Search Results (408)

This study describes the first complete genomic sequence of an NDM-19 and QnrS11-producing multidrug-resistant (MDR) Escherichia coli isolate collected from a fecal swab from a poultry farm in 2019 in Egypt. The bla_NDM-19 was identified by PCR screening and DNA sequencing. The isolate was then subjected to antimicrobial susceptibility testing, conjugation and transformation experiments, and complete genome sequencing. The chromosome of strain M2-13-1 measures 4,738,278 bp and encodes 4557 predicted genes, with an average G + C content of 50.8%. M2-13-1 is classified under ST167, serotype O101:H5, phylogroup A, and shows an MDR phenotype, having minimum inhibitory concentrations (MICs) of 64 mg/L for both meropenem and doripenem. The genes bla_NDM-19 and qnrS11 are present on 49,816 bp IncX3 and 113,285 bp IncFII: IncFIB plasmids, respectively. M2-13-1 harbors genes that impart resistance to sulfonamides (sul1), trimethoprim (dfrA14), β-lactams (bla_TEM-1B), aminoglycosides (aph(6)-Id, aph(3′)-Ia, aph(3″)-Ib, aac(3)-IV, and aph(4)-Ia), tetracycline (tet(A)), and chloramphenicol (floR). It was susceptible to aztreonam, colistin, fosfomycin, and tigecycline. The genetic context surrounding bla_NDM-19 includes ISAba125-IS5-bla_NDM-19-ble_MBL-trpF-hp1-hp2-IS26. Hierarchical clustering of the core genome MLST (HierCC) indicated M2-13-1 clusters with global ST167 E. coli lineages, showing HC levels of 100 (HC100) core genome allelic differences. Plasmids of the IncX3 group and the insertion sequence (ISAba125) are critical vehicles for the dissemination of bla_NDM and its related variants. To our knowledge, this is the first genomic report of a bla_NDM-19/IncX3-carrying E. coli isolate of animal origin globally. Full article

The sustainable production of plant bioactive compounds is increasingly important as natural habitats decline. This study investigates whether in vitro cell cultures of Eryngium planum, Lychnis flos-cuculi, and Kickxia elatine can serve as alternative sources of biologically active biomass with antimicrobial and anti-Acanthamoeba properties. Callus cultures were established under optimized and controlled conditions, and metabolomic profiling was completed using UPLC-HRMS/MS. In silico analysis, using a molecular docking approach, was applied to understand the interaction between target compounds and Acanthamoeba profilin and identify possible targets for antimicrobial properties. Untargeted metabolomic analysis confirmed the presence of valuable compounds in the callus cultures of the studied species. Biological activity was assessed through anti-Acanthamoeba and antimicrobial assays. Lychnis flos-cuculi and Kickxia elatine callus extracts showed significant inhibitory effects on Acanthamoeba trophozoites, with 87.5% and 80.1% inhibition at 10 mg/mL, respectively. In contrast, E. planum extract stimulated amoebic growth. The anti-Acanthamoeba activity correlated with the presence of ferulic acid and p-coumaric acid in L. flos-cuculi extract, and acteoside in K. elatine extract. Antibacterial testing revealed moderate activity of E. planum and K. elatine extracts against Staphylococcus spp., while Gram-negative bacteria and fungi were largely resistant. These findings highlight the potential of in vitro cultures—particularly those from L. flos-cuculi and K. elatine—as promising, sustainable sources of anti-Acanthamoeba and antimicrobial agents, warranting further investigation into their pharmacologically active constituents. Full article

Esophageal adenocarcinoma (EAC) is a highly aggressive malignancy with rising incidence and poor prognosis. TP53, previously identified as the most frequently mutated gene in EAC in our studies, plays a central role in tumor suppression and regulation. However, the metabolic consequences of TP53 mutations in EAC remain largely uncharacterized. We metabolically profiled three TP53-mutant EAC cell models (OE33, OE19, and FLO1) representing progressive stages of tumor differentiation and harboring distinct TP53 alterations. Our analyses revealed different metabolic phenotypes associated with TP53 status. OE33 cells predominantly use glycolytic metabolism but display limited adaptability to environmental changes, possibly due to a higher differentiation state. FLO1 cells exhibit a strong glycolytic dependence, elevated lactate production, and robust proliferation under acidic conditions, consistent with an aggressive and metastatic phenotype. OE19 cells preferentially utilize oxidative phosphorylation, demonstrated by resilience to glucose and glutamine deprivation, and ROS accumulation. These findings highlight the metabolic plasticity of EAC and suggest that TP53 mutation type might influence bioenergetic dependencies. Targeting these metabolic vulnerabilities may offer novel therapeutic avenues for personalized treatment in EAC. Full article

