Kappelvick1322

Prodrug nanoparticles with cleavable moieties sensitive to intracellular stimuli have drawn great attention on cancer chemotherapy. Herein, a reactive oxygen species (ROS)-responsive doxorubicin prodrug mPEG-Phe-TK-Phe-hyd-DOX was synthesized, in which hydrophilic methoxy poly(ethylene glycol) (mPEG) and hydrophobic anticancer drug doxorubicin (DOX) were conjugated with hydrazone (hyd) and ROS-responsive thioketal (TK) moieties. The ROS-responsiveness of prodrug was confirmed by proton nuclear magnetic resonance (1H NMR) and dynamic light scattering (DLS). Unexpectedly, the results of in vitro drug release indicated that the hydrazone bond of prodrug nanoparticles was insensitive to pH, which may be due to the strong hydrophobicity, π-π interactions and cation-π interactions jointly inhibited the hydrolysis of hydrazone bonds under acidic conditions. The cellular uptake and in vitro anticancer study showed that ROS-responsive prodrug nanoparticles exhibited faster cellular uptake and better anticancer efficacy. The in vivo experiments showed that the ROS-responsive prodrug nanoparticles had comparable antitumor efficacy with free anticancer drug DOX and reduced organ toxicity. Our results provide novel idea of successfully design multi-stimuli-responsive nano-drug carrier.The objective of this work, is to study adamantanes and to tune their bandgap, since pure adamantane is considered as an insulator due to its high bandgap energy. For this, we doped adamantane with oxygen and sulfur atoms, thus obtaining 730 different structures with double bonds and 730 different structures with single bonds, for a total of 1460 structures, and compared their properties. Among all, 31 molecules were selected that best represented the reduced bandgap behavior. The calculations with greater precision in its results were made using the Local Density Approximation (LDA), in the Density-Functional Theory (DFT) formalism, with PWC functional and TNP basis set. The electronic and optical properties were analyzed, by calculating the energy gap and absorption spectrum. Importantly, we observed that molecules doped with sulfur atoms (double bonds) had their energy gap reduced significantly compared to molecules doped with sulfur and/or oxygen atom with single bonds and pristine adamantane. It was found that in the absorption spectrum, the sulfur-doped structures had their spectrum shifted to the visible region, a fact that becomes relevant for potential dyes and optoelectronic applications. From the seven selected functionalized adamantanes (ADD-04, ADD-05, ADD-07, ADD-19, ADD-20, ADD-41, and ADD-48), any of these could be used as a dye. However, the ADD-20 molecule in particular, which presented optical absorption near (RGB) primary colors, could indicate a potential quantum dot material for application in developing screens of various electronic devices.A priori knowledge of physicochemical properties such as melting and boiling could expedite materials discovery. However, theoretical modeling from first principles poses a challenge for efficient virtual screening of potential candidates. As an alternative, the tools of data science are becoming increasingly important for exploring chemical datasets and predicting material properties. Herein, we extend a molecular representation, or set of descriptors, first developed for quantitative structure-property relationship modeling by Yalkowsky and coworkers known as the Unified Physicochemical Property Estimation Relationships (UPPER). This molecular representation has group-constitutive and geometrical descriptors that map to enthalpy and entropy; two thermodynamic quantities that drive thermal phase transitions. We extend the UPPER representation to include additional information about sp2-bonded fragments. Additionally, instead of using the UPPER descriptors in a series of thermodynamically-inspired calculations, as per Yalkowsky, we use the descriptors to construct a vector representation for use with machine learning techniques. The concise and easy-to-compute representation, combined with a gradient-boosting decision tree model, provides an appealing framework for predicting experimental transition temperatures in a diverse chemical space. An application to energetic materials shows that the method is predictive, despite a relatively modest energetics reference dataset. We also report competitive results on diverse public datasets of melting points (i.e., OCHEM, Enamine, Bradley, and Bergström) comprised of over 47k structures. Open source software is available at https//github.com/USArmyResearchLab/ARL-UPPER.This study aimed to investigate the expression pattern of spermatogenesis associated protein 6 (SPATA6) in Hu sheep testis and to ascertain the effects of SPATA6 on sheep Leydig cells (LCs) function linked to spermatogenesis. In the present study, we detected a 1970 bp cDNA fragment of SPATA6 included a 1467 bp coding sequence which encoded 487 amino acids. Meanwhile, sheep SPATA6 shared 51.70%-97.41% amino acid sequences with its orthologs compared with other species. In addition, SPATA6 was highly expressed in testis and localized in cytoplasm and nucleus of LCs as well as spermatogenic cells at different stages. Compared to the negative control (NC), SPATA6 interference promoted apoptosis of LCs with the increase of BAX/BCL-2 mRNA and protein levels, while the results of SPATA6 overexpression were on the contrary. Meanwhile, cell cycle was blocked at G2/M phase and CDK1 and CCNB1 were down-regulated after SPATA6 interference. SPATA6 overexpression induced cell cycle transfer G0/G1 into S and G2/M phase with upregulation of CDK1, CDK4, CCND1 and CCND2. Moreover, the secretion of testosterone hormone and the expression of StAR in LCs with SPATA6 overexpression were significantly promoted. Overall, our data suggest that SPATA6 is an important functional molecule of spermatogenesis, via regulating the proliferation, apoptosis and testosterone biosynthesis of Hu sheep LCs. These findings will enhance the understanding of the roles of SPATA6 in sheep spermatogenesis.Our aim was to establish an efficient culture system to produce embryos by SCNT of the endangered Vietnamese Ỉ pig. Reducing the serum concentration from 10.0% to 0.2% during culture efficiently synchronized Ỉ pig fibroblasts used as donor cells at the G0/G1 stage. Oocyte maturation in a defined porcine oocyte medium (POM) supplemented with EGF and gonadotrophins resulted in higher cleavage and blastocyst rates compared with a non-defined POM containing pig follicular fluid (but without EGF) and both the defined and non-defined variants of NCSU-37. selleck products For embryo culture PZM3 and PZM5 media were superior to NCSU-37, in terms of the percentage of cleaved embryos. Addition of serum to PZM3 medium on Day 5 of culture (Day 0 = SCNT) improved blastocyst development. When SCNT embryos were transferred at the blastocyst stage, 7 of 11 recipients became pregnant. However, live offspring were not obtained. In conclusion, we established a system for the production of Ỉ pig embryos by SCNT and achieved blastocyst production rate at 26.