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The outcome of certain plant-virus interaction is symptom recovery, which is accompanied with the emergence of asymptomatic tissues in which the virus accumulation decreased dramatically. This phenomenon shows the potential to reveal critical molecular factors for controlling viral disease. MicroRNAs act as master regulators in plant growth, development, and immunity. However, the mechanism by which miRNA participates in regulating symptom recovery remains largely unknown. Here, we reported that miR172 was scavenged in the recovered tissue of tobacco mosaic virus (TMV)-infected Nicotiana tabacum plants. Overexpression of miR172 promoted TMV infection, whereas silencing of miR172 inhibited TMV infection. Then, TARGET OF EAT3 (TOE3), an APETALA2 transcription factor, was identified as a downstream target of miR172. Overexpression of NtTOE3 significantly improved plant resistance to TMV infection, while knockout of NtTOE3 facilitated virus infection. Furthermore, transcriptome analysis indicated that TOE3 promoted the expression of defense-related genes, such as KL1 and MLP43. Overexpression of these genes conferred resistance of plant against TMV infection. Importantly, results of dual-luciferase assay, chromatin immunoprecipitation-quantitative PCR, and electrophoretic mobility shift assay proved that TOE3 activated the transcription of KL1 and MLP43 by binding their promoters. Moreover, overexpression of rTOE3 (the miR172-resistant form of TOE3) significantly reduced TMV accumulation compared to the overexpression of TOE3 (the normal form of TOE3) in miR172 overexpressing Nicotiana benthamiana plants. Taken together, our study reveals the pivotal role of miR172/TOE3 module in regulating plant immunity and in the establishment of recovery in virus-infected tobacco plants, elucidating a regulatory mechanism integrating plant growth, development, and immune response.
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The RNA regulatory network is a complex and dynamic regulation in plant cells involved in mRNA modification, translation, and degradation. Ras-GAP SH3 domain-binding protein (G3BP) is a scaffold protein for the assembly of stress granules (SGs) and is considered an antiviral component in mammals. However, the function of G3BP during virus infection in plants is still largely unknown. In this study, four members of the G3BP-like proteins (NtG3BPLs) were identified in Nicotiana tabacum and the expression levels of NtG3BPL1 were upregulated during chilli veinal mottle virus (ChiVMV) infection. NtG3BPL1 was localized in the nucleus and cytoplasm, forming cytoplasmic granules under transient high-temperature treatment, whereas the abundance of cytoplasmic granules was decreased under ChiVMV infection. Overexpression of NtG3BPL1 inhibited ChiVMV infection and delayed the onset of symptoms, whereas knockout of NtG3BPL1 promoted ChiVMV infection. In addition, NtG3BPL1 directly interacted with ChiVMV 6K2 protein, whereas 6K2 protein had no effect on NtG3BPL1-derived cytoplasmic granules. Further studies revealed that the expression of NtG3BPL1 reduced the chloroplast localization of 6K2-GFP and the NtG3BPL1-6K2 interaction complex was localized in the cytoplasm. Furthermore, NtG3BPL1 promoted the degradation of 6K2 through autophagy pathway, and the accumulation of 6K2 and ChiVMV was affected by autophagy activation or inhibition in plants. Taken together, our results demonstrate that NtG3BPL1 plays a positive role in tobacco resistance against ChiVMV infection, revealing a novel mechanism of plant G3BP in antiviral strategy.
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Nicotiana , Enfermedades de las Plantas , Proteínas de Plantas , Nicotiana/virología , Nicotiana/genética , Nicotiana/metabolismo , Enfermedades de las Plantas/virología , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Resistencia a la Enfermedad/genética , Regulación de la Expresión Génica de las Plantas , Plantas Modificadas Genéticamente , Potyvirus/fisiologíaRESUMEN
MiRNAs play an important role in regulating plant growth and immune response. Mosaic diseases are recognized as the most important plant diseases in the world, and mosaic symptoms are recovery tissues formed by plants against virus infection. However, the mechanism of the formation of mosaic symptoms remains elusive. In this study, two typical mosaic systems consisting of Nicotiana tabacum-cucumber mosaic virus (CMV) and N. tabacum-tobacco mosaic virus (TMV) were used to investigate the relevance of miRNAs to the appearance of mosaic symptoms. The results of miRNA-seq showed that there were significant differences in miRNA abundance between dark green tissues and chlorotic tissues in mosaic leaves caused by the infection of CMV or TMV. Compared with healthy tissues, miRNA expression was significantly increased in chlorotic tissues, but slightly increased in dark green tissues. Three miRNAs, namely miR1919, miR390a, and miR6157, were identified to be strongly up-regulated in chlorotic tissues of both mosaic systems. Results of overexpressing or silencing of the three miRNAs proved that they were related to chlorophyll synthesis, auxin response, and small GTPase-mediated immunity pathway, which were corresponding to the phenotype, physiological parameters and susceptibility of the chlorotic tissues in mosaic leaves. Besides, the newly identified novel-miRNA48, novel-miRNA96 and novel-miRNA103 may also be involved in this formation of mosaic symptoms. Taken together, our results demonstrated that miR1919, miR390a and miR6157 are involved in the formation of mosaic symptoms and plant antiviral responses, providing new insight into the role of miRNAs in the formation of recovery tissue and plant immunity.
