2,2'-Bipyridine-Enabled Photocatalytic Radical [4+2] Cyclization of N-Aryl-α-amino Acids for Synthesizing Polysubstituted Tetrahydroquinolines.

A facile photocatalytic radical [4+2] cyclization of N-aryl-α-amino acids with various alkenes to access structurally polysubstituted tetrahydroquinolines has been developed. Using a simple bipyridine as a catalyst, different N-aryl-α-amino acids could be utilized as the radical precursors to react with diverse electrophilic alkenes, including exocyclic terminal alkenes, acyclic terminal alkenes, and cycloalkenes, producing 10 types of nitrogen-containing heterocyclic compounds fused in multiple frameworks in generally moderate yields with good diastereoselectivities. Scale-up synthesis and transformations of the products further demonstrated the synthetic application of this protocol. Moreover, a decarboxylative radial pathway via a proton-coupled electron transfer process for illustration of this [4+2] cyclization was proposed on the basis of the control experiments. This process is highlighted by a simple bipyridine photocatalysis, mild reaction conditions, various N-aryl-α-amino acids and alkene materials, and application for the modification of natural products.

Iron(II)-Catalyzed Radical [3 + 2] Cyclization of N-Aryl Cyclopropylamines for the Synthesis of Polyfunctionalized Cyclopentylamines.

A facile iron(II)-catalyzed radical [3 + 2] cyclization of N-aryl cyclopropylamines with various alkenes to access the structurally polyfunctionalized cyclopentylamine scaffolds has been developed. Using low-cost FeCl2·4H2O as catalyst, N-aryl cyclopropylamines could be utilized to react with a wide range of alkenes including exocyclic/acyclic terminal alkenes, cycloalkenes, alkenes from the natural-occurring compounds (Alantolactone, Costunolide), and known drugs (Ibuprofen, l-phenylalanine, Flurbiprofen) to obtain a variety of cyclopentylamines fused with different useful motifs in generally good yields and diastereoselectivities. The highlight of this protocol is also featured by no extra oxidant, no base, EtOH as the solvent, gram-scale synthesis, and further diverse transformations of the synthetic products. More importantly, an iron(II)-mediated hydrogen radical dissociation pathway was proposed based on the mechanism research experiments.

Novel practical stereoselective synthesis of a bicyclic hydantoino-thiolactone as the key intermediate for production of (+)-biotin.

Bicyclic hydantoinothiolactone (1), as the key intermediate for production of (+)-biotin, has been efficiently and high-stereoselectively synthesized from the cheap starting material l-cystine via nine steps in 44% overall yield. In this new practical synthesis, there are two characteristic steps worthy of note. One step is TMSOTf-catalyzed efficient cyanation of (3S,7aR)-6-benzyl-5-oxo-3-phenyltetrahydro-1H,3H-imidazo[1,5-c]thiazol-7-yl acetate, the other step is DBU-catalyzed rapid isomerization of trans-isomer to cis-isomer of the bicyclic hydantoinothiolactone.

Relative risk factors associated with the development of fundic gland polyps.

OBJECTIVES: The prevalence of fundic gland polyps (FGPs) is increasing. Some researchers consider this increase to be associated strongly with the long-term use of proton-pump inhibitors (PPIs); however, not all researchers share this belief. There are minimal data on the development of FGPs in China. Therefore, we aimed to investigate the prevalence of FGPs and risk factors associated with the development of this disease. MATERIALS AND METHODS: We studied 10 904 consecutive patients who underwent gastroduodenal endoscopies at our digestive endoscopy center between February 2011 and January 2013. Information on sex, age, Helicobacter pylori infection, PPIs intake, and the pathological results of the polyps were collected in the FGPs group and in the control group. The use of PPIs, sex, and H. pylori infection were statistically evaluated as dichotomous variables using a χ-test; age was evaluated as a continuous variable using a t-test. Finally, these factors were evaluated using a multiple logistic regression analysis. RESULTS: Gastric polyps were found in 759 (7.0%) patients, and 213 (2.0%) of these patients had FGPs. FGPs accounted for 28.1% of the gastric polyps. In the FGPs group, the percentage of H. pylori infection was 66.8% and the percentage of PPIs intake for at least 12 months was 23.1%. In the control group, the percentage of H. pylori infection was 77.4% and the percentage of PPIs intake for at least 12 months was 2.3%. The difference in the long-term use of PPIs was statistically significant between these two groups [χ=33.98, P<0.05, odds ratio (OR)=12.83, 95% confidence interval (CI): 4.47-36.80]. The results of the logistic regression were as follows: long-term use of PPIs (P<0.01, OR=14.11, 95% CI: 4.15-47.93); age (P<0.01, OR=1.69, 95% CI: 1.31-2.18). The P-values for sex and H. pylori infection were higher than 0.05. CONCLUSION: Age and the long-term use of PPIs were risk factors for the presence of FGPs; the long-term use of PPIs was a particularly strong risk factor.

