Search Results (21,206)

Vancomycin-resistant Enterococcus faecium (VREfm) is an emerging pathogen responsible for healthcare-associated infections. For this reason, 44 VREfm isolates collected during 2021–2023 were characterized using phenotypic and genomic approaches. VREfm isolates were identified by MALDI-TOF and antimicrobial susceptibility tests were performed with Vitek 2, Sensititre, or E-test. Sequence type (ST), antibiotic resistance genes, virulence factors and genetic relatedness were determined using Next Generation Sequencing. Forty-three isolates had a VanA phenotype and vanHAX genotype and one had a VanB phenotype and vanHBX genotype. Isolates showed high antibiotic resistance to various antibiotics, but generally remained susceptible to quinupristin/dalfopristin, tigecycline and eravacycline. Two isolates were resistant to linezolid, showing the chromosomal mutation G2576T in domain V of the 23S rRNA gene in one isolate, and the transferable linezolid resistance genes cfr(D) and optrA in the other. Thirty-eight isolates belonged to ST80, one to ST17 (ST80 and ST17 are included in CC17) and one to ST697. Genomic analysis of the ST80 isolates showed that nearly all of them belonged to a single cluster. To prevent further spread of VREfm in the nosocomial environment, in addition to the application of up-to-date infection control strategies and antibiotic stewardship programs, the implementation of genomic surveillance is recommended. Full article

Barley is a marginalized crop subjected to several types of abiotic stress but need to intensify for future climate smart crop. This study investigated the drought resistance of barley landraces focusing on agro-morphological and physiological traits under controlled drought conditions. The experiment employed a two-factorial completely randomized design (CRD) with 14 barley landraces (of which 8 completed the maturity period examination) subjected to drought stress at three growth stages (CRI, tillering, and grain filling). Key parameters such as SPAD values (chlorophyll content), tiller number, and yield attributes were measured and analyzed using drought tolerance indices. Fourteen genotypes were initially tested, of which six failed to reach maturity; eight genotypes completed the full growth cycle and were used for yield and stress index analysis. Results revealed significant genotypic variation in drought response. Eight landraces exhibited higher SPAD values under drought, indicating better photosynthetic retention. Notably, AFU202501 demonstrated high yield stability (Stress Tolerance Index, STI = 1.782) under both stress and non-stress conditions, while Saptari Local showed exceptional drought avoidance (low Stress Susceptibility Index, SSI = −0.068) through early maturity and minimal yield reduction. In contrast, genotypes like Muktinath and NGRC 6010 were highly sensitive to drought, with significant yield losses (49–87%). Physiological traits such as chlorophyll retention and phenological plasticity (e.g., accelerated maturity under stress) were critical for drought adaptation. The findings highlight the potential of landraces like AFU202501 and Saptari Local as genetic resources for breeding climate-resilient barley varieties. The study underscores the importance of integrating traditional landraces into modern breeding programs to enhance food security in drought-prone regions. Full article

This paper describes the development and characterization of surface-enhanced Raman spectroscopy (SERS) substrates that employ the excitation of surface plasmon polaritons (SPPs) on periodic metal diffraction gratings to amplify the Raman signal of an analyte. The gratings were fabricated via interference photolithography on As₄₀S₄₀Se₂₀ thin films. The resulting surface relief was subsequently coated with either aluminium (Al gratings) or aluminium followed by silver (Ag gratings). The ratio of the relief depth to the grating period (h/a) was optimized to maximize SPP excitation efficiency. For both types of gratings, a strong angular dependence of the Raman scattering intensity of the analyte molecule (Rhodamine 6G) was observed, which anticorrelates with the angular dependence of the specularly reflected light intensity. The enhancement factor is 2 × 10² for the aluminium grating and 1 × 10³ for the silver grating. This finding suggests that aluminium-based SERS substrates may serve as a cost-effective alternative to those coated with noble metals. Although the overall amplification is significantly lower than that achieved by SERS substrates based on localized surface plasmon (LSP) excitation, the grating-based SPP substrates offer a crucial advantage for quantitative measurements due to their uniform enhancement across the entire substrate area. Full article

