Riisryberg2324

Quercetin-3-rutinoside (rutin) is a bioflavonoid that is common in foods. The finding that quercetin-3-rutinoside inhibits protein disulfide isomerase (PDI) and potently blocks thrombosis in vivo has enabled the evaluation of PDI inhibition in multiple animal models of thrombus formation and has prompted clinical studies of PDI inhibition in thrombosis. Nonetheless, how quercetin-3-rutinoside blocks PDI activity remains an unanswered question. Combining NMR spectroscopy, site-directed mutagenesis, and biological assays, we identified H256 as the key residue for PDI interacting with quercetin-3-rutinoside. Quercetin-3-rutinoside inhibited the activity of PDI (WT) but not PDI (H256A). selleck compound Molecular dynamic simulations indicated that the flavonoid skeleton, but not the rutinoside conjugate, is embedded in the major binding pocket on the b' domain. Among several quercetin-3-rutinoside analogues tested, only compounds with a phenoxyl group at position 7 showed direct binding to PDI, further supporting our molecular model. Studies using purified coagulation factors showed that quercetin-3-rutinoside inhibited the augmenting effects of PDI (WT), but not PDI (H256A), on tissue factor (TF) activity. Quercetin-3-rutinoside also inhibited chemotherapy-induced TF activity enhancement on endothelial cells. Together, our studies show that residue H256 in PDI and the phenoxyl group at position 7 in quercetin-3-rutinoside are essential for inhibition of PDI by quercetin-3-rutinoside. These results provide new insight into the molecular mechanism by which flavonoids block PDI activity.The rapid manufacturing of transparent SiO2 glass components via a hybridized 3D structuring approach for photo-curing and green machining, followed by a fast debinding/sintering process (at a heating rate of 20 °C min-1), is reported to be based on the design of a new series of interparticle photo-cross-linkable suspensions. In these suspensions, small amounts of multifunctional acrylates and silane alkoxides with acryloyl groups (A-Si) are co-photo-polymerized and further reacted with SiO2 particles modified using functionalized polyethyleneimine to form hybridized interparticle networks. The addition of A-Si increases the interparticle cross-linking densities, leading to an improvement in the mechanical properties and green machinability of the photo-cured bodies. Furthermore, the A-Si component in the cross-links forms siloxane-based networks among SiO2 particles in situ during the debinding/sintering process, which increases the mechanical strength of the debinded bodies and successfully prevents structural collapses under rapid heating conditions. The study demonstrates that the photo-cured body from the newly designed suspensions can be green-machined into pillars, microfluids, and assembling blocks and can be sintered into highly transparent SiO2 glass components. Overall, this work provides new options for the time- and energy-effective processing of SiO2 glass materials with tailor-made 3D structures.The toxicity of perfluorinated compounds (PFCs) to mammals has recently received increasing attention. However, the effects of maternal sodium p-perfluorous nonenoxybenzene sulfonate (OBS) exposure during pregnancy and lactation on the liver function of dams (F0) and offspring (F1) mice are still unknown. The results demonstrated that maternal OBS treatment could not only induce lipid metabolism dysfunction but also disrupt amino acid metabolism in the liver of F0 and F1 generations. OBS had marked accumulation in the liver, and the serum and liver triglyceride (TG) levels increased in the F0 and F1 generations after maternal OBS exposure. Moreover, maternal OBS exposure changed the transcriptional levels of genes related to lipid metabolism (fatty acid (FA) synthesis, TG synthesis, and transport) and induced changes in the amino acid level in dams and 20-day-old mice offspring (F1-20 d). Additionally, the regulation of lipid metabolism by OBS was mainly dependent on the activation of peroxisome proliferator-activated receptor γ (PPARγ) and cluster of differentiation 36 (CD36). Interestingly, OBS could also disturb tyrosine (TYR) metabolism by increasing the TYR level and downregulating fumarate acetoacetate hydrolase (FAH). Together, these results indicated that the liver can be perceived as the major target tissue of OBS, which strongly affected metabolic function and ultimately led to an imbalance in the metabolism of lipids and TYR. In summary, maternal OBS exposure during pregnancy and lactation has toxic effects on the hepatic metabolism of dams and offspring, indicating that the toxic effects could obviously cross generations of mice, and we should pay more attention to understanding the health risk to both dams and offspring.Cytoskeletal elements, like actin and myosin, have been reconstituted inside lipid vesicles toward the vision to reconstruct cells from the bottom up. Here, we realize the de novo assembly of entirely artificial DNA-based cytoskeletons with programmed multifunctionality inside synthetic cells. Giant unilamellar lipid vesicles (GUVs) serve as cell-like compartments, in which the DNA cytoskeletons are repeatedly and reversibly assembled and disassembled with light using the cis-trans isomerization of an azobenzene moiety positioned in the DNA tiles. Importantly, we induced ordered bundling of hundreds of DNA filaments into more rigid structures with molecular crowders. We quantify and tune the persistence length of the bundled filaments to achieve the formation of ring-like cortical structures inside GUVs, resembling actin rings that form during cell division. Additionally, we show that DNA filaments can be programmably linked to the compartment periphery using cholesterol-tagged DNA as a linker. The linker concentration determines the degree of the cortex-like network