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We report an electrocatalyst, Co bases (metallic Co and Co(OH)2) with fluoride-incorporated CoO coating on the surface of (CoO-F/Co), was synthesized by the electro-deposition method. The porous network architecture of CoO-F/Co on the glassy carbon electrode exhibited an ultra-low overpotential of 15 mV, achieving the geometric current density of 10 mA cm-2 in 1.0 M KOH, which were comparable with the HER performance of numerous reported noble metal electrocatalysts. It is demonstrated that fluoride incorporation improved the electrodeposition particle size, electronic density, conductivity and hydrophilicity of CoO-F/Co the HER performance.
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Despite a comprehensive study on the biosynthesis and function of nitric oxide, biological metabolism of nitric oxide, especially when its concentration exceeds the cytotoxic level, remains elusive. Oxidation of nitric oxide by O2 in aqueous solution has been known to yield NO2-. On the other hand, a biomimetic study on the metal-mediated conversion of NO to NO2-/NO3- via O2 reactivity disclosed a conceivable pathway for aerobic metabolism of NO. During the NO-to-NO3- conversion, transient formation of metal-bound peroxynitrite and subsequent release of â¢NO2 via O-O bond cleavage were evidenced by nitration of tyrosine residue or 2,4-di-tert-butylphenol (DTBP). However, the synthetic/catalytic/enzymatic cycle for conversion of nitric oxide into a nitrite pool is not reported. In this study, sequential reaction of the ferrous complex [(PMDTA)Fe(κ2-O,O'-NO2)(κ1-O-NO2)] (3; PMDTA = pentamethyldiethylenetriamine) with NO(g), KC8, and O2 established a synthetic cycle, complex 3 â {Fe(NO)2}9 DNIC [(PMDTA)Fe(NO)2][NO2] (4) â {Fe(NO)2}10 DNIC [(PMDTA)Fe(NO)2] (1) â [(PMDTA)(NO)Fe(κ2-O,N-ONOO)] (2) â complex 3, for the transformation of nitric oxide into nitrite. In contrast to the reported reactivity of metal-bound peroxynitrite toward nitration of DTBP, peroxynitrite-bound MNIC 2 lacks phenol nitration reactivity toward DTBP. Presumably, the [(PMDTA)Fe] core in {Fe(NO)}8 MNIC 2 provides a mononuclear template for intramolecular interaction between Fe-bound peroxynitrite and Fe-bound NO-, yielding Fe-bound nitrite stabilized in the form of complex 3. This [(PMDTA)Fe]-core-mediated concerted peroxynitrite homolytic O-O bond cleavage and combination of the O atom with Fe-bound NO- reveals a novel and effective pathway for NO-to-NO2- transformation. Regarding the reported assembly of the dinitrosyliron unit (DNIU) [Fe(NO)2] in the biological system, this synthetic cycle highlights DNIU as a potential intermediate for nitric oxide monooxygenation activity in a nonheme iron system.
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Complejos de Coordinación/química , Compuestos Férricos/química , Compuestos Ferrosos/química , Óxido Nítrico/química , Nitritos/química , Poliaminas/química , Complejos de Coordinación/síntesis química , Estructura Molecular , Oxígeno/químicaRESUMEN
Background and Objective: Most patients with giant pulmonary bulla (GPB) are treated by surgery; however, there is a subset for whom surgery is not a viable option, such as those with contraindications, or those unwilling to undergo operation. Therefore, an alternative minimally invasive method is desired for this subpopulation. The aim of this study was to explore an alternative procedure for treating GPB. Methods: This was a prospective, nonrandomized, single-arm, unblinded study evaluating the efficacy and safety of intrabulla adhesion pexia (IBAP) procedure in GPB patients. The study was conducted between December 2004 and April 2017. Results: There were 38 cases in 36 patients (33 males and 3 females) with the target GPB cavities varying in size (range, 10 cm × 7 cm × 5 cm to 15 cm × 8 cm × 30 cm (anteroposterior diameter × medial-lateral diameter × superoinferior diameter)). After IBAP treatment, the closure ratio of GPB in one month was 86.84% (33/38), while the dyspnea index significantly decreased from 4.11 ± 1.11 to 2.24 ± 1.15 (P < 0.01). In addition, the mean FEV1 (L) increased from 1.06 ± 0.73 to 1.57 ± 1.13 (P < 0.01), while RV (L) decreased from 2.77 ± 0.54 to 2.36 ± 0.38 (P < 0.01) and TLC (L) decreased from 6.46 ± 1.21 to 5.86 ± 1.08 (P < 0.01). Moreover, PaO2 (mmHg) increased from 52.18 ± 8.31 to 68.29 ± 12.34, while the 6 MWD increased by 129.36% from 131.58 ± 105.24 to 301.79 ± 197.90 (P < 0.01). Collectively, these data indicated significant improvement in pulmonary function and exercise tolerance after IBAP treatment. Furthermore, no deaths occurred during IBAP treatment, and no cases of aggravated GPB relapse were reported during the 12-month follow-up period. Conclusions: IBAP is a promising strategy for the treatment of GPB. Our findings demonstrated that IBAP had a noteworthy therapeutic effect, desirable safety, and ideal long-term efficacy for GPB.
