Search Results (11,412)

In Hungary, on-site mixed stabilization of cohesive soil is considered only as soil improvement not a proper pavement layer, therefore its bearing capacity is not taken into account when designing pavement. It was our hypothesis that on low-volume roads built on cohesive soil, lime or lime–cement stabilization can be an alternative to granular base layers. A case study was conducted to obtain initial results and to verify the research methodology. The efficacy of lime stabilization was evaluated across eight experimental road sections, with a view of assessing its structural and economic performance in comparison with crushed stone base layers reinforced with geo-synthetics. The results of the testing demonstrated elastic moduli of 120–180 MPa for the lime-stabilized layers, which closely matched the 200–280 MPa range observed for the crushed stone bases. The results demonstrated that lime stabilization offers a comparable load-bearing capacity while being the most cost-effective solution. Furthermore, this approach enhances sustainability by enabling the utilization of local soils, reducing reliance on imported materials, minimizing transport-related costs, and lowering carbon emissions. Lime stabilization provides a durable, environmentally friendly alternative for road construction, effectively addressing the challenges of material scarcity and rising construction costs while supporting infrastructure resilience. The findings highlight its potential to replace traditional base layers without compromising structural performance or economic viability. Full article

The glyoxalase pathway intermediate S-d-lactoylglutathione was recently implicated in protein post-translational modifications in animal systems. Here, we examined the spontaneous modification of the Arabidopsis thaliana cytosolic glyceraldehyde-3-phosphate dehydrogenase C1 (GAPC1) by this compound. Incubation of GAPC1 with S-d-lactoylglutathione resulted in the inhibition of enzyme activity. The inhibitory effect was concentration dependent and increased at alkaline pHs. Furthermore, the inhibition of GAPC1 by S-d-lactoylglutathione was favored by oxidative conditions and reversed by reduction with dithiothreitol. Analyses of the S-d-lactoylglutathione-treated protein by nanoLC-MS/MS revealed S-glutathionylation of its two Cys residues and N-lactoylation of six Lys residues. Protein structure predictions showed that the double S-glutathionylation is accommodated by the GAPC1 catalytic pocket, which likely explains enzyme inhibition. N-lactoylated sites overlap partially with previously reported N-acetylated sites at the surface of the GAPC1 tetramer. The efficiency of cytosolic glutaredoxin and thioredoxin isoforms was tested for reversing the S-d-lactoylglutathione-induced modification. In these assays, recovery of GAPC1 activity after inhibition by S-d-lactoylglutathione treatment was used as indicator of efficiency. The results show that both types of redoxins were able to reverse inhibition. We propose a model describing the mechanisms involved in the two types of post-translational modifications found on GAPC1 following exposure to S-d-lactoylglutathione. The possible involvement of these findings for the control over glycolytic metabolism is discussed. Full article

Tumor mutational burden (TMB) and tumor-infiltrating lymphocytes (TILs) are key biomarkers for predicting immunotherapy responses in cutaneous melanoma. The discordance between brisk TIL morphology and absent cytokine signals complicates immune profiling. We examined the interactions between TMB, TIL patterns, cytokine expression, and genomic alterations to uncover immune escape mechanisms and refine prognostic tools. A structure-based BRAF druggability analysis was performed to anchor the genomic findings in a therapeutic context. Primary cutaneous melanoma cases (N = 205) were classified as brisk (n = 65), non-brisk (n = 60), or absent TILs (n = 80) according to the American association for cancer research (AACR) guidelines. Inter-observer concordance was measured using intraclass correlation. Tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels were graded using immunohistochemistry. Eleven brisk TIL cases lacking TNF-α expression were analyzed using the (Illumina TruSight Oncology 500, Illumina-San Diego, CA, USA). Dabrafenib docking to the BRAF ATP site was performed with Glide SP/XP and rescored with Prime MM-GBSA. Brisk TILs lacking cytokine signals suggested post-translational silencing of TNF-α/IFN-γ. Among the 11 profiled cases, eight exhibited high TMB and copy number alterations, with enrichment of nine metastasis/immune regulation genes. Inter-observer concordance was high (absent TILs, 95%; brisk TILs, 90.7%). BRAF docking yielded a canonical type-I pose and strong ATP pocket engagement (ΔG_bind −84.93 kcal·mol⁻¹). Single biomarkers are insufficient for diagnosis. A multiparametric framework combining histology, cytokine immunohistochemistry (IHC), and genomic profiling enhances stratification and reveals immune escape pathways, with BRAF modeling providing a mechanistic anchor for the targeted therapy. Full article