Ovarian cancer, the most lethal form of gynecological cancer worldwide with a poor prognosis, is largely driven by an immunosuppressive tumor microenvironment. In this study, we investigated the anticancer effects of hydnocarpin, a natural flavonolignan derived from the flowers of Pueraria lobata, focusing on its effects on ovarian cancer and tumor-associated immune cells, including ovarian cancer-stimulated macrophages (MQs) and T cells. Hydnocarpin exhibited potent cytotoxicity against multiple ovarian cancer cell lines but only minimal toxicity against normal ovarian surface epithelial cells. Mechanistically, hydnocarpin triggered caspase-dependent apoptosis, as evidenced by the activation of caspase-9 and -3, with limited involvement of caspase-8, indicating the activation of the intrinsic apoptotic pathway. Experimental data implicated reactive oxygen species generation as a key mediator of hydnocarpin cytotoxicity, and reactive oxygen species inhibition significantly inhibited this cytotoxicity. In addition to its direct tumoricidal effects, hydnocarpin reprogrammed the tumor-associated immune cells, ovarian cancer-stimulated macrophages and T cells, by downregulating the levels of M2 MQ markers and pro-tumoral factors (matrix metalloproteinase-2/9, C–C motif chemokine ligand 5, transforming growth factor-β, and vascular endothelial growth factor) and enhancing MQ phagocytosis. Additionally, hydnocarpin promoted T-cell activation (interferon-γ and interleukin-2) and reduced the expression levels of immune evasion markers (CD80, CD86, and VISTA). Overall, this study demonstrated the dual anti-tumor effects of hydnocarpin on both ovarian cancer cells and immunosuppressive immune components in the tumor microenvironment, highlighting its potential as a novel therapeutic candidate for ovarian cancer. Full article

Analyze the quality differences of Magnoliae Flos (MF) at different developmental stages and determine its optimal harvest period. In this study, a detection method for the main chemical components of MF was established based on GC-MS and UPLC, and the volatile oil and lignan components were determined. The quality differences between MF at different developmental stages were compared based on chemical composition. Chromaticity values of MF samples were measured using electronic eye technology, followed by correlation analysis to reveal the relationship between internal compositional changes and external color differences. The results indicated that the harvesting period significantly affected the chemical composition of MF. Specifically, the contents of volatile oils and lignans initially increased and then decreased as the flower buds developed. There are obvious correlations between six different volatile components and some lignans of MF and their chromaticity values (p < 0.05). This study clarified the dynamic changes in relevant indicators during the development of MF, which can provide a reference for the rational utilization and scientific harvesting of MF resources. Full article

Suyukou Gully, located on the eastern slope of the Helan Mountains in northwest China, is a typical debris-flow-prone catchment characterized by a steep terrain, fractured bedrock, and abundant loose colluvial material. The area is subject to intense short-duration convective rainfall events, which often trigger destructive debris flows that threaten the Suyukou Scenic Area. To investigate the dynamics and risks associated with such events, this study employed the FLO-2D two-dimensional numerical model to simulate debris flow propagation, deposition, and hazard distribution under four rainfall return periods (10-, 20-, 50-, and 100-year scenarios). The modeling framework integrated high-resolution digital elevation data (original 5 m DEM resampled to 20 m grid), land-use classification, rainfall design intensities derived from regional storm atlases, and detailed field-based sediment characterization. Rheological and hydraulic parameters, including Manning’s roughness coefficient, yield stress, dynamic viscosity, and volume concentration, were calibrated using post-event geomorphic surveys and empirical formulations. The model was validated against field-observed deposition limits and flow depths, achieving a spatial accuracy within 350 m. Results show that the debris flow mobility and hazard intensity increased significantly with rainfall magnitude. Under the 100-year scenario, the peak discharge reached 1195.88 m³/s, with a maximum flow depth of 20.15 m and velocities exceeding 8.85 m·s⁻¹, while the runout distance surpassed 5.1 km. Hazard zoning based on the depth–velocity (H × V) product indicated that over 76% of the affected area falls within the high-hazard zone. A vulnerability assessment incorporated exposure factors such as tourism infrastructure and population density, and a matrix-based risk classification revealed that 2.4% of the area is classified as high-risk, while 74.3% lies within the moderate-risk category. This study also proposed mitigation strategies, including structural measures (e.g., check dams and channel straightening) and non-structural approaches (e.g., early warning systems and land-use regulation). Overall, the research demonstrates the effectiveness of physically based modeling combined with field observations and a GIS analysis in understanding debris flow hazards and supports informed risk management and disaster preparedness in mountainous tourist regions. Full article

