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A silver-catalyzed chemoselective [4+2] annulation of aryl and heteroaryl isocyanides with α-substituted isocyanoacetamides was developed for the facile and efficient synthesis of 2-aminoquinolones, naphthyridines, and phenanthrolines. A mechanism for this multistep domino reaction is proposed on the basis of a 13 C-labeling experiment, according to which an unprecedented chemoselective heterodimerization of two different isocyanides generates an α-amidoketenimine intermediate, which undergoes 1,3-amino migration to form an α-imidoylketene, followed by 6 π electrocyclization.
RESUMO
Abnormal expression of circular RNAs (circRNAs) in cancer-associated fibroblasts (CAFs) is involved in the tumor-promoting ability of CAFs. Hsa_ circ_ 0056686 has been reported to affect leiomyoma size. The purpose of this study is to investigate the regulatory role of hsa_circ_0056686 in CAFs on uterine leiomyoma (ULM). The primary CAFs and corresponding normal fibroblasts (NFs) were isolated from the tumor zones of ULM tissues and adjacent, respectively. Hsa_circ_0056686 level was higher in CAFs than NFs, and also higher in ULM tissues than in adjacent tissues. CAFs-CM significantly increased the proliferation and migration and inhibited apoptosis of ULM cells, as confirmed by CCK-8, transwell, and flow cytometry assays. Moreover, conditioned medium (CM) from CAFs transfected with hsa_circ_0056686 shRNA (CAFssh-circ_0056686-CM) abolished CAFs-mediated proliferation, migration and apoptosis of ULM cells. CAFs-CM suppressed the expression of endoplasmic reticulum stress (ERS) marker proteins and induced the expression of extracellular matrix (ECM) marker proteins, thus suppressing ERS and increasing ECM accumulation, which could be declined by CAFssh-circ_0056686-CM. Meanwhile, knockdown of hsa_circ_0056686 reversed the inhibitory effects of CAFs-CM on brefeldin A-induced cell apoptosis. Luciferase gene reporter and RNA pull-down assays indicated that miR-515-5p directly bound with hsa_circ_0056686. MiR-515-5p overexpression restored the hsa_circ_0056686-shRNA-mediated malignant biological behaviors of ULM cells. Hsa_circ_0056686 contributed to tumor-promoting effects of CAFs in ULM, manifested by promoting ULM cell proliferation and migration and reducing ERS-induced apoptosis through sponging miR-515-5p.
Assuntos
Fibroblastos Associados a Câncer , Estresse do Retículo Endoplasmático , Leiomioma , RNA Circular , Neoplasias Uterinas , Apoptose/genética , Fibroblastos Associados a Câncer/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Humanos , Leiomioma/genética , MicroRNAs/genética , RNA Circular/genética , RNA Interferente Pequeno , Neoplasias Uterinas/genéticaRESUMO
BACKGROUND: Prolonged hospitalization and immobility of critical care patients elevate the risk of long-term physical and cognitive impairments. However, the therapeutic effects of early mobilization have been difficult to interpret due to variations in study populations, interventions, and outcome measures. We conducted a meta-analysis to assess the effects of early mobilization therapy on cardiac surgery patients in the intensive care unit (ICU). METHODS: PubMed, Excerpta Medica database (EMBASE), Cumulative Index of Nursing and Allied Health Literature (CINAHL), Physiotherapy Evidence Database (PEDro), and the Cochrane Library were comprehensively searched from their inception to September 2018. Randomized controlled trials were included if patients were adults (≥18âyears) admitted to any ICU for cardiac surgery due to cardiovascular disease and who were treated with experimental physiotherapy initiated in the ICU (pre, post, or peri-operative). Data were extracted by 2 reviewers independently using a pre-constructed data extraction form. Length of ICU and hospital stay was evaluated as the primary outcomes. Physical function and adverse events were assessed as the secondary outcomes. Review Manager 5.3 (RevMan 5.3) was used for statistical analysis. For all dichotomous variables, relative risks or odds ratios with 95% confidence intervals (CI) were