KRAS is one of the most frequently mutated genes in all human cancers, and its oncogenic mutation hotspots are glycine 12 (G12), glycine 13 (G13), glutamine 61 (Q61) and alanine 146 (A146). Among these hotspot mutations, A146 substitution mutations (A146X) occur relatively infrequently, except for haematopoietic and lymphoid cancers, suggesting that A146X causes intrinsically distinct KRAS signalling compared to other KRAS oncogenic alleles. However, due to the absence of model A146X cell lines derived from haematopoietic sources, the cellular mechanisms that cause the differences between KRAS.A146X and other common KRAS mutants, such as KRAS.G12X, remain largely unexplored. In this study, we developed a set of isogenic model haematopoietic cell lines expressing KRAS.A146T, KRAS.G12V and KRAS.G12G (non-mutated) from the endogenous locus by genetically modifying the human lymphoblastoid TK6 cell line. We found that TK6 cells carrying KRAS^A146T/+ or KRAS^G12V/+ exhibited increased replication stress compared to KRAS wild-type cells. Strikingly, KRAS^A146T/+ cells strongly rely on PrimPol for maintaining cellular survival upon replication stress. In contrast, KRAS^G12V/+ cells exhibited hypersensitivity to inhibitors for the ATR-Chk1 checkpoint signalling axis and to nucleoside analogues commonly used to treat cancers and viral infections. Our findings demonstrate that the endogenously expressed oncogenic KRAS mutations exacerbate the replication stress and reveal KRAS allele-specific replication phenotypes, facilitating the development of effective chemotherapies tailored to specific oncogenic KRAS mutation alleles and types of cancer. Moreover, our study offers valuable model cell lines for investigating mechanisms underlying replication vulnerability in cancers harbouring oncogenic KRAS mutations. Full article

We introduce a new hybrid contraction condition in the setting of G-metric spaces that unifies Banach-, Kannan-, and Chatterjea-type contractions applied to an iterate $T^p$ of a self-map T. Under a natural coefficient constraint, we prove that such a map admits a unique fixed point in a complete G-metric space. An illustrative example is provided to demonstrate the applicability of the result beyond classical contractions. Full article

Microbiota-derived indoles and short-chain fatty acids (SCFAs) modulate intestinal immunity via the aryl hydrocarbon receptor (AhR) and vitamin D receptor (VDR). This review proposes an operational AhR–VDR axis—three testable models (sequential, parallel, reciprocal)—to explain how indoles (AhR) and SCFAs/vitamin D (VDR) may cooperate to drive IL-22–mediated repair, antimicrobial peptide production, autophagy, and tight-junction restoration. We critically evaluate prebiotics, probiotics, and postbiotics: prebiotics shift fermentation toward SCFAs but show context-dependent effects; probiotics can supply indole-type AhR ligands yet are strain-specific; postbiotics offer standardized ligand delivery but face formulation challenges. We distinguish Salmonella-specific findings (e.g., SCFA suppression of SPI-1) from general colitis data and prioritize molecular validation, temporal mapping, multi-omics responder stratification, and standardized postbiotic development for clinical translation. Full article

Geodiamolides are depsipeptides previously isolated from marine sponges that are able to disrupt cytoskeleton microfilaments, inhibit cell migration and invasion, and reverse the malignant phenotype of human breast cancer cell lines to polarized spheroid-like structures. Such cytotoxicity to different cellular targets in breast cancer cells suggests that these molecules might also act in other cancer types such as non-melanoma skin cancer (NMSC), one of the cancer types with high incidence worldwide. Thus, the goal of this work was to study the effects of the marine sponge depsipeptides Geodiamolide A and H (Geo A and Geo H) in human squamous cell carcinoma (A431, NMSC) in order to investigate their effects on cell proliferation and cell death. While no significant statistical difference was observed after Geo H treatment, an expressive dose-dependent reduction in A431 cell viability (IC₅₀ of 368 nM, MTT assay; p < 0.05) and proliferation pattern (real-time cell analysis assay) was shown after 48 h exposure with Geo A. The cell proliferation blockade was confirmed after 24 h of Geo A treatment at 500 nM, with a 46% (p < 0.0001) reduction in the total number of cells (cell counting) and G2/M phase cell cycle arrest. Other cytotoxic evidence such as DNA fragmentation, phosphatidylserine exposure (flow cytometry), and time-dependent plasma membrane damage (Trypan Blue) suggested cell death by apoptosis. Therefore, Geo A showed both cytostatic and cytotoxic effects on A431 cells. Taken together, these data point out Geo A as a promising therapeutic molecule for NMSC treatment and is the first depsipeptide (marine or terrestrial), to our knowledge, to target this type of cancer cell. Full article

