RESUMEN
In this work, two series of chemically reactive polymers, silane coupling agents (SCAs) and water-soluble polymers, were specifically designed as an additive to improve the ductility of slag geopolymer paste by vibration pressure technique. The influences of organic polymers on the fluidity, rheological behavior, mechanical property, porosity, and toughening mechanism of slag geopolymer were investigated. The polycondensation and bonding characteristics of organic-inorganic products were calculated by 1H liquid nuclear magnetic resonance (NMR) technology and Fourier transform infrared (FT-IR). The polymerization degree of composite geopolymer was evaluated by 29Si NMR and X-ray photoelectron spectroscopy (XPS). The microscopic morphology of the geopolymer matrix was analyzed using scanning electron microscopy (SEM). The results showed that the dosage of the KH570 and PAA-Na with 5 wt% behaved best in improving the flexural strength and the compressive strength of geopolymer in their corresponding organic series, respectively. The addition of polymers decreased the fluidity and the fluidity loss ratio of geopolymer slurry but reduced the harmful pores of hardened geopolymer. The organic polymers acting as bridge-fixed water molecules weakened the repulsion force, and formed a three-dimensional network through molecular interweaving in a geopolymer matrix. Methacryloxy in silane coupling agents and carboxyl group in water-soluble polymers may contribute to the improvement of hydration product structure through strong bonding with C-A-S-H. Microscopic measurements indicated that the addition of KH570 and PAA-Na in geopolymer could form 73.55% and 72.48% Si-O-Si with C-A-S-H gel, higher than the reference, and increase the polycondensation degree of C-A-S-H phase, reflected by the increased generation of Q2 and Q2(1Al) and the longer chain length, leading to a higher densified geopolymer matrix with high ductility.
RESUMEN
Methods and materials that effectively remove heavy metals, such as lead and copper, from wastewater are urgently needed. In this study, steel slag, a low-cost byproduct of steel manufacturing, was utilized as a substrate material for carbon nanotube (CNT) growth by chemical vapor deposition (CVD) to produce a new kind of efficient and low-cost absorbent without any pretreatment. The synthesis parameters of the developed CNT-steel slag composite (SS@CNTs) were optimized, and its adsorption capacities for Pb(II) and Cu(II) were evaluated. The results showed that the optimal growth time, synthesis temperature and acetylene flow rate were 45 min, 600 °C and 200 sccm (standard cubic centimeter per minute), respectively. The SS@CNTs composite had a high adsorption capacity with a maximum removal amount of 427.26 mg·g-1 for Pb(II) and 132.79 mg·g-1 for Cu(II). The adsorption proceeded rapidly during the first 15 min of adsorption and reached equilibrium at approximately 90 min. The adsorption processes were in accordance with the isotherms of the Langmuir model and the pseudo-second-order model, while the adsorption thermodynamics results indicated that the removal for both metals was an endothermic and spontaneous process. This study showed that compared with other adsorbent materials, the SS@CNTs composite is an efficient and low-cost adsorbent for heavy metals such as lead and copper.
RESUMEN
Increased GP73 expression in hepatocytes from patients with acute hepatitis, through disease progression to cirrhosis and chronic liver disease suggests that progressive tissue remodeling and fibrogenesis are driving forces for GP73 upregulation. Nevertheless, details about regulation of GP73 expression and its biological functions remain elusive and await further characterization. In this study, we demonstrate that GP73 is a direct target of TGF-ß1 transcriptional regulation. Its induced expression inhibits TGF-ß-Smad mediated growth suppression. On the other hand, elevated GP73 results in upregulation of ERK/Akt signaling induced by TGF-ß1. Mechanistically, upregulation of lipid raft and caveolae-1 induced by GP73 overexpression mediates its regulatory effect on TGF-ß1 signaling. Notably, lipid raft expression is elevated in HCC tumors and tissues with higher GP73 expression yield more intensive Flotillin staining. Our results establish the linkage between GP73 and TGF-ß signaling, indicating that GP73 may promote HCC tumorigenesis by selectively regulating TGF-ß signaling through lipid raft modulation.
Asunto(s)
Proteínas de la Membrana/metabolismo , Transducción de Señal , Proteínas Smad/antagonistas & inhibidores , Factor de Crecimiento Transformador beta1/fisiología , Animales , Carcinoma Hepatocelular/metabolismo , Caveolina 1/metabolismo , Línea Celular , Células Cultivadas , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Regulación de la Expresión Génica , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Microdominios de Membrana/metabolismo , Proteínas de la Membrana/biosíntesis , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Fosfoproteínas/biosíntesis , Fosfoproteínas/genética , Transcripción GenéticaRESUMEN
We report a turn-on tetravalent sialic acid-coated tetraphenylethene luminogen (TPE4S) with excellent hydrophilicity, good stability, high sensitivity and unique selectivity towards sialidases, and the maximum fluorescence enhancement was â¼40 fold. More importantly, TPE4S was successfully utilized for the screening of sialidase inhibitors and diagnosis of bacterial vaginosis.
