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The electrochemical N2 fixation, which is far from practical application in aqueous solution under ambient conditions, is extremely challenging and requires a rational design of electrocatalytic centers. We observed that bismuth (Bi) might be a promising candidate for this task because of its weak binding with H adatoms, which increases the selectivity and production rate. Furthermore, we successfully synthesized defect-rich Bi nanoplates as an efficient noble-metal-free N2 reduction electrocatalyst via a low-temperature plasma bombardment approach. When exclusively using 1 Hâ NMR measurements with N2 gas as a quantitative testing method, the defect-rich Bi(110) nanoplates achieved a 15 NH3 production rate of 5.453â µg mgBi -1 h-1 and a Faradaic efficiency of 11.68 % at -0.6â V vs. RHE in aqueous solution at ambient conditions.
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AIM: Although targeted therapy is very efficient for lung cancer, traditional platinum-based chemotherapies are still the principal strategy in the absence of positive biomarkers. The aim of the present study is to evaluate the contribution of RAD18 polymorphisms to platinum-chemotherapy response and its potential side effects in Chinese patients with non-small cell lung cancer (NSCLC). METHODS: A total of 1021 Chinese patients with histological diagnosis of advanced NSCLC were enrolled. Treatment responses were classified into 4 categories (complete response, partial response, stable disease and progressive disease). Gastrointestinal and hematological toxicity incidences were assessed twice a week during the first-line treatment. Ten RAD18 SNPs were genotyped. A logistic regression model was utilized to analyze the associations between RAD18 SNPs and treatment response or toxicity. RESULTS: Among the 10 SNPs tested, none was significantly correlated with the treatment response in a combined cohort. For gastrointestinal toxicity incidences, rs586014 was significantly associated with an increased risk of grade 3 or 4 gastrointestinal toxicity in non-smokers and in the combined cohort; rs654448 and rs618784 were significantly associated with gastrointestinal toxicity in non-smokers; rs6763823 was significantly associated with gastrointestinal toxicity in smokers. For hematological toxicity incidences, rs586014, rs654448 and rs618784 were significantly associated with hematologic toxicity in non-smokers; rs6763823 and rs9880051 were significantly associated with leukocytopenia in smokers. CONCLUSION: RAD18 polymorphisms are correlated with the side effects of platinum-chemotherapy in Chinese patients with advanced NSCLC.
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Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/efectos adversos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Cisplatino/efectos adversos , Proteínas de Unión al ADN/genética , Neoplasias Pulmonares/tratamiento farmacológico , Ubiquitina-Proteína Ligasas/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Carcinoma de Pulmón de Células no Pequeñas/genética , Daño del ADN/efectos de los fármacos , Femenino , Tracto Gastrointestinal/efectos de los fármacos , Estudios de Asociación Genética , Humanos , Neoplasias Pulmonares/genética , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Adulto JovenRESUMEN
AIM: To elucidate the roles of receptor tyrosine kinases RET and VEGFR2 and the RAF/MEK/ERK signaling cascade in cancer treatment with sorafenib. METHODS: The cell lines A549, HeLa, and HepG2 were tested. The enzyme activity was examined under cell-free conditions using 384-well microplate assays. Cell proliferation was evaluated using the Invitrogen Alarmar Blue assay. Gene expression was analyzed using the Invitrogen SYBR Green expression assays with a sequence detection system. Protein expression analysis was performed using Western blotting. RESULTS: Sorafenib potently suppressed the activities of cRAF, VEGFR2, and RET with IC(50) values of 20.9, 4 and 0.4 nmol/L, respectively. Sorafenib inhibited cRAF, VEGFR2, and RET via non-ATP-competitive, ATP-competitive and mixed-type modes, respectively. In contrast, sorafenib exerted only moderate cytotoxic effects on the proliferation of the 3 cell lines. The IC(50) values for inhibition of A549, HeLa, and HepG2 cells were 8572, 4163, and 8338 nmol/L, respectively. In the 3 cell lines, sorafenib suppressed the cell proliferation mainly by blocking the MEK/ERK downstream pathway at the posttranscriptional level, which in turn regulated related gene expression via a feed-back mechanism. CONCLUSION: This study provides novel evidence that protein kinases RET and VEGFR2 play crucial roles in cancer treatment with sorafenib.
