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Aim To explore the effect of oxaliplatin combined with epidermal growth factor receptor tyrosine kinase inhibitor AG1478 on autophagy in non-small cell lung cancer H1975 cells. Methods H1975 cells were cultured in vitro using gradient concentrations of AG1478 (0, 5, 10, 15, 20, 25, 30, 35, 40 jjimol • IT
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Purpose: We evaluated he effects of molecular guided-targeted therapy for intractable cancer. Also, the epidemiology of druggable gene alterations in Chinese population was investigated. Materials and methods: The Long March Pathway (ClinicalTrials.gov identifier: NCT03239015) is a non-randomized, open-label, phase II trial consisting of several basket studies examining the molecular profiles of intractable cancers in the Chinese population. The trial aimed to 1) evaluate the efficacy of targeted therapy for intractable cancer and 2) identify the molecular epidemiology of the tier II gene alterations among Chinese pan-cancer patients. Results: In the first stage, molecular profiles of 520 intractable pan-cancer patients were identified, and 115 patients were identified to have tier II gene alterations. Then, 27 of these 115 patients received targeted therapy based on molecular profiles. The overall response rate (ORR) was 29.6% (8/27), and the disease control rate (DCR) was 44.4% (12/27). The median duration of response (DOR) was 4.80 months (95% CI, 3.33-27.2), and median progression-free survival (PFS) was 4.67 months (95% CI, 2.33-9.50). In the second stage, molecular epidemiology of 17,841 Chinese pan-cancer patients demonstrated that the frequency of tier II gene alterations across cancer types is 17.7%. Bladder cancer had the most tier-II alterations (26.1%), followed by breast cancer (22.4%), and non-small cell lung cancer (NSCLC; 20.2%). Conclusion: The Long March Pathway trial demonstrated a significant clinical benefit for intractable cancer from molecular-guided targeted therapy in the Chinese population. The frequency of tier II gene alterations across cancer types supports the feasibility of molecular-guided targeted therapy under basket trials.
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Aim To investigate the effect of tyrosine kinase inhibitor AG1478 combined with oxaliplatin (OXA) on apoptosis of colorectal cancer HCT116 cells. Methods MTT assay was used to measure the effect of AG1478 combined with OXA on proliferation of HCT116 cells. RT-qPCR was used to detect the mRNA expression levels of p53, caspase-3, Bcl-2 and Bax. Western blot was used to detect the proteins expression of p53, caspase-3, cleaved-caspase 3, Bcl-2, Bax, p62, LC3 and IL-6. Results Both OXA and AG1478 inhibited the proliferation of HCT116 (P < 0. 01). IC
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At the High Energy Photon Source (HEPS; Beijing, People's Republic of China), where up to 90 beamlines can be provided in the future, minimization of workload for individual beamlines and maximization of knowledge about one beamline that can be applied to other beamlines is essential to minimize the total complexity in beamline control. Presented in this paper are our efforts to achieve these goals by composing relatively simple utilities and mechanisms to automate tasks, while always remembering to keep our automation solutions simple and clear. After an introduction to our choice of basic software in EPICS-based beamline control, the issues encountered in introducing package management to EPICS modules, as well as solutions to them, are presented; the design and implementation of the packaging system is concisely discussed. After a presentation of our efforts to reduce the need for self-built multi-device EPICS `input/output controller' (IOC) applications by providing reusable modular IOC executables, implementation of easily maintainable multi-IOC setups through the separation and minimization of each user's IOC configurations is given. The ongoing project of comprehensive beamline services at HEPS to further simplify configuration management on multiple scales, ranging from individual beamline devices to all beamlines at HEPS, is introduced.
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The biomass of filamentous fungi is an important cost-effective biomass for heavy metal biosorption. However, use of free fungal cells can cause difficulties in the separation of biomass from the effluent. In this study, we immobilized the living conidia of the heavy metal-resistant Penicillium janthinillum strain GXCR by polyvinyl alcohol (PVA)-sodium alginate (SA) beads to remove heavy metals from an aqueous solution containing a low concentration (70 mg/L) of Cu, Pb, and Cd. The PVA-SA-conidia beads showed perfect characters of appropriate mechanical strength suitable for metal removal from the dynamic wastewater environment, an ideal settleability, easy separation from the solution, and a high metal biosorption and removal rate even after four cycles of successive sorption-desorption of the beads, overcoming disadvantages when fungal biomasses alone are used for heavy metal removal from wastewater. We also discuss the major biosorption-affecting factors, biosorption models, and biosorption mechanisms.
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Biomasa , Metales Pesados/química , Penicillium/química , Esporas Fúngicas/química , Aguas Residuales/química , Contaminantes Químicos del Agua/química , Purificación del Agua/métodos , Penicillium/fisiologíaRESUMEN
Abundant nsSNPs have been found in genes coding for human solute carrier (SLC) transporters, but there is little known about the relationship between the genotype and phenotype of nsSNPs in these membrane proteins. It is unknown which prediction method is better suited for the prediction of nonneutral nsSNPs of SLC transporters. We have identified 2,958 validated nsSNPs in human SLC family members 1-47 from the Ensembl genome database and the NCBI SNP database. Using three different algorithms, 37-45 % of nsSNPs in SLC genes were predicted to have functional impacts on transporter function. Predictions largely agreed with the available experimental annotations. Overall, 76.5, 74.4, and 73.5 % of nonneutral nsSNPs were predicted correctly as damaging by SNAP, SIFT, and PolyPhen, respectively, while 67.4, 66.3, and 76.7 % of neutral nsSNPs were predicted correctly as nondamaging by the three methods, respectively. This study identified many amino acids that were likely to be functionally critical but have not yet been studied experimentally. There was a significant concordance between the predicted results of different methods. Evolutionarily nonneutral (destabilizing) amino acid substitutions are predicted to be the basis for the pathogenic alteration of SLC transporter activity that is associated with disease susceptibility and altered drug/xenobiotic response.
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Algoritmos , Biología Computacional/métodos , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Polimorfismo de Nucleótido Simple , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Sustitución de Aminoácidos , Bases de Datos Genéticas , Genotipo , Humanos , Bombas Iónicas/genética , Bombas Iónicas/metabolismo , Proteínas de Transporte de Membrana/química , Fenotipo , Conformación Proteica , Reproducibilidad de los Resultados , Relación Estructura-ActividadRESUMEN
A novel bioflocculant-producing bacterium, ZHT4-13, was isolated from Ruditapes philippinarum conglutination mud. By biomicroscope morphological observation, 16S rDNA sequence identification and physiological and biochemical characteristics, strain ZHT4-13 was identified as Rothia sp. The bioflocculant MBF4-13 produced by strain ZHT4-13 had a flocculating efficiency of 86.22% for 5 g L(-1) Kaolin clay suspension when the initial pH was 9 and the temperature was 20 degrees C. It had flocculating effect in a wide range, pH 1-13 and temperature 4-100 degrees C. Analysis of MBF4-13 by UV-Vis spectrophotometer, Fourier-transform infrared spectrophotometer (FT-IR) and (1)H nuclear magnetic resonance (NMR) indicated that the main component of MBF4-13 is polysaccharide. The culture conditions to produce strain ZHT4-13 were optimized with orthogonal design of experiments. MBF4-13 had high efficiency in decolorizing dye solutions, had some abilities to remove heavy metal ions (Cr(2)O(7)(2-), Ni(2+)) and improve performance of activated sludge.