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Infecciones por Citomegalovirus , MicroARNs , Nicotiana/genética , Ácidos Indolacéticos , MicroARNs/genética , FenotipoRESUMEN
BACKGROUND: For patients with stage III epithelial ovarian cancer, there are limited studies on the effects of postoperative adjuvant radiotherapy (RT). Here we assessed the therapeutic efficacy and toxicity of postoperative radiotherapy to the abdominal and pelvic lymphatic drainage area for stage III epithelial ovarian cancer patients, who had all received surgery and chemotherapy (CT). METHODS: We retrospectively collected patients with stage III epithelial ovarian cancer after cytoreductive surgery (CRS) and full-course adjuvant CT. The chemoradiotherapy (CRT) group patients were treated with intensity modulated radiotherapy (IMRT) to the abdominal and pelvic lymphatic drainage area in our hospital between 2010 and 2020. A propensity score matching analysis was conducted to compare the results between the CRT and CT groups. Kaplan-Meier analysis estimated overall survival (OS), disease-free survival (DFS), and local control (LC) rates. The log-rank test determined the significance of prognostic factors. RESULTS: A total of 132 patients with median follow-up of 73.9 months (9.1-137.7 months) were included (44 and 88 for the CRT and RT groups, retrospectively). The baseline characteristics of age, histology, level of CA12-5, surgical staging, residual tumour, courses of adjuvant CT, and courses to reduce CA12-5 to normal were all balanced. The median DFS time, 5-year OS, and local recurrence free survival (LRFS) were 100.0 months vs 25.9 months (P = .020), 69.2% vs 49.9% (P = .002), and 85.9% vs 50.5% (P = .020), respectively. The CRT group mainly presented with acute haematological toxicities, with no statistically significant difference compared with grade III intestinal adverse effects (3/44 vs 6/88, P = .480). CONCLUSION: This report demonstrates that long-term DFS could be achieved in stage III epithelial ovarian cancer patients treated with IMRT preventive radiation to the abdominal and pelvic lymphatic area. Compared with the CT group, DFS and OS were significantly prolonged and adverse effects were acceptable.
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Estadificación de Neoplasias , Humanos , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Ováricas/patología , Neoplasias Ováricas/terapia , Neoplasias Ováricas/mortalidad , Adulto , Anciano , Carcinoma Epitelial de Ovario/terapia , Carcinoma Epitelial de Ovario/patología , Procedimientos Quirúrgicos de Citorreducción/métodos , Radioterapia de Intensidad Modulada/métodos , Radioterapia Adyuvante/métodosRESUMEN
OBJECTIVE: This study aimed to analyse long term outcomes and risk factors for endovascular repair of aortic pseudoaneurysms in patients with vascular Behçet's disease (BD). METHODS: Medical records of 26 aortic vascular BD patients who underwent endovascular treatment at the vascular department of Peking Union Medical College Hospital between January 2002 and December 2021 were reviewed retrospectively. Erythrocyte sedimentation rate (ESR) and C reactive protein were used to assess BD activity. Computed tomography angiography (CTA) was obtained pre- and post-operatively for almost all patients. Univariable logistic regression analysis was used to analyse risk factors for endovascular repair, such as inflammatory indicators, drug usage, and stent graft parameters. RESULTS: The abdominal aorta (n = 17) was the most common site of 27 vascular BD pseudoaneurysms in this study. CTA also revealed one aortic arch pseudoaneurysm, seven descending thoracic aortic pseudoaneurysms, one thoraco-abdominal aortic pseudoaneurysm, and one pseudoaneurysm at the aortic bifurcation. Most of the pseudoaneurysms were treated with covered stent grafts. The technical success rate was 96% and no deaths occurred during hospital stay. The mean follow up was 5.8 ± 5.5 years and 31% (8/26) experienced post-operative complications. Overall one, three, and five year event free survival rates were 87%, 78%, and 74%, respectively. Univariable logistic regression analysis revealed that pre-operative ESR ≥ 16.0 mm/h (p = .040), pre-operative glucocorticoid (GC) use ≤ 11.5 days (p = .024), pre-operative immunosuppressant use ≤ 15.5 days (p = .028), and length of proximal landing zone ≤ 1.95 cm (p = .034) were associated with a worse prognoses following endovascular treatment. Proximal oversize ≥ 9.5% (p = .074) was also regarded as a risk factor, although not statistically significant. CONCLUSION: This study further confirmed the feasibility of endovascular repair for aortic vascular BD patients. Risk factors predicting poor prognoses included elevated pre-operative ESR, insufficient pre-operative GC use or immunosuppressant use, inadequate proximal landing zone, and larger proximal oversize percentage.
