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排序方式: 共有2758条查询结果,搜索用时 15 毫秒
1.
Dr. Jie Zang Dr. Fei Ye Dr. Sara M. Ø. Solbak Dr. Lars J. Høj Prof. Mingjie Zhang Prof. Anders Bach 《ChemMedChem》2021,16(6):949-954
Inhibition of PSD-95 has emerged as a promising strategy for the treatment of ischemic stroke, as shown with peptide-based compounds that target the PDZ domains of PSD-95. In contrast, developing potent and drug-like small molecules against the PSD-95 PDZ domains has so far been unsuccessful. Here, we explore the druggability of the PSD-95 PDZ1-2 domain and use fragment screening to investigate if this protein is prone to binding small molecules. We screened 2500 fragments by fluorescence polarization (FP) and validated the hits by surface plasmon resonance (SPR), including an inhibition counter-test, and found four promising fragments. Three ligand efficient fragments were shown by 1H,15N HSQC NMR to bind in the small hydrophobic P0 pockets of PDZ1-2, and one of them underwent structure-activity relationship (SAR) studies. Overall, we demonstrate that fragment screening can successfully be applied to PDZ1-2 of PSD-95 and disclose novel fragments that can serve as starting points for optimization towards small-molecule PDZ domain inhibitors. 相似文献
2.
Hybrid electrospun nanofibers of polycaprolactone (PCL)/gelatin are considered as drug-delivery systems for increasing the treatment efficacy in superficial (skin) wounds. Continuous delivery of therapeutic agents, skin extracellular matrix similarity, management of wound exudate, and antimicrobial barrier effect are the major advantages of electrospun nanofibers in skin applications. Additionally, combining the favorable properties of PCL and gelatin, regarding their biocompatibility, biodegradability and mechanical performance have been revealed promising parameters to be considered for blend in hybrid structures. However, the usual optimization protocol of nanofibers’ production in electrospinning is based on the observation of one-variable-at-time being this methodology expensive and time-consuming. Therefore, in this research work, a statistical model based on four input variables namely, the flow rate, the needle-working distance, the applied voltage, and the ratio of PCL in the solution, is developed to predict the behavior of nanofibers. The performance of nanofibers is monitored by measurements of fiber's diameter, mesh's thickness, and mesh's permeability. Overall, the model showed to be statistically significant (p-value < 0.05) and an independent analysis validated the predicted response for optimal condition. Finally, a delivery study is performed to evaluate the electrospun mesh performance as a drug carrier. 相似文献
3.
Maryam Oroujeni Sara S. Rinne Anzhelika Vorobyeva Annika Loftenius Joachim Feldwisch Per Jonasson Vladimir Chernov Anna Orlova Fredrik Y. Frejd Vladimir Tolmachev 《International journal of molecular sciences》2021,22(5)
Radionuclide imaging of HER2 expression in tumours may enable stratification of patients with breast, ovarian, and gastroesophageal cancers for HER2-targeting therapies. A first-generation HER2-binding affibody molecule [99mTc]Tc-ZHER2:V2 demonstrated favorable imaging properties in preclinical studies. Thereafter, the affibody scaffold has been extensively modified, which increased its melting point, improved storage stability, and increased hydrophilicity of the surface. In this study, a second-generation affibody molecule (designated ZHER2:41071) with a new improved scaffold has been prepared and characterized. HER2-binding, biodistribution, and tumour-targeting properties of [99mTc]Tc-labelled ZHER2:41071 were investigated. These properties were compared with properties of the first-generation affibody molecules, [99mTc]Tc-ZHER2:V2 and [99mTc]Tc-ZHER2:2395. [99mTc]Tc-ZHER2:41071 bound specifically to HER2 expressing cells with an affinity of 58 ± 2 pM. The renal uptake for [99mTc]Tc-ZHER2:41071 and [99mTc]Tc-ZHER2:V2 was 25–30 fold lower when compared with [99mTc]Tc-ZHER2:2395. The uptake in tumour and kidney for [99mTc]Tc-ZHER2:41071 and [99mTc]Tc-ZHER2:V2 in SKOV-3 xenografts was similar. In conclusion, an extensive re-engineering of the scaffold did not compromise imaging properties of the affibody molecule labelled with 99mTc using a GGGC chelator. The new probe, [99mTc]Tc-ZHER2:41071 provided the best tumour-to-blood ratio compared to HER2-imaging probes for single photon emission computed tomography (SPECT) described in the literature so far. [99mTc]Tc-ZHER2:41071 is a promising candidate for further clinical translation studies. 相似文献
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位于谢莱夫特奥(Skellefte?)的莫罗·贝克学校(Mor?backeskolan)是一所注重可持续发展的学校,木结构在其承重结构和室内设计中扮演着重要的角色.尤其是在有阶梯剧场感觉的大中厅,木结构发挥了其巨大影响. 相似文献
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7.