BACH1 (BTB And CNC Homology 1) and NRF2 (Nuclear Factor Erythroid 2-related Factor 2) are transcription factors that regulate antioxidant and iron metabolism genes by competing for binding to cis-regulatory Maf-binding elements (CsMBEs) as heterodimers with small Maf proteins (sMafs). To dissect the mechanisms underlying this competition, we developed a chimeric tethering system where the DNA-binding domains of BACH1 or NRF2 were covalently linked to sMafG via a flexible, cleavable linker. This design enables efficient heterodimer formation on DNA and circumvents kinetic barriers to partner exchange in the solution. The site-specific fluorescent labelling of proteins allowed for the tracking of complex compositions by electrophoretic mobility shift assays. Both BACH1/sMafG and NRF2/sMafG heterodimers bind CsMBEs with similar affinities. Notably, DNA binding by BACH1 was impaired in a C574-dependent, redox-sensitive manner and promoted the exchange of heterodimer partners. Competition assays demonstrated that BACH1 and NRF2 can displace each other from preformed DNA-bound complexes, with greater efficiency when presented as preassembled heterodimers with sMafG. These findings reveal a redox-sensitive mechanism for regulating transcriptional switches at CsMBEs and highlight how preformed heterodimers facilitate the rapid displacement at target promoters. Full article

Schisandra chinensis (Turcz.) Baill. (S. chinensis) is a widely used medicinal plant whose therapeutic efficacy is closely linked to its lignan content. While previous studies have focused on soil fertility and cultivar variation, the interplay among soil nutrients, rhizosphere microbiota, and lignan accumulation remains poorly understood. This study investigated S. chinensis grown across 20 cultivation sites to elucidate the relationships among soil nutrient profiles, fruit lignan composition, and rhizosphere microbial communities. Six major lignans were quantified using HPLC, soil nutrients were analyzed via standard chemical assays, and rhizosphere bacterial communities were profiled using 16S rRNA sequencing. Multivariate analyses revealed significant variation in soil properties and lignan content across sites. Notably, available phosphorus, organic matter, and total nitrogen showed strong correlations with specific lignan compounds. From the top 50 taxa ranked by relative abundance at the genus level, 18 bacterial genera associated with lignan components were identified. Among them, Mycobacterium, Arthrobacter, Haliangium, Bacillus, Sphingomonas, Rhodanobacter, Ellin6067, Bradyrhizobium, Pseudolabrys, Chujaibacter, Gemmatimonas, Bryobacter, MND1, Candidatus Sollbacter, Gaiella, Paenibacillus, RB41, and Candidatus_Udaeobacter were significantly associated with lignan levels, suggesting potential microbial involvement in lignan biosynthesis. These findings provide insights into the ecological factors shaping the medicinal quality of S. chinensis and offer a foundation for targeted cultivation and breeding strategies. Full article

This work thoroughly investigated the compound 4-(2,5-Dimethoxyphenyl)-3,4-dihydrobenzo[g]chromene-2,5,10-trione (DMDCT) using molecular docking, quantum chemical analysis, and vibrational spectroscopy methodology. The medicinal chemistry group has been particularly interested in chromene and benzochromene derivatives due to their wide range of pharmacological actions, including anticancer, antibacterial, anti-inflammatory, antioxidant, antiviral, and neuroprotective capabilities. In this connection, DMDCT has been explored to evaluate its biological, electrical, and structural properties. DFT using the B3LYP functional and 6–31G basis was established to conduct theoretical computations with the Gaussian 09 program. The findings from these computations provide insight into the following topics: NBO interactions, optimal molecular geometry, Mulliken charge distribution, frontier molecular orbitals, and MEP. Second-order perturbation theory has been used to assess stabilization energies arising from donor–acceptor interactions. Furthermore, general features such as chemical hardness, softness, and electronegativity were studied. The results suggest that DMDCT has stable electronic configurations and biologically relevant active sites. This integrated experimental and theoretical study supports the potential of DMDCT as a practical scaffold for future therapeutic applications and contributes valuable information regarding its vibrational and electronic behavior. Full article

