High-expression of the innate-immune related gene UNC93B1 predicts inferior outcomes in acute myeloid leukemia

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy with dismal prognosis. Identification of better biomarkers remained a priority to improve established stratification and guide therapeutic decisions. Therefore, we extracted the RNA sequence data and clinical characteristics of AML from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression database (GTEx) to identify the key factors for prognosis. We found UNC93B1 was highly expressed in AML patients and significantly linked to poor clinical features (p < 0.05). We further validated the high expression of UNC93B1 in another independent AML cohort from GEO datasets (p < 0.001) and performed quantitative PCR of patient samples to confirm the overexpression of UNC93B1 in AML (p < 0.005). Moreover, we discovered high level of UNC93B1 was an independent prognostic factor for poorer outcome both in univariate analysis and multivariate regression (p < 0.001). Then we built a nomogram model based on UNC93B1 expression, age, FAB subtype and cytogenetic risk, the concordance index of which for predicting overall survival was 0.729 (p < 0.001). Time-dependent ROC analysis for predicting survival outcome at different time points by UNC93B1 showed the cumulative 2-year survival rate was 43.7%, and 5-year survival rate was 21.9%. The differentially expressed genes (DEGs) between two groups divided by UNC93B1 expression level were enriched in innate immune signaling and metabolic process pathway. Protein–protein interaction (PPI) network indicated four hub genes (S100A9, CCR1, MRC1 and CD1C) interacted with UNC93B1, three of which were also significantly linked to inferior outcome. Furthermore, we discovered high UNC93B1 tended to be infiltrated by innate immune cells, including Macrophages, Dendritic cells, Neutrophils, Eosinophils, and NK CD56dim cells. We also found UNC93B1 had a significantly positive correlation with CD14, CD68 and almost all Toll-like receptors. Finally, we revealed negatively correlated expression of UNC93B1 and BCL2 in AML and conjectured that high-UNC93B1 monocytic AML is more resistant to venetoclax. And we found high MCL-1 expression compensated for BCL-2 loss, thus, we proposed MCL-1 inhibitor might overcome the resistance of venetoclax in AML. Altogether, our findings demonstrated the utility of UNC93B1 as a powerful poor prognostic predictor and alternative therapeutic target

Truncated Metallo-Dielectric Omnidirectional Reflector: Collecting Single Photons in the Fundamental Gaussian Mode with 95% Efficiency

We propose a novel antenna structure that funnelssingle photons from a single emitter with unprecedented efficiencyinto a low-divergence fundamental Gaussian mode. Our devicerelies on the concept of creating an omnidirectional photonicbandgap to inhibit unwanted large-angle emission and to enhancesmall-angle defect-guided-mode emission. The new photoncollection strategy is intuitively illustrated, rigorously verified,and optimized by implementing an efficient, body-of-revolution,finite-difference, time-domain method for in-plane dipole emitters.We investigate a few antenna designs to cover various boundaryconditions posed by fabrication processes or material restrictions and theoretically demonstrate that collection efficiencies into thefundamental Gaussian mode exceeding 95% are achievable. Our antennas are broadband, insensitive to fabrication imperfections andcompatible with a variety of solid-state emitters such as organic molecules, quantum dots, and defect centers in diamond.Unidirectional and low-divergence Gaussian-mode emission from a single emitter may enable the realization of a variety of photonicquantum computer architectures as well as highly efficient light−matter interfaces

Advances in Autoimmune Epilepsy Associated with Antibodies, Their Potential Pathogenic Molecular Mechanisms, and Current Recommended Immunotherapies

In this comprehensive article, we present an overview of some most common autoimmune antibodies believed to be potentially pathogenic for autoimmune epilepsies and elaborate their pathogenic mode of action in molecular levels based on the existing knowledge. Findings of the studies of immunemodulatory treatments for epilepsy are also discussed, and guidelines for immunotherapy are sorted out. We aim to summarize the emerging understanding of different pathogenic mechanisms of autoantibodies and clinical immunotherapy regimens to open up therapeutic possibilities for future optimum therapy. We conclude that early diagnosis of autoimmune epilepsy is of great significance, as early immune treatments have useful disease-modifying effects on some epilepsies and can facilitate the recovery

An Overview of Pickering Emulsions: Solid-Particle Materials, Classification, Morphology, and Applications

Pickering emulsion, a kind of emulsion stabilized only by solid particles locating at oil–water interface, has been discovered a century ago, while being extensively studied in recent decades. Substituting solid particles for traditional surfactants, Pickering emulsions are more stable against coalescence and can obtain many useful properties. Besides, they are more biocompatible when solid particles employed are relatively safe in vivo. Pickering emulsions can be applied in a wide range of fields, such as biomedicine, food, fine chemical synthesis, cosmetics, and so on, by properly tuning types and properties of solid emulsifiers. In this article, we give an overview of Pickering emulsions, focusing on some kinds of solid particles commonly serving as emulsifiers, three main types of products from Pickering emulsions, morphology of solid particles and as-prepared materials, as well as applications in different fields

Salvianolic Acid B Alleviates Heart Failure by Inactivating ERK1/2/GATA4 Signaling Pathway after Pressure Overload in Mice

<div><p>Background</p><p>Heart failure(HF) is a dangerous disease that affects millions of patients. Radix Salvia is widely used in Chinese clinics to treat heart diseases. Salvianolic acid B(SalB) is the major active component of Radix Salvia. This study investigated the mechanisms of action and effects of SalB on HF in an experimental mouse model of HF.</p><p>Methods</p><p>We created a mouse model of HF by inducing pressure overload with transverse aortic constriction(TAC) surgery for 2 weeks and compared among 4 study groups: SHAM group (n = 10), TAC group (n = 9), TAC+MET group (metprolol, positive drug treatment, n = 9) and TAC+SalB group (SalB, 240 mg•kg^-1•day^-1, n = 9). Echocardiography was used to evaluate the dynamic changes in cardiac structure and function <i>in vivo</i>. Plasma brain natriuretic peptide (BNP) concentration was detected by Elisa method. In addition, H9C2 rat cardiomyocytes were cultured and Western blot were implemented to evaluate the phosphorylation of ERK1/2, AKT, and protein expression of GATA4.</p><p>Results</p><p>SalB significantly inhibited the phosphorylation of Thr202/Tyr204 sites of ERK1/2, but not Ser473 site of AKT, subsequently inhibited protein expression of GATA4 and plasma BNP(P < 0.001), and then inhibited HF at 2 weeks after TAC surgery.</p><p>Conclusions</p><p>Our data provide a mechanism of inactivating the ERK1/2/GATA4 signaling pathway for SalB inhibition of the TAC-induced HF.</p></div

Echocardiographic data of the four models.

<p>Echocardiographic data of the four models.</p