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This study aimed to determine changes in the hydrolysis of vicagrel, a substrate drug of arylacetamide deacetylase (Aadac) and carboxylesterase 2 (Ces2), in P-glycoprotein (P-gp)-deficient or P-gp-inhibited mice and to elucidate the mechanisms involved.Male wild-type (WT) and P-gp knock-out (KO) mice were used to investigate the systemic exposure of vicagrel thiol active metabolite H4 and platelet response to vicagrel, and the mRNA and protein expression levels of intestinal Aadac and Ces2. Moreover, WT mice were administered vicagrel alone or in combination with elacridar (a potent P-gp inhibitor) to determine drug-drug interactions.Compared with WT mice, P-gp KO mice exhibited significant increases in the systemic exposure of H4, the protein expression levels of intestinal Aadac and Ces2, and inhibition of ADP-induced platelet aggregation by vicagrel. Further, the H4 exposure was positively correlated with intestinal Aadac protein expression levels but did not vary with short-term inhibition of P-gp efflux activity by elacridar.P-gp-deficient mice, rather than elacridar-treated mice, exhibited significant upregulation of intestinal Aadac and Ces2 and thus, enhanced metabolic activation of and platelet response to vicagrel, suggesting that the metabolic activation of vicagrel may vary with P-gp deficiency, not P-gp inhibition, in mice.
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To address the lightweight and real-time issues of coal sorting detection, an intelligent detection method for coal and gangue, Our-v8, was proposed based on improved YOLOv8. Images of coal and gangue with different densities under two diverse lighting environments were collected. Then the Laplacian image enhancement algorithm was proposed to improve the training data quality, sharpening contours and boosting feature extraction; the CBAM attention mechanism was introduced to prioritize crucial features, enhancing more accurate feature extraction ability; and the EIOU loss function was added to refine box regression, further improving detection accuracy. The experimental results showed that Our-v8 for detecting coal and gangue in a halogen lamp lighting environment achieved excellent performance with a mean average precision (mAP) of 99.5%, was lightweight with FLOPs of 29.7, Param of 12.8, and a size of only 22.1 MB. Additionally, Our-v8 can provide accurate location information for coal and gangue, making it ideal for real-time coal sorting applications.
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This study utilized hyperspectral imaging technology combined with mathematical modeling methods to predict the protein content of rice grains. Firstly, the Kjeldahl method was used to determine the protein content of rice grains, and different preprocessing techniques were applied to the spectral information. Then, a prediction model for rice grain protein content was developed by combining the spectral data with the protein content. After performing multiplicative scatter correction (MSC) preprocessing and selecting feature wavelengths based on successive projections algorithm (SPA), the multivariate linear regression (MLR) model showed the best prediction performance, with a calibration set R2C of 0.9393, a validation set R2V of 0.8998, an RMSEV of 0.1725, and an RPD of 3.16. Finally, the quantitative protein content model was mapped pixel by pixel to visualize the distribution of rice protein, providing possibilities for non-destructive protein content detection.
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Imageamento Hiperespectral , Oryza , Proteínas de Plantas , Oryza/química , Imageamento Hiperespectral/métodos , Proteínas de Plantas/análise , Algoritmos , Grão Comestível/química , Modelos LinearesRESUMO
Congenital sideroblastic anemia (CSA) is a group of disorders caused by different genetic mutations that result in low iron utilization and ineffective erythropoiesis. Current treatments are limited, and some patients do not respond to vitamin B6 therapy. Luspatercept is a novel erythropoietic maturation agent approved for adult ß-thalassemia and Myelodysplastic syndromes with ring sideroblasts (MDS-RS) associated with ineffective erythropoiesis. Here we report 2 patients with CSA due to mutations in ALAS2 and SLC25A38 genes who became unresponsive after a period of treatment with vitamin B6 and iron chelators but achieved transfusion independence and a markedly reduced spleen after combination with luspatercept.
