To study the synthetic method and antibacterial activity of water-soluble fused heterocyclic compounds containing piperazine group, the nucleophilic substitution of 3-(4-chlorophenyl)-6-substituted-s-triazolo-[3, 4-b] [1, 3, 4] thiadiazoles (2a - n) with piperazine in the presence of phase transfer catalyst TBAI afforded 3-(4-piperazin-1-yl-phenyl)-6-substituted-s-triazolo [3, 4-b] [1, 3, 4] thiadiazole and then followed by acid treatment afforded 3-(4-piperazin-1-yl-phenyl)-6-substituted-s-triazolo [ 3, 4-b] [1, 3, 4] thiadiazole hydrochlorides (3a - n). Twenty-eight new compounds were synthesized and their structures were confirmed by IR, 1H NMR, MS and element analysis. The in vitro antibacterial activities of all newly synthesized compounds were tested against Gram positive bacteria and Gram negative bacteria with the standard 2-fold agar dilution method. Fourteen title compounds exhibited potential antibacterial activities in vitro. The structures of these compounds needed to be further optimized.
Anti-Bacterial Agents ; chemical synthesis ; chemistry ; pharmacology ; Bacillus subtilis ; drug effects ; Escherichia coli ; drug effects ; Microbial Sensitivity Tests ; Molecular Structure ; Pseudomonas aeruginosa ; drug effects ; Staphylococcus aureus ; drug effects ; Structure-Activity Relationship ; Thiadiazoles ; chemical synthesis ; chemistry ; pharmacology ; Triazoles ; chemical synthesis ; chemistry ; pharmacology

AIMTo study the synthetic method and antibacterial activity of amino-heterocyclic compounds coupled oxime-ether group.

METHODSThe treatment of 4-amino-3-methyl-5-mercapto-s-triazole (3) with beta-chlorophenyl-propanone to form amino-s-triazole sulfanylphenyl-propanone (4) sequentially followed by oximation with hydroxyl-amine to produce the oximes (5) and etherification with various oxadiazole chloromethanes (6a - j) to yield the title compounds (1a - j). The in vitro antibacterial activities of all newly synthesized compounds were tested against Gram positive bacteria and Gram negative bacteria with the standard 2-fold agar dilution method.

RESULTSTwelve new compounds including two intermediates were synthesized and their structures were confirmed by IR, 1H NMR, MS and elemental analyses. The ten title compounds exhibited the potential antibacterial activities in vitro.

CONCLUSIONTheses compounds should be optimized.

Anti-Bacterial Agents ; chemical synthesis ; pharmacology ; Oxadiazoles ; chemical synthesis ; pharmacology ; Oximes ; chemical synthesis ; pharmacology ; Triazoles ; chemical synthesis ; pharmacology