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Antineoplásicos/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/farmacología , Proteínas Proto-Oncogénicas c-ret/antagonistas & inhibidores , Receptor 2 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Antineoplásicos/uso terapéutico , Western Blotting , Técnicas de Cultivo de Célula , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Sistema de Señalización de MAP Quinasas/genética , Neoplasias/enzimología , Neoplasias/patología , Niacinamida/farmacología , Niacinamida/uso terapéutico , Compuestos de Fenilurea/uso terapéutico , Proteínas Proto-Oncogénicas c-ret/genética , Interferencia de ARN/efectos de los fármacos , Reacción en Cadena en Tiempo Real de la Polimerasa , Sorafenib , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genéticaAsunto(s)
Erupciones por Medicamentos/etiología , Medicamentos Herbarios Chinos/efectos adversos , Panax notoginseng , Fitoterapia/efectos adversos , Saponinas , Anciano , Dermis/patología , Erupciones por Medicamentos/inmunología , Erupciones por Medicamentos/patología , Células Epitelioides/patología , Granuloma/patología , Humanos , MasculinoRESUMEN
OBJECTIVE: To quantitatively summarize the association of NFKBIA gene polymorphisms with autoimmune and inflammatory diseases. METHODS: We surveyed studies on the association of NFKBIA gene polymorphisms with autoimmune and inflammatory diseases in PubMed. Meta-analysis was performed in a fixed/random effect model. RESULTS: We identified 14 studies using a PubMed search. Meta-analysis was performed for NFKBIA gene polymorphisms at positions 2758 (A/G, 5 studies), -881 (A/G, 3 studies), -826 (C/T, 3 studies), and -297 (C/T, 3 studies). We did not detect associations of NFKBIA gene polymorphisms at positions 2758, -881, -297 with autoimmune and inflammatory diseases. An association of NFKBIA gene -826C/T polymorphism with autoimmune and inflammatory diseases was found (C vs. T: OR = 1.81, 95% CI = 0.97-3.36, P = 0.06; CT + TT vs. CC: OR = 2.11, 95% CI = 1.07-4.19, P = 0.03; TT vs. CC + CT: OR = 2.20, 95% CI = 0.78-6.21, P = 0.06; TT vs. CC: OR = 2.87, 95% CI = 0.78-10.62, P = 0.11; CT vs. CC: OR = 2.02, 95% CI = 1.22-3.36, P = 0.006). CONCLUSION: This meta-analysis demonstrates that autoimmune and inflammatory diseases are associated with NFKBIA gene -826C/T polymorphism, but not with 2758A/G, -881A/G, and -279C/T.
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Enfermedades Autoinmunes/genética , Predisposición Genética a la Enfermedad , Proteínas I-kappa B/genética , Inflamación/genética , Polimorfismo Genético , Frecuencia de los Genes , Genotipo , Humanos , Inhibidor NF-kappaB alfa , PubMedAsunto(s)
Métodos de Alimentación , Sífilis/etiología , Humanos , Lactante , Masculino , MasticaciónRESUMEN
OBJECTIVE: To study a Chinese pedigree with Hailey-Hailey disease (HHD) and identify the ATP2C1 gene mutation in this family. METHODS: All exons of the ATP2C1 gene were analyzed with polymerase chain reaction and DNA sequencing in all patients of this family and 80 unrelated population-matched controls. RESULTS: We identified a nonsense mutation 163C to T, resulting in a premature termination codon in ATP2C1 gene. The mutation was not found in normal individuals of the family and controls. CONCLUSION: The mutation can affect the result of transcription and translation of ATP2C1 gene, and it is firstly reported in the Chinese pedigree with HHD.
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Pueblo Asiatico/genética , ATPasas Transportadoras de Calcio/genética , Pénfigo Familiar Benigno/genética , Análisis Mutacional de ADN , Humanos , LinajeRESUMEN
We identified the superoxide anion as the intermediate in the oxygen (O2) reduction reaction on a platinum (Pt) electrode in alkaline solution (pH = 11) using a surface-enhanced infrared spectroscopy technique with an attenuated total reflection mode. Spectral and voltammetry data, together with the vibrational frequencies calculated using the density functional theory, provide evidence for the formation of O2-. The supporting evidence includes similar spectra that we obtained for O2 reduction on Pt in acetonitrile solutions and a lack of spectra in the absence of O2 or its reduction. The appearance of O2- means that the series reaction pathway operates during O2 reduction on Pt electrodes in alkaline solutions and very likely also in acid solutions. This finding opens up the possibility of formulating a detailed reaction mechanism on surfaces supporting a four-electron reduction, which is critical in completely understanding the kinetics of O2 reduction, thus resolving dilemmas in the theoretical treatment of its kinetics and the design of new electrocatalysts.
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We have synthesized new electrocatalysts for the O2 reduction reaction that does not contain Pt. They consist of carbon-supported Pd-Fe alloys and have very high oxygen reduction. The nanoparticles with a Pd:Fe molar ratio of 3:1 (Pd3Fe/C) show a higher mass activity than that of commercial Pt/C. The surface-specific activity of the Pd-Fe alloys is related to the Pd-Pd bond distance: the shorter the bond distance, the higher the activity. This new class of electrocatalysts promises to alleviate some major problems of existing fuel cell technology by simultaneously decreasing materials cost and enhancing performance.