Machine learning (ML) algorithms have promoted the development of predictive modeling of mineral prospectivity, enabling data-driven decision-making processes by integrating multi-source geological information, leading to efficient and accurate prediction of mineral exploration targets. However, it is challenging to conduct ML-based mineral prospectivity mapping (MPM) in under-explored areas where scarce data are available. In this study, the Narigongma district of the Qiangtang block in the Himalayan–Tibetan orogen was chosen as a case study. Five typical alterations related to porphyry mineralization in the study area, namely pyritization, sericitization, silicification, chloritization and propylitization, were extracted by remote sensing interpretation to enrich the data source for MPM. The extracted alteration evidences, combined with geological, geophysical and geochemical multi-source information, were employed to train the ML models. Four machine learning models, including artificial neural network (ANN), random forest (RF), support vector machine and logistic regression, were employed to map the Cu-polymetallic prospectivity in the study area. The predictive performances of the models were evaluated through confusion matrix-based indices and success-rate curves. The results show that the classification accuracy of the four models all exceed 85%, among which the ANN model achieves the highest accuracy of 96.43% and a leading Kappa value of 92.86%. In terms of predictive efficiency, the RF model outperforms the other models, which captures 75% of the mineralization sites within only 3.5% of the predicted area. A total of eight exploration targets were delineated upon a comprehensive assessment of all ML models, and these targets were further ranked based on the verification of high-resolution geochemical anomalies and evaluation of the transportation condition. The interpretability analyses emphasize the key roles of spatial proxies of porphyry intrusions and geochemical exploration in model prediction as well as significant influences everted by pyritization and chloritization, which accords well with the established knowledge about porphyry mineral systems in the study area. The findings of this study provide a robust ML-based framework for the exploration targeting in greenfield areas with good outcrops but low exploration extent, where fusion of a remote sensing technique and multi-source geo-information serve as an effective exploration strategy. Full article

This study aims to investigate whether a combined action observation–motor imagery practice may enhance the effects of conventional physical rehabilitation in a stroke survivor population. A total of 8 (7 male, 1 female) post-stroke patients with upper limb hemiparesis were enrolled into a single-blinded, randomised, study. Five times per week for three weeks, four patients experienced 60’ conventional physical therapy, while the other 4 experienced 30’ conventional physical therapy and 30’ action observation–motor imagery practice. The Fugl-Meyer Assessment-Upper Extremity and the Wolf Motor Function Test scores from the baseline and post-physiotherapy were used to evaluate upper extremity motor function. Patients who received the AO + MI alongside conventional physical rehabilitation benefitted more than those who received only conventional physical rehabilitation. However, the sample size was very small (only eight participants), which reduces both the statistical power and the ability to generalise the results. Moreover, there was no follow-up; therefore, it is unclear whether the observed improvements lasted over time. Finally, some potentially confounding factors, such as stroke type or lesion site, were not statistically controlled. Notwithstanding these limitations, our findings may serve as a basis for future large-scale, well-controlled studies on AO + MI in stroke rehabilitation. Full article

Background and Clinical Significance: Palatal swellings may originate from various pathological disorders. These swellings may include congenital or acquired factors. The posterior hard palate, which contains many minor salivary glands, is a common site for such swellings. Case Presentation: We present a rare case of intraoral palatal myoepithelioma in a 45-year-old Egyptian male with a significant history of smoking. Detailed clinical, radiographic, and operative findings are discussed alongside histopathological evaluation, surgical management, and postoperative outcomes. This case highlights the importance of considering myoepithelioma lesions in the differential diagnosis of posterior palatal swelling. Conclusions: Palatal myoepithelioma is a rare but important benign salivary gland tumor that may resemble multiple other intraoral lesions. A complete clinical, radiographic, and histological investigation is required for a definitive diagnosis. Complete surgical excision achieved a favorable outcome. Increased awareness and reporting of this unusual pathology are critical for deepening knowledge and guiding clinical decisions. Full article