Folate-targeted polymeric micelles loaded with ultrasmall superparamagnetic iron oxide: combined small size and high MRI sensitivity.

Targeted delivery of contrast agents is a highly desirable strategy for enhancing diagnostic efficiency and reducing side effects and toxicity. Water-soluble and tumor-targeting superparamagnetic iron oxide nanoparticles (SPIONs) were synthesized by loading hydrophobic SPIONs into micelles assembled from an amphiphilic block copolymer poly(ethylene glycol)- poly(ε-caprolactone) (PEG-PCL) bearing folate in the distal ends of PEG chains. Compared to the water-soluble SPIONs obtained by small molecular surfactant coating, ultrasmall SPION encapsulation with PEG-PCL micelles (PEG-PCL-SPIONs) simultaneously increases transverse (r(2)) and decreases longitudinal (r(1)) magnetic resonance (MR) relaxivities of water proton in micelle solution, leading to a notably high r(2)/r(1) ratio up to 78, which makes the PEG-PCL-SPIONs a highly sensitive MR imaging (MRI) T(2) contrast agent. The mean size of folate-attached SPION micelles (Fa-PEG-PCL-SPIONs) is 44 ± 3 nm on average, ideal for in vivo MRI applications in which long circulation is greatly determined by small particle size and is highly desirable. Prussian blue staining of BEL-7402 cells over-expressing folate receptors, after incubation with micelle-containing medium, demonstrated that folate functionalization of the magnetic particles significantly enhanced their cell uptake. The potential of Fa-PEG-PCL-SPIONs as a potent MRI probe for in vivo tumor detection was assessed. At 3 hours after intravenous injection of the Fa-PEG-PCL-SPION solution into mice bearing subcutaneous xenografts of human BEL-7402 hepatoma, a 41.2% signal intensity decrease was detected in the T(2)-weighted MR images of the tumor, indicating the efficient accumulation of Fa-PEG-PCL-SPIONs in the tumor tissue.

Clinical features of thyrotoxic periodic paralysis caused by inwardly rectifying potassium channel 18 gene mutations / 中华神经科杂志

Objective To report the clinical features and inwardly rectifying potassium channel 18 (KCNJ18) gene mutation in a group of patients with thyrotoxic periodic paralysis (TTP).Methods Fiftyseven TTP cases (55 male and 2 female) were collected in our clinic from July 2002 to October 2011.The KCNJ18 gene was directly sequenced in 57 TTP patients and 50 health Chinese controls through the nested PCR.According to the results of gene screening,the clinical features of KCNJ18 patients and non-KCNJ18 patients were retrospectively summarized and analyzed.Results In 4 male patients with TPP,we found 3 novel heterogeneous mutations (p.Q126X,p.K360T,p.E388K) and 1 reported mutation (p.A200P) in the KCNJ18 gene.The age of onset was 19-25 years old,and the duration ranged from 2 to 8 hours.The 4 patients all presented severe muscle weakness.The attacks of muscle weakness preceded overt symptoms of hyperthyroidism in the 4 patients. Three patients showed recurrent weakness during the 13-28 months follow-up,while the episodic weakness never appeared when patients got euthyroid. Conclusions The mutations in the KCNJ18 gene are responsible for a part of Chinese patients with TPP.The patients with KCNJ18 mutations have a shorter disease course,severer manifestation,and higher prevalence of recurrence as compared with those TPP patients without KCNJ18 mutations.

[Calculation of dislocation destiny using X-ray diffraction for 4H-SiC homoepitaxial layers].

A theoretical and experimental study on calculating dislocation destiny for 4H-SiC homoepitaxial layers has been carried out. There is some difficulty in measuring dislocation density if it is more than 10(6) * cm(-2). In the paper, a theoretical analysis is made about the effects of dislocation density on the results of X-ray diffraction, and the relationship of dislocation density and FWHM spread is obtained. Then the X-ray diffraction curves of 4H-SiC in omego2theta with two different crystal faces are presented from which the density of dislocation is calculated. According to the result, the cause of dislocation origin is analyzed and the methods of decreasing dislocation density are proposed.

An online method combining a thermal conversion elemental analyzer with isotope ratio mass spectrometry for the determination of hydrogen isotope composition and water concentration in geological samples.

