Transition-Metal-Free, Site-Selective C-F Arylation of Polyfluoroarenes via Electrophotocatalysis.

Direct C-F arylation is effective and sustainable for synthesis of polyfluorobiaryls with different degrees of fluorination, which are important motifs in medical and material chemistry. However, with no aid of transition metals, the engagement of C-F bond activation has proved difficult. Herein, an unprecedented transition-metal-free strategy is reported for site-selective C-F arylation of polyfluoroarenes with simple (het)arenes.

Discovery of RRx-001, a Myc and CD47 Downregulating Small Molecule with Tumor Targeted Cytotoxicity and Healthy Tissue Cytoprotective Properties in Clinical Development.

After extensive screening of aerospace compounds in an effort to source a novel anticancer agent, RRx-001, a first-in-class dinitroazetidine small molecule, was selected for advancement into preclinical and clinical development. RRx-001 is a minimally toxic small molecule with a distinct chemical structure and mechanism of action. The paradox of RRx-001 is that it mediates both antitumor cytotoxicity and normal tissue protection.

Photoinduced Borylation for the Synthesis of Organoboron Compounds.

Organoboron compounds have important synthetic value and can be applied in numerous transformations. The development of practical and convenient ways to synthesize boronate esters has thus attracted significant interest. Photoinduced borylations originated from stoichiometric reactions of alkanes and arenes with well-defined metal-boryl complexes.

Visible-Light-Induced Ni-Catalyzed Radical Borylation of Chloroarenes.

A highly selective and general photoinduced C-Cl borylation protocol that employs [Ni(IMes)] (IMes = 1,3-dimesitylimidazoline-2-ylidene) for the radical borylation of chloroarenes is reported. This photoinduced system operates with visible light (400 nm) and achieves borylation of a wide range of chloroarenes with Bpin at room temperature in excellent yields and with high selectivity, thereby demonstrating its broad utility and functional group tolerance. Mechanistic investigations suggest that the borylation reactions proceed via a radical process.

Ni-Catalyzed Traceless, Directed C3-Selective C-H Borylation of Indoles.

A highly efficient and general protocol for traceless, directed C3-selective C-H borylation of indoles with [Ni(IMes)] as the catalyst is reported. Activation and borylation of N-H bonds by [Ni(IMes)] is essential to install a Bpin moiety at the N-position as a traceless directing group, which enables the C3-selective borylation of C-H bonds. The N-Bpin group which is formed is easily converted back to an N-H group by the oxidative addition product of [Ni(IMes)] and -generated HBpin.

The role of oxygen in cluster headache.

High-flow oxygen inhalation is one of the most effective acute treatments for cluster headache. The therapy was first described for the treatment of cluster headache in 1952 by Horton, and has exhibited some advantages and efficacy compared to other acute medicines. The mechanism is not very clear, but some evidence has demonstrated its relationship to the trigeminovascular system and neuroinflammation.

Selective Photocatalytic C-F Borylation of Polyfluoroarenes by Rh/Ni Dual Catalysis Providing Valuable Fluorinated Arylboronate Esters.

A highly selective and general photocatalytic C-F borylation protocol that employs a rhodium biphenyl complex as a triplet sensitizer and the nickel catalyst [Ni(IMes)] (IMes = 1,3-dimesitylimidazoline-2-ylidene) for the C-F bond activation and defluoroborylation process is reported. This tandem catalyst system operates with visible (blue, 400 nm) light and achieves borylation of a wide range of fluoroarenes with Bpin at room temperature in excellent yields and with high selectivity. Direct irradiation of the intermediary C-F bond oxidative addition product trans-[NiF(Ar)(IMes)] leads to very fast decomposition when Bpin is present.

A new central post-stroke pain rat model: autologous blood injected thalamic hemorrhage involved increased expression of P2X4 receptor.

Stroke is the leading cause of disability and death in the world. Central post-stroke pain (CPSP), a central neuropathic pain syndrome occurring after cerebral stroke, is a serious problem. But on account of the lack of reliable animal models, the mechanisms underlying CPSP remains poorly understood.

