Search Results (5)

The crystals of Mn⁴⁺-activated fluorides, such as those of the hexafluorometallate family, are widely known for their luminescence properties. The most commonly reported red phosphors are A₂XF₆: Mn⁴⁺ and BXF₆: Mn⁴⁺ fluorides, where A represents alkali metal ions such as Li, Na, K, Rb, Cs; X=Ti, Si, Ge, Zr, Sn, B = Ba and Zn; and X = Si, Ge, Zr, Sn, and Ti. Their performance is heavily influenced by the local structure around dopant ions. Many well-known research organizations have focused their attention on this area in recent years. However, there has been no report on the effect of local structural symmetrization on the luminescence properties of red phosphors. The purpose of this research was to investigate the effect of local structural symmetrization on the polytypes of K₂XF₆ crystals, namely O_h-K₂MnF₆, C_3v-K₂MnF₆, O_h-K₂SiF₆, C_3v-K₂SiF₆, D_3d-K₂GeF₆, and C_3v-K₂GeF₆. These crystal formations yielded seven-atom model clusters. Discrete Variational Xα (DV-Xα) and Discrete Variational Multi Electron (DVME) were the first principles methods used to compute the Molecular orbital energies, multiplet energy levels, and Coulomb integrals of these compounds. The multiplet energies of Mn⁴⁺ doped K₂XF₆ crystals were qualitatively reproduced by taking lattice relaxation, Configuration Dependent Correction (CDC), and Correlation Correction (CC) into account. The ⁴A_2g→⁴T_2g (⁴F) and ⁴A_2g→⁴T_1g (⁴F) energies increased when the Mn-F bond length decreased, but the ²E_g → ⁴A_2g energy decreased. Because of the low symmetry, the magnitude of the Coulomb integral became smaller. As a result, the decreasing trend in the R-line energy could be attributed to a decreased electron–electron repulsion. Full article

Multiple myeloma (MM) remains an incurable hematological malignancy. Bortezomib (BTZ) is a proteasome inhibitor widely used in MM therapy whose potent activity is often hampered by the development of resistance. The immune system is vital in the pathophysiology of BTZ resistance. Vitamins D (VD) and K (VK) modulate the immune system; therefore, they are potentially beneficial in MM. The aim of the study was to evaluate the effect of BTZ therapy and VD and VK supplementation on the proliferation potential and gene expression profiles of MM cells in terms of the development of BTZ resistance. The U266 MM cell line was incubated three times with BTZ, VD and VK at different timepoints. Then, proliferation assays, RNA sequencing and bioinformatics analysis were performed. We showed BTZ resistance to be mediated by processes related to ATP metabolism and oxidative phosphorylation. The upregulation of genes from the SNORDs family suggests the involvement of epigenetic mechanisms. Supplementation with VD and VK reduced the proliferation of MM cells in both the non-BTZ-resistant and BTZ-resistant phenotypes. VD and VK, by restoring proper metabolism, may have overcome resistance to BTZ in vitro. This observation forms the basis for further clinical trials evaluating VD and VK as potential adjuvant therapies for MM patients. Full article

Vitamin K (VK) is a fat-soluble vitamin necessary for fish metabolism and health. VK stability as dietary component during aquafeed storage and its potential effect on intestinal microbiome in fish have not yet been completely elucidated. The convenient storage conditions of aquafeeds when supplemented with phylloquinone (VK1), as well as its potential effects on the gut microbiota of Senegalese sole (Solea senegalensis) juveniles, have been explored. Experimental feeds were formulated to contain 0, 250 and 1250 mg kg⁻¹ of VK1 and were stored at different temperatures (4, −20 or −80 °C). VK stability was superior at −20 °C for short-term (7 days) storage, while storing at −80 °C was best suited for long-term storage (up to 3 months). A comparison of bacterial communities from Senegalese sole fed diets containing 0 or 1250 mg kg⁻¹ of VK1 showed that VK1 supplementation decreased the abundance of the Vibrio, Pseudoalteromonas, and Rhodobacterace families. All these microorganisms were previously associated with poor health status in aquatic organisms. These results contribute not only to a greater understanding of the physiological effects of vitamin K, particularly through fish intestinal microbiome, but also establish practical guidelines in the industry for proper aquafeed storage when supplemented with VK1. Full article

Immunoglobulin superantigens play an important role in affinity purification of antibodies and the microbiota-immune axis at mucosal areas. Based on current understanding, Staphylococcal Protein A (SpA), Streptococcal Protein G (SpG) and Finegoldia Protein L (PpL) are thought to only bind specific regions of human antibodies, allowing for selective purification of antibody isotypes and chains. Clinically, these superantigens are often classified as toxins and increase the virulence of the producing pathogen through unspecific interactions with immune proteins. To perform an in-depth interaction study of these three superantigens with antibodies, bio-layer interferometry (BLI) measurements of their interactions with a permutation panel of 63 IgG1 variants of Pertuzumab and Trastuzumab CDRs grafted to the six human Vκ and seven human VH region families were tested. Through this holistic and systemic analysis of IgG1 variants with various antibody regions modified, comparisons revealed novel PpL–antibody interactions influenced by other non-canonical antibody known light-chain framework regions, whereas SpA and SpG showed relatively consistent interactions. These findings have implications on PpL-based affinity antibody purification and design that can guide the engineering and understanding of PpL-based microbiota-immune effects. Full article

Previously, we reported that vitamin K₃ (VK₃), but not VK₁ or VK₂ (=MK-4), inhibits the activity of human DNA polymerase γ (pol γ). In this study, we chemically synthesized three intermediate compounds between VK₂ and VK₃, namely MK-3, MK-2 and MK-1, and investigated the inhibitory effects of all five compounds on the activity of mammalian pols. Among these compounds, MK-2 was the strongest inhibitor of mammalian pols α, κ and λ, which belong to the B, Y and X families of pols, respectively; whereas VK₃ was the strongest inhibitor of human pol γ, an A-family pol. MK-2 potently inhibited the activity of all animal species of pol tested, and its inhibitory effect on pol λ activity was the strongest with an IC₅₀ value of 24.6 μM. However, MK-2 did not affect the activity of plant or prokaryotic pols, or that of other DNA metabolic enzymes such as primase of pol α, RNA polymerase, polynucleotide kinase or deoxyribonuclease I. Because we previously found a positive relationship between pol λ inhibition and anti-inflammatory action, we examined whether these compounds could inhibit inflammatory responses. Among the five compounds tested, MK-2 caused the greatest reduction in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced acute inflammation in mouse ear. In addition, in a cell culture system using mouse macrophages, MK-2 displayed the strongest suppression of the production of tumor necrosis factor (TNF)-α induced by lipopolysaccharide (LPS). Moreover, MK-2 was found to inhibit the action of nuclear factor (NF)-κB. In an in vivo mouse model of LPS-evoked acute inflammation, intraperitoneal injection of MK-2 in mice led to suppression of TNF-α production in serum. In conclusion, this study has identified VK₂ and VK₃ intermediates, such as MK-2, that are promising anti-inflammatory candidates. Full article