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The circadian clock (CC) has biological and clinical implications in gliomas. Most studies focused on CC effects on the tumor microenvironment and the application of chronotherapy. The present study focused on CC gene expression patterns and intracellular oncogenic activities. Glioma gene expression data were collected from The Human Cancer Genome Atlas (TCGA) project. After applying inclusion and exclusion criteria, we selected 666 patients from TCGA-GBM and TCGA-LGG projects and included important clinicopathological variables. The entire cohort was subjected to clustering analysis and divided into CC1 and CC2 subtypes based on statistical, biological, and clinical criteria. CC2 gliomas showed higher expression of BMAL1 and CRY1 and lower expression of CRY2 and PER2 (adjusted P < .001). CC2 gliomas had q higher activity of cell proliferation, metabolic reprogramming, angiogenesis, hypoxia, and many oncogenic signals (P < .001). The CC2 subtype contained a higher proportion of glioblastomas (P < .001) and had a worse prognosis (P < .001). Stratified Kaplan-Meier and multivariable Cox analyses illustrated that the CC subtype is an independent prognostic factor to clinicopathological characteristics (P < .001), genetic aberrations (P = .006), and biological processes (P < .001). Thus, this study shows statistical evidence of CC subtypes and their biological, and clinicopathological significance in adult gliomas.
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Neoplasias Encefálicas , Relojes Circadianos , Epigénesis Genética , Glioma , Humanos , Glioma/genética , Glioma/patología , Glioma/metabolismo , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Relojes Circadianos/genética , Femenino , Masculino , Adulto , Persona de Mediana Edad , Regulación Neoplásica de la Expresión Génica/genética , Anciano , Estudios de CohortesRESUMEN
Recently, the hazardous effects of antibiotic micropollutants on the environment and human health have become a major concern. To address this challenge, semiconductor-based photocatalysis has emerged as a promising solution for environmental remediation. Our study has developed Bi2WO6/g-C3N4 (BWCN) photocatalyst with unique characteristics such as reactive surface sites, enhanced charge transfer efficiency, and accelerated separation of photogenerated electron-hole pairs. BWCN was utilized for the oxidation of tetracycline antibiotic (TCA) in different water sources. It displayed remarkable TCA removal efficiencies in the following order: surface water (99.8%) > sewage water (88.2%) > hospital water (80.7%). Further, reusability tests demonstrated sustained performance of BWCN after three cycles with removal efficiencies of 87.3, 71.2 and 65.9% in surface water, sewage, and hospital water, respectively. A proposed photocatalytic mechanism was delineated, focusing on the interaction between reactive radicals and TCA molecules. Besides, the transformation products generated during the photodegradation of TCA were determined, along with the discussion on the potential risk assessment of antibiotic pollutants. This study introduces an approach for utilizing BWCN photocatalyst, with promising applications in the treatment of TCA from various wastewater sources.
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Antibacterianos , Oxidación-Reducción , Tetraciclina , Contaminantes Químicos del Agua , Contaminantes Químicos del Agua/química , Antibacterianos/química , Tetraciclina/química , Catálisis , Aguas Residuales/química , Bismuto/química , Grafito/química , Compuestos de Nitrógeno/química , Compuestos de Tungsteno/química , Fotólisis , Purificación del Agua/métodos , Aguas del Alcantarillado/químicaRESUMEN
In this study, surface-enhanced Raman scattering substrates were investigated by the electrodeposition method to detect low concentrations of pesticides via the electrodeposition method with different agents from silver and gold precursors on APTES-modified ITO glass. A dual-potential method supplied three electrodes and was performed with a nucleation potential of 0.7 V for 2 s and a growth potential of -0.2 V for 500 s. The Ag film produced by the electrodeposition approach has great surface uniformity and good SERS signal amplification for the thiram insecticide at low concentrations. Interestingly, the ITO/APTES/Ag substrate extensively increased the sensitivity than the other investigated ones, thanks to the adequate assistance of amino groups of APTES in the denser and hierarchical deposition of Ag NPs. These observations were additionally elucidated via finite-difference time-domain (FDTD) calculation. For thiram, the detection was set at 10-8 M with an enhancement factor of up to 3.6 × 107 times. Comparing the SERS spectra of thiram at concentrations of 10-3, 10-4, and 10-5 M with a relative standard deviation (RSD) of less than 7.0% demonstrates excellent reproducibility of the ITO/APTES/Ag substrate. In addition, the special selectivity of the ITO/APTES/Ag substrate for thiram demonstrates that these nanostructures can identify pesticides with extreme sensitivity.
