Direct conversion of indoles to 3,3-difluoro-2-oxindoles via electrophilic fluorination.

3,3-Difluoro-2-oxindoles can be obtained directly from indoles in moderate yields via electrophilic fluorination using N-fluorobenzenesulfonimide as a mild fluorinating reagent. The presence of tert-butyl hydroperoxide during the reaction, together with additional heating after quenching the reaction with triethylamine, is beneficial to the formation of the desired product.

Functionalizing biodegradable dextran scaffolds using living radical polymerization: new versatile nanoparticles for the delivery of therapeutic molecules.

Conferring biodegradability to nanoparticles is vitally important when nanomedicine applications are being targeted, as this prevents potential problems with bioaccumulation of byproducts after delivery. In this work, dextran has been modified (and rendered hydrophobic) by partial acetalation. A solid state NMR method was first developed to fully characterize the acetalated polymers.

BML-275, an AMPK inhibitor, induces DNA damage, G2/M arrest and apoptosis in human pancreatic cancer cells.

Adenosine monophosphate-activated protein kinase (AMPK) is a principal intracellular energy sensor which regulates energy producing pathways and energy requiring pathways when the cellular AMP/ATP ratio is altered. BML-275 (compound C), a well-known inhibitor of AMPK, has been found to induce apoptosis in myeloma, glioma and prostate cancer cells. However, the mechanisms responsible for the selective apoptotic effect(s) by BML-275 in cancer cells remain unknown.

Effects of phytoplankton cell size and chloride concentration on the bioaccumulation of methylmercury in marine phytoplankton.

In the current study, the effects of phytoplankton cell size and methylmercury (MeHg) speciation on the bioaccumulation of MeHg by marine phytoplankton were investigated. Volume concentration factors (VCFs) of MeHg were determined in relation to the surface area to volume ratio of the cells for four species of diatom and a cyanobacteria species cultured in unenriched seawater. The VCFs of MeHg, ranging from 7.

The discovery of [Ni(NHC)RCN]2 species and their role as cycloaddition catalysts for the formation of pyridines.

The reaction of Ni(COD)(2), IPr, and nitrile affords dimeric [Ni(IPr)RCN](2) in high yields. X-ray analysis revealed these species display simultaneous η(1)- and η(2)-nitrile binding modes. These dimers are catalytically competent in the formation of pyridines from the cycloaddition of diynes and nitriles.

Single nucleotide polymorphism array lesions, TET2, DNMT3A, ASXL1 and CBL mutations are present in systemic mastocytosis.

We hypothesized that analysis of single nucleotide polymorphism arrays (SNP-A) and new molecular defects may provide new insight in the pathogenesis of systemic mastocytosis (SM). SNP-A karyotyping was applied to identify recurrent areas of loss of heterozygosity and bidirectional sequencing was performed to evaluate the mutational status of TET2, DNMT3A, ASXL1, EZH2, IDH1/IDH2 and the CBL gene family. Overall survival (OS) was analyzed using the Kaplan-Meier method.

Pro-apoptotic role of the MEK/ERK pathway in ursodeoxycholic acid-induced apoptosis in SNU601 gastric cancer cells.

Ursodeoxycholic acid (UDCA) has been regarded as a suppressor of gastrointestinal cancer, but the mechanisms underlying its antitumor effects are not fully understood. Previously, we reported the antitumor effect of UDCA by demonstrating that UDCA induces apoptosis of gastric cancer cells. Bile acids are known to activate the ERK pathway and ERK is a representative oncogenic kinase in cancer cells.

Copper-catalyzed alkene arylation with diaryliodonium salts.

Alkenes and arenes represent two classes of feedstock compounds whose union has fundamental importance to synthetic organic chemistry. We report a new approach to alkene arylation using diaryliodonium salts and Cu catalysis. Using a range of simple alkenes, we have shown that the product outcomes differ significantly from those commonly obtained by the Heck reaction.

Aldehyde dehydrogenase 1A1 confers intrinsic and acquired resistance to gemcitabine in human pancreatic adenocarcinoma MIA PaCa-2 cells.

Gemcitabine (GEM) is the front-line standard chemotherapy used for the treatment of pancreatic cancer; however, chemoresistance to GEM remains the major obstacle to the successful control of this disease. Both the expression levels and activity of aldehyde dehydrogenase 1A1 (ALDH1A1) are important features of tumor-initiating and/or cancer stem cell properties in multiple types of human cancer. As one of the intrinsic properties of cancer stem cells is drug resistance, in this study, we examined the correlation between the level and activity of endogenous ALDH1A1 and GEM resistance in the MIA PaCa-2 cell line that contains high expression levels and activity of ALDH1A1.

Approaching a stable, green twisted heteroacene through "clean reaction" strategy.

A new, longest, stable, green twisted heteroacene 2-methyl-1,4,6,13-tetraphenyl-7:8,11:12-bisbenzo-anthro[g]isoquinolin-3(2H)-one (3) was synthesized by employing a "clean reaction" strategy based on thermally eliminating lactam bridges. Calculation shows that the HOMO-LUMO bandgap is in good agreement with experimental data.

Automated capillary electrophoresis with on-line preconcentration by solid phase extraction using a sequential injection manifold and contactless conductivity detection.

An extension of a capillary electrophoresis instrument coupled to a sequential injection analysis manifold was developed for automated measurements with on-line solid-phase extraction preconcentration. An in-house built capacitively coupled contactless conductivity detector was employed for sensitive detection with narrow capillaries of 25 μm internal diameter. The system was assembled into standardized 19 in.

Pulmonary artery endothelium resident endothelial colony-forming cells in pulmonary arterial hypertension.