Synergistic Effect of Segregated Pd and Au Nanoparticles on Semiconducting SiC for Efficient Photocatalytic Hydrogenation of Nitroarenes.

Efficient catalytic hydrogenation of nitroarenes to anilines with molecular hydrogen at room temperature is still a challenge. In this study, this transformation was achieved by using a photocatalyst of SiC-supported segregated Pd and Au nanoparticles. Under visible-light irradiation, the nitrobenzene hydrogenation reached a turnover frequency as high as 1715 h at 25 °C and 0.

Red pigments and Boraginaceae leaves in mortuary ritual of late Neolithic China: A case study of Shengedaliang site.

Investigation of mortuary ritual is an important method to reconstruct many aspects of past societies. Due to the lack of relevant analytical work, little evidence related to organic materials in a burial can be found in China. Here we report materials collected from a burial during the excavation of the Shengedaliang site.

Visible-Light-Driven Selective Photocatalytic Hydrogenation of Cinnamaldehyde over Au/SiC Catalysts.

Highly selective hydrogenation of cinnamaldehyde to cinnamyl alcohol with 2-propanol was achieved using SiC-supported Au nanoparticles as photocatalyst. The hydrogenation reached a turnover frequency as high as 487 h(-1) with 100% selectivity for the production of alcohol under visible light irradiation at 20 °C. This high performance is attributed to a synergistic effect of localized surface plasmon resonance of Au NPs and charge transfer across the SiC/Au interface.

Visible-light-driven Photocatalytic N-arylation of Imidazole Derivatives and Arylboronic Acids on Cu/graphene catalyst.

N-aryl imidazoles play an important role as structural and functional units in many natural products and biologically active compounds. Herein, we report a photocatalytic route for the C-N cross-coupling reactions over a Cu/graphene catalyst, which can effectively catalyze N-arylation of imidazole and phenylboronic acid, and achieve a turnover frequency of 25.4 h(-1) at 25°C and the irradiation of visible light.

In situ grafted carbon on sawtooth-like SiC supported Ni for high-performance supercapacitor electrodes.

A novel C-Ni-SiC composite using sawtooth-like SiC as support and carbon as modified material was prepared by hydrothermal synthesis and thermochemical pyrolysis. As a supercapacitor electrode, it exhibits very high specific capacitance (1780 F g(-1)) and excellent cycling performance (>96% for 2500 cycles).

Carbon coated Co-SiC nanocomposite with high-performance microwave absorption.

A carbon coated Co-SiC nanocomposite was fabricated via in situ pyrolysis of methane on a hierarchical Co3O4-SiC nanostructure, which was obtained by hydrothermal synthesis. By the reduction of methane, the Co3O4 was in situ converted to cobalt nanoparticles, and coated by carbon or filled in the CNTs. The as-prepared composite exhibits excellent microwave absorption performance in the frequency range of 2-18 GHz.

Avoiding Loss of Catalytic Activity of Pd Nanoparticles Partially Embedded in Nanoditches in SiC Nanowires.

Nanoditches from selective etching of periodically twinned SiC nanowires were employed to hinder the migration and coalescence of Pd nanoparticles supported on the nanowires, and thus to improve their catalytic stability for total combustion of methane. The results show that the etched Pd/SiC catalyst can keep the methane conversion of almost 100% while the unetched one has an obvious decline in the catalytic activity from 100 to 82% after ten repeated reaction cycles. The excellent catalytic stability originates from the limitation of the nanoditches to the migration and growth of Pd nanoparticles.

[Investigation of heart rate turbulence after atrial premature beats before onset of paroxysmal atrial fibrillation].

Objective: To discuss the clinical significance of heart rate turbulence (HRT) after atrial premature beats in accessing the temporal changes of vagus nerve before the onset of paroxysmal atrial fibrillation.

Methods: The HRT parameters: turbulence onset (TOA) and turbulence slope (TSA) after atrial premature impulses occurring 0 to 60 min before and after the onset of AF 56 patients with atrial fibrillation (AF). The heart rate variability (HRV) time domain parameter SDNN and the frequency-domain parameters, low frequency (LF), high frequency (HF), and LF/HF ratio were also analyzed.