The human gut microbiome is a complex ecosystem integral to host health, with butyrate-producing bacteria (BPB) playing a critical role in maintaining intestinal homeostasis. This scoping review explores the composition, function, and systemic influence of BPB, focusing on their metabolic product, butyrate, and its implications for gut integrity, immune modulation, and gut–brain axis (GBA) communication. Disruptions to BPB abundance, which is correlated with Western dietary patterns, food additives, and antibiotic exposure, are linked to gut dysbiosis and associated with a wide spectrum of chronic diseases, including inflammatory bowel disease (IBD), obesity, type 2 diabetes, neurodegenerative disorders, and psychiatric conditions. Butyrate supports colonocyte energy metabolism, reinforces epithelial barrier function, regulates goblet cell mucus production, and exerts anti-inflammatory effects via histone deacetylase inhibition and G-protein-coupled receptor signaling. The depletion of BPB and the resultant butyrate deficiency may represent a unifying pathophysiological mechanism underlying these conditions. Therapeutic strategies that restore BPB populations and butyrate levels, such as prebiotics, dietary fiber, and microbiota-targeted interventions, hold promise for mitigating inflammation and enhancing systemic health through microbiome modulation. Full article

Background/Objectives: Cold-smoked salmon (CSS) is a ready-to-eat product with minimal preservation hurdles and a microbiota shaped by raw-material contamination and processing environments. Short breaks in refrigeration commonly occur during shopping and transport, yet their microbiological impact remains unclear. Here, we used ASV-resolved 16S rRNA gene metataxonomics to characterize storage-driven microbiota dynamics in CSS—quantifying ASV-level genetic diversity and phylogeny-aware (UniFrac) community structure—and to evaluate the effect of a brief, consumer-mimicking 2 h room-temperature cold-chain disruption. Methods: Three CSS types (organic, conventional Norwegian, and conventional Scottish) were stored at 5 °C for 35 days. On day 16, half of each batch was exposed to 2 h at room temperature (RT) before analysis; paired controls remained refrigerated. Culture-based counts (total mesophiles, lactic acid bacteria, Photobacterium spp.; indicator/pathogen screens) were performed per ISO methods. Community profiling used 16S rRNA (V3–V4) amplicon sequencing with QIIME 2/DADA2 and SILVA taxonomy. Linear mixed effects modelled alpha diversity; beta diversity by PERMANOVA on UniFrac distances; differential abundance by ANCOM-BC. Results: ASV-resolved 16S rRNA gene profiles of CSS were dominated by Pseudomonadota and Bacillota, with storage-driven shifts and taxon-specific trajectories (e.g., increasing Latilactobacillus). Both time and product type significantly explained phylogeny-aware community structure (unweighted and weighted UniFrac), consistent with storage-driven phylogenetic convergence across products. At day 16, ASV-level genetic diversity (Shannon/Observed features) and genus-level composition did not differ between RT-disrupted and continuously refrigerated samples. Culture-dependent counts increased from baseline to day 16 and largely plateaued by day 35, with lactic acid bacteria in Norwegian CSS continuing to rise; no systematic effect of the 2 h RT exposure was observed in culture-based comparisons. Indicator/pathogen screens detected no unexpected pathogenic species throughout the study period. Conclusions: Refrigerated storage drives pronounced, phylogeny-aware microbiota shifts and cross-product convergence in cold-smoked salmon, whereas a single 2 h RT interruption at mid-storage did not measurably alter ASV-level genetic diversity or community structure under the tested conditions. Integrating culture-based enumeration with ASV-resolved 16S rRNA gene metataxonomics provides complementary insights for shelf-life evaluation and risk assessment in ready-to-eat seafood. Full article