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Adhesivo de Tejido de Fibrina/uso terapéutico , Enfermedades Pulmonares/cirugía , Paracentesis/métodos , Adulto , Anciano , Femenino , Humanos , Enfermedades Pulmonares/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos , Tomografía Computarizada por Rayos XRESUMEN
In artificial photosynthesis, water splitting plays an important role for the conversion and storage of renewable energy sources. Here, we report a study on the electrocatalytic properties of the electrodeposited-film electrodes derived from irreversible electro-reduction/-oxidation of a molecular dinitrosyl iron complex (DNIC) {Fe(NO)2}9 [(Me6tren)Fe(NO)2]+ (Me6tren = tris[2-(dimethylamino)ethyl]amine) for the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) in alkaline solution, individually. For HER, the overpotential and Tafel slope for the electrodeposited-film cathode are lower than those of the equiv.-weight Pt/C electrode. The electrodeposited-film anode for the OER is stable for 139 h. Integration of the electrodeposited-film cathode and anode into a single electrode-pair device for electrocatalytic water splitting exhibits an onset voltage of 1.77 V, achieving a geometrical current density of 10 mA cm-2.
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BACKGROUND: Peritoneum metastasis of lung cancer is a rare event which, in addition to the peritoneum, usually involves multiple metastatic tissues. Here we report a case of a patient with lung adenosquamous cell carcinoma with the peritoneum as the sole distant metastatic site. CASE PRESENTATION: An 82-year-old Han Chinese man, in the teaching profession, was diagnosed with lung adenosquamous cell carcinoma in the upper lobe of his left lung with the involvement of ipsilateral hilar and mediastinal lymph nodes, and was initially staged as IIIa (cT2N2M0). Molecular testing identified a mutation at KRAS G12A. Due to his poor physical condition, our patient was given gamma knife radiotherapy with a total dose of 28.0 Gy. Two weeks later, our patient was diagnosed as peritoneal metastasis identified by using magnetic resonance imaging and confirmed with ascitic cytology and peritoneal histology. No other distant metastatic sites such as liver, brain, bone, paranephroi, and lungs were found. Subsequently, our patient received palliative intraperitoneal chemotherapy, and died within 2 months. CONCLUSIONS: Our patient represented a rare case of lung adenosquamous cell carcinoma harboring the KRAS G12A mutation, which metastasized distantly to the peritoneum only, and progressed rapidly.
