Search Results (553)

Five Salsola species have been studied as sources of bioactive compounds using a comprehensive, untargeted metabolomic and bioactivity assessment. Plant material was extracted using ethyl acetate (EA), water, and methanol (MeOH). S. ruthenica exhibited the highest total phenolic content (46.04 mg GAE/g, MeOH extract) and antioxidant capacity (DPPH: 47.21 mg TE/g; ABTS: 97.40 mg TE/g; CUPRAC: 141.38 mg TE/g; FRAP: 80.30 mg TE/g). Extracts of S. stenoptera and S. ruthenica showed potent cholinesterase inhibition, while S. crassa was notably active against tyrosinase. A total of 265 metabolites were annotated, revealing strong solvent- and species-specific differences in phenolic composition, as confirmed by AMOPLS analysis. Flavanols, anthocyanins, and lignans emerged as the major chemotaxonomic markers, based on PCA, contributing the most to the total variance. Strong correlations were observed between TPC and CUPRAC (r = 0.93) and between flavanols and DPPH (r = 0.70), suggesting functional relevance of these compounds in redox activity, confirming the importance of different classes of phenolic constituents. VIP markers also revealed species- and solvent-specific enrichments of metabolites. Regularized canonical correlation analysis (rCCA) further linked specific metabolites, namely Quercetin 3-O-glucosyl-xyloside and 6″-O-Acetylgenistin, the flavanone sakuranetin, the lignans Secoisolariciresinol, Anhydro-secoisolariciresinol, and Medioresinol, and p-Coumaric acid ethyl ester, with antioxidant functions. These findings underscore the pharmacological potential of Salsola species and highlight the importance of valorizing metabolic diversity in the search for new sources of health-promoting natural compounds. Furthermore, the work shows the need for a tailored solvent selection in bioactivity-guided phytochemical research. Full article

Cholangiocarcinoma (CCA) is a highly aggressive cancer of the biliary tract, distinguished by significant intratumoral heterogeneity (ITH), which contributes to therapy resistance and unfavorable clinical outcomes. Traditional genome profiling has revealed recurring driver changes in CCA; yet, genomic data alone fails to elucidate functional pathway activation, adaptive signaling, and the diverse treatment responses reported among tumor locations and disease subtypes. This review analyses the use of integrated sequencing technologies, proteogenomics, and phosphoproteomics to systematically characterize intratumoral heterogeneity in cholangiocarcinoma and convert molecular diversity into therapeutically applicable discoveries. We present evidence that the combination of genomic sequencing and mass spectrometry–based proteomics facilitates the direct correlation of genetic mutations with protein expression, post-translational modifications, and signaling system activity. Phosphoproteomic profiling specifically offers functional insights into kinase-driven networks that dictate tumor aggressiveness, therapeutic susceptibility, and adaptive resistance mechanisms, which cannot be anticipated only from DNA-level analysis. We propose that integrating proteogenomic and phosphoproteomic analyses into diagnostic and therapeutic assessments can enhance molecular classification, reveal subtype- and region-specific therapeutic dependencies, and guide rational combination treatment strategies, based on recent extensive proteogenomic studies and functional proteomic investigations in CCA. Pathway-level analysis of intratumoral heterogeneity provides a framework for selecting targeted medicines, predicting resistance, and informing personalized treatment strategies in CCA. The combination of sequencing, proteogenomics, and phosphoproteomics is essential for advancing precision oncology in cholangiocarcinoma. The implementation of this multi-layered analytical approach may better patient classification, refine therapy choices, and eventually improve clinical outcomes for individuals with this particular heterogeneous cancer. Full article

Objectives: The repurposing of existing drugs as anticancer agents has attracted attention in cancer drug discovery. This study aimed to examine the anticancer efficacy of rosiglitazone (RSG) against cholangiocarcinoma (CCA) and its underlying mechanisms. Methods: The effect of RSG on the viability of KKU-100 CCA cells was examined. The possible molecular targets were identified using proteomic analysis and verified by a series of cell-based assays. Furthermore, the expression of PPARγ protein in CCA tissues was also assessed. Results: RSG exhibited a cytotoxic effect against KKU-100 cells. Proteomic analysis demonstrated a significant different expression protein pattern of the 100 μM RSG-treated group compared to the control group. Significant alteration of several proteins was found, including the up-regulation of calcium-binding, cytoskeletal, and metabolic proteins, concomitant with the down-regulation of antioxidant enzymes. Detailed analyses revealed that RSG induced apoptosis in CCA cells, accompanied by increased caspase 3/7 activities, reactive oxygen species (ROS) generation, and disruption of mitochondrial function. RSG altered the expressions of annexin A1 and antioxidant enzymes, according to Western blot analysis. GW9662, a PPARγ antagonist, did not affect the viability and apoptosis of KKU-100 cells caused by RSG. Immunohistochemistry analysis revealed that PPARγ expression in CCA patients was associated with sex, but not with other common clinicopathological parameters. Its expression did not correlate with patients’ overall survival time. Conclusions: RSG induced apoptotic cell death in CCA cells, which was accompanied by increased ROS levels and impaired antioxidant defense. Its apoptosis-inducing effect is independent of PPARγ activation. These findings underscore the therapeutic potential of RSG for CCA treatment. Full article

