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Diazo-Based Copolymers to the Moist Energy Enhancement of Papers Based on Thermally Induced CH-Insertion Cross-Linking.
Xenograft tumor model was used to evaluate biological function in vivo. TSN limited the proliferation, migration, invasion, EMT progression in GC, and these results could be inverted by silencing of miR-874. Moreover, the putative binding sites between miR-874 and HMGB2 were predicted by starBase software online. Meanwhile, enforced expression of HMGB2, negatively correlated with that of miR-874, reversed the positive effects of TSN administration on cells. Mechanically, TSN restrained the GC progression by miR-874/HMGB2/β-catenin signaling in vitro. Additionally, in vivo experiments confirmed that TSN inhibited the GC progression as well. TSN restrained the GC progression by regulating miR-874/HMGB2/β-catenin pathways in vitro and in vivo.Addition of P-H species to carbonyl groups, namely the Pudovik reaction, normally delivers hydroxyl phosphorus compounds, along with phosphate byproducts in some cases. A few controllable systems starting from phosphites were set up to mainly provide the phosphates. Herein, we present a highly selective protocol starting from phosphonate precursors leading to phosphinate derivatives. Enantioenriched phosphinates were successfully achieved from chiral phosphine oxide precursors. Experimental and theoretical investigations were conducted to understand the mechanistic details.Genome mining of an indolocarbazole-type gene cluster from a marine-derived Nocardiopsis flavescens NA01583 strain led to the discovery of three new indolocarbazole alkaloids (1-3). Heterologous expression of the intact loo gene cluster in a surrogate host Streptomyces lividans K4-114 led to the successful production of 3. Notably, compound 1 showed potent cytotoxic activities toward eight cancer cell lines with IC50 values ranging from 41 to 283 nM.Herein an efficient Pd-catalyzed asymmetric allylic substitution cascade of both (E)- and (Z)-but-2-ene-1,4-diyl dimethyl dicarbonates with α-substituted cyano ketones is described for the preparation of chiral 2,3-dihydrofurans in up to 97% yield with 98% ee. A suggested steric control process has been proposed to illustrate the differences in enantioselectivity between the reactions of (E)- and (Z)-allyl substrates. The cascade reaction could be conducted on a gram-scale, and the resulting product allows for several transformations.Naturally occurring sinapine was successfully synthesized through a proline-mediated Knoevenagel-Doebner condensation in ethanol. This synthetic process involving biobased syringaldehyde, Meldrum's acid, and choline chloride offers a sustainable alternative to the existing low-yield pathways. This two-step strategy gives access to sinapine in a 52% overall yield and has been implemented in the synthesis of sinapine analogues, using 4-hydroxybenzaldehyde, 3,4-dihydroxybenzaldehyde, and vanillin as precursors, giving target molecules with 34-61% overall isolated yields. The purity of synthetic sinapine and its analogues (ca. 95%) was assessed by NMR and high-performance liquid chromatography-mass spectrometry analyses. Furthermore, the antioxidant and antimicrobial activities were assessed, and the potential of this series of molecules was confirmed.Copper(II) carbosilane metallodendrimers are promising nanosized anticancer metallodrugs. The precise control on their design enables an accurate structure-to-activity study. We hypothesized that different structural features, such as the dendrimer generation and metal counterion, modulate the interaction with tumor cells, and subsequently, the effectivity and selectivity of the therapy. A computer-aided analysis of the electron paramagnetic resonance (EPR) spectra allowed us to obtain dynamical and structural details on the interactions over time between the dendrimers and the cells, the myeloid U937 tumor cells and peripheral blood mononuclear cells (PBMC). The intracellular fate of the metallodendrimers was studied through a complete in vitro evaluation, including cytotoxicity, cytostaticity, and sublethal effects regarding mitochondria function, lysosomal compartments, and autophagic organelle involvement. EPR results confirmed a higher membrane stabilization for chloride dendrimers and low generation complexes, which ultimately influence the metallodrug uptake and intracellular fate. The in vitro evaluation revealed that Cu(II) metallodendrimers are cytostatic and moderate cytotoxic agents for U937 tumor cells, inducing death processes through the mitochondria-lysosome axis as well as autophagic vacuole formation, while barely affecting healthy monocytes. The study provided valuable insight into the mechanism of action of these nanosized metallodrugs and relevant structural parameters affecting the activity.Human type II topoisomerases, molecular motors that alter the DNA topology, are a major target of modern chemotherapy. Groups of catalytic inhibitors represent a new approach to overcome the known limitations of topoisomerase II poisons such as cardiotoxicity and induction of secondary tumors. Here, we present a class of substituted 4,5'-bithiazoles as catalytic inhibitors targeting the human DNA topoisomerase IIα. Based on a structural comparison of the ATPase domains of human and bacterial type II topoisomerase, a focused chemical library of 4,5'-bithiazoles was assembled and screened to identify compounds that better fit the topology of the human topo IIα adenosine 5'-triphosphate (ATP) binding site. Selected compounds showed inhibition of human topo IIα comparable to that of the etoposide topo II drug, revealing a new class of inhibitors targeting this molecular motor. Further investigations showed that compounds act as catalytic inhibitors via competitive ATP inhibition. We also confirmed binding to the truncated ATPase domain of topo IIα and modeled the inhibitor molecular recognition with molecular simulations and dynophore