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Carcinoma Adenoescamoso/patología , Neoplasias Pulmonares/patología , Neoplasias Peritoneales/secundario , Anciano de 80 o más Años , Progresión de la Enfermedad , Resultado Fatal , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Cuidados Paliativos , Neoplasias Peritoneales/tratamiento farmacológico , Neoplasias Peritoneales/fisiopatología , Proteínas Proto-Oncogénicas p21(ras) , RadiocirugiaRESUMEN
AIM: To evaluate whether berberine hydrochloride (BBR) could modify the pharmacokinetic profiles of midazolam (MDZ), a substrate of CYP3A, and rhodamine 123 (Rh123), a substrate of P-glycolprotein (P-gp), in male rats. METHODS: The rats were given with varied does of BBR or 75 mg/kg ketoconazole as a positive control for 10 days by intragastric administration. Single-pass duodenum perfusion of 20 mg/kg MDZ and inguinal artery canulated rats were used in the study. Plasma concentrations of MDZ and 1'-hydroxymidazolam (1'-OH-MDZ) were analyzed by high performance liquid chromatography (HPLC). The rats were given with varied does of BBR or 4 mg/kg verapamil as a positive control for 10 days by intragastric administration. Blood was obtained from the caudal vein of rats after single-pass intragastric administration of 5 mg/kg Rh123. HPLC was used to analyze the plasma concentrations of Rh123. RESULTS: BBR produced similar results as the ketoconazole (positive control group) with a dose-dependent increase in the AUC(0-t) and AUMC (0-t) of midazolam except at the dose of 50 mg/kg (p < 0.01). And BBR could significantly increase the peak plasma concentrations (Cmax) of MDZ (p < 0.01), but reduce the clearance rate (CLz) and the apparent volume of the distribution (Vz) of MDZ (p < 0.05). The results also indicated that BBR had no significant impact on the half-life period (t1/2) and the time to reach peak concentration (tmax). Meanwhile, BBR could dose-dependently decrease AUC(0-t) and AUMC(0-t) of 1'-OH-MDZ significantly (p < 0.05), and expedite the clearance rate of 1'-OH-MDZ while gaining its apparent volume of distribution (p < 0.05), but had no significant impact on t1/2 and Tmax. The result also showed that BBR, except at the dose of 50 mg/kg, and the positive verapamil group could significantly increase the AUC(0-t) and AUC(0-∞) of Rh123 (p < 0.001), meanwhile raise Cmax of Rh123 and shorten its Vz inversely (p < 0.05). Additionally, pre-treatment with BBR had no significant influence with the half-life period of Rh123, while significantly reduced its clearance rate (p < 0.05). CONCLUSION: The metabolism of MDZ and Rh123 was controlled by BBR. The results were most likely due to the inhibition by BBR on CYP3A enzymes and P-gp transporter.
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Blind source separation (BSS) based x-ray image denoising from an image sequence is proposed. Without priori knowledge, the useful image signal can be separated from an x-ray image sequence, for original images are supposed as different combinations of stable image signal and random image noise. The BSS algorithms such as fixed-point independent component analysis and second-order statistics singular value decomposition are used and compared with multi-frame averaging which is a common algorithm for improving image's signal-to-noise ratio (SNR). Denoising performance is evaluated in SNR, standard deviation, entropy, and runtime. Analysis indicates that BSS is applicable to image denoising; the denoised image's quality will get better when more frames are included in an x-ray image sequence, but it will cost more time; there should be trade-off between denoising performance and runtime, which means that the number of frames included in an image sequence is enough.
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To investigate the possible drug interaction, this study is designed to evaluate the ability of Schisandrin B (Sch B) to modulate cytochrome P450 3A activity (CYP3A) in vivo and to alter the pharmacokinetic profiles of CYP3A substrate (midazolam) in treated rats. Rats were repeated administered with physiological saline (negative control group), ketoconazole (75 mg/kg, positive control group) or varied doses of Sch B (experimental groups) for three consecutive days. Subsequently, changes in hepatic microsomal CYP3A activity and the pharmacokinetic profiles of midazolam and 1'-hydroxy midazolam in plasma were studied to evaluate CYP3A activity. The results indicated that Sch B significantly dose-dependently inhibited rat hepatic microsomal CYP3A activity with Ki value of 16.64 mg/kg and showed the characteristic of a noncompetitive inhibitor. Oral administration of Sch B for 3 days in rats produced significant effect on the pharmacokinetics of oral midazolam. Sch B resulted in a significant, dose-dependent increase in midazolam AUC0-∞ except at the dose of 2 mg/kg, while AUC0-∞ increased by 26.1% (8 mg/kg) and 60.6% (16 mg/kg), respectively. In the pharmacokinetic profiles of 1'-hydroxy midazolam, the significant, dose-dependent decrease in AUC0-∞ was observed except at the dose of 2 mg/kg, while AUC0-∞ reduced by 44.5% (8 mg/kg) and 49.2% (16 mg/kg), respectively. These results suggested that 3-day treatment of Sch B could increase concentration and oral bioavailability of drug metabolized by CYP3A. When the drug, consisting of Sch B, is used in the clinic for more than 3 days, the possible drug-drug interactions should be taken into consideration.