Palladium, a non-toxic platinum-group metal, is widely used in catalysis, electronics, hydrogen storage, and chemical industries because of its excellent physical and chemical properties. However, given that the number of palladium-producing countries is limited, recycling is considered essential for ensuring a stable and sustainable global supply. Here, I describe a simple and efficient method for palladium recovery from electronic waste (e-waste) using Enterobacter oligotrophicus CCA6^T. To clarify biomineralization capacity, the role of electron donors in modulating biomineralization capacity was examined. Findings showed that formic acid was the most effective donor, enhancing the relative recovery rate to 44% compared to 23% without electron donors. Transmission electron microscopy analysis revealed palladium particles (1–10 nm) distributed across the cell wall, periplasmic space and cytoplasm, confirming active biomineralization rather than passive biosorption. Moreover, based on a comparison with the biomineralization mechanism of Escherichia coli, the biomineralization mechanism of E. oligotrophicus CCA6^T was estimated . Reaction parameters were then optimized by testing the effects of formic acid concentration, reaction temperature, and reaction pH. Under optimized conditions, the relative recovery rate exceeded 99% within 6 h using 40 mg/L palladium. When this method was applied to a metal dissolution solution prepared from e-waste , a recovery rate of 94% was achieved from trace concentrations (36 µg/L), and palladium loss from bacteria after the palladium recovery test was negligible (<0.01%). Taken together, these results demonstrate that biomineralization using E. oligotrophicus CCA6^T could potentially be applied to the recovery of palladium from e-waste, particularly for trace-level concentrations where conventional methods are ineffective. Full article

Mild traumatic brain injury (mTBI) frequently causes subtle brain changes that are difficult to detect with conventional diagnostic approaches. In this exploratory pilot study, we combined tri-exponential intravoxel incoherent motion (IVIM) and pseudocontinuous arterial spin labeling (pCASL) MRI with Multimodal Canonical Correlation Analysis and joint independent component analysis (mCCA+jICA) to identify imaging signatures distinguishing mTBI patients from healthy controls (HCs) and their associations with clinical function. Cerebral blood flow (CBF) and IVIM-derived metrics were extracted from 90 brain regions in 19 mTBI patients and 24 HCs, and multivariate components were identified using mCCA+jICA. Two independent components (IC2, IC15) showed group differences at the uncorrected level (p < 0.05) but did not survive false discovery rate (FDR) correction. IC2 correlated positively with CBF and perfusion fraction (F_p) and negatively with tissue diffusion fraction (F_s), consistent with reduced vascular integrity in mTBI, while IC15 showed similar trends. One component correlated with Glasgow Outcome Scale–Extended (GOS-E) scores (uncorrected p = 0.046). Although this study is preliminary and limited by a small sample size, our findings suggest that mTBI is associated with perfusion and microstructural alterations, particularly in subcortical regions, and demonstrate the potential value of combining IVIM and ASL within multivariate fusion frameworks to reveal patterns not captured by single-modality approaches. Full article

Background: Cholangiocarcinoma (CCA) has the highest incidence in Northeastern Thailand, where patients generally present with late diagnosis and poor prognosis. Opisthorchis viverrini (OV) infection is the major cause of CCA, with oxidative stress driving DNA mutations and genetic instability. Microsatellite instability (MSI) is a predictive biomarker in several cancers. This study aimed to investigate MSI status and its association with clinicopathological features and survival of CCA patients. Methods: Tissue and serum samples were collected from 25 surgical CCA patients. MSI status and mismatch repair (MMR) proteins were evaluated using an MSI scanner and immunohistochemistry (IHC). Serum OV IgG was assessed by ELISA, while tumor-infiltrating lymphocytes (TILs) were evaluated by two pathologists. Associations of MSI with clinicopathological features, OV status, MMR, and survival were analyzed. Results: Among CCA patients, 66.7% were MSI-high and 33.3% were MSI-low. MSI-high significantly correlated with age < 57 years, intraductal growth pattern, OV positivity, and early-stage disease. Patients with MSI-high and high TILs showed markedly improved median survival compared to MSI-low with low TILs (94.0 vs. 16.8 and 3.0 months; HR = 6.82 and 14.10; p = 0.004 and 0.001). Incorporation of MSI and TILs remained an independent prognostic factor in multivariate analysis (p < 0.05). Conclusions: MSI-high is highly prevalent in OV-associated CCA and is associated with intraductal growth, OV infection, and early-stage disease. Combined MSI and TIL status may serve as an independent prognostic factor, warranting validation in larger cohorts. Full article