Asunto(s)
Inhibidores Enzimáticos/farmacología , Colorantes Fluorescentes/farmacología , Neuraminidasa/análisis , Ácidos Siálicos/farmacología , Estilbenos/farmacología , Vaginosis Bacteriana/diagnóstico , Adulto , Clostridium perfringens/enzimología , Inhibidores Enzimáticos/síntesis química , Femenino , Fluorescencia , Colorantes Fluorescentes/síntesis química , Fluorometría/métodos , Ensayos Analíticos de Alto Rendimiento/métodos , Humanos , Interacciones Hidrofóbicas e Hidrofílicas , Cinética , Límite de Detección , Persona de Mediana Edad , Ácido N-Acetilneuramínico/análogos & derivados , Ácido N-Acetilneuramínico/farmacología , Neuraminidasa/antagonistas & inhibidores , Oseltamivir/análogos & derivados , Oseltamivir/farmacología , Ácidos Siálicos/síntesis química , Estilbenos/síntesis química , Vibrio cholerae/enzimología , Adulto Joven , Zanamivir/farmacologíaRESUMEN
BACKGROUND: The death after liver transplantation (LT) was most commonly caused by HCC recurrence. Golgi protein 73 (GP73), a type II Golgi membrane protein, has been proved to be a better serum marker for HCC. OBJECTIVE: This study aims to clarify the relationship between serum GP73 levels and tumor recurrence as well as survival of HCC patients after LT. METHODS: Between November 2003 and July 2008, serum samples from 60 liver transplantation patients and 72 healthy individuals were collected. ELISA and microparticle enzyme immunoassay were used to measure serum GP73 and AFP levels. Patient survival was analyzed using log-rank test along with Kaplan-Meier method. Receiver operating characteristic (ROC) curve was utilized to analyze the diagnostic value of serum GP73 levels. Cox regression was utilized to analyze prognostic factors with multiple variables. RESULTS: Serum GP73 concentrations in HCC patients were much higher than that in healthy controls (P<0.001). Patients with lower serum GP73 levels at LT-6Month had better overall survival and recurrence-free survival than those with higher serum GP73 levels. ROC analyzing results showed that higher serum GP73 levels at 6 month post-LT could significantly predict mortality (P=0.020) as well as HCC recurrence (P=0.001) after liver transplantation. Multivariate analysis revealed that serum GP73 levels at LT-6Month was an independent predictor of good prognosis (P=0.002). CONCLUSION: Serum GP73 levels could be used to predict tumor recurrence and survival in HCC sufferers after LT.
RESUMEN
The use of fragments with low binding affinity for their targets as starting points has received much attention recently. Screening of fragment libraries has been the most common method to find attractive starting points. Herein, we describe a unique, alternative approach to generating fragment leads. A binding model was developed and a set of guidelines were then selected to use this model to design fragments, enabling our discovery of a novel fragment with high LE.
Asunto(s)
Química Farmacéutica , Diseño de Fármacos , Modelos MolecularesRESUMEN
Benzothiazine-substituted tetramic acids were discovered as highly potent non-nucleoside inhibitors of HCV NS5B polymerase. X-ray crystallography studies confirmed the binding mode of these inhibitors with HCV NS5B polymerase. Rational optimization of time dependent inactivation of CYP 3A4 and clearance was accomplished by incorporation of electron-withdrawing groups to the benzothiazine core.
Asunto(s)
Antivirales/síntesis química , Hepacivirus/efectos de los fármacos , Pirrolidinonas/química , Tiazinas/química , Proteínas no Estructurales Virales/antagonistas & inhibidores , Animales , Antivirales/química , Antivirales/farmacocinética , Sitios de Unión , Cristalografía por Rayos X , Pirrolidinonas/síntesis química , Pirrolidinonas/farmacocinética , Ratas , Relación Estructura-Actividad , Proteínas no Estructurales Virales/metabolismoRESUMEN
A series of benzo[d]isothiazole-1,1-dioxides were designed and evaluated as inhibitors of HCV polymerase NS5B. Structure-based design led to the incorporation of a high affinity methyl sulfonamide group. Structure-activity relationship (SAR) studies of this series revealed analogues with submicromolar potencies in the HCV replicon assay and moderate pharmacokinetic properties. SAR studies combined with structure based drug design focused on the sulfonamide region led to a novel and potent cyclic analogue.
Asunto(s)
Antivirales/síntesis química , Hepacivirus/efectos de los fármacos , Tiazoles/química , Proteínas no Estructurales Virales/antagonistas & inhibidores , Animales , Antivirales/química , Antivirales/farmacocinética , Sitios de Unión , Cristalografía por Rayos X , Haplorrinos , Ratas , Relación Estructura-Actividad , Tiazoles/síntesis química , Tiazoles/farmacocinética , Proteínas no Estructurales Virales/metabolismoRESUMEN
A new series of benzothiazine-substituted quinolinediones were evaluated as inhibitors of HCV polymerase NS5B. SAR studies on this series revealed a methyl sulfonamide group as a high affinity feature. Analogues with this group showed submicromolar potencies in the HCV cell based replicon assay. Pharmacokinetic and toxicology studies were also performed on a selected compound (34) to evaluate in vivo properties of this new class of inhibitors of HCV NS5B polymerase.