Proliferative pulmonary vascular remodeling is the pathologic hallmark of pulmonary arterial hypertension (PAH) that ultimately leads to right heart failure and death. Highly proliferative endothelial cells known as endothelial colony-forming cells (ECFC) participate in vascular homeostasis in health as well as in pathological angiogenic remodeling in disease. ECFC are distinguished by the capacity to clonally proliferate from a single cell.

Synthesis of functional core, star polymers via RAFT polymerization for drug delivery applications.

Poly(oligoethylene glycol) methyl ether acrylate was polymerized via reversible addition fragmentation transfer polymerization (RAFT), and then chain extended in the presence of both a cross-linker and vinyl benzaldehyde (VBA), yielding monodisperse star polymers. The presence of aldehyde groups in the core was exploited to attach doxorubicin. The drug loading was controlled by the amount of VBA incorporated (until 28 wt% in drug).

Mercury capture into biogenic amorphous selenium nanospheres produced by mercury resistant Shewanella putrefaciens 200.

Shewanella putrefaciens 200, resistant to high concentration of Hg(II), was selected for co-removal of mercury and selenium from aqueous medium. Biogenic Hg(0) reduced from Hg(II) by S. putrefaciens 200 was captured into extracellular amorphous selenium nanospheres, resulting in the formation of stable HgSe nanoparticles.

Is maternal parity an independent risk factor for birth defects?

Background: Although associations between maternal parity and birth defects have been observed previously, few studies have focused on the possibility that parity is an independent risk factor for birth defects. We investigated the relation between levels of parity and a range of birth defects, adjusting each defect group for the same covariates.

Methods: We included infants who had an estimated delivery date between 1997 and 2007 and participated in the National Birth Defects Prevention Study, a multisite case-control study.

Conversion of cortisone to cortisol and prostaglandin F2α production by the reproductive tract of cows at the late luteal stage in vivo.

Previous in vitro studies demonstrated that bovine endometrium has the capacity to convert inactive cortisone to biologically active cortisol (Cr) and that Cr inhibits cytokine-stimulated prostaglandin F(2α) (PGF) production. This study was carried out to test the hypothesis that bovine reproductive tract has the capacity to convert cortisone to Cr in vivo and to evaluate the effects of intravaginal application of exogenous cortisone on uterine PGF secretion during the late luteal stage. The temporal relationships between PGF and Cr levels in uterine plasma were also determined.

Permeability of three-dimensional fibrin constructs corresponds to fibrinogen and thrombin concentrations.

Research in the last few years have focused on the use of three-dimensional (3D) fibrin construct to deliver growth factors and cells. Three-dimensional construct permeability and porosity are important aspects for proper nutrient uptake, gas exchange, and waste removal-factors that are critical for cell growth and survival. We have previously reported that the mechanical strength (stiffness) of 3D fibrin constructs is dependent on the fibrinogen and thrombin concentration.

Protection against LPS-induced pulmonary edema through the attenuation of protein tyrosine phosphatase-1B oxidation.

One hallmark of acute lung injury is the disruption of the pulmonary endothelial barrier. Such disruption correlates with increased endothelial permeability, partly through the disruption of cell-cell contacts. Protein tyrosine phosphatases (PTPs) are known to affect the stability of both cell-extracellular matrix adhesions and intercellular adherens junctions (AJs).

Effects of cortisol on pregnancy rate and corpus luteum function in heifers: an in vivo study.

To determine whether glucocorticoids affect the function of the bovine corpus luteum (CL) during the estrous cycle and early pregnancy, we examined the effects of exogenous cortisol or reduced endogenous cortisol on the secretion of progesterone (P4) and on pregnancy rate. In preliminary experiments, doses of cortisol and metyrapone (an inhibitor of cortisol synthesis) were established (n=33). Cortisol in effective doses of 10 mg blocked tumor necrosis factor-induced prostaglandin F(2α) secretion as measured by its metabolite (PGFM) concentrations in the blood.

Risk factors for 30-day hospital readmission following myeloablative allogeneic hematopoietic cell transplantation (allo-HCT).

Patient readmission within 30 days from discharge has been perceived by the Centers for Medicare and Medical Services as an indicator of poor healthcare quality for specific high-cost medical conditions. Patients who undergo allogeneic hematopoietic cell transplantation (allo-HCT) are often being readmitted. Our study identified the risk factors for 30-day readmission among 618 adult recipients of myeloablative allo-HCT from 1990 to 2009.

ZSTK474, a PI3K inhibitor, suppresses proliferation and sensitizes human pancreatic adenocarcinoma cells to gemcitabine.

The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway is important in cell proliferation and survival, and it is frequently and aberrantly activated in pancreatic adenocarcinoma. Potential anti-tumor effect(s) of ZSTK474, a PI3K/Akt inhibitor, together with a key clinically relevant anti-tumor agent, gemcitabine (GEM), have been reported in a human pancreatic cancer xenograft mouse model. However, the precise molecular mechanism of these anti-tumor effects has not been well elucidated.

Intravenous compared with oral busulfan as preparation for allogeneic hematopoietic progenitor cell transplantation for AML and MDS.

BU and CY is a common conditioning regimen for allogeneic hematopoietic progenitor cell transplantation (HPCT). I.v.

Pro-angiogenic hematopoietic progenitor cells and endothelial colony-forming cells in pathological angiogenesis of bronchial and pulmonary circulation.

Dysregulation of angiogenesis is a common feature of many disease processes. Vascular remodeling is believed to depend on the participation of endothelial progenitor cells, but the identification of endothelial progenitors in postnatal neovascularization remains elusive. Current understanding posits a role for circulating pro-angiogenic hematopoietic cells that interact with local endothelial cells to establish an environment that favors angiogenesis in physiologic and pathophysiologic responses.