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Chiral N-cyclopropyl pyrazoles and structurally related heterocycles are prepared using an earth-abundant copper catalyst under mild reaction conditions with high regio-, diastereo-, and enantiocontrol. The observed N2:N1 regioselectivity favors the more hindered nitrogen of the pyrazole. Experimental and DFT studies support a unique mechanism that features a five-centered aminocupration.

The non-API standard series of oil country tubular goods (OCTG) have been developed rapidly to meet the increasing demand of the oil and gas fields, while the frequent accidents of non-API OCTG still occur due to the lack of a perfect quality management system. In this paper, the main types, service conditions, and the current status of quality evaluation technology of non-API OCTG at home and abroad were introduced. For the quality problems of non-API OCTG during the domestic application, the needs of the industry development needs and continuous improvement of quality management system were taken into consideration. Based on the working conditions, the quantitative evaluation method of quality grading was built by the grading idea represented by capability maturity model integration (CMMI) based on the field working conditions. And an evaluation method, including process maturity level, items, indexes and procedures, was proposed and verified. The results showed that the average value and level of quantitative evaluation results of quality grading were 81.5 and C, respectively, which was in good accordance with the current status of non-API product management. The evaluation method is more quantitative and targeted, which would provide for the completeness of the non-API product quality management system with methodological support and theoretical reference.

Objective To investigate the effect of human papillomavirus oncogene E6(HPV16-E6) on the growth and apoptosis of cervical cancer cells via macrophage migration inhibitory factor(MIF). Methods Cervical cancer cells C33A, SiHa and Caski which could secrete MIF were transfected with HPV16-E6 overexpression vector or shRNA; Western blot, qRT-PCR and ELISA were used to examine MIF protein and mRNA expression and its supernatant. The cells above were co-cultured with human macrophages, and then we detected the expression of MIF in macrophages. MIF inhibitor was added or not in C33A group which was transfected with HPV16-E6; the cell proliferation, cell cycle and apoptosis were detected by CCK-8 method and flow cytometry. The association of HPV16-E6 expression with MIF and survival were analyzed using Pearson and Kaplan-Meier methods. Results The expression of MIF in cervical cancer cells, supernatant and macrophages were increased or decreased by up-regulation or down-regulation of HPV16-E6 expression(P < 0.05). HPV16-E6 over-expression could induce C33A cells proliferation, shorten G0/G1 phase and inhibit cell apoptosis, and these effects were reversed using MIF inhibitor(P < 0.05). There was positive correlation between HPV16-E6 expression and MIF in cervical cancer tissues(P < 0.05). Survival analysis suggested the expression of HPV16-E6 in cervical cancer tissues had a significant relationship with overall survival rate and progression-free survival rate(P < 0.05). Conclusion HPV16-E6 could induce the expression of MIF in cervical cancer cells and macrophages, promote the growth and inhibit the apoptosis of cervical cancer cells through up-regulation of MIF.

Pulsed field ablation is a novel approach to treating 33.5 million patients with atrial fibrillation and offers a tissue‐specific advantage over conventional radiofrequency ablation and cryoablation. However, for complex structural targets in the heart, current electrodes often damage non‐target areas due to inaccurate ablation and have to employ electrical pulses with amplitudes of several kilovolts. Herein, materials and designs of a catheter‐integrated microelectrode and sensors that can be used for high‐precision and low‐voltage pulsed field ablation through minimally invasive operation on a large animal model, is reported. The device with a new electrode configuration supports point‐by‐point ablation with a width of 3.8 mm (≈1/10 that of a typical ablation electrode) for individual lesions at the voltage of 300 V (an order of magnitude reduction compared to the current state‐of‐the‐art). More impressively, the integrated catheter allows for pulsed field ablation on the large animal heart through minimally invasive surgery and blocks the electrical conduction pathway on the heart, which is the key to treating atrial fibrillation. This catheter‐integrated device will enhance the efficiency and safety of pulsed field ablation, especially for complex cardiac structures, thus facilitating its move to the clinic. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer-related deaths worldwide. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) showed great therapeutic efficacy for non-small cell lung cancer (NSCLC) patients. However, acquired resistance severely limits the clinical application and efficacy of EGFR-TKIs. In the current study, we found that solamargine (SM), a natural alkaloid derived from the fruit of Lycium tomato lobelia, has been found to inhibit the progression of NSCLC and enhance the anticancer effect of EGFR-TKIs. In brief, SM significantly inhibited the cell viability of NSCLC cells and enhanced the anticancer effect of gefitinib (GFTN) and erlotinib (ERL). Mechanistically, SM decreased the expression of MALAT1 and induced miR-141-3p, whereas reduced SP1 protein levels. Interestingly, both MALAT1 and Sp1 have classical and conservative binding sites of miR-141-3p in their 3ʹ-UTR regions. Silence of MALAT1 and overexpression of miR-141-3p both decreased the protein expression of Sp1. Subsequently, promoter activity and protein expression of IGFBP1 were upregulated by SM, which was not observed in cells with SP1 overexpression. Moreover, the inhibitory effect of SM on cell growth was significantly blocked by knockdown of IGFBP1 expression. More importantly, the combination of SM and GFTN synergistically inhibited the progression of lung cancer. Similar results were observed in experiments in vivo. Finally, the clinical relevance of MALAT1, Sp1 and IGFBP1 was further validated using bioinformatics analysis. Taken together, we confirmed that SM significantly enhanced the anticancer effect of EGFR-TKIs by regulating the MALAT1/miR-141-3p/Sp1/IGFBP1 signaling pathway. This study unravels a novel mechanism and suggests a new potential NSCLC-associated therapy. [ABSTRACT FROM AUTHOR]