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OBJECTIVE: This study aims to describe the diagnostic performance of alpha-fetoprotein (AFP), alpha-fetoprotein L3 isoform (AFP-L3), protein induced by vitamin K absence II (PIVKA-II), and combined biomarkers for non-B non-C hepatocellular carcinoma (NBNC-HCC). RESULTS: A total of 681 newly-diagnosed primary liver disease subjects (385 non-HCC, 296 HCC) who tested negativity for the hepatitis B surface antigen (HBsAg) and hepatitis C antibody (anti-HCV) enrolled in this study. At the cut-off point of 3.8 ng/mL, AFP helps to discriminate HCC from non-HCC with an area under the curve (AUC) value of 0.817 (95% confidence interval [CI]: 0.785-0.849). These values of AFP-L3 (cut-off 0.9%) and PIVKA-II (cut-off 57.7 mAU/mL) were 0.758 (95%CI: 0.725-0.791) and 0.866 (95%CI: 0.836-0.896), respectively. The Bayesian Model Averaging (BMA) statistic identified the optimal model, including patients' age, aspartate aminotransferase, AFP, and PIVKA-II combination, which helps to classify HCC with better performance (AUC = 0.896, 95%CI: 0.872-0.920, P < 0.001). The sensitivity and specificity of the optimal model reached 81.1% (95%CI: 76.1-85.4) and 83.2% (95%CI: 78.9-86.9), respectively. Further analyses indicated that AFP and PIVKA-II markers and combined models have good-to-excellent performance detecting curative resected HCC, separating HCC from chronic hepatitis, dysplastic, and hyperplasia nodules.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , alfa-Fetoproteínas/análisis , alfa-Fetoproteínas/metabolismo , Neoplasias Hepáticas/patología , Vitamina K , Vitaminas , Teorema de Bayes , Curva ROC , Biomarcadores , Biomarcadores de TumorRESUMEN
Background: SLC22A3, the gene which encodes organic cation transporter (OCT)-3, has been linked to the prognosis of several types of cancer. However, its role in lung squamous cell carcinoma (LSCC) has not been addressed elsewhere. Methods: We analyzed gene expression, DNA methylation, and clinicopathological data from The Cancer Genome Atlas - Lung Squamous Cell Carcinoma (TCGA-LUSC) (n=501), a publicly available database exclusively consisting of LSCC patients. Using a 5 FPKM (fragments per kilobase of exon per million mapped fragments) cut-off, we divided LSCC patients into two groups: patients with tumors possessing high and low SLC22A3 expression (SLC22A3-high and SLC22A3-low, respectively). Prognostic significance was determined through Cox analyses and Kaplan-Meier curves for overall survival (OS) and disease-free survival (DFS). Differential methylation position (DMP), differentially gene expression, and pathway analyses were performed. Validation was carried out in GSE74777 (n=107), GSE37745 (n=66), GSE162520 (n=45) and GSE161537 (n=17). Results: SLC22A3-high LSCC patients had lower OS and DFS rates than SLC22A3-low LSCC patients. The different expression levels of SLC22A3 in LSCC were correlated with the methylation status of the SLC22A3 gene. Pathway analysis indicated that SLC22A3 expression levels were positively correlated with immune-related pathways such as inflammatory response and abundance of infiltrating immune cells in the tumor microenvironment (TME). Notably, in the SLC22A3-high group, many genes encoding immunological checkpoint inhibitory molecules were upregulated. In addition, SLC22A3 expression positively correlated with the Hot Oral Tumor (HOT) score, indicating high tumor immunogenicity. Conclusions: These findings suggest that high expression of SLC22A3 is associated with poor prognosis and high immunogenicity in LSCC tumors.