models. The compounds also displayed promising cytotoxicity against HepG2 and MCF-7 cell lines comparable to that of etoposide. In a more detailed study with the HepG2 cell line, there was no induction of DNA double-strand breaks (DSBs), and the compounds were able to reduce cell proliferation and stop the cell cycle mainly in the G1 phase. This confirms the mechanism of action of these compounds, which differs from topo II poisons also at the cellular level. Substituted 4,5'-bithiazoles appear to be a promising class for further development toward efficient and potentially safer cancer therapies exploiting the alternative topo II inhibition paradigm.Accurate determination of the binding affinity of the ligand to the receptor remains a difficult problem in computer-aided drug design. Here, we study and compare the efficiency of Jarzynski's equality (JE) combined with steered molecular dynamics and the linear interaction energy (LIE) method by assessing the binding affinity of 23 small compounds to six receptors, including β-lactamase, thrombin, factor Xa, HIV-1 protease (HIV), myeloid cell leukemia-1, and cyclin-dependent kinase 2 proteins. It was shown that Jarzynski's nonequilibrium binding free energy ΔGneqJar correlates with the available experimental data with the correlation levels R = 0.89, 0.86, 0.83, 0.80, 0.83, and 0.81 for six data sets, while for the binding free energy ΔGLIE obtained by the LIE method, we have R = 0.73, 0.80, 0.42, 0.23, 0.85, and 0.01. Therefore, JE is recommended to be used for ranking binding affinities as it provides accurate and robust results. In contrast, LIE is not as reliable as JE, and it should be used with caution, especially when it comes to new systems.The crystal structure of the ferroelastic and ferroelectric tungsten bronze Ba2NaNb5O15 (BNN) has been debated. Here, we re-examine the crystal structure of BNN by ambient powder X-ray diffraction combined with density functional theory calculations. We demonstrate that the room temperature space group is Cmm2 with significant cation disorder on the Ba and Na cation sublattices. Density functional theory calculations reveal a relatively flat energy landscape between structures of different symmetries, including the energetics of cation disorder. We also study the structural evolution and the ferroelectric and ferroelastic phase transitions by high-temperature X-ray diffraction and dilatometry. The ferroelectric phase transition at 570 °C is of first order and cause the cell to expand in the c direction, while the ferroelastic distortion starting at 270 °C takes place in the ab plane and does not affect the polarization. The phase transitions are not coupled, which means that BNN is a ferroic material with two primary and uncoupled order parameters.We report an Fmoc-compatible and external-thiol-free method of peptide C-terminus thioesterification with cysteinylprolyl imide. The newly synthesized structure, i.e., cysteinylprolyl-thiazolidinone, provided high conversion and sequence-independent fast kinetics (90 min) in the diketopiperazine thioester formation under relatively mild conditions pH 6.0, 37 °C. Employing this thioesterification method, we synthesized histone H3.2 bearing K56 acetylation.The adoption of solution-processed active layers in the production of thin-film photovoltaics is hampered by the transition from research fabrication techniques to scalable processing. We report a detailed study of the role of processing in determining the morphology and performance of organic photovoltaic devices using a commercially available, low-solubility, high-molar mass diketopyrrolopyrrole-based polymer donor. Ambient blade coating of thick layers in an inverted architecture was performed to best model scalable processing. Device performance was strongly dependent on the introduction of either o-dichlorobenzene (DCB), 1,8-diiodooctane, or diphenyl ether cosolvent into the chloroform (CHCl3) solution, which were all shown to drastically improve the morphology. To understand the origin of these morphological changes as a result of the addition of the cosolvent, in situ studies with grazing-incidence X-ray scattering and optical reflection interferometry were performed. Use of any of the cosolvents decreases the domain size relative to the single solvent system and moved the drying mechanism away from what is likely liquid-liquid phase separation to solid-liquid phase separation driven by polymer aggregation. Comparing the CHCl3 + DCB cast films to the CHCl3-only cast films, we observed both the formation of small domains and an increase in crystallinity during the evaporation of DCB due to a high nucleation rate from supersaturation. this website This resulted in percolated bulk heterojunction networks that performed similarly well with a wide range of film thicknesses from 180 to 440 nm, making this system amenable to continuous roll-to-roll processing methods.DNA self-assembled monolayers (SAMs) were prepared using potential-assisted deposition on clean gold single-crystal bead electrodes under a number of conditions (constant or square-wave potential perturbations in TRIS or phosphate immobilization buffers with and without Cl-). The local environment around the fluorophore-labeled DNA tethered to the electrode surface was characterized using in situ fluorescence microscopy during electrochemical measurements as a function of the underlying surface crystallography. Potential-assisted deposition from a TRIS buffer containing Cl- created DNA SAMs that were uniformly distributed on the surface with little preference to the underlying crystallography. A constant (+0.4 V/SCE) or a square-wave potential perturbation (+0.4 to -0.3 V/SCE, 50 Hz) resulted in similar DNA-modified surfaces in TRIS immobilization buffer. Deposition using a square-wave potential without Cl- resulted in lower DNA surface coverage. Despite this, the local environment around the DNA in the SAM appears to be densely packed.
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