RESUMO
Ulcerative colitis (UC) is an inflammatory disease with abdominal pain, diarrhea, and bloody stool as the main symptoms. Several studies have confirmed that polysaccharides are effective against UC. It is commonly accepted that the traditional benefits of Radix Codonopsis can be attributed to its polysaccharide contents, and inulin-type fructan CP-A is the main active monomer in the polysaccharide components. Herein, we established a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced UC rat model and lipopolysaccharide (LPS)-induced colonic epithelial cell model (NCM460) to investigate the effect of CP-A on UC. Untargeted metabolomics studies were conducted to identify differential metabolites using ultra-high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS) and enrich metabolic pathways in rat serum. The in vivo assays demonstrated that CP-A reduces colonic macroscopic injury, disease activity index (DAI), histopathological score, interleukin (IL)-8, and tumor necrosis factor-α (TNF-α) levels, as well as the expression of intercellular adhesion molecules. On the other hand, CP-A increases IL-10 and transforming growth factor-ß (TGF-ß) levels. The in vitro experiments indicated that CP-A treatment could reduce nitric oxide (NO) and IL-1ß after LPS stimulation. The metabolomics results suggested that CP-A therapy for UC may be related to the mammalian target of rapamycin (mTOR) signaling pathway. The in vitro and in vivo validation of the pathway showed similar results, indicating that CP-A alleviates UC by preventing the activation of mTOR/p70S6K signaling pathway. These findings offer a fresh approach to treating UC and a theoretical foundation for the future advancement of CP-A.NEW & NOTEWORTHY We report that an inulin-type fructan from Codonopsis pilosula CP-A exhibits a therapeutic effect on experimental colitis. Its mechanism may be to alleviate intestinal inflammation by preventing the activation of mammalian target of rapamycin (mTOR)/p70S6K signaling pathway. These findings offer a fresh approach to treating ulcerative colitis (UC) and a theoretical foundation for the future advancement of CP-A.
Assuntos
Codonopsis , Colite Ulcerativa , Colite , Ratos , Animais , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Inulina/farmacologia , Frutanos/efeitos adversos , Frutanos/química , Codonopsis/química , Proteínas Quinases S6 Ribossômicas 70-kDa/uso terapêutico , Ácidos Sulfônicos/efeitos adversos , Lipopolissacarídeos , Polissacarídeos , Serina-Treonina Quinases TOR , Colite/induzido quimicamente , Colite/tratamento farmacológico , Modelos Animais de Doenças , MamíferosRESUMO
Artificially designed metamaterial structures can manipulate electromagnetic waves, endowing them with exotic physical properties that are not found in natural materials, such as negative refractive index, superlens, and inverse Doppler effect. These characteristics are widely applied in various engineering and military applications. Due to increasingly complex application environments and innovation in radar detection technology, the combination of broadband absorption performance under thin thickness and efficient preparation methods at low cost is often the focus of research on new generation stealth materials. Here, we propose Al@SiO2 composite conductive film metamaterial (Al@SiO2 CCFM) to achieve wideband absorption of electromagnetic waves. This metamaterial structure combines two resonant units, resulting in three absorption bands in the absorption curve. The results show that the absorption rate of the metamaterial is above 90% in the frequency range of 10.6â GHz to 26.0â GHz. The resonance mechanism between multiple structures is a prerequisite for achieving wideband absorption. The materials Al and SiO2 used in Al@SiO2 CCFM are inexpensive and abundant, and the fabrication method is simple. Therefore, they hold great potential for large-scale applications in the multispectral stealth and electromagnetic shielding field.
RESUMO
Lane detection plays a pivotal role in the successful implementation of Advanced Driver Assistance Systems (ADASs), which are essential for detecting the road's lane markings and determining the vehicle's position, thereby influencing subsequent decision making. However, current deep learning-based lane detection methods encounter challenges. Firstly, the on-board hardware limitations necessitate an exceptionally fast prediction speed for the lane detection method. Secondly, improvements are required for effective lane detection in complex scenarios. This paper addresses these issues by enhancing the row-anchor-based lane detection method. The Transformer encoder-decoder structure is leveraged as the row classification enhances the model's capability to extract global features and detect lane lines in intricate environments. The Feature-aligned Pyramid Network (FaPN) structure serves as an auxiliary branch, complemented by a novel structural loss with expectation loss, further refining the method's accuracy. The experimental results demonstrate our method's commendable accuracy and real-time performance, achieving a rapid prediction speed of 129 FPS (the single prediction time of the model on RTX3080 is 15.72 ms) and a 96.16% accuracy on the Tusimple dataset-a 3.32% improvement compared to the baseline method.