Systemic therapy is the mainstay of treatment in inoperable cholangiocarcinoma (CCA). The aim of this study was to evaluate the overall survival (OS), progression-free survival (PFS), recurrence patterns, and the association between biliary complications and OS in patients with inoperable, localized cholangiocarcinoma treated with radiotherapy (RT) alone. Records of patients treated between 2004 and 2022 who received a minimum of 32.5 Gy BED10 were retrospectively reviewed. Survival was estimated using the Kaplan–Meier method, and prognostic factors were assessed using univariate and multivariable analyses. A total of 56 patients (median age 67.5) were included, most of whom had intrahepatic (78.6%) CCA, and most of whom received SBRT (76.8%). The median dose was 36 Gy (BED 55 Gy), and the median OS and PFS were 20 months and 10 months, respectively. One-year local control was 92.1% and the primary site of progression was intrahepatic (64.9%). On univariate analyses, pre-radiation biliary obstruction, elevated baseline CA 19-9, larger tumor size, and age were associated with worse outcomes; on multivariable analysis, only lesion size was prognostic. Biliary complications were associated with inferior OS. These findings highlight the high intrahepatic out-of-field failure rates and suggest the incorporation of biliary-event-free survival as a clinically relevant endpoint. Full article

This paper presents a brain–computer interface (BCI) system based on steady-state visual evoked potential (SSVEP) for controlling an electric wheelchair integrated with a speech aid module. The system targets individuals with severe motor disabilities, such as amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS), who may experience limited mobility and speech impairments. EEG signals from the occipital lobe are recorded using wet electrodes and classified using deep learning models, including ResNet50, InceptionV4, and VGG16, as well as Canonical Correlation Analysis (CCA). The ResNet50 model demonstrated the best performance for nine-class SSVEP signal classification, achieving an offline accuracy of 81.25% and a real-time performance of 72.44%, thereby clarifying that these results correspond to SSVEP-based analysis rather than motor imagery. The classified outputs are used to trigger predefined wheelchair movements and vocal commands using an Arduino-controlled system. The prototype was successfully implemented and verified through experimental evaluation, demonstrating promising results for mobility and communication assistance. Full article

Alzheimer’s disease (AD) involves oxidative stress in brain tissue, creating a need for stable neuroprotective agents. Anthocyanins are potent antioxidants, but they are highly susceptible to degradation. This study evaluated anthocyanins from purple corn (PCA) and camu-camu (CCA) and the copigmentation effects of the phenolic acids cinnamic (C), ferulic acid (F), resveratrol (R) and polyaspartic acid (P) on the stability and neuroprotective capacity of these anthocyanins. HPLC-MS analysis identified twelve anthocyanins in PCA, including a new one (petunidin sophoroside). Copigmentation was assessed via UV-Vis spectroscopy, FTIR, TG, and stability tests at pH 7.4. The TBARS assay evaluated protection against oxidative stress in brain tissue. Copigment R provided the strongest hyperchromic effect for PCA, while P was most effective for CCA. TG analysis showed that copigmentation with R significantly improved the thermal and pH stability of both anthocyanin sources. All single copigmented samples showed improved stability of anthocyanins in physiological conditions. Furthermore, R-copigmented anthocyanins exhibited the most potent neuroprotective effects, significantly inhibiting lipid peroxidation. Thus, copigmentation, particularly with R, is a highly effective strategy for stabilizing anthocyanins and enhancing their potential as neuroprotective agents against oxidative stress. Full article