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Ethyl caffeate (EC) is a natural phenolic compound that is present in several medicinal plants used to treat inflammatory disorders. However, its anti-inflammatory mechanisms are not fully understood. Here, we report that EC inhibits aryl hydrocarbon receptor (AhR) signaling and that this is associated with its anti-allergic activity. EC inhibited AhR activation, induced by the AhR ligands FICZ and DHNA in AhR signaling-reporter cells and mouse bone marrow-derived mast cells (BMMCs), as assessed by AhR target gene expressions such as CYP1A1. EC also inhibited the FICZ-induced downregulation of AhR expression and DHNA-induced IL-6 production in BMMCs. Furthermore, the pretreatment of mice with orally administered EC inhibited DHNA-induced CYP1A1 expression in the intestine. Notably, both EC and CH-223191, a well-established AhR antagonist, inhibited IgE-mediated degranulation in BMMCs grown in a cell culture medium containing significant amounts of AhR ligands. Furthermore, oral administration of EC or CH-223191 to mice inhibited the PCA reaction associated with the suppression of constitutive CYP1A1 expression within the skin. Collectively, EC inhibited AhR signaling and AhR-mediated potentiation of mast cell activation due to the intrinsic AhR activity in both the culture medium and normal mouse skin. Given the AhR control of inflammation, these findings suggest a novel mechanism for the anti-inflammatory activity of EC.
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Mastocitos , Receptores de Hidrocarburo de Aril , Ratones , Animales , Receptores de Hidrocarburo de Aril/metabolismo , Mastocitos/metabolismo , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Ligandos , Antiinflamatorios/metabolismoRESUMEN
The pathology of asthma is characterized by marked day-night variation, which is likely controlled by circadian clock activity. This study aimed to clarify the association of core circadian clock gene expression with clinical features of asthma. For this purpose, we accessed the National Center for Biotechnology Information database and analyzed transcriptomes of peripheral blood mononuclear cells and clinical characteristics of 134 pediatric/adolescent patients with asthma. Based on the expression patterns of seven core circadian clock genes (CLOCK, BMAL1, PER1-3, CRY1-2), we identified three circadian clusters (CCs) with distinct comorbidities and transcriptomic expressions. In the three CC subtypes, allergic rhinitis, and atopic dermatitis, both asthma comorbidities occurred in different proportions: CC1 had a high proportion of allergic rhinitis and atopic dermatitis; CC2 had a high proportion of atopic dermatitis but a low proportion of allergic rhinitis; and CC3 had a high proportion of allergic rhinitis but a low proportion of atopic dermatitis. This might be associated with the low activity of the FcεRI signaling pathway in CC2 and the cytokine-cytokine receptor interaction pathways in CC3. This is the first report to consider circadian clock gene expression in subcategories of patients with asthma and to explore their contribution to pathophysiology and comorbidity.
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Asma , Relojes Circadianos , Dermatitis Atópica , Rinitis Alérgica , Humanos , Niño , Adolescente , Dermatitis Atópica/genética , Dermatitis Atópica/complicaciones , Relojes Circadianos/genética , Leucocitos Mononucleares , Asma/complicaciones , Rinitis Alérgica/genética , Comorbilidad , Expresión GénicaRESUMEN
This article presents a review of many types of SERS sensors for food safety and environmental pollution monitoring based on detecting rhodamine. It introduces the basic concepts of substrates, enhancement factors, and mechanisms, devices' sensors integrated with the microstructure. Here, we review the state-of-the-art research in the field of rhodamine monitoring and highlight the applications of SERS sensors. The trends in the development of substrates for different applications have been mentioned with the aim of providing an overview of the development of different SERS substrates. Thus, an efficient approach for rhodamine detection has a good perspective for application in environmental monitoring.