An online continuous-flow method, combining a thermal conversion elemental analyzer (TC/EA) with isotope ratio mass spectrometry (MS), is evaluated for the determination of both the hydrogen isotope composition and the water concentration of hydrous and nominally anhydrous minerals. The technique involves reduction of hydrous minerals or nominally anhydrous minerals by reaction with glassy carbon at 1450 degrees C in a helium stream. The product gases, H2 and CO, are separated on a gas chromatographic column prior to analysis in the mass spectrometer. Calibration curves for the H concentration analysis were generated from a standard of benzoic acid (C7H6O2) that has an H concentration of 5.0 wt%; the analytical uncertainties were better than +/-0.05% in our runs. Two standards of material with given D values, polyethylene IAEA-CH-7 and biotite NBS-30, were tested for the purpose of calibrating a natural garnet 04BXL02 representing nominally anhydrous minerals. Preheating at 90 degrees C for 12 h was found to be suitable for removing adsorption water on the sample surface. This results in constant D values and total H2O contents for the garnet, with weighted means of -94 +/- 1 and 522 +/- 11 ppm (wt), respectively. The TC/EA-MS technique allows routine analysis of sample sizes as small as 0.01 microL H2O. For natural minerals, absolute reproducibilities for D values are +/-0.5 to +/-2 (1) and relative uncertainties for total H2O concentrations are at levels of +/-1% to +/-3% (1). Therefore, this online method can be used for the quantitative determination of H isotope composition and H2O concentration of either hydrous or anhydrous minerals.

[Effect of NK4 gene transfection on tumor growth of human pancreatic cancer xenograft in nude mice].

BACKGROUND & OBJECTIVE: NK4 is not only an antagonist of hepatocyte growth factor but also an angiogenesis inhibitor. Studies have confirmed that NK4 can inhibit tumor growth and metastasis, but its effect on pancreatic cancer remains unknown. This study was designed to observe the effect of NK4 gene on human pancreatic cancer in nude mice and the possible mechanisms. METHODS: The nude mouse model of pancreatic cancer was established with human pancreatic cancer cell line SW1990. The eukaryotic expression vector of NK4 gene was constructed and transfected into the tumors. The mice weight, tumor size and volume were measured before and after transfection. The apoptotic cells, microvessel density (MVD), and the expression of proliferating cell nuclear antigen (PCNA) in the tumors were observed using immunohistochemistry and terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) technique. RESULTS: Four weeks after NK4 gene transfection, the tumor volume and weight was significantly smaller in NK4-transfected group than in PBS control group and empty vector group [(1.39+/-0.33) cm(3) vs. (2.06+/-0.55) cm(3) and (1.90+/-0.36) cm(3), P<0.01; (1.30+/-0.81) g vs. (3.45+/-1.88) g and (3.14+/-1.51) g, P<0.01]; the inhibition rate was 62.29%. The tumor cell apoptotic index was significantly higher in NK4-transfected group than in the rest 2 groups (9.34+/-0.91 vs. 4.13+/-0.79 and 3.94+/-1.03, P<0.001); the MVD was significantly lower in NK4-transfected group than in the rest 2 groups (12.24+/-4.63 vs. 20.13+/-7.00 and 19.70+/-6.15, P<0.05); the expression of PCNA in NK4-transfected group was not different from those of the rest 2 groups (53.88+/-4.30 vs. 56.24+/-4.03 and 54.33+/-5.41,P>0.05). CONCLUSION: NK4 gene transfection may inhibit the growth of human pancreatic cancer in mouse model through suppressing angiogenesis and enhancing the apoptosis of pancreatic cancer cells.

[Effect of transferred NK4 gene on biological characteristics of human pancreatic cancer cell line SW1990].

BACKGROUND & OBJECTIVE: Hepatocyte growth factor (HGF) plays an important role in the regulation of migration, invasion,and angiogenesis of cancer via the activation of its receptor, c-Met. NK4 is not only an antagonist of HGF but also an angiogenesis inhibitor. The blockade of HGF/c-Met signal pathway and tumor angiogenesis may be a new strategy for cancer treatment. This study was designed to construct eukaryotic expressing vector of NK4 gene, transfer it into human pancreatic cancer cell line SW1990, and observe the effect of transfected NK4 gene on the biological behaviors of SW1990 cells,and its expression in SW1990 cells. METHODS: The recombinant of pcDNA3/hNK4 plasmid was digested by restrictive enzyme,NK4 gene was cloned into a high effective eukaryotic expressing vector pRC/CMV2, and the recombinant of pRC/CMV2-hNK4 plasmid was transiently introduced into SW1990 cells by lipofectamine. Reverse transcriptase-polymerase chain reaction (RT-PCR),and Western blot were used to detect the expression of NK4 at mRNA, and protein levels,respectively. Migration, and invasion capabilities of the transfected cells were evaluated by Transwall chamber, and Matrigel invasion chamber, respectively. RESULTS: Expressions of NK4 gene after lipofectamine mediated transfection were observed in SW1990 cells, expected fragment of 453 bp has been amplified by RT-PCR, and Western blot analysis showed positive expression of NK4 protein (50 KDa). NK4 gene had no inhibitory effect on the growth of SW1990 cells (2.2x10(5) vs 2.5x10(5), P >0.05), while it had significantly suppressive effect on the migration and invasion of SW1990 cells driven by HGF or fibroblasts (P< 0.01). CONCLUSION: NK4 gene transfection may inhibit spreading and invasion of pancreatic cancer cells, which would play an important role in the anti-metastasis therapy for pancreatic cancer.