The sintering and dielectric properties of (1 − x)Li2Mg0.95Co0.05SiO4 + xTiO2 ceramics created by the solid state reaction method were investigated. X-ray diffraction and energy-dispersive X-ray ...spectroscopy were used to obtain phase composition of the ceramics, and scanning electron microscopy was used to observe their microstructure. A network analyzer was used to measure dielectric properties, while mechanical, simultaneous-thermal, and dynamic mechanical analyzers were used to obtain mechanical and chemical properties. Li2Mg0.95Co0.05SiO4 (LMCS) and TiO2 co-exist in the composite system. TiO2 addition resulted in decreasing grain size and crystallite size, increasing starting temperature of shrinkage, increasing activation energy, and increasing elasticity and stiffness. A 4%/volume addition of TiO2 and sintering at 1075 °C changed the LMCS τf to 1.57 ppm/°C and resulted in dielectric properties of εr = 6.33 and Q × f = 17,000 GHz (16 GHz) with a relative density equals to 96.13%.
The effects of magnesium oxide (MgO) on the flame retardant performance of intumescent systems based on ammonium polyphosphate (APP) and pentaerythritol (PER) in ethylene vinyl acetate copolymer ...(EVA) were studied. The results showed that MgO affects both the quality and quantity of residual char. There is an optimal value for the loading amount of MgO. More or less MgO loading may cause the formation of defective char layers and worsen the flame retardancy of EVA. According to the results of limiting oxygen index (LOI), vertical flammability test (UL94 rating) and cone calorimetry (CONE), the best flame retardancy with a strong and well intumescent char is obtained from the sample with 1 wt% of MgO, which has the highest LOI value of 27.9, UL94 rating of V-0 and the lowest peak heat release rate of 242 kW·m-2.
We aim to investigate genes associated with myasthenia gravis (MG), specifically those potentially implicated in the pathogenesis of dilated cardiomyopathy (DCM). Additionally, we seek to identify ...potential biomarkers for diagnosing myasthenia gravis co-occurring with DCM.
We obtained two expression profiling datasets related to DCM and MG from the Gene Expression Omnibus (GEO). Subsequently, we conducted differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) on these datasets. The genes exhibiting differential expression common to both DCM and MG were employed for protein-protein interaction (PPI), Gene Ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Additionally, machine learning techniques were employed to identify potential biomarkers and develop a diagnostic nomogram for predicting MG-associated DCM. Subsequently, the machine learning results underwent validation using an external dataset. Finally, gene set enrichment analysis (GSEA) and machine algorithm analysis were conducted on pivotal model genes to further elucidate their potential mechanisms in MG-associated DCM.
In our analysis of both DCM and MG datasets, we identified 2641 critical module genes and 11 differentially expressed genes shared between the two conditions. Enrichment analysis disclosed that these 11 genes primarily pertain to inflammation and immune regulation. Connectivity map (CMAP) analysis pinpointed SB-216763 as a potential drug for DCM treatment. The results from machine learning indicated the substantial diagnostic value of midline 1 interacting protein1 (MID1IP1) and PI3K-interacting protein 1 (PIK3IP1) in MG-associated DCM. These two hub genes were chosen as candidate biomarkers and employed to formulate a diagnostic nomogram with optimal diagnostic performance through machine learning. Simultaneously, single-gene GSEA results and immune cell infiltration analysis unveiled immune dysregulation in both DCM and MG, with MID1IP1 and PIK3IP1 showing significant associations with invasive immune cells.
We have elucidated the inflammatory and immune pathways associated with MG-related DCM and formulated a diagnostic nomogram for DCM utilizing MID1IP1/PIK3IP1. This contribution offers novel insights for prospective diagnostic approaches and therapeutic interventions in the context of MG coexisting with DCM.
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•Our investigation unveils immune dysfunction as the focal point in the pathogenesis of MG and DCM.•We identified MID1IP1 and PIK3IP1 as pivotal crosstalk genes in MG-associated DCM, exhibiting robust diagnostic effectiveness.•Immune infiltration analysis has elucidated the correlation between MID1IP1 and PIK3IP1 and infiltrating immune cells.
•The influence ratio between deviant and distinctive conditions changes overtime.•The instances’ semantic dilution level increases with degree of marginality.•Speakers categorize innovations by ...assessing their similarity to exemplars.•Instances may undergo mutating extension if semantic dilution level is too high.•Mutating extension may take place along multiple semantic dimensions.
Diachronically the schematic constructions consistently sanction innovative instances. There is generally a correlation between the semantic distance from the innovative (and hence marginal) instances to the exemplars and the historical period of the instances’ emergence; usually, the later that the emergence of the innovative instances occurs, the more marginal that the instances are. If the semantic distance crosses the threshold in terms of the disimilarity from the exemplars, the innovative instances may not be endorsed as the members of the existing schematic constructions by the speakers any longer. Instead, these instances can be readily interpreted differently from the existing schematic constructions to which they originally belong. They cluster and give rise to new schematic constructions that share the formal specifications with the existing constructions but have the idiomatic interpretations different from the latter, a process that can be called the mutating extension.