Background: Antimicrobial resistance (AMR) is a critical global health threat, with AMR Salmonella enterica serovar Typhimurium strains being a major foodborne pathogen. Integrons, a type of mobile genetic element, capture and transfer resistance genes, thereby playing a role in the spread of AMR. Objectives: This study aimed to characterize the locations of integrons carrying AMR genes within the whole genomes of 32 Salmonella Typhimurium isolates collected from dairy cattle by two U.S. Veterinary Diagnostic Laboratories between 2009 and 2012. Methods: Class I integrons were sequenced from PCR-amplified products. DNA was extracted, quantified, barcoded, and sequenced on the Illumina MiSeq platform. Whole genome sequences were trimmed and assembled using the SPAdes assembler in Geneious Prime^®, and plasmids were identified with the PlasmidFinder pipeline in Linux. Integron locations were determined by aligning their sequences with whole genome contigs and plasmids, while AMR genes were identified through BLAST with the MEGARes 3.0 database and confirmed by alignment with isolate, plasmid, and integron sequences. Statistical analysis was applied to compare the proportions of isolates harboring integrons on their chromosome versus plasmids and also to examine the associations between integron presence and AMR gene presence. Results: Seven plasmid types were identified from all isolates: IncFII(S) (n = 14), IncFIB(S) (n = 13), IncC (n = 7), Inc1-I(Alpha) (n = 3), and ColpVC, Col(pAHAD28), and Col8282 (1 isolate each). Of the 32 isolates, 16 (50%) carried at least one size of integron. Twelve of them carried both 1000 and 1200 bp; 3 carried only 1000 bp and 1 carried 1800 bp integrons. Of the 15 isolates that carried 1000 bp integron, 12 harbored it on IncFIB(S) plasmids, 2 on IncC plasmids, and 1 on the chromosome. The 1200 bp integrons from all 12 isolates were located on chromosomes. There were significant positive associations between the presence of integrons and the presence of several AMR genes including sul1, aadA2, blaCARB-2, qacEdelta1, tet(G), and floR (p < 0.05). AMR genes were located as follows: aadA2 on IncFIB(S) and IncC plasmids; bla_CMY-2 on IncC plasmid; qacEdelta1 on IncFIB(S), IncC, and chromosome; bla_CARB-2, floR, tet(A) and tet(G) on the chromosome. Conclusions: The findings highlight the genomic and plasmid complexity of Salmonella Typhimurium which is impacted by the presence and location of integrons, and this study provides genomic insights that can inform efforts to enhance food safety and protect both animal and public health. Full article

Aim of the study: Traditional Chinese herbs have a unique therapeutic effect on stroke and numerous successful clinical cases. However, these clinical cases are highly dispersed, creating challenges for translational research. This study employs a new paradigm to identify treatment patterns and the active compound interactions contained within these clinical cases, with experimental validation after target screening. Methods and Materials: Stroke-related targets were identified through GEO, DisGeNET, and Genecards. Active ingredients were extracted from BATMAN-TCM 2.0. All herbs and diseases were confirmed by the Pharmacopoeia of the People’s Republic of China (2020 edition) and Medical Subject Heading (MeSH). All networks in this study were constructed by Cytoscape, and data analysis was done by Python. All formulations and herbs were retrieved from the literature review. For the molecular docking process, Autodock was applied as the docking platform, and all the protein structures were downloaded from PDB. For experimental validation after target screening, HT22 cells were incubated with glucose-free DMEM and placed in an anaerobic chamber for 2 h. Subsequently, HT22 cells were reoxygenated for 24 h. Estrogen Receptor 1 (ESR1) protein levels were measured in vitro. Results: seven materials, including Angelicae Sinensis Radix, Pheretima, Chuanxiong Rhizoma, Persicae Semen, Astragali Radix, Carthami Flos, and Radix Paeoniae Rubra, were identified as the core herbs for the treatment of stroke. The targets of the stroke mechanism were screened, and the herbs-compound-target network was constructed. Among them, paeoniflorin (PF) was identified as the core active compound, and its interaction with ESR1 was verified by molecular docking as the key interaction for the treatment of stroke. In vitro experiments showed that PF inhibited cell apoptosis under hypoxia by increasing the expression of ESR1 compared with the oxygen-glucose deprivation-reperfusion (OGD/R) model group. Western showed that PF (100 μM, 200 μM) can significantly increase the decreased ESR1 protein level caused by the OGD/R model. Conclusions: seven key herbs were screened. Further bioinformatics and network pharmacology studies suggested that PF is expected to become a new active compound for the treatment of stroke. In vitro validation further demonstrated that PF enhanced neuronal survival and ESR1 expression under ischemic conditions, supporting its therapeutic candidacy. Full article