Objective To evaluate the effect and mechanism of terminal fucosylation inhibitor 2-deoxy-D-galactose (2-D-gal) on ciclosporin (CsA)-induced renal epithelial-mesenchymal transition (EMT). Methods Fifteen male C57BL/6 mice aged 8-10 weeks were randomly and evenly divided into the control group (Ctrl group), CsA group and CsA+2-D-gal group (n=5). The expression levels of fucosyltransferase 1 (FUT1), EMT-associated proteins including E-cadherin, Vimentin, α-smooth muscle actin (α-SMA) in the kidney tissues of the Ctrl and CsA groups were detected by Western blot. The expression levels of terminal fucose in the kidney tissues of Ctrl and CsA groups were determined by immunofluorescence. The renal fibrosis of mice in each group was evaluated by Masson staining. The blood urea nitrogen and serum creatinine levels of mice in each group were detected. The in vitro EMT model of renal tubular epithelial cell HK2 was induced by CsA. HK2 cells were stimulated with 0, 2.5, 5.0 and 10.0 μmol/L CsA for 24 h, respectively. In addition, HK2 cells were divided into the Ctrl, 2-D-gal, CsA and CsA+2-D-gal groups. The morphology of HK2 cells after stimulation with different concentrations of CsA and in each group was observed. The expression levels of FUT1, E-cadherin, Vimentin and α-SMA in HK2 cells after stimulation with different concentrations of CsA and in each group were detected by Western blot. The expression level of terminal fucose in HK2 cells of the Ctrl and CsA groups was measured by immunofluorescence. Results Compared with the Ctrl group, the relative expression of E-cadherin protein was down-regulated, those of FUT1, Vimentin and α-SMA proteins were up-regulated (all P < 0.05), and that of terminal fucose in the mouse kidney tissues was up-regulated in the CsA group. Compared with the Ctrl group, the blood urea nitrogen and serum creatinine levels in the CsA and CsA+2-D-gal groups were up-regulated (all P < 0.05). Compared with the CsA group, the blood urea nitrogen and serum creatinine levels in the CsA+2-D-gal group were down-regulated (both P < 0.05). Compared with the Ctrl group, the collagen fiber deposition was increased and the relative expression of α-SMA protein was up-regulated in the mouse kidney tissues of CsA and CsA+2-D-gal groups (all P < 0.05). Compared with the CsA group, the collagen fiber deposition was decreased and the relative expression of α-SMA protein in the mouse kidney tissues was down-regulated in the CsA+2-D-gal group (both P < 0.05). With the increase of CsA concentration, the morphology of HK2 cells gradually became longer and thinner from original normal cobblestone shape, the relative expression levels of FUT1, Vimentin and α-SMA protein in HK2 cells were up-regulated, and that of E-cadherin protein was down-regulated in a concentration-dependent manner. Compared with the Ctrl group, the expression level of terminal fucose of HK2 cells was up-regulated in the CsA group. After CsA treatment combined with 2-D-gal intervention, the morphology of HK2 cells in the CsA+2-D-gal group was restored to resemble that of normal HK2 cells. Compared with the CsA group, the relative expression of E-cadherin protein in HK2 cells was up-regulated, whereas those of Vimentin and α-SMA proteins were down-regulated in the CsA+2-D-gal group (all P < 0.05). Conclusions CsA may induce EMT both in vivo and in vitro, and the terminal fucosylation is increased. 2-D-gal may inhibit CsA-induced EMT by suppressing the terminal fucosylation.

OBJECTIVE To provide reference for the improvement of the price system of innovative drugs in China. METHODS Based on the current situation of innovative drug healthcare management in China， innovation recognition and price management of innovative drugs in typical countries or regions were compared and analyzed， and the suggestions were put forward to improve the price system of innovative drugs in China. RESULTS & CONCLUSIONS Taiwan of China， Japan， Australia， Germany and the United Kingdom have different practices in recognition and grading of drug innovation， differentiated pricing and subsequent price management. However， the mainstream practice is to identify and grade drugs mostly based on clinical value， differentiate pricing based on the grading， and carry out risk-sharing agreement or active price adjustment to manage the price. Based on the comparative analysis， it is suggested that China should further clarify the connotation and classification of innovation in the management of innovative drugs， apply a variety of pricing methods to promote differentiated management of innovative drugs， explore the introduction of risk-sharing agreements， and further build an active drug price adjustment mechanism to improve the price system of innovative drugs in China.

Aiming at the problems of missing important features, inconspicuous details and unclear textures in the fusion of multimodal medical images, this paper proposes a method of computed tomography (CT) image and magnetic resonance imaging (MRI) image fusion using generative adversarial network (GAN) and convolutional neural network (CNN) under image enhancement. The generator aimed at high-frequency feature images and used double discriminators to target the fusion images after inverse transform; Then high-frequency feature images were fused by trained GAN model, and low-frequency feature images were fused by CNN pre-training model based on transfer learning. Experimental results showed that, compared with the current advanced fusion algorithm, the proposed method had more abundant texture details and clearer contour edge information in subjective representation. In the evaluation of objective indicators, Q ^AB/F, information entropy (IE), spatial frequency (SF), structural similarity (SSIM), mutual information (MI) and visual information fidelity for fusion (VIFF) were 2.0%, 6.3%, 7.0%, 5.5%, 9.0% and 3.3% higher than the best test results, respectively. The fused image can be effectively applied to medical diagnosis to further improve the diagnostic efficiency.
Image Processing, Computer-Assisted/methods* ; Neural Networks, Computer ; Tomography, X-Ray Computed ; Magnetic Resonance Imaging/methods* ; Algorithms