The severity of osteoarthritis (OA) and cartilage degeneration is highly associated with synovial inflammation. Although recent investigations have revealed a dysregulated crosstalk between ...fibroblast‐like synoviocytes (FLSs) and macrophages in the pathogenesis of synovitis, limited knowledge is available regarding the involvement of exosomes. Here, increased exosome secretion is observed in FLSs from OA patients. Notably, internalization of inflammatory FLS‐derived exosomes (inf‐exo) can enhance the M1 polarization of macrophages, which further induces an OA‐like phenotype in co‐cultured chondrocytes. Intra‐articular injection of inf‐exo induces synovitis and exacerbates OA progression in murine models. In addition, it is demonstrated that inf‐exo stimulation triggers the activation of glycolysis. Inhibition of glycolysis using 2‐DG successfully attenuates excessive M1 polarization triggered by inf‐exo. Mechanistically, HIF1A is identified as the determinant transcription factor, inhibition of which, both pharmacologically or genetically, relieves macrophage inflammation triggered by inf‐exo‐induced hyperglycolysis. Furthermore, in vivo administration of an HIF1A inhibitor alleviates experimental OA. The results provide novel insights into the involvement of FLS‐derived exosomes in OA pathogenesis, suggesting that inf‐exo‐induced macrophage dysfunction represents an attractive target for OA therapy.
Exosome secretion from fibroblast‐like synoviocytes (FLSs) is elevated in synovium during osteoarthritis (OA). The exosomes from inflammatory FLSs lead to inflammation activation and M1 polarization in macrophages through HIF1A‐mediated hyperglycolysis, which further exert detrimental effects on chondrocytes and exacerbate OA. Inhibition of HIF1A can alleviate such macrophage dysfunction triggered by exosomes and attenuate experimental OA.
The Glioma-associated oncogene (Gli) family members of zinc finger DNA-binding proteins are core effectors of Sonic hedgehog (SHH) signaling pathway. Studies in model organisms have identified that ...the
genes play critical roles during organ development, including the heart, brain, kidneys,
. Deleterious mutations in
genes have previously been revealed in several human developmental disorders, but few in congenital heart disease (CHD). In this study, the mutations in
genes were captured by next generation sequencing in human cohorts composed of 412 individuals with CHD and 213 ethnically matched normal controls. A total of 20 patient-specific nonsynonymous rare mutations in coding regions of human
genes were identified. Functional analyses showed that
c.820G> T (p.G274C) is a gain-of-function mutation, while
c.878G>A (p.R293H) and c.1442T>A (p.L481X) are loss-of-function mutations. Our findings suggested that deleterious rare mutations in
gene broke the balance of the SHH signaling pathway regulation and may constitute a great contribution to human CHD, which shed new light on understanding genetic mechanism of embryo cardiogenesis regulated by SHH signaling.
MicroRNAs (miRNAs) possess an important regulating effect among numerous renal diseases, while their functions in the process of epithelial-to-mesenchymal transition (EMT) after podocyte injury ...remain unclear. The purpose of our study is to identify the potential functions of miR-30a in EMT of podocytes and explore the underlying mechanisms of miR-30a in the impaired podocytes. The results revealed that downregulation of miR-30a in podocyte injury animal models and patients, highly induced the mesenchymal markers of EMT including Collagen I, Fibronectin and Snail. Furthermore, overexpression of miR-30a enhances epithelial markers (E-cadherin) but diminished mesenchymal markers (Collagen I, Fibronectin and Snail) in podocytes. In addition, we established miR-30a target NFATc3, an important transcription factor of Non-canonical Wnt signaling pathway. More importantly, our findings demonstrated that the augmentation of miR-30a level in podocytes inhibits the nuclear translocation of NFATc3 to protect cytoskeleton disorder or rearrangement. In summary, we uncovered the protective function of miR30a targeting NFATc3 in the regulation of podocyte injury response to EMT.
A new strategy for nanocrystal encapsulation, release and application based on pH-sensitive covalent dynamic hyperbranched polymers is described. The covalent dynamic hyperbranched polymers, with ...multi-arm hydrophobic chains and a hydrophilic hyperbranched poly(amidoamine) (HPAMAM) core connected with pH-sensitive imine bonds (HPAMAM-DA), could encapsulate CdTe quantum dots (QDs) and Au nanoparticles (NPs). Benefiting from its pH response property, CdTe QDs and Au NPs encapsulated by HPAMAM-DA could be released to aqueous phase after imine hydrolysis. The released CdTe/HPAMAM and Au/HPAMAM nanocomposites exhibited excellent biological imaging behavior and high catalytic activities on
-nitrophenol hydrogenation, respectively.
Background
Benzobicyclon (BBC) is a β-triketone herbicide (bTH) used in rice paddy fields. It has the advantages of high efficiency, low toxicity, high crop safety, and good environmental ...compatibility, and shows efficacy against paddy weeds resistant to other types of herbicides. However, as some important
indica
rice varieties are susceptible to BBC, BBC is currently only registered and applied in
japonica
rice cultivation areas.
Results
By analyzing haplotypes of the bTHs broad-spectrum resistance gene
HIS1
and phenotypes for BBC in 493 major
indica
rice accessions in China, we identified a novel non-functional allelic variant of
HIS1
in addition to the previously reported 28-bp deletion. Through detection with markers specific to the two non-functional mutations, it was clear that 25.4% of
indica
conventional varieties, 59.9% of fertility restorers, and 15.9% of sterile lines were susceptible to BBC. In addition, due to natural allelic variations of the
HIS1
gene in the sterile and restorer lines, some two-line hybrid sterile lines were sensitive to bTHs, and the corresponding restorers were resistant. We showed the potential effectiveness of using bTHs to address the issue of two-line hybrid rice seed purity stemming from the self-crossing of sterile lines during hybrid rice seed production. Finally, allelic variations of the
HIS1
gene may also play an important role in the mechanized seed production of hybrid rice.
Conclusions
Our findings offer guidance for the application of BBC in
indica
rice areas and provide a non-transgenic approach to address the seed purity issue of two-line hybrid rice.