The rhizosphere, a confined area of soil plant roots, is an intersection of microbial activity and root exudates. Known as the rhizosphere effect, it enhances crop yield and sustainability by improving nutrient availability, beneficial compounds, and pathogen control. This study combines a field-based rhizosphere–bulk soil comparison for peanut with a geostatistical approach to quantify the spatial variability of rhizosphere-driven changes in soil quality indicators in the Ghardaïa region (southern Algeria), which is known for its sandy–clay and sandy–loam soils. Samples of rhizosphere and bulk soils were prospected using a systematic plan. Subsequently, the pH, electrical conductivity, calcium carbonate, organic matter, total nitrogen, available phosphorus, total potassium, and soluble sodium were determined for each soil (rhizosphere and bulk soil). To assess the spatial variability of rhizosphere soil parameters, semi-variograms of the fitted models were generated using auto-kriging. The results showed that both types of soils were moderately alkaline, with a reduction of 5.52% in the pH of the rhizosphere compared to the bulk soils. Soils were relatively low in organic matter, with only 3.3% of soils having organic matter levels above 20 g kg⁻¹. However, organic matter contents were consistently higher in the rhizosphere (8.51 ± 4.59 g kg⁻¹) than in the bulk soil (6.78 ± 3.52 g kg⁻¹). In the rhizosphere, an increase of 10% in labile phosphorus was noted. Total nitrogen was increased by 52.57%. T-tests suggested no significant difference in potassium and sodium levels, and they were moderately present in both soils. Significantly positive relationships were noted between available phosphorus and total nitrogen (R = 0.59, p < 0.001). However, negative correlations were revealed between pH and organic matter available phosphorus (R = −0.77, p < 0.001) and pH and total nitrogen (R = −0.56, p < 0.01). These results indicate the effects of rhizosphere interactions on soil property improvements and their implications for sustainable agricultural practices, including crop rotation, intercropping, and green manure applications. Full article

In the present study, the effects of electrode geometry and welding current on the tensile-shear strength, failure energy, fracture type, and joint microstructure were investigated during the RSW of ultra-high-strength MS1500 steel to high-strength low-alloy SPFC590 steel, both 1.2 mm in thickness. Three electrode geometries—designated as G0-6 mm, G0-8 mm, and A0—recommended for 1.2 mm sheets according to ISO 5821 were examined. It was found that in the G0-6 mm electrode geometry, which has the smallest contact area, excessive expulsion occurred at lower current levels compared to the other geometries. Consequently, this configuration resulted in lower maximum tensile-shear strength and failure energy values. The highest mechanical performance was achieved with the G0-8 mm electrode geometry, where the tensile-shear strength and failure energy were measured as 19.42 kN and 43.81 J, respectively. For the A0 electrode, although the maximum tensile-shear strength (19.68 kN) was comparable to that of the G0-8 mm geometry, the failure energy was approximately 7% lower (40.94 J). For all electrode geometries corresponding to maximum mechanical strength, a pull-out failure mode was observed, where the nugget region of the SPFC590 steel detached from the base metal and remained adhered to the ultra-high-strength MS1500 sheet. Full article

Word segmentation is a fundamental component of lexical processing, and Chinese reading—lacking inter-word spacing—requires readers to identify word boundaries based on prior experience. Previous studies have shown that contextual predictability facilitates lexical identification in Chinese reading; however, its influence on word segmentation remains unclear. This study used eye-tracking to examine the relationship between contextual predictability and readers’ segmentation preferences during Chinese sentence reading. Overlapping ambiguous three-character strings (e.g., 花生长) were used as the region of interest (ROI), and a 2 (segmentation type: AB-C (e.g., 花生/长) vs. A-BC (e.g., 花/生长)) × 2 (contextual predictability: high vs. low) within-subjects design was adopted. A total of 76 native Chinese speakers completed the task. The results showed that contextual predictability had a significant effect on skipping probability: Highly predictable target character strings were skipped more often than low-predictability words. However, contextual predictability did not influence any eye-movement measure. In contrast, segmentation type produced consistent effects across all measures, with shorter reading times for AB-C than for A-BC, indicating a stable preference for two-character segmentation. More importantly, no interaction emerged between contextual predictability and segmentation type, and Bayesian model comparison further supported this conclusion. These findings suggest that Chinese reading involves a robust preference for AB-C segmentation and that contextual predictability and word segmentation operate as independent processes, with predictability exerting minimal influence on word segmentation during reading. This result supports the Chinese Reading Model (CRM). Full article