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Aneurisma Falso , Síndrome de Behçet , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Humanos , Aneurisma Falso/diagnóstico por imagen , Aneurisma Falso/etiología , Aneurisma Falso/cirugía , Síndrome de Behçet/complicaciones , Síndrome de Behçet/diagnóstico , Estudios Retrospectivos , Implantación de Prótesis Vascular/efectos adversos , Resultado del Tratamiento , Stents/efectos adversos , Procedimientos Endovasculares/efectos adversos , Factores de Riesgo , Inmunosupresores/uso terapéutico , Prótesis Vascular/efectos adversosRESUMEN
Catalases (CATs) play important roles in plant growth, development and defense responses. Previous studies have shown that CATs exhibit different or even opposite effects on plant immunity in different plant-pathogen interactions, but little is known about the mechanisms. In this study, Nicotiana tabacum plants with overexpression or knockout of CAT genes, tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) were employed to investigate the role of CAT in compatible plant-virus interactions. The results showed that there were dynamic changes in the effect of CAT on N. tabacum defense responses. Overexpression of catalase 1 (CAT1) and catalase 3 (CAT3) improved N. tabacum resistance in the early stage of virus infection but depressed it during the late stages of pathogenesis, especially in CAT3 overexpressing plants. The lower level of electrolyte leakage, lower contents of malonaldehyde and hydrogen peroxide (H2 O2 ), higher activities of antioxidant enzymes and improved functions of photosystem II corresponded to the milder symptoms and higher resistance of infected tobacco plants. In addition, the infection of TMV and CMV resulted in expression changes of CATs in tobacco plants, and pretreatment with H2 O2 facilitated TMV and CMV infection. Further experiments showed that the content of salicylic acid (SA) and the expression of genes related to SA signaling pathway were positively correlated with plant resistance, whereas auxin and its related signaling pathway were related to the viral susceptibility of plants. Taken together, our results demonstrated that CAT1 and CAT3 mediated tobacco resistance to virus infection through crosstalk between SA and auxin signaling pathways.
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Infecciones por Citomegalovirus , Virosis , Ácido Salicílico/metabolismo , Catalasa/metabolismo , Nicotiana/metabolismo , Transducción de Señal , Ácidos Indolacéticos/metabolismo , Enfermedades de las PlantasRESUMEN
BACKGROUND: Rectal cancer (RC) is one of the most common malignant tumors. Ferroptosis is an iron-dependent form of cell death, which plays an important role in various cancers. However, the correlation between ferroptosis-related genes (FRGs) and prognosis in RC remains unclear. METHODS: Gene expression data from The Cancer Genome Atlas Rectum adenocarcinoma (TCGA-READ) and GSE87211 were downloaded. Clustering and functional enrichment were evaluated. A FRGs risk score was established based on the univariate Cox analysis and the Least absolute shrinkage and selection operator (LASSO) analysis. K-M analysis and ROC analysis were conducted to determine prognostic values. qRT-PCR was performed to validate levels of mRNA expression. Multivariate Cox analysis was used to build a prognostic prediction model based on the risk score. RESULTS: Based on FRGs, RC patients were grouped into two clusters. In the functional enrichment of differentially expressed genes between the two clusters, immune-related pathways dominated. A novel FRGs signature with 14 genes related to the overall survival (OS) of RC was established. qRT-PCR of the 14 genes identified TP63, ISCU, PLIN4, MAP3K5, OXSR, FANCD2 and ATM were overexpressed in RC tissue; HSPB1, MAPK1, ABCC1, PANX1, MAPK9 and ATG7 were underexpressed; TUBE1 had no difference. The high-risk group had a significantly lower OS than the low-risk group (P < 0.001), and ROC curve analysis confirmed the signature's predictive capacity. Multivariate analysis demonstrated that the risk score and age were independent prognostic factors. CONCLUSION: A novel FRGs model can be used to predict the prognosis in RC, as well as to guide individual treatment.