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Receptores de Activinas Tipo II , Anemia Sideroblástica , Doenças Genéticas Ligadas ao Cromossomo X , Proteínas Recombinantes de Fusão , Adulto , Humanos , 5-Aminolevulinato Sintetase , Receptores de Activinas Tipo II/efeitos adversos , Anemia Sideroblástica/tratamento farmacológico , Anemia Sideroblástica/genética , Anemia Sideroblástica/congênito , Fragmentos Fc das Imunoglobulinas/efeitos adversos , Proteínas Recombinantes de Fusão/efeitos adversos , Vitamina B 6RESUMO
Growth period determination and color coordinates prediction are essential for comparing postharvest fruit quality. This paper proposes a tomato growth period judgment and color coordinates prediction model based on hyperspectral imaging technology. It utilizes the most effective color coordinates prediction model to obtain a color visual image. Firstly, hyperspectral images were taken of tomatoes at different growth periods (green-ripe, color-changing, half-ripe, and full-ripe), and color coordinates (L*, a*, b*, c, h) were obtained using a colorimeter. The sample set was divided by the sample set partitioning based on joint X-Y distances (SPXY). The support vector machine (SVM), K-nearest neighbors (KNN), and linear discriminant analysis (LDA) were used to discriminate growth period. Results show that the LDA model has the best prediction effect with a prediction set accuracy of 93.1%. In addition, effective wavelengths were selected using competitive adaptive reweighted sampling (CARS) and successive projections algorithm (SPA), and chromaticity prediction models were established using partial least squares regression (PLSR), multiple linear regression (MLR), principal component regression (PCR) and support vector machine regression (SVR) Finally, the color of each pixel of the tomato is calculated using the optimal model, generating a visual distribution image of the color coordinate. The results showed that hyperspectral imaging can non-destructively detect tomatoes' growth stage and color coordinates, providing great significance for designing a tomato quality grading system.
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Cor , Frutas , Imageamento Hiperespectral , Solanum lycopersicum , Máquina de Vetores de Suporte , Solanum lycopersicum/crescimento & desenvolvimento , Imageamento Hiperespectral/métodos , Análise Discriminante , Frutas/crescimento & desenvolvimento , Frutas/química , Análise dos Mínimos Quadrados , Análise de Componente Principal , Algoritmos , Modelos LinearesRESUMO
Background: Neoadjuvant therapy has become a mainstay of treatment for locally advanced resectable esophageal cancer. The objective of this research was to investigate the effectiveness and safety of neoadjuvant immunotherapy combined with chemotherapy in treating surgically removable esophageal squamous cell carcinoma (ESCC). Methods: From January 1, 2016 to April 1, 2023, we conducted a retrospective analysis of patients diagnosed with resectable esophageal cancer who underwent neoadjuvant immunotherapy combined with chemotherapy at The First Affiliated Hospital of Nanchang University. The primary endpoints of this study were pathologic complete response (pCR), major pathologic response (MPR) and disease-free survival (DFS). The secondary endpoints of this study were overall survival (OS), objective response rate (ORR) and safety. Results: A total of 122 patients with ESCC receiving neoadjuvant immune-chemotherapy (nICT) were included. Fifty-four patients achieved partial response (PR) and two patients achieved complete response (CR), with an ORR of 45.9%. Of the 106 patients who underwent surgery, a total of 28 patients achieved pCR (26.4%) and a total of 37 patients achieved MPR (34.9%). Grade 3 or higher adverse events occurred in 26 patients (21.3%). The most common postoperative complication was pneumonitis (25.5%). Conclusions: Neoadjuvant immunotherapy combined with chemotherapy demonstrates satisfactory efficacy in the treatment of locally advanced ESCC, with manageable treatment-related adverse events and postoperative complications.
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The COVID-19 pandemic has resulted in a substantial surge in the usage of disposable plastic masks, generating a significant volume of waste and contributing to environmental pollution. Wetland ecosystems function as crucial repositories for terrestrial pollutants and are highly effective in retaining disposable masks composed mainly of PP material. These masks can endure extended periods in wetlands, experiencing natural degradation that may have potential implications on wetland ecosystems. Our findings demonstrate the natural aging process of disposable masks, resulting in the generation of microplastics (MPs) ranging in diameter from 10 to 30 µm over a 180-day timeframe. Examination of 16S rDNA data unveiled temporal fluctuations in microbial diversity in the wetland ecosystem. Initially, microbial diversity displayed a modest incline, which was succeeded by a subsequent decrease. With the progressive accumulation of plastic within the wetland, an ongoing decline in microbial diversity linked to nitrogen transformation was observed. This study provides valuable insights into the retention of disposable masks by wetlands amidst the COVID-19 pandemic, along with their consequential effects on wetland ecosystems, specifically pertaining to nitrogen cycling. It underscores the urgency of augmenting the safeguarding measures for wetland ecosystems.