Establishment of the active catalytic domain of human PDGFRbeta tyrosine kinase-based ELISA assay for inhibitor screening.

Tyrosine kinases are emerging as frequent targets of primary oncogenic events and therefore represent an optimal focus of therapeutic intervention. In an effort towards therapeutic PDGFR inactivation, we expressed the catalytic domain of PDGFRbeta as a soluble active kinase using Bac-to-Bac expression system, and studied the correlations between PDGFRbeta activity and enzyme concentration, ATP concentration, substrate concentration and divalent cation type. And a convenient, effective and non-radioactive ELISA screening model is then established for identification of the potential inhibitors targeting PDGFRbeta kinase.

Mutant PIK3CA-bearing colon cancer cells display increased metastasis in an orthotopic model.

Mutations in the PIK3CA gene are common in human cancers, including colon cancer. We compared two pairs of colon cancer cells (HCT116 and DLD1) bearing only the wild-type (WT) or mutant (MUT) PIK3CA allele for their survival capacity under stress conditions in vitro as well as their metastatic properties in an in vivo orthotopic model. When subjected to growth factor deprivation stress (GFDS), the MUT PIK3CA cells displayed resistance to GFDS-induced apoptosis relative to the WT cells.

TKI-31 inhibits angiogenesis by combined suppression signaling pathway of VEGFR2 and PDGFRbeta.

Tyrosine kinases have been strongly implicated as therapeutic targets that influence the angiogenic process in growing tumors. In this study, we revealed that TKI-31 is a potent broad spectrum tyrosine kinase inhibitor, which inhibits vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor beta (PDGFRbeta) and also inhibits kinases of other class, such as c-Kit and c-Src on molecular base, but showed no activity against vascular endothelial growth factor receptor 1 (VEGFR1) and epidermal growth factor receptor (EGFR). TKI-31 inhibits VEGF-induced phosphorylation of VEGFR2 in endothelial cells as well as PDGF(BB)-induced phosphorylation in fibroblast cells, and leading to the inhibition of down-stream signaling triggered by these receptors such as PI3K/Akt/mTOR, MAPK42/44(ERK) and paxillin.

In vitro pharmacological characterization of TKI-28, a broad-spectrum tyrosine kinase inhibitor with anti-tumor and anti-angiogenic effects.

Tyrosine kinases are used as important biomarkers in many tumor types. Preclinical and clinical anti-tumor studies have shown that broadly acting tyrosine kinase inhibitors may be more useful than specific inhibitors, since the former might overcome redundancies and crosstalk in tumor cell growth signaling pathways. Here, we aim to identify a novel potent tyrosine kinase inhibitor.

11,11'-dideoxy-verticillin: a natural compound possessing growth factor receptor tyrosine kinase-inhibitory effect with anti-tumor activity.

11,11'-dideoxy-verticillin, a compound of the novel epidithiodioxopiprazine structural class, is isolated from the traditional Chinese medicinal herb Shiraia bambusicola. The present study demonstrated for the first time that 11,11'-dideoxy-verticillin has potent tyrosine kinase-inhibitory and anti-tumor activities. In the cell-free ELISA tyrosine kinase assay, 11,11'-dideoxy-verticillin significantly inhibited the activities of epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor-1/fms-like tyrosine kinase-1 (VEGFR-1/Flt-1) and human epidermal growth factor receptor-2 (HER2/ErbB-2), with relative specificity on EGFR and VEGFR-1 with IC50s of 0.

Expression and purification of the catalytic domain of human vascular endothelial growth factor receptor 2 for inhibitor screening.

Vascular endothelial growth factor (VEGF), an endothelial cell-specific mitogen, can act in tumor-induced angiogenesis by binding to specific receptors on the surface of endothelial cells. One such receptor, VEGFR-2/KDR, plays a key role in VEGF-induced angiogenesis. Here, we expressed the catalytic domain of VEGFR-2 as a soluble active kinase using Bac-to-Bac expression system, and investigated correlations between VEGFR-2 activity and enzyme concentration, ATP concentration, substrate concentration and divalent cation type.