The flower buds of Magnolia biondii Pamp. (MBP), one of the botanical sources of Xinyi (Flos Magnoliae), are widely used in traditional medicine; however, their potential role in melanoma treatment remains unexplored. In this study, the phytochemical composition, antioxidant activity, and anti-melanoma mechanisms of MBP extracts were systematically investigated. Phytochemical profiling using UHPLC-Q-Exactive Orbitrap MS identified 26 bioactive compounds. The ethanol extract exhibited high total flavonoid and polyphenol contents, correlating with enhanced antioxidant capacity as demonstrated by DPPH and ABTS assays. Network pharmacology analysis highlighted the JAK/STAT signaling pathway, identifying STAT3 and STAT1 as core targets. Western blot analysis confirmed MBP significantly inhibited the phosphorylation of JAK1 and STAT1 in melanoma cells. Connectivity Map (CMap) and network analyses further pinpointed naringenin as a primary active constituent. In vitro assays demonstrated that MBP and naringenin inhibited the proliferation and migration of A375 and B16F10 melanoma cells, while exhibiting relatively low cytotoxicity toward normal keratinocytes. Molecular docking and dynamics simulations revealed strong and stable binding interactions between naringenin and JAK1/STAT1 proteins. These findings collectively support MBP and naringenin as promising candidates for melanoma treatment, providing mechanistic evidence for their targeted activity and laying a foundation for future research and clinical applications. Full article

Vegetal sources are a continuous research field and different types of extracts have been obtained over time. The most challenging part is compounding them in a pharmaceutical product. This study aimed to integrate a mixture (EX) of four extracts (SE-Sophorae flos, GE-Ginkgo bilobae folium, ME-Meliloti herba, CE-Calendulae flos) in formulations with polymers (polyhydroxybutyrate, polylactic-co-glycolic acid) and their physicochemical profiling. The resulting samples consist of particle suspensions, which were subjected to Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy analysis. When compared to single-extract formulations spectra, they revealed band changes, depending on the complex interactions. Using X-ray Diffractometry, the partially crystalline phase was highlighted for EX-PLGA, while the others were amorphous. Moreover, Atomic Force Microscopy pointed out the nanoscale particles and the topography of the samples, and the outstanding roughness belonging to EX-PHB-PLGA. A 30 min period of immersion was enough for the formulations to spread on the surface of the compression stockings material (CS) and after drying, it became a polymeric film. TGA analysis was performed, which evaluated the impregnated content: 5.9% CS-EX-PHB, 6.4% CS-EX-PLGA, and 7.5% CS-EX-PHB-PLGA. In conclusion, the extract’s phytochemicals and the interactions established with the polymers or with the other extracts from the mixture have a significant impact on the physicochemical properties of the obtained formulations, which are particularly important in pharmaceutical product development. Full article

The increasing demand for induction hobs necessitates efficient cooling systems to ensure the safe operation of electronic cut-outs. This study investigates the thermal representation of three different ignition designs integrated into an induction hob cooling system. A simplified model consisting of a radial fan, a daughterboard, and the electronics installed in the systems is used for the maintenance of the system. Remote measurements of air velocities at the cooler outlets are compared with the results obtained through programmable system dynamics (CFD) operations using FloEFD v2021.1 software. The findings of the study using the k-ε turbulence model show that Type 1 temperature is resistant to the lowest surface temperature for both the closest (IGBT 1) and the farthest (IGBT 2) temperature to the fan. Conversely, Type 3 temperatures exhibited high temperatures. Air velocity comparisons showed a maximum error rate of 30%, which is acceptable considering the variability in Type 1. Measurement system evaluation and DOE study were continued to increase the experimental range. This study demonstrates the utility offered by heatsink design in optimizing the cooling system of induction hobs and provides valuable insights for integrating thermal management systems. Full article