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Ferroptosis , Neoplasias del Recto , Humanos , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Ferroptosis/genética , Regulación Neoplásica de la Expresión Génica , Pronóstico , Neoplasias del Recto/genéticaRESUMEN
Small GTPases play critical roles in the regulation of plant growth and development. However, the mechanism of action of small GTPases in plant response to virus infection remains largely unknown. Here, the gene encoding a Rho-type GTPase, NtRHO1, was identified as one of the genes up-regulated after tobacco mosaic virus (TMV) infection. Subcellular localization of NtRHO1 showed that it was located in the cytoplasm, plasma membrane, and nucleus. Transient overexpression of NtRHO1 in Nicotiana benthamiana accelerated TMV reproduction and led to the production of reactive oxygen species. By contrast, silencing of NtRHO1 reduced the sensitivity of N. benthamiana to TMV-GFP. Further exploration revealed a direct interaction between NtRHO1 and NtWRKY50, a positive regulator of the N. benthamiana response to virus infection. Yeast one-hybrid and electrophoretic mobility shift assays showed that this regulation was related to the capacity of NtWRKY50 to bind to the WK-box of the PR1 promoter, which was weakened by the interaction between NtRHO1 and NtWRKY50. Thus, our results indicate that the small GTPase NtRHO1 plays a negative role in tobacco response to TMV infection by interacting with transcription factor NtWRKY50, resulting in reduced plant immunity.
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Proteínas de Unión al GTP Monoméricas , Virus del Mosaico del Tabaco , Enfermedades de las Plantas , Inmunidad de la Planta , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Nicotiana/metabolismo , Virus del Mosaico del Tabaco/metabolismoRESUMEN
BACKGROUND: The International Classification of Diseases (ICD) and the International Classification of Diseases for Oncology (ICD-O) are both widely used global classification systems. In 2018, the initial release of the ICD-11 was published by the World Health Organization (WHO), integrating the morphology section of the ICD-O. METHODS: This paper aims to provide potential ICD-11 users with a profound understanding of the neoplasm classifications of the ICD-11 by analysing the differences and relationships between the ICD-11 and ICD-O in terms of the coding framework, compatibility and intelligence level. RESULTS: The ICD-11 and ICD-O have remarkable differences in coding structure. Compared to the ICD-O, the ICD-11 has the following advantages: adding histopathology to the stem codes, obtaining a meaningful minimum amount of information through stem codes for statistics, supporting the usage of ICD-O morphology categories and capturing clinical details via extension codes for multiaxial coding. In addition, the rich Foundation Component, linearization derived from the Foundation Component and updating mechanism all support the compatibility of the ICD-11 with other classification systems. Notably, the WHO provides terminology coding with a smart coding tool, and coding in the ICD-11 can draw on statistical codes and uniform resource identifiers (URIs) simultaneously. CONCLUSIONS: The ICD-11 represents a novel classification system with distinguishing features that include facilitating statistics, multiaxial coding, coding granularity, compatibility and intelligence. These features enable the ICD-11 to be more powerful for neoplasm coding than the ICD-O and basically meet the needs of stakeholders.