Most electric vehicles use 400 V batteries, while some companies are moving to 800 V to reduce current in electric drives. More cars are expected to adopt 800 V at the DC terminals of the batteries, but 400 V will remain common for the duration of this transition, so future off-board chargers must support a wide voltage output range. Silicon carbide switches are used to keep the power–electronics interface compact and scalable. The AC/DC stage of a modular silicon carbide-based interface is designed using a T-type active front end and a dual active bridge. The T-type front end is optimized with a genetic algorithm. The resulting model is used to tune the inner current and outer voltage controllers. Bode analysis shows an inner current loop bandwidth of 4.25 kHz with a phase margin of ${53}^{\circ }$ and a gain margin of 30 dB. The outer voltage loop reaches 50 Hz with a phase margin of ${108}^{\circ }$ and a gain margin of 33 dB. The controller is implemented on a dSPACE MicroLabBox. Tests show peak efficiency of 98.5% in G2V mode and 98.3% V2G mode. THD stays under 5% above 4 kW and reaches 3% at peak power. Full article

With the progressive release of data from numerous sky surveys, humanity has entered the era of astronomical big data. Multi-wavelength, multi-method research is playing an increasingly crucial role. Binaries account for a substantial fraction of all stellar systems, and research into binaries is of fundamental importance. The low-resolution spectra from Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) suggest that LAMOST J064137.77+045743.8 is a binary consisting of an A7-type subgiant star and a cool red dwarf star. LAMOST J064137.77+045743.8 has not yet been recorded in the SIMBAD astronomical database. We conducted a comprehensive analysis of the binary based on multi-wavelength and multi-method research. The spectral analysis suggests that the A7-type subgiant primary star has parameters of $T_{\mathrm{eff}}$ ∼ 7500 K and log g ∼ 3.9, and the red dwarf companion star is cool. Additional flux observations in the infrared bands further corroborate the presence of the red dwarf companion, and the near-infrared color index indicates a K4-type red dwarf. Astrometric data from Gaia support the binary speculation with a Renormalized Unit Weight Error metric value of 1.9. The i-band flare detected by the Zwicky Transient Facility (ZTF) photometric observations bolsters the interpretation of the M- or K-type red dwarf companion. Both the radial velocity variations in the H$\alpha$ lines from LAMOST medium-resolution spectra and the light curves from ZTF support the classification of the A7 subgiant as a pulsating star. No clear evidence of binary eclipses was detected in 1789 days of photometric observations from the ZTF. Future asteroseismology studies will enable us to further probe the internal physics of the A7 subgiant primary star. Full article

Large Language Model (LLM) agents depend heavily on multiple external tools such as APIs, databases and computational services to perform complex tasks. However, these tool executions create latency and introduce costs, particularly when agents handle similar queries or workflows. Most current caching methods focus on LLM prompt–response pairs or execution plans and overlook redundancies at the tool level. To address this, we designed a multi-level caching architecture that captures redundancy at both the workflow and tool level. The proposed system integrates four key components: (1) hierarchical caching that operates at both the workflow and tool level to capture coarse and fine-grained redundancies; (2) dependency-aware invalidation using graph-based techniques to maintain consistency when write operations affect cached reads across execution contexts; (3) category-specific time-to-live (TTL) policies tailored to different data types, e.g., weather APIs, user location, database queries and filesystem and computational tasks; and (4) session isolation to ensure multi-tenant cache safety through automatic session scoping. We evaluated the system using synthetic data with 2.25 million queries across ten configurations in fifteen runs. In addition, we conducted four targeted evaluations—write intensity robustness from 4 to 30% writes, personalized memory effects under isolated vs. shared cache modes, workflow-level caching comparison and workload sensitivity across five access distributions—on an additional 2.565 million queries, bringing the total experimental scope to 4.815 million executed queries. The architecture achieved 76.5% caching efficiency, reducing query processing time by 13.3× and lowering estimated costs by 73.3% compared to a no-cache baseline. Multi-tenant testing with fifteen concurrent tenants confirmed robust session isolation and 74.1% efficiency under concurrent workloads. Our evaluation used controlled synthetic workloads following Zipfian distributions, which are commonly used in caching research. While absolute hit rates vary by deployment domain, the architectural principles of hierarchical caching, dependency tracking and session isolation remain broadly applicable. Full article