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Citocromo P-450 CYP3A/efectos de los fármacos , Lignanos/administración & dosificación , Midazolam/farmacocinética , Compuestos Policíclicos/administración & dosificación , Administración Oral , Animales , Disponibilidad Biológica , Ciclooctanos/administración & dosificación , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Cetoconazol/administración & dosificación , Hígado/metabolismo , Masculino , Medicina Tradicional China , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Midazolam/sangre , Ratas , Ratas Sprague-DawleyRESUMEN
The objective of this study was to evaluate the ability of schisandrin A (SchA) to inhibit the P450 enzyme CYP3A in vivo. Male Sprague-Dawley rats were intragastrically administered with varied doses of SchA (8 mg/kg or 16 mg/kg or 32 mg/kg) or 75 mg/kg ketoconazole for three consecutive days. Ketoconazole, a chemical inhibitor of CYP3A, was used as positive control. Subsequently, changes in hepatic microsome CYP3A activity and the pharmacokinetic profiles of midazolam (MDZ), a specific CYP3A substrate, were studied as indicators of rat hepatic microsomal activity of CYP3A. Differences in the plasma concentrations of MDZ and its related metabolites and the hepatic microsome concentrations of 1'-hydroxymidazolam were analysed by high-performance liquid chromatography. The current results provide direct and explicit evidence that SchA produced concentration-dependent inhibition of MDZ metabolite formation in rat liver microsomes (p < 0.01 or p < 0.001). Regular SchA consumption also caused concentration-dependent increase in Cmax and area under the concentration-time curve (AUC0-t and AUC0-∞ ) of peroral MDZ (p < 0.05 or p < 0.01) compared to vehicle-treated rats, whereas those of its metabolites (1'-hydroxymidazolam) were reduced (p < 0.05 or p < 0.01). Analysis of the data suggests that changes in the pharmacokinetic profiles of peroral MDZ in the rat model were contributed mainly to SchA inhibition of CYP3A activity. These results suggest that SchA, as an inhibitor of CYP3A, possesses a clinically beneficial property of altering the disposition of drugs metabolized by CYP3A.
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Ciclooctanos/administración & dosificación , Inhibidores del Citocromo P-450 CYP3A/administración & dosificación , Citocromo P-450 CYP3A/metabolismo , Lignanos/administración & dosificación , Compuestos Policíclicos/administración & dosificación , Administración Oral , Animales , Área Bajo la Curva , Cromatografía Líquida de Alta Presión , Ciclooctanos/farmacocinética , Citocromo P-450 CYP3A/genética , Inhibidores del Citocromo P-450 CYP3A/farmacocinética , Relación Dosis-Respuesta a Droga , Cetoconazol/administración & dosificación , Cetoconazol/farmacocinética , Lignanos/farmacocinética , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Midazolam/administración & dosificación , Midazolam/análogos & derivados , Midazolam/sangre , Midazolam/farmacocinética , Compuestos Policíclicos/farmacocinética , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND & OBJECTIVE: The authors previously discovered that the intracellular pH values (pHi) of tumor cells could be decreased, which led tumor cells to acidify and die, when the expressions of the first subtype of monocarboxylate transporter (MCT1) gene and the first subtype of Na+/H+ exchanger (NHE1) gene in tumor cell membranes had been inhibited by each corresponding antisense gene respectively. However it was not clear whether there were co-effects on the pHi, proliferation, and growth of tumor cells, after two genes were inhibited at the same time. METHODS: pLXSN-MCT1 and pLXSN-NHE1, the corresponding antisense gene expression vectors of MCT1 and NHE1 genes, were introduced into human lung adenocarcinoma A549 cells at the same time with electroporation. The positive colonies were selected by G418. Using PCR and RT-PCR technique, it was confirmed that antisense genes of MCT1 and NHE1 genes integrated with A549 genomic DNA. The pHi and lactate content were detected with spectrophotometry. Cell growth cycle was measured with flow cytometer. The cells co-transfected antisense genes, cells transfected MCT1 antisense gene and A549 cells were respectively inoculated in nude mouse subcutaneous to observe the growth of transplantation tumors. RESULTS: Compared with A549 cells, the pHi of cells co-transfected antisense genes was remarkably decreased (P < 0.05), while lactate content was remarkably increased (P < 0.001). The cell cycle was blocked at G0-G1 period. And the transplantation tumors of nude mice inoculated co-transfected antisense gene-cells and inoculated MCT1-antisense-gene-transfected cells were significantly lighter and smaller than ones inoculated A549 cells (P < 0.001). CONCLUSION: MCT1 and NHE1 genes play important regulation roles in proliferation and growth of tumor cells, probably by affecting pHi.