Here we report that N-phosphonium pyridinium intermediates are unusually reactive for pyridine S N Ar reactions. Specifically, forming phosphonium salts from halopyridines typically requires elevated temperatures and Lewis acid additives. The alternative activation mode described in this paper permits C-P bond formation to occur at ambient temperatures in many cases, and functions across a broad range of substrates.I present a generalization of Chew's first algorithm for Delaunay mesh refinement. I split the line segments of an input planar straight line graph (PSLG) such that the lengths of split segments are asymptotically proportional to the local feature size at their endpoints. By employing prior algorithms, I then refine the truly or constrained Delaunay triangulation of the PSLG by inserting off-center Steiner vertices of "skinny" triangles while prioritizing triangles with shortest edges first. This technique inserts Steiner vertices in an advancing front manner such that we obtain a size-optimal, truly or constrained Delaunay mesh if the desired minimum angle is less than 30° (in the absence of small input angles). This is an improvement over prior algorithms that produce size-optimal meshes with minimum angles of about 26.4°and 28.6°for truly and constrained Delaunay meshes, respectively. Even in the presence of small input angles, the upper bound on the maximum angle is an angle strictly greater than 120° (an improvement from about 137°). The lower bound on the minimum angle in the presence of small angles is identical to prior bounds.Alzheimer's disease and other neurodegenerative disorders are becoming more prevalent as advances in technology and medicine increase living standards and life expectancy. Alzheimer's disease is thought to initiate development early in the patient's life and progresses continuously into old age. This process is characterized molecularly by the amyloid hypothesis, which asserts that self-aggregating amyloid peptides are core to the pathophysiology in Alzheimer's progression. Precise quantification of amyloid peptides in human bodily fluid samples (i.e. cerebrospinal fluid, blood) may inform diagnosis and prognosis, and has been studied using established biosensing technologies like liquid chromatography, mass spectrometry, and immunoassays. However, existing methods are challenged to provide single molecule, quantitative analysis of the disease-causing aggregation process. Ultra-sensitive nanopore biosensors can step in to fill this role as a dynamic mapping tool. The work in this paper establishes characteristic signals of β-amyloid 40 monomers, oligomers, and soluble aggregates, as well as a proof-of-concept foundation where a biological nanopore biosensor is used to monitor the extent of in vitro β-amyloid 40 peptide aggregation at the single molecule level. This foundation allows for future work to expand in drug screening, diagnostics, and aggregation dynamic experiments.We aimed to investigate the effect of propofol on the growth of human ovarian cancer cells ES2 and OVCAR-3 in vitro by regulating long non-coding RNA HOST2 (human ovarian cancer-specific transcript 2) and the inhibition of JAK2/STAT3 signaling pathway. In the present study, ES-2 and OVCAR-3 cells were firstly treated with different concentrations of propofol (0, 1, 5 and 10 μg/ml). The expression of HOST2 in ES-2 and OVCAR-3 cells were detected by quantitative reverse transcription-PCR (qRT-PCR). Then, the expression of HOST2 was changed by transfection of HOST2 overexpression plasmid into ES-2 and OVCAR-3 cells. Cell proliferation, migration, invasion and apoptosis were performed using CCK-8, wound-healing, Transwell assays and Flow Cytometry. Western blot analysis was performed to detect the expressions of apoptosis-associated proteins and JAK2/STAT3 pathway-related proteins. Results showed that cell viability and intracellular HOST2 expression in ES-2 and OVCAR-3 cells were decreased gradually with the increase of propofol concentration in a dose-dependent manner. Compared with the propofol group, overexpression of HOST2 significantly promoted the cell proliferation, migration, invasion and inhibited apoptosis, and ameliorated the inhibitory effect of propofol on the growth of tumor cells. Western blot analysis showed that compared with propofol group, the expression of Bcl-2 was significantly increased whereas Bax and the ratio of Cleaved caspase3/caspase3 were significantly decreased in pcDNA-HOST2 group. In addition, overexpression of HOST2 significantly enhanced the phosphorylation level of JAK2 and STAT3, and reduced the suppressive effect of propofol on JAK2/STAT3 signaling. Our results illustrated that propofol could significantly inhibit the proliferation, migration, invasion and induce apoptosis of ES-2 and OVCAR-3 cells by downregulating HOST2. The regulation mechanism may be achieved by inhibiting the activation of JAK2/STAT3 signaling pathway.Hepatic stellate cells (HSCs) activation is a key step that promotes hepatic fibrosis. Emerging evidence suggests that aerobic glycolysis is one of its important metabolic characteristics. Our previous study has reported that CD147, a glycosylated transmembrane protein, contributes significantly to the activation of HSCs. However, whether and how it is involved in the aerobic glycolysis of HSCs activation is unknown. The objective of the present study was to validate the effect of CD147 in HSCs activation and the underlying molecular mechanism. Our results showed that the silencing of CD147 decreased the expression of α-smooth muscle-actin (α-SMA) and collagen I at both mRNA and protein levels. Furthermore, CD147 silencing decreased the glucose uptake, lactate production in HSCs, and repressed the lactate dehydrogenase (LDH) activity, the expression of hexokinase 2 (HK2), glucose transporter 1 (Glut1). The effect of galloflavin, a well-defined glycolysis inhibitor, was similar to CD147 siRNA.  https://www.selleckchem.com/products/dir-cy7-dic18.html  Mechanistically, CD147 silencing suppressed glycolysis-associated HSCs activation through inhibiting the hedgehog signaling. Moreover, the hedgehog signaling agonist SAG could rescue the above effect of CD147 silencing. In conclusion, CD147 silencing blockade of aerobic glycolysis via suppression of hedgehog signaling inhibited HSCs activation, suggesting CD147 as a novel therapeutic target for hepatic fibrosis.
  The online version contains supplementary material available at 10.1007/s10616-021-00460-9.
 The online version contains supplementary material available at 10.1007/s10616-021-00460-9.