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BACKGROUND: The lymph node ratio (LNR) is an emerging prognostic biomarker in multiple malignancies. This study aimed to explore the prognostic role of LNR in patients with non-metastatic cervical cancer undergoing radical hysterectomy. METHODS: Data were extracted from the SEER 17 registry. Univariate and multivariate Cox analyses were performed to identify the prognostic factors associated with cancer-specific survival (CSS). A nomogram was constructed to predict the 5-year and 10-year CSS. Survival analyses stratified by the status of LNR and different adjuvant treatments were performed using the Kaplan-Meier method. RESULTS: A total of 8128 female patients with non-metastatic cervical cancer who underwent radical hysterectomy and regional node examination (≥8) were enrolled. Of these, 1269 (15.6%) were confirmed as lymph node-positive. Cox regression analyses showed that age, race, tumor size, tumor grade, histology, and LNR were significant factors affecting CSS. A nomogram was developed for predicting the 5-year and 10-year CSS, which showed good discrimination and calibration. Patients without lymph node involvement had inferior CSS with adjuvant treatments compared to those who did not receive further treatment. In patients with LNR ≤10%, only those receiving adjuvant radiotherapy had a trend of better CSS. In patients with an LNR between 10% and 30% and more than 30%, concurrent radiochemotherapy (CCRT) proved to be the best treatment. CONCLUSIONS: LNR is an independent prognostic factor in patients with non-metastatic cervical cancer undergoing radical hysterectomy. For patients with negative lymph nodes, no further treatment is recommended. Patients with positive lymph nodes could benefit more from CCRT.
Assuntos
Neoplasias do Colo do Útero , Humanos , Feminino , Prognóstico , Neoplasias do Colo do Útero/cirurgia , Neoplasias do Colo do Útero/patologia , Razão entre Linfonodos , Metástase Linfática/patologia , Linfonodos/patologia , Histerectomia , Estadiamento de NeoplasiasRESUMO
In an ongoing effort to explore more potent antifungal pogostone (Po) analogues, we maintained the previously identified 3-acetyl-4-hydroxy-2-pyrone core motif while synthesizing a series of Po analogues with variations in the alkyl side chain. The in vitro bioassay results revealed that compound 21 was the most potent antifungal analogue with an EC50 value of 1.1 µg/mL against Sclerotinia sclerotiorum (Lib.) de Bary. Meanwhile, its Cu(II) complex 34 manifested significantly enhanced antibacterial activity against Xanthomonas campestris pv campestris (Xcc) with a minimum inhibitory concentration (MIC) value of 300 µg/mL compared with 21 (MIC = 700 µg/mL). Complex 34 exhibited a striking preventive effect against S. sclerotiorum and Xcc in rape leaves, with control efficacies of 98.8% (50 µg/mL) and 80.7% (1000 µg/mL), respectively. The 3D-QSAR models generated using Topomer comparative molecular field analysis indicated that a shorter alkyl chain (carbon atom number <8), terminal rings, or electron-deficient groups on the alkyl side chain are beneficial for antifungal potency. Further, bioassay results revealed that the component of 21 in complex 34 dominated the antifungal activity, but the introduction of Cu(II) significantly enhanced its antibacterial activity. The toxicological observations demonstrated that 21 could induce abnormal mitochondrial morphology, loss of mitochondrial membrane potential, and reactive oxygen species (ROS) accumulation in S. sclerotiorum. The enzyme assay results showed that 21 is a moderate promiscuous inhibitor of mitochondrial complexes II and III. Besides, the introduction of Cu(II) to 34 could promote the disruption of the cell membrane and intracellular proteins and the ROS level in Xcc compared with 21. In summary, these results highlight the potential of 34 as a dual antifungal and antibacterial biocide for controlling rape diseases or as a promising candidate for further optimization.