The formation of rivet holes is a critical step in aeronautical assembly, as hole quality directly influences the fatigue resistance and structural reliability of riveted joints. Nickel-based alloys, such as Inconel 625, present additional challenges due to their poor machinability and the stringent surface integrity requirements imposed by the aerospace sector. This study investigates innovative and sustainable drilling strategies for rivet hole preparation, focusing on the comparative performance of two environmentally friendly cooling and lubrication methods: minimum quantity lubrication with an eco-friendly fluid (MQL-Eco) and cold compressed air (CCA). A comprehensive experimental campaign was carried out to analyze the combined effects of spindle speed, S, feed rate, f, and cooling method, R, on hole surface roughness parameters (Ra and Rz). These values are measured inside the drilled hole using optical scanner 3D equipment. Statistical tools, including analysis of variance (ANOVA) and response surface methodology (RSM), were employed to identify the most significant factors and optimize cutting conditions. The results reveal that the interaction between spindle speed and coolant type is the dominant contributor to surface roughness variability, with MQL-Eco consistently achieving values within the aeronautical standard range (Ra = 0.8–1.6 µm), and the coolant factor is the second cause of variability in both roughness Ra and Rz. Moreover, correlations between roughness parameters and tool wear confirm the relevance of sustainable cooling methods in extending tool life while maintaining compliance with aerospace quality requirements. The findings demonstrate that innovative eco-friendly drilling approaches can effectively replace conventional lubrication, offering a viable pathway towards greener manufacturing practices in metal forming and joining technologies. Full article

Background: Theta-band cordance is a quantitative EEG (qEEG) metric that integrates absolute and relative spectral power and correlates with regional cerebral perfusion. Although widely applied in psychiatric and neurophysiological research, its longitudinal trajectory in healthy adults remains largely unknown. This study aimed to characterize multi-year changes in theta cordance across cortical regions, determine which areas show stability versus decline, and evaluate whether individuals maintain a trait-like cordance profile over time. Methods: Nineteen cognitively healthy, medication-free adults underwent resting-state EEG recordings at two time points, separated by an average of 6.4 years (range: 1.9–14.8). Theta cordance (4–8 Hz) was computed at 19 scalp electrodes using the Leuchter algorithm and aggregated into eight lobar regions (left/right frontal, temporal, parietal, occipital). Paired-samples t-tests assessed longitudinal changes. Inter-regional Pearson correlations examined evolving connectivity patterns. Canonical correlation analysis (CCA), validated via LOOCV and bootstrap confidence intervals, evaluated multivariate stability between baseline and follow-up cordance profiles. Results: Theta cordance remained normally distributed at both time points. Significant longitudinal decreases emerged in the right temporal (t(18) = 5.34, p < 0.001, d = 1.23) and right frontal (t(18) = 2.65, p = 0.016, d = 0.61) regions, while other lobes showed no significant change. Midline Cz demonstrated a robust increase over time (p < 0.001). CCA revealed a strong cross-time association (Rc = 0.999, p = 0.029), indicating preservation of a stable, frontally anchored cordance profile despite regional right-hemisphere decline. Inter-regional correlation matrices showed both preserved posterior synchrony and emerging inverse anterior–posterior and cross-hemispheric relationships, suggesting age-related reorganization of cortical connectivity. Conclusions: Theta cordance exhibits a mixed pattern of trait-like stability and region-specific aging effects. A dominant, stable fronto-central profile persists across years, yet the right frontal and right temporal cortices show significant decline, consistent with lateralized vulnerability in normative aging. Evolving inter-regional correlation patterns further indicate network-level reorganization. Longitudinal cordance assessment may provide a noninvasive marker of functional brain aging and help differentiate normal aging trajectories from early pathological change. This longitudinal quantitative EEG (qEEG) study examined theta-band cordance dynamics across cortical regions in healthy adults over an average follow-up of 6.4 years (range: 1.9–14.8). Resting-state EEGs were recorded at two time points from 19 participants and analyzed using Leuchter’s cordance algorithm across 19 scalp electrodes. Regional cordance values were computed for frontal, temporal, parietal, and occipital lobes. Paired-samples t-tests revealed significant longitudinal decreases in theta cordance in the right frontal (p = 0.016, d = 0.61) and right temporal lobes (p < 0.001, d = 1.23), while other regions remained stable. Inter-regional Pearson correlations showed strong bilateral synchrony in posterior regions and emergent inverse anterior–posterior relationships over time. Canonical correlation analysis revealed a robust multivariate association (Rc = 0.999, p = 0.029) between baseline and follow-up patterns. Partial correlations (controlling for follow-up interval) identified region-specific trait stability, highest in left occipital and right frontal cortices. These findings suggest that theta cordance reflects both longitudinally stable neural traits and regionally specific aging effects in cortical physiology. Full article