One of the sometimes-neglected fields is the landscape design of hospital premises. This study focuses on the perception and preferences of responders regarding hospital site design. The objective was to determine if people are aware of the benefits of restorative contact with nature and if there were preferences for any specific landscape type. The online questionnaire with color figures was distributed using emails and social media from 4th May to 2nd August 2024. Some 110 respondents returned the questionnaire. Most of the respondents were women under 25. Most respondents declared that the surroundings of the healthcare building influence the health and well-being of patients (96%) and health personnel (86%). The results confirmed the awareness of the importance of contact with nature (89%). Moreover, this study demonstrated a preference for calm garden compositions, stimulating physical and mental recovery with trees, flowers, and water features, as well as stabilized paths and sheltered sitting places. The results confirm previous studies and demonstrate the importance of landscape architecture design of hospital premises for the well-being of patients. The findings may influence urban landscape planning and the design of hospital sites. Full article

Rainfall-induced landslide deformation is governed by both intrinsic geological conditions and external dynamic triggers. However, many existing predictive models rely primarily on rainfall inputs, which limits their interpretability and robustness. To address these shortcomings, this study introduces a group-based data augmentation method informed by displacement curve morphology and proposes a multi-slope predictive framework that integrates static geological attributes with dynamic triggering factors. Using monitoring data from 274 sites across China, the framework was implemented with a Temporal Fusion Transformer (TFT) and benchmarked against baseline models, including SVR, XGBoost, and LSTM models. The results demonstrate that group-based augmentation enhances the stability and accuracy of predictions, while the integrated dynamic–static TFT framework delivers superior accuracy and improved interpretability. Statistical significance testing further confirms consistent performance improvements across all groups. Collectively, these findings highlight the framework’s effectiveness for short-term landslide forecasting and underscore its potential to advance early warning systems. Full article

A surface molecularly imprinted ratiometric fluorescent sensor (Eu/CDs@SiO₂@IIPs) was constructed for the selective and visual detection of Cu²⁺. The sensor integrates blue-emitting carbon dots as an internal reference and a custom-designed Eu(III) complex, Eu(MAA)₂(2,9-phen), as both the functional and fluorescent monomer within a surface-imprinted polymer layer, enabling efficient ratiometric fluorescence response. This structural design ensured that all fluorescent monomers were located at the recognition sites, thereby reducing background fluorescence interference and enhancing the accuracy of signal changes. Under optimized conditions, the sensor exhibited a detection limit of 2.79 nM, a wide linear range of 10–100 nM, and a rapid response time of 3.0 min. Moreover, the uncoordinated nitrogen atoms in the phenanthroline ligand improved resistance to interference from competing ions, significantly enhancing selectivity. Practical applicability was validated by spiked recovery tests in deionized and river water, with results showing good agreement with ICP-MS analysis. These findings highlight the potential of Eu/CDs@SiO₂@IIPs as a sensitive, selective, and portable sensing platform for on-site monitoring of Cu²⁺ in complex water environments. Full article