formation, and we demonstrate that the DNA cortex-like network can deform GUVs from within. All in all, this showcases the potential of DNA nanotechnology to mimic the diverse functions of a cytoskeleton in synthetic cells.Zirconolite is considered to be a suitable wasteform material for the immobilization of Pu and other minor actinide species produced through advanced nuclear separations. Here, we present a comprehensive investigation of Dy3+ incorporation within the self-charge balancing zirconolite Ca1-xZr1-xDy2xTi2O7 solid solution, with the view to simulate trivalent minor actinide immobilization. Compositions in the substitution range 0.10 ≤ x ≤ 1.00 (Δx = 0.10) were fabricated by a conventional mixed oxide synthesis, with a two-step sintering regime at 1400 °C in air for 48 h. Three distinct coexisting phase fields were identified, with single-phase zirconolite-2M identified only for x = 0.10. A structural transformation from zirconolite-2M to zirconolite-4M occurred in the range 0.20 ≤ x ≤ 0.30, while a mixed-phase assemblage of zirconolite-4M and cubic pyrochlore was evident at Dy concentrations 0.40 ≤ x ≤ 0.50. Compositions for which x ≥ 0.60 were consistent with single-phase pyrochlore. The formation of zirconolite-4M and pyrochlore polytype phases, with increasing Dy content, was confirmed by high-resolution transmission electron microscopy, coupled with selected area electron diffraction. Analysis of the Dy L3-edge XANES region confirmed that Dy was present uniformly as Dy3+, remaining analogous to Am3+. Fitting of the EXAFS region was consistent with Dy3+ cations distributed across both Ca2+ and Zr4+ sites in both zirconolite-2M and 4M, in agreement with the targeted self-compensating substitution scheme, whereas Dy3+ was 8-fold coordinated in the pyrochlore structure. The observed phase fields were contextualized within the existing literature, demonstrating that phase transitions in CaZrTi2O7-REE3+Ti2O7 binary solid solutions are fundamentally controlled by the ratio of ionic radius of REE3+ cations.With the in-depth application of quartz crystal microbalance (QCM) sensors in the fields of science and engineering, there is an urgent need for QCM sensors with high mass sensitivity. The mass sensitivity of a QCM is closely related to its resonance frequency, and the high resonance frequency leads to improve its mass sensitivity. However, the resonance frequency of a QCM resonator cannot be increased all the time due to the fragility of quartz wafer and the limits of energy trapping effect. Few studies are associated with mass sensitivity of a QCM resonator under overtone modes. Herein, we propose to make a QCM resonator work in its n-th overtone (n = 3, 5, 7, 9 in this study) mode to increase its resonance frequency during operating. Thereby, the purpose of improving QCM mass sensitivity is achieved, and the mass sensitivity of a QCM working in the n-th overtone mode can be called as n-th overtone mass sensitivity. Then, the n-th overtone mass sensitivity of a QCM sensor is measured by an electrodeposition method. The experimental results show that the n-th overtone mass sensitivity of a QCM is a bit more than n times that of the fundamental mass sensitivity, and it is consistent with the theoretical calculation results. The application of overtone mass sensitivity will greatly improve the sensitivity of QCM sensors, which is very attractive for the research fields that require QCM sensors with high sensitivity.The bottom-up construction of an autonomously growing, self-reproducing cell represents a great challenge for synthetic biology. Synthetic cellular systems are envisioned as out-of-equilibrium enzymatic networks encompassed by a selectively open phospholipid bilayer allowing for protein-mediated communication; internal metabolite recycling is another key aspect of a sustainable metabolism. Importantly, gaining tight control over the external medium is essential to avoid thermodynamic equilibrium due to nutrient depletion or waste buildup in a closed compartment (e.g., a test tube). Implementing a sustainable strategy for phospholipid biosynthesis is key to expanding the cellular boundaries. However, phospholipid biosynthesis is currently limited by substrate availability, e.g., of glycerol 3-phosphate, the essential core of phospholipid headgroups. Here, we reconstitute an enzymatic network for sustainable glycerol 3-phosphate synthesis inside large unilamellar vesicles. We exploit the Escherichia coli glycerol kinase GlpK to synthesize glycerol 3-phosphate from externally supplied glycerol. We fuel phospholipid headgroup formation by sustainable l-arginine breakdown. In addition, we design and characterize a dynamic dialysis setup optimized for synthetic cells, which is used to control the external medium composition and to achieve sustainable glycerol 3-phosphate synthesis.Circularly polarized luminescence (CPL) in two subregions of the near-infrared (NIR) has been achieved. By leveraging the rigidity and diminishing detrimental vibrations of the heterobimetallic binolate complexes of erbium [(Binol)3ErNa3], species exhibiting an exceptionally high dissymmetry factor (|glum |) of 0.47 at 1550 nm were obtained. These erbium complexes are the first reported examples of CPL observed beyond 1200 nm. Analogous complexes of ytterbium and neodymium also exhibited strong CPL (|glum| = 0.17, 0.05, respectively) in a higher energy NIR window (800-1200 nm). All complexes exhibit high quantum yields (Er 0.58%, Yb 17%, Nd 9.3%) and high BCPL values (Er 57 M-1 cm-1, Yb 379 M-1 cm-1, Nd 29 M-1 cm-1). Because of their strong CPL emission in the telecom band (1550 nm), biologically relevant NIR emission window (800-1100 nm), and synthetic versatility, the complexes reported here could permit further promising developments in quantum communication technologies and biologically relevant sensors.