Accurately characterizing historical drought events is critical for understanding their spatial and temporal variability and for improving future drought projections. This study investigates extreme drought years across Europe using three complementary drought indicators: the Palmer drought severity index (PDSI, based on tree-ring width), the standardized precipitation evapotranspiration index (SPEI, based on stable oxygen isotopes in tree rings), and the soil moisture index (SMI, based on high-resolution climate modeling). We analyze the common period 1766–2018 simultaneously across all three reconstructions to enable direct cross-indicator comparisons, a scope not typical of prior single-indicator studies. When analyzing year-to-year variability, the driest European years differ by indicator (PDSI—1874, SPEI—2003, and SMI—1868). Quantitatively, the values exhibited are as follows: PDSI 1874 (M = −1.97; A = 64.4%), SPEI 2003 (M = −1.16; A = 90.1%), and SMI 1868 (M = 0.21; A = 83.4%). Multi-year extremes also diverge: while PDSI identifies 1941–1950 as the driest years (M = −0.82; A = 42.1%), SPEI highlights 2011–2018 (M = −0.36; A = 46.6%), and SMI points to 1781–1790 as the driest years, followed by 2011–2018. Trends in drought-covered areas show a significant European-scale increase for SMI (+0.52%/decade, p < 0.05) and regional increases for MED in SMI (~+1.1%/decade, p < 0.001) and for CEU in SPEI (+0.42%/decade, p < 0.05) and SMI (+0.6%/decade, p < 0.001). At the regional scale (Mediterranean—MED, central Europe—CEU, and northern Europe—NEU), the driest years/decades and spatial footprints vary by indicator, yet all the indicators consistently identify drought hotspots such as the MED. We also found that drought is significantly influenced by large-scale atmospheric drivers. A canonical correlation analysis (CCA) between summer geopotential height at 500 mb (Z500) and drought reconstructions indicates that drought-affected regions are, in general, associated with atmospheric blocking. The canonical series are significantly correlated at r = 0.82 (p < 0.001), with explained variances of 12.78% (PDSI), 8.41% (SPEI), and 14.58% (SMI). Overall, our study underscores the value of multi-indicator approaches: individual indicators provide distinct but complementary perspectives on European drought dynamics, improving the historical context for assessing future risk. Full article

This study investigates the elastic properties of bio-epoxy composites reinforced with natural fibres (flax, hemp) and synthetic fibres (S-glass), with particular focus on the effect of the fibre volume fraction (VF) ranging from 10% to 70%. Three-dimensional representative volume element (RVE) models were developed for single-fibre, hybrid, and multi-fibre systems. The mean-field homogenisation (MF) approach, based on the Mori–Tanaka scheme, and finite element analysis (FEA) with periodic boundary conditions were employed to predict the effective elastic properties, including longitudinal, transverse, and shear moduli, as well as Poisson’s ratio. These numerical predictions were validated against analytical models, including the rule of mixtures, Chamis, and composite cylinder assemblage (CCA) methods. The results demonstrate that increasing the VF enhances longitudinal, transverse, and shear moduli while reducing Poisson’s ratio in natural fibre composites. The good agreement between numerical, semi-analytical, and analytical methods validates the 3D RVE models as useful tools for predicting the properties of multi-hybrid natural fibre composites, supporting their design for lightweight structural applications. Full article

Cervical cancer (CCa) is the fourth leading cause of cancer-related deaths among women worldwide, with nearly 90% of cases in low- and middle-income countries, especially in Sub-Saharan Africa. This study explores the roles of circular ribonucleic acids (circRNAs), hsa_circ_0001038 and circRNA_400029, and the impact of the serine/arginine-rich splicing factor 3 (SRSF3) inhibitor, theophylline, in CCa cell lines. We utilized cell cycle fluorescence-activated cell sorting (FACS) and Annexin V/propidium iodide (PI) assays to evaluate theophylline’s effects on SiHa and C33A cell lines. Results showed S-phase arrest in SiHa and G2/M arrest in C33A, with significant cytotoxic effects indicated by apoptosis analysis. Using CircAtlas, we identified micro ribonucleic acids (miRNAs) binding to hsa_circ_0001038, particularly miR-205-5p, which has a tumour-suppressive role. miRTarBase identified miR-16-5p as a key interacting miRNA for circRNA_400029. We constructed a competing endogenous ribonucleic acid (ceRNA) network, revealing multiple miRNA targets. Pathway analysis via the Kyoto Encyclopedia of Genes and Genomes (KEGG) highlighted critical signalling pathways involved in CCa oncogenesis. In conclusion, theophylline demonstrates cytotoxicity in CCa cells, suggesting its potential for repurposing in CCa theranostics, though further optimization is necessary. Full article