The methylation of CpG sites with 5mC mark is a dynamic epigenetic modification. However, the relationship between the methylation and the surrounding genomic sequence context remains poorly explored. Investigation of the allele methylation provides an opportunity to decipher the interplay between differences in the primary DNA sequence and epigenetic variation. Here, we performed high-coverage long-read whole-genome direct DNA sequencing of one individual using Oxford Nanopore technology. We also used Illumina whole-genome sequencing of the parental genomes in order to identify allele-specific methylation sites with a trio-binning approach. We have compared the results of the haplotype-specific methylation detection and revealed that trio binning outperformed other approaches that do not take into account parental information. Also, we analysed the cis-regulatory effects of the genomic variations for influence on CpG methylation. To this end, we have used available Deep Learning models trained on the primary DNA sequence to score the cis-regulatory potential of the genomic loci. We evaluated the functional role of the allele-specific epigenetic changes with respect to gene expression using long-read Nanopore RNA sequencing. Our analysis revealed that the frequency of SNVs near allele-specific methylation positions is approximately four times higher compared to the biallelic methylation positions. In addition, we identified that allele-specific methylation sites are more conserved and enriched at the chromatin states corresponding to bivalent promoters and enhancers. Together, these findings suggest that significant impact on methylation can be encoded in the DNA sequence context. In order to elucidate the effect of the SNVs around sites of allele-specific methylation, we applied the Deep Learning model for detection of the cis-regulatory modules and estimated the impact that a genomic variant brings with respect to changes to the regulatory activity of a DNA loci. We revealed higher cis-regulatory impact variants near differentially methylated sites that we further coupled with transcriptomic long-read sequencing results. Our investigation also highlights technical aspects of allele methylation analysis and the impact of sequencing coverage on the accuracy of genomic phasing. In particular, increasing coverage above 30X does not lead to a significant improvement in allele-specific methylation discovery, and only the addition of trio binning information significantly improves phasing. We investigated genomic variation in a single human individual and coupled computational discovery of cis-regulatory modules with allele-specific methylation (ASM) profiling. In this proof-of-concept analysis, we observed that SNPs located near methylated CpG sites on the same haplotype were enriched for sequence features suggestive of high-impact regulatory potential. This finding—derived from one deeply sequenced genome—illustrates how phased genetic and epigenetic data analyses can jointly put forward a hypotheses about the involvement of regulatory protein machinery in shaping allele-specific epigenetic states. Our investigation provides a methodological framework and candidate loci for future studies of genomic imprinting and cis-mediated epigenetic regulation in humans. Full article

Climate change in Antarctica has profound global implications, influencing sea level rise, atmospheric circulation, and the Earth’s energy balance. This study presents a data-driven baseline analysis of meteorological observations from a British Antarctic Survey automatic weather station (2020–2024). Temporal and seasonal analyses reveal strong insolation-driven variability in temperature, snow depth, and solar radiation, reflecting the extreme polar day–night cycle. Correlation analysis highlights solar radiation, upwelling longwave flux, and snow depth as the most reliable predictors of near-surface temperature, while humidity, pressure, and wind speed contribute minimally. A linear regression baseline and a Random Forest model are evaluated for temperature prediction, with the ensemble approach demonstrating superior accuracy. Although the short data span limits long-term trend attribution, the findings underscore the potential of lightweight, reproducible pipelines for site-specific climate monitoring. All analysis codes are openly available in github, enabling transparency and future methodological extensions to advanced, non-linear models and multi-site datasets. Full article

Background: The 4CMenB vaccine (Bexsero^®) contains surface proteins from Neisseria meningitidis serogroup B and is recommended from 2 months of age. The most frequently reported adverse events are fever, injection site pain, and fatigue. Thus, this study aimed to estimate the incidence of local and systemic adverse events associated with the administration of the 4CMenB (Bexsero^®) vaccine. Methods: A systematic review and meta-analysis of clinical trials published up to 28 February 2025 were conducted using PubMed, ScienceDirect, and Web of Science. Human studies available in English, Spanish, French, German, or Italian were exclusively included. Adverse events following the first dose of the vaccine were analyzed. Pooled proportions with 95% confidence intervals were calculated, and heterogeneity across studies was assessed using the I² statistics. Results: Ten clinical trials comprising 13,345 participants were included. The most common adverse event was local pain (occurring in up to 94% of cases), followed by induration, erythema, and edema, with frequencies ranging from 25% to 45%. The most frequently reported systemic events were irritability (up to 75%), fatigue (51–59%), fever (up to 60%), headache (42–49%), and persistent crying (50–65%). Most adverse events were mild and self-limiting. Conclusions: The 4CMenB (Bexsero) vaccine exhibits a favorable safety profile, characterized by a predominance of mild and transient local adverse events. Although several systemic events were reported, their overall frequency was generally low. These findings support the continued inclusion of Bexsero^® in routine childhood immunization programs. Full article