the degradation framework, the resulting lifetime prediction model effectively captures reliability variations arising from real-world fabrication non-uniformities. Validation against simulation data demonstrates that the inclusion of LER effects significantly improves the accuracy of predicted lifetime curves, yielding closer alignment with observed device behavior under accelerated stress conditions. Full article

Honeydew honey represents a bee-derived product with different organoleptic characteristics and distinct properties with respect to floral honey. The market interest in honeydew honey has been growing in recent years due to its higher bioactive characteristics with respect to floral honey. The need for a deeper chemical characterization aimed to evaluate a possible botanical differentiation attracted the use of different analytical approaches. The present work aims to distinguish the botanical honeydew origin by using Nuclear Magnetic Resonance (NMR) spectroscopy and a multivariate approach. Two different data pretreatments have been considered to obtain the best sample discrimination. The saccharide content significantly affects the differentiation of the botanical variety consisting of fir, oak, citrus fruits, eucalyptus, and forest mainly by using a classification approach taking advantage of the Orthogonal Signal Correction filters. Notwithstanding the botanical diversity of the honeydew honey (HDH) samples, fir honeydew (F-HDH), oak honeydew (O-HDH), and eucalyptus honeydew (E-HDH) resulted always well discriminated among all the botanical varieties investigated, while citrus fruits honeydew (CF-HD) and forest honeydew (FO-HDH) did not. In particular, F-HDH resulted characterized by sucrose, erlose, maltose, maltotriose, maltotetraose, and melezitose, E-HDH resulted enriched in α, β-glucose and β-fructose in furanosidic form, and O-HDH enriched in β-fructose in furanosidic form, isomaltose. Full article

Intergovernmental Panel on Climate Change (IPCC) guidelines have been standardized and widely used to calculate methane (CH₄) emissions from paddy fields. The emission factor (EF) is a key parameter in these guidelines, and it is different for each location globally and regionally. However, limited studies have been conducted to measure locally specific EFs (EFlocal) through on-site assessments and modeling their spatial distribution effectively. This study aims to investigate the potential of multisensor satellite data to develop a spatial model of CH₄ emission estimation on rice paddy fields under different water management practices, i.e., continuous flooding (CF) and alternate wetting and drying (AWD) in Subang, West Java, Indonesia. The model employed the national EF (EFnational) and EFlocal using the IPCC guidelines. In this study, we employed the multisensor satellite data to derive the key parameters for estimating CH₄ emission, i.e., rice cultivation area, rice age, and EF. Optical high-resolution images were used to delineate the rice cultivation area, Sentinel-1 SAR imagery was used for identifying transplanting and harvesting dates for rice age estimation, and ALOS-2/PALSAR-2 was used to map the water regime for determining the scaling factor of the EF. The closed-chamber method has been used to measure the daily CH₄ flux rate on the local sites. The results revealed spatial variability in CH₄ emissions, ranging from 1–5 kg/crop/season to 20–30 kg/crop/season, depending on the water regime. Fields under CF exhibited higher CH₄ emissions than those under AWD, underscoring the critical role of water management in mitigating CH₄ emissions. This study demonstrates the feasibility of combining remote sensing data with the IPCC model to spatially estimate CH₄ emissions, providing a robust framework for sustainable rice cultivation and greenhouse gas (GHG) mitigation strategies. Full article

This study focuses on investigating the manufacturing, characterization, and assessment of palm kernel nut oil as a cutting fluid (CF) in the machining of aluminium 6061 alloy. Cutting fluids are vital in machining operations as they reduce friction, dissipate heat, and prolong the lifespan of tools. Palm kernel nut oil, derived from the fruit of a palm kernel, has attracted attention due to its environmentally friendly and readily biodegradable characteristics. This study involved the extraction, refinement, and characterization of palm kernel nut oil for its potential application as a cutting fluid. An experimental investigation was conducted to evaluate the performance of palm kernel nut oil (PKNO) as a CF through turning operations on aluminium 6061 alloy. The experimental parameters included the cutting speed, feed rate, and depth of cut, while the effectiveness of the CF was assessed based on key performance indicators such as surface roughness and cutting temperature. The findings demonstrated that the PKNO-CF exhibited favourable physical properties, including optimal viscosity, density, and pH levels. Furthermore, a detailed chemical analysis confirmed the absence of hazardous components, establishing palm kernel nut oil as a safer and more environmentally friendly alternative to conventional cutting fluids. This study aligns with United Nations Sustainable Development Goal (SDG) 12: Responsible Consumption and Production as it promotes the use of an environmentally friendly and biodegradable cutting fluid, reducing reliance on conventional, potentially hazardous cutting fluids and reducing environmental pollution. By utilizing palm kernel nut oil as a sustainable alternative, this research supports eco-friendly manufacturing practices and minimizes environmental impact in machining operations Full article

Background: Donor-derived cell-free DNA (dd-cfDNA) testing offers a non-invasive approach for monitoring allograft health in transplant recipients. However, its diagnostic performance and clinical utility remain insufficiently characterized across diverse populations. Objectives: This study assesses concordance between dd-cfDNA, donor-specific antibody (DSA) testing, and biopsy, while also comparing two commercial assays (AlloSure and Prospera) in kidney and pancreas transplant recipients. Methods: We retrospectively analyzed 271 transplant patient records from 2019 to 2024 at our institution, focusing on dd-cfDNA testing. Statistical analyses evaluated assay performance in relation to DSA and biopsy results. The impact of multi-organ transplantation (MOT) on dd-cfDNA levels was also assessed. Results: In our predominantly Caucasian cohort (61.5%) with a mean age of 53 years, increased levels of dd-cfDNA were significantly associated with DSA positivity, particularly within the Prospera group (p = 0.002), and were particularly higher in patients with HLA class II DSA. Both assays showed a limited correlation with biopsy-confirmed rejection. AlloSure had high specificity (80%) but low sensitivity (19%), whereas Prospera showed higher sensitivity (75%) with moderate specificity (60%). Dd-cfDNA levels were elevated in MOT recipients in a vendor-dependent manner. Conclusions: Our findings highlight the differing clinical strengths of dd-cfDNA assays: AlloSure demonstrates greater preference for ruling out rejection, whereas Prospera appears better suited for early detection. Dd-cfDNA interpretation in MOT recipients warrants cautious consideration. Overall, tailoring assay selection and optimizing diagnostic thresholds to clinical context may enhance transplant surveillance and patient management strategies. Full article