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COVID-19 , Microbiota , Humanos , Áreas Alagadas , Ecossistema , Polipropilenos , Pandemias , Plásticos , Envelhecimento , NitrogênioRESUMO
The present study sought to propose Ganoderma guixiense sp. nov. as a new species based on phenotypic and genotypic evidence. Phylogenetic analyses were carried out based on the internal transcribed spacer (ITS), the large subunit of nuclear ribosomal RNA gene (nLSU), and the second subunit of RNA polymerase II (RPB2) sequence data. G. guixiense has been characterized by pileate basidiomata, long stipe, in addition to reddish-black zonate pileal surface. Basidiospores are broadly ellipsoid with one end tapering at maturity, and measuring 9-12.8 × 6.5-9.3 µm. Basidia are oval to subglobose. This study marks the first exploration of the biological characteristics of G. guixiense. The result indicated that the optimal medium of mycelial growth was observed on malt extract agar (MEA) and yeast extract peptone dextrose agar (YPD) while the optimal temperature was found to be 25-30 °C with pH range of 6-7.
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OBJECTIVE: To investigate predictors of anticoagulation efficacy in deep venous thrombosis (DVT) by ultrasound elastography (UE). METHODS: The basic clinical, laboratory and ultrasound treatment data of fifty-eight patients with DVT were collected and analyzed. Then the results of ultrasound after 3-month anticoagulation treatment were compared among different groups. Multiple logistic regression analysis was used to identify independent risk factors that affected anticoagulation efficacy. The predictive efficacy of each independent risk factor was accessed by drawing operating characteristic (ROC) curves. RESULTS: According to the regression analysis, the elastic modulus (ORâ=â0.631, Pâ=â0.001) and strain rate ratio (ORâ=â0.332, Pâ=â0.006) were identified as independent risk factors for the effectiveness of anticoagulation therapy in patients with DVT. According to the ROC curves, elastic modulus and strain rate ratio could predict effective anticoagulation therapy for DVT, and the optimal threshold values were 22.10âkPa and 1.80 respectively. The corresponding AUC values were 0.879 and 0.854, with a sensitivity of 71.4% and 59.5%, a specificity of 93.7%, and a Youden index of 65.1% and 62.7%, respectively. CONCLUSIONS: The elastic modulus (≤22.10âkPa) or strain rate ratio (≤1.80) of the thrombus were independent predictors for the effectiveness of anticoagulation therapy.
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Anticoagulantes , Técnicas de Imagem por Elasticidade , Extremidade Inferior , Trombose Venosa , Humanos , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/tratamento farmacológico , Técnicas de Imagem por Elasticidade/métodos , Masculino , Anticoagulantes/uso terapêutico , Feminino , Pessoa de Meia-Idade , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/diagnóstico por imagem , Adulto , Idoso , Fatores de RiscoRESUMO
Dry powder inhalers (DPIs) are widely employed to treat respiratory diseases, offering numerous advantages such as high dose capacity and stable formulations. However, they usually face challenges in achieving sufficient pulmonary drug delivery and minimizing excessive oropharyngeal deposition. This review provides a new viewpoint to address these challenges by focusing on the role of swirling flow, a crucial yet under-researched aspect that induces strong turbulence. In the review, we comprehensively discuss both key classic designs (tangential inlet, swirling chamber, grid mesh, and mouthpiece) and innovative designs in inhalers, exploring how the induced swirling flow initiates powder dispersion and promotes delivery efficiency. Valuable design considerations to effectively coordinate inhalers with formulations and patients are also provided. It is highlighted that the delicate manipulation of swirling flow is essential to maximize benefits. By emphasizing the role of swirling flow and its potential application, this review offers promising insights for advancing DPI technology and optimizing therapeutic outcomes in inhaled therapy.