D. Kherifi H. Belhouchet S. Ramesh K.Y. Sara Lee A. Kenzour S. Djoualah M.K.G. Abbas Y.H. Wong S. Ramesh 《Ceramics International》2021,47(12):16483-16490
In this work, the sintering behaviour of fluorapatite (FAp)–silicate composites prepared by mixing variable amounts of natural quartz (2.5 wt% to 20 wt%) and FAp was studied. The composites were pressureless sintered in air at temperatures from 1000 °C to 1350 °C. The effects of temperatures on the densification, phase formation, chemical bonding and Vickers hardness of the composites were evaluated. All the samples exhibited mixed phase, comprising FAp and francolite as the major constituents along with some minor phases of cristobalite, wollastonite, dicalcium silicate and/or whitlockite dependent on the quartz content and sintering temperature. The composite containing 2.5 wt% quartz exhibited the best sintering properties. The highest bulk density of 3 g/cm3 and a Vickers hardness of >4.2 GPa were obtained for the 2.5 wt% quartz–FAp composite when sintered at 1100 °C. The addition of quartz was found to alter the microstructure of the composites, where it exhibited a rod-like morphology when sintered at 1000 °C and a regular rounded grain structure when sintered at 1350 °C. A wetted grain surface was observed for composites containing high quartz content and was believed to be associated with a transient liquid phase sintering. 相似文献
8.
Policicchio Alfonso Putz Ana-Maria Conte Giuseppe Stelitano Sara Bonaventura Carlo Poselle Ianăşi Cătălin Almásy László Wacha András Horváth Zsolt Endre Agostino Raffaele G. 《Journal of Porous Materials》2021,28(4):1049-1058
Journal of Porous Materials - The present study reports a systematic analysis of morphology and hydrogen sorption capacity of mesoporous organic-inorganic silica prepared by varying the silica... 相似文献
9.
Sara Asadi Mohsen Jahan Alireza Farid Hosseini 《International journal of remote sensing》2019,40(18):7153-7168
Rapid and accurate estimation of Ground Cover (GC) at regional and global scales for agricultural management application is only possible by using remote sensing (RS). In this study, two Vegetation Indices (VIs) including the Perpendicular Vegetation Index (PVI) and Normalized Difference Vegetation Index (NDVI) were used for estimating GC. Since the parameters of the bare soil line have an important role in calculating GC based on PVI, this line was extracted based on the red-NIRmin (minimum near infrared) method with different intervals (0.0001, 0.0005, and 0.0010). In addition to traditional statistics such as Root Mean Square Error (RMSE), the sensitivity analysis (S) was also used to sharpen the accuracy of the models' estimations. The results indicated that the PVI-based method, in contrast to the NDVI-based approach, had a better performance in estimating GC of wheat. The highest correlation between the observed GC and the estimated GC based on PVI method was achieved in interval length of 0.0005 (R2 = 0.91) with RMSE equal to 8.82. This regression line (GCEST = -3.47 + 0.96 GCOBS) was not significantly different from the 1:1 line. As expected, the best estimation was achieved when the sensitivity of estimated GC based on PVI (length of the interval: 0.0005) was almost constant and low compared to the other models. 相似文献