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Clasificación Internacional de Enfermedades , Neoplasias , Humanos , Neoplasias/diagnósticoRESUMEN
PURPOSE: Diagnostic statements for pituitary adenomas (PAs) are complex and unstandardized. We aimed to determine the most commonly used elements contained in the statements and their combination patterns and variations in real-world clinical practice, with the ultimate goal of promoting standardized diagnostic recording and establishing an efficient element extraction process. METHODS: Patient medical records from 2012 to 2020 that included PA among the first three diagnoses were included. After manually labeling the elements in the diagnostic texts, we obtained element types and training sets, according to which an information extraction model was constructed based on the word segmentation model "Jieba" to extract information contained in the remaining diagnostic texts. RESULTS: A total of 576 different diagnostic statements from 4010 texts of 3770 medical records were enrolled in the analysis. The first ten diagnostic elements related to PA were histopathology, tumor location, endocrine status, tumor size, invasiveness, recurrence, diagnostic confirmation, Knosp grade, residual tumor, and refractoriness. The automated extraction model achieved F1-scores that reached 100% for all ten elements in the second round and 97.3-100.0% in the test set consisting of an additional 532 diagnostic texts. Tumor location, endocrine status, histopathology, and tumor size were the most commonly used elements, and diagnoses composed of the above elements were the most frequent. Endocrine status had the greatest expression variability, followed by Knosp grade. Among all the terms, the percentage of loss of tumor size was among the highest (21%). Among statements where the principal diagnoses were PAs, 18.6% did not have information on tumor size, while for those with other diagnoses, this percentage rose to 48% (P < 0.001). CONCLUSION: Standardization of the diagnostic statement for PAs is unsatisfactory in real-world clinical practice. This study could help standardize a structured pattern for PA diagnosis and establish a foundation for research-friendly, high-quality clinical information extraction.
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Neoplasias Hipofisarias , Humanos , Neoplasias Hipofisarias/diagnóstico , Registros Electrónicos de Salud , Almacenamiento y Recuperación de la InformaciónRESUMEN
The nickel-catalyzed aminomethylation of mercaptans has been disclosed that offers efficient and expedient access to synthesize α-aminosulfides. The intramolecular fragment coupling shows excellent chemoselectivity. This transformation shows good functional-group compatibility, tolerates a wide range of electron-withdrawing, electron-neutral, and electron-donating substituents in this process, and can serve as a powerful synthetic tool for the synthesis of α-aminosulfides at a gram scale. Thus, the newly developed methodology enables a facile route for C-S bond formation in a straightforward fashion.
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Níquel , Compuestos de Sulfhidrilo , Aminoácidos , Catálisis , ElectronesRESUMEN
Transition metal-catalyzed cross-couplings have been widely employed in the synthesis of many important molecules in synthetic chemistry for the construction of diverse C-C bonds. Conventional cross-coupling reactions require active electrophilic coupling partners, such as organohalides or sulfonates, which are not environmentally friendly enough. Herein, we disclose the first nickel-catalyzed Suzuki-Miyaura cross-coupling of aryl anhydrides and arylboronic acids for the synthesis of biaryls in a decarbonylation manner. The reaction tolerates a wide range of electron-withdrawing, electron-neutral, and electron-donating substituents in this process.
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A nickel-catalyzed decarbonylation or decarbonylation accompanied by decarboxylation cross-coupling reaction of aryl anhydrides with thiophenols as coupling partners was disclosed. This method is promoted by a commercially available, moisture-stable, and inexpensive nickel(II) precatalyst. The process can tolerate a variety of functional groups using ubiquitous aryl anhydrides as cross-coupling precursors to produce thioethers in moderate to excellent yields.
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Efficient one-pot synthesis of N-imidoyl-(1 H)-indoles has been described, which is achieved by the palladium-catalyzed oxidative insertion of 2-(phenylethynyl)aniline, arylboronic acid, and isonitrile. This method provides a new way to synthesize N-imidoyl-(1 H)-indoles, which has a wide substrate scope, good functional group tolerance, and mild reaction condition.
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Sixteen novel pyrazole carboxamides with diarylamines scaffold were designed, synthesized and characterized in detail via 1H NMR, 13C NMR and ESI-HRMS. Preliminary bioassays showed that some of the target compounds exhibited good antifungal activity against Rhizoctonia solani, Fusarium oxysporum, Phytophthora infestans and Fusarium graminearum. Among them, compound 1c exhibited the highest antifungal activities against R. solani in vitro with EC50 value of 0.005â¯mg/L, superior to the commercially available fungicide fluxapyroxad (EC50â¯=â¯0.033â¯mg/L). And compound 1c (IC50â¯=â¯0.034â¯mg/L) showed higher inhibition abilities against succinate dehydrogenase than fluxapyroxad (IC50â¯=â¯0.037â¯mg/L). This study suggests that compound 1c could be regarded as a potential succinate dehydrogenase inhibitor.
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Aminas/farmacología , Antifúngicos/farmacología , Inhibidores Enzimáticos/farmacología , Pirazoles/farmacología , Succinato Deshidrogenasa/antagonistas & inhibidores , Aminas/química , Antifúngicos/síntesis química , Antifúngicos/química , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Fusarium/efectos de los fármacos , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Phytophthora infestans/efectos de los fármacos , Pirazoles/química , Rhizoctonia/efectos de los fármacos , Relación Estructura-Actividad , Succinato Deshidrogenasa/metabolismoRESUMEN
Twelve novel fenfuram-diarylether hybrids were designed, synthesized and characterized by 1H NMR and MS. Their in vitro antifungal activities were evaluated against five phytopathogenic fungi by mycelial growth inhibition method. Most compounds showed significant antifungal effect on Rhizoctonia solani and Sclerotinia sclerotiorum. Compound 1c exhibited the most potent antifungal effect on R. solani with an EC50 value of 0.242mg/L, superior to the commercial fungicide boscalid (EC50=1.758mg/L) and the lead fungicide fenfuram (EC50=7.691mg/L). Molecular docking revealed that compound 1c featured a higher affinity for succinate dehydrogenase (SDH) than fenfuram. Furthermore, it was shown that the 2-chlorophenyl group of compound 1c formed a π-π stacking with D/Tyr-128 and a Cl-π interaction with B/His-249, which made compound 1c more active than fenfuram against SDH.
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Antifúngicos/farmacología , Inhibidores Enzimáticos/farmacología , Éteres/farmacología , Furanos/farmacología , Rhizoctonia/efectos de los fármacos , Succinato Deshidrogenasa/antagonistas & inhibidores , Antifúngicos/síntesis química , Antifúngicos/química , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Éteres/química , Furanos/química , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Estructura Molecular , Rhizoctonia/enzimología , Relación Estructura-Actividad , Succinato Deshidrogenasa/metabolismoRESUMEN
BACKGROUND: A rapid and sensitive analytical method using liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-MS/MS) was developed for the determination of paclitaxel, docetaxel, vinblastine, and vinorelbine in human plasma. METHODS: A simple liquid-liquid extraction procedure was applied using only 100-µL plasma. Chromatographic separation of these anticancer drugs was achieved with an isocratic mobile phase consisting of acetonitrile/aqueous buffer (10 mmol/L ammonium acetate and 0.1% formic acid in 70:30, vol/vol) at a flow rate of 0.25 mL/min in a short time (4.5 minutes). RESULTS: The calibration curves for paclitaxel, docetaxel, vinblastine, and vinorelbine in spiked human plasma ranged from 25 to 2500, 10 to 1000, 10 to 1000, and 10 to 1000 ng/mL, respectively. The squares of the linear correlation coefficients were all more than 0.99. The intraday and interday relative standard deviations across 3 validation runs over the entire concentration range were less than 9.2%. CONCLUSIONS: The established method should be helpful for the pharmacokinetic monitoring of paclitaxel, docetaxel, vinblastine, and vinorelbine in the human plasma of non-small cell lung cancer patients.
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Antineoplásicos/sangre , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Monitoreo de Drogas/métodos , Neoplasias Pulmonares/tratamiento farmacológico , Calibración , Cromatografía Líquida de Alta Presión , Docetaxel , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Paclitaxel/sangre , Sensibilidad y Especificidad , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en Tándem , Taxoides/sangre , Vinblastina/análogos & derivados , Vinblastina/sangre , VinorelbinaRESUMEN
Five new terpenes (1-5) and ten known compounds (6-15) were isolated from Inula japonica, and their structures were identified by spectroscopic analysis. Compounds 3 and 14 showed positive inhibitory effects on nitric oxide production. Furthermore, compound 14 suppressed both leukotriene C4 synthesis and degranulation in c-kit ligand-induced bone marrow-derived mast cells.
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Antiinflamatorios/farmacología , Degranulación de la Célula/efectos de los fármacos , Inula/química , Mastocitos/fisiología , Extractos Vegetales/farmacología , Terpenos/farmacología , Animales , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Línea Celular , Modelos Animales de Enfermedad , Flores/química , Concentración 50 Inhibidora , Leucotrieno C4/análisis , Leucotrieno C4/metabolismo , Lipopolisacáridos/metabolismo , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Mastocitos/efectos de los fármacos , Medicina Tradicional de Asia Oriental , Ratones , Ratones Endogámicos BALB C , Estructura Molecular , Óxido Nítrico/análisis , Óxido Nítrico/metabolismo , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Plantas Medicinales , Terpenos/química , Terpenos/aislamiento & purificaciónRESUMEN
BACKGROUND: The International Classification of Diseases, Eleventh Revision (ICD-11) improved neoplasm classification. OBJECTIVE: We aimed to study the alterations in the ICD-11 compared to the Chinese Clinical Modification of the International Classification of Diseases, Tenth Revision (ICD-10-CCM) for neoplasm classification and to provide evidence supporting the transition to the ICD-11. METHODS: We downloaded public data files from the World Health Organization and the National Health Commission of the People's Republic of China. The ICD-10-CCM neoplasm codes were manually recoded with the ICD-11 coding tool, and an ICD-10-CCM/ICD-11 mapping table was generated. The existing files and the ICD-10-CCM/ICD-11 mapping table were used to compare the coding, classification, and expression features of neoplasms between the ICD-10-CCM and ICD-11. RESULTS: The ICD-11 coding structure for neoplasms has dramatically changed. It provides advantages in coding granularity, coding capacity, and expression flexibility. In total, 27.4% (207/755) of ICD-10 codes and 38% (1359/3576) of ICD-10-CCM codes underwent grouping changes, which was a significantly different change (χ21=30.3; P<.001). Notably, 67.8% (2424/3576) of ICD-10-CCM codes could be fully represented by ICD-11 codes. Another 7% (252/3576) could be fully described by uniform resource identifiers. The ICD-11 had a significant difference in expression ability among the 4 ICD-10-CCM groups (χ23=93.7; P<.001), as well as a considerable difference between the changed and unchanged groups (χ21=74.7; P<.001). Expression ability negatively correlated with grouping changes (r=-.144; P<.001). In the ICD-10-CCM/ICD-11 mapping table, 60.5% (2164/3576) of codes were postcoordinated. The top 3 postcoordinated results were specific anatomy (1907/3576, 53.3%), histopathology (201/3576, 5.6%), and alternative severity 2 (70/3576, 2%). The expression ability of postcoordination was not fully reflected. CONCLUSIONS: The ICD-11 includes many improvements in neoplasm classification, especially the new coding system, improved expression ability, and good semantic interoperability. The transition to the ICD-11 will inevitably bring challenges for clinicians, coders, policy makers and IT technicians, and many preparations will be necessary.
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Sulfamethoxazole (SMX) is a common antibiotic pollutant in aquatic environments, which is highly persistent under various conditions and significantly contributes to the spread of antibiotic resistance. Biodegradation is the major pathway to eliminate antibiotics in the natural environment. The roles of bacteria and eukaryotes in the biodegradation of antibiotics have received considerable attention; however, their successions and co-occurrence patterns during the biodegradation of antibiotics remain unexplored. In this study, 13C-labled SMX was amended to sediment samples from Zhushan Bay (ZS), West Shore (WS), and Gonghu Bay (GH) in Taihu Lake to explore the interplay of bacterial and eukaryotic communities during a 30-day incubation period. The cumulative SMX mineralization on day 30 ranged from 5.2 % to 19.3 %, which was the highest in WS and the lowest in GH. The bacterial community showed larger within-group interactions than between-group interactions, and the positive interactions decreased during incubation. However, the eukaryotic community displayed larger between-group interactions than within-group interactions, and the positive interactions increased during incubation. The proportion of negative interactions between bacteria and eukaryotes increased during incubation. Fifty genera (including 46 bacterial and 4 eukaryotic genera) were identified as the keystone taxa due to their dominance in the co-occurrence network and tolerance to SMX. The cumulative relative abundance of these keystone taxa significantly increased during incubation and was consistent with the SMX mineralization rate. These taxa closely cooperated and played vital roles in co-occurrence networks and microbial community interactions, signifying their crucial role in SMX mineralization. These findings broadened our understanding of the complex interactions of microorganisms under SMX exposure and their potential functions during SMX mineralization, providing valuable insights for in situ bioremediation.