Sinhyotaklisan (SHTLS) is a traditional herbal prescription composed of Lonicerae Flos, Angelicae Gigantis Radix, Astragali Radix, and Glycyrrhizae Radix et Rhizoma, commonly used to treat skin disorders. This study aimed to investigate the therapeutic effects and underlying mechanisms of SHTLS in psoriasis through the network pharmacology analysis and experimental validation in vitro and in vivo. Bioactive compounds and molecular targets were identified using the Traditional Chinese Medicine Systems Pharmacology database, and key protein–protein interaction networks were analyzed via STRING and Cytoscape. In vitro, HaCaT cells were pretreated with SHTLS and stimulated with TNF-α, followed by assessments using proliferation assays, scratch assays, quantitative real-time PCR, and Western blotting. In vivo, the anti-psoriatic effects of SHTLS were evaluated in an imiquimod-induced psoriatic mouse model. A total of 36 key targets were significantly enriched in TNF-α, MAPK, HIF-1α, and IL-17 signaling pathways. SHTLS suppressed TNF-α-induced expression of VEGF and HIF-1α, while upregulating p53, thereby inhibiting keratinocyte hyperproliferation and angiogenesis. It also reduced IL-6 and IL-8 levels and blocked activation of the NF-κB and MAPK pathways. Histological analysis confirmed that SHTLS alleviated psoriatic lesions in vivo. These findings suggest that SHTLS may be a promising therapeutic candidate for psoriasis by targeting hyperproliferation, angiogenesis, and inflammation. Full article

This study presents a biorefinery approach for Aphanizomenon flos-aquae, demonstrating its potential as a dual source for phycocyanin and biogas. The antioxidant capacity of the extract was evaluated using the ABTS^•+ assay, while flow cytometry determined its cytotoxic effects on breast cancer (HCC1806) and brain glioma (U-118 MG) cell lines, comparing pure C-phycocyanin to the non-purified extract. The non-purified extract scavenged 77% of ABTS^•+ radicals at 2.4 mg/mL, compared to 22% for pure C-phycocyanin. In U-118 MG cells, pure C-phycocyanin accounted for 55.5% of the 29.9 ± 6.1% total mortality observed with the non-purified extract at 0.75 mg/mL. HCC1806 cytotoxicity (80.9 ± 5.1% at 1 mg/mL) was attributed to synergistic effects of other extract components. The spent biomass was valorized through anaerobic digestion for biogas production, enhancing process sustainability. At a 2:1 inoculum-to-substrate ratio, the anaerobic digestion of the spent biomass yielded 447 ± 18 mL CH₄/gVS, significantly higher than the 351 ± 19 mL CH₄/gVS from the initial biomass. LCA estimated the environmental impacts of the A. flos-aquae biorefinery for phycocyanin production, targeting the cosmetic, food, and nutraceutical sectors, and highlighting the benefits of spent biomass valorization to produce biogas within a circular economy framework. This integrated approach demonstrates the potential of A. flos-aquae for the sustainable production of high-value compounds and renewable energy. Full article

The aim of this study was to evaluate the effect of different bleaching protocols, including laser-assisted techniques, on the microhardness, surface roughness, and tribological resistance of selected light-cured composites. Three Estelite Universal Flow composites with different flow properties and G-aenial Universal Flo composites were tested. Each group underwent bleaching procedures using Opalescence agents at 10%, 16%, and 40% concentrations, with and without laser activation. Surface microhardness was assessed using the Vickers method, roughness was measured with 3D confocal laser microscopy, and friction coefficients and wear patterns were evaluated using tribological testing. All bleaching protocols resulted in reduced microhardness and increased surface roughness. The most significant changes were observed after treatment with 40% hydrogen peroxide. Laser application, particularly at 16% concentration of carbamide peroxide, helped to partially mitigate these effects in some materials. Bleaching procedures, especially those involving high peroxide concentrations, significantly deteriorated the surface properties of dental composites, which may have clinical implications for the patients. Full article

Accurate and efficient detection of floating waste is crucial for environmental protection and aquatic ecosystem preservation, yet remains challenging due to environmental interference and the prevalence of small targets. To address these limitations, we propose a Multi-scale Adaptive Real-time Detector (RTDETR-MARD) based on RT-DETR that introduces three key innovations for improved floating waste detection using unmanned surface vessels (USVs). First, our hierarchical multi-scale feature integration leverages the gather-and-distribute mechanism to enhance feature aggregation and cross-layer interaction. Second, we develop an advanced feature fusion module incorporating feature alignment, Information Fusion, information injection, and Scale Sequence Feature Fusion components to ensure precise spatial alignment and semantic consistency. Third, we implement the Wise-IoU loss function to optimize localization accuracy through high-quality anchor supervision. Extensive experiments demonstrate the framework’s effectiveness, achieving state-of-the-art performance of 86.6% mAP50 at 96.8 FPS on the FloW dataset and 49.2% mAP50 at 107.5 FPS on our custom water surface waste dataset. These results confirm RTDETR-MARD’s superior accuracy, real-time capability, and robustness across diverse environmental conditions, making it particularly suitable for practical deployment in ecological monitoring systems where both speed and precision are critical requirements. Full article