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PURPOSE: Meningococcal disease is a major global health concern due to its severe and sudden clinical manifestations, devastating long-term sequelae, and predominance in younger age groups. This study evaluated the safety of a quadrivalent meningococcal polysaccharide diphtheria toxoid conjugate vaccine (MenACWY-D; Menactra) in participants aged 9 months to 55 years in Vietnam. METHODS: This was an open-label, single-arm study conducted between June and December 2016. Participants received one 0.5-mL dose of the vaccine, and those aged 9 to 23 months received a second 0.5-mL dose 3 months later. Participants (or their parents or legal guardians) reported adverse events during the 28 days after each dose. RESULTS: The study included 112 participants aged 9 to 23 months and 112 participants aged 2 to 55 years. Of these 224 participants, 100 (44.6%) had one or more solicited reactions within 7 days following any MenACWY-D dose, mostly injection site pain, lost appetite (in 9 to 23-month-olds), and malaise (in 2 to 55-year-olds). Most solicited reactions were of mild or moderate intensity and resolved within 3 days. Five participants had unsolicited adverse reactions (ARs), two of which (tonsillitis and febrile convulsion), in 9 to 23-month-olds, were considered by the investigator as serious adverse events related to the vaccine. No immediate unsolicited ARs, severe unsolicited nonserious ARs, or unsolicited injection site reactions were reported, and both participants who experienced vaccine-related serious adverse events recovered. CONCLUSION: Consistent with studies in other countries, MenACWY-D had an acceptable safety profile in individuals from Vietnam aged 9 months to 55 years (WHO Universal Trial Number: U1111-1143-9207).
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Apetito/efectos de los fármacos , Reacción en el Punto de Inyección/epidemiología , Infecciones Meningocócicas/prevención & control , Vacunas Meningococicas/efectos adversos , Adolescente , Adulto , Niño , Preescolar , Femenino , Voluntarios Sanos , Humanos , Esquemas de Inmunización , Lactante , Reacción en el Punto de Inyección/diagnóstico , Inyecciones Intramusculares/efectos adversos , Masculino , Infecciones Meningocócicas/microbiología , Vacunas Meningococicas/administración & dosificación , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Vietnam , Adulto JovenRESUMEN
Accurate and rapid blood-based detection of dopamine levels can aid in the diagnosis and monitoring of diseases related to dopaminergic dysfunction. For the sensitive detection of dopamine levels in human blood plasma (i.e., plasma dopamine levels), a silver-plated Au bimetallic nanocluster (so called plasmonic Au/Ag nanocluster) was prepared as a surface-enhanced Raman scattering (SERS) substrate by the combination of electrodeposition and electroless plating methods. The plasmonic effect of the Au/Ag nanocluster substrate was optimized by controlling the particle morphology, packing density, and interparticle distance, showing the best performance in its SERS activity. The lowest detection limit of dopamine was â¼10-11 M. A linear standard curve was obtained by plotting the log-scale of dopamine concentration (log C) versus Raman intensity at 1152 cm-1. The optimized SERS substrate quantified the plasma dopamine levels of patients with antipsychotic drug-induced Parkinsonism (n = 15) as 3.24 × 10-9 M and healthy control subjects (n = 15) as 2.31 × 10-8 M. Patients with drug-induced Parkinsonism had â¼86% lower plasma dopamine concentration than healthy subjects (two-tailed p-value = 0.000002), indicating a clear separation between the groups. Our study provides the first report on the quantitative SERS detection of dopamine levels in human blood plasma with Parkinsonism. The results highlight the potential clinical utility of the optimized SERS technique in screening clinical populations with dopaminergic dysfunction, i.e., differentiating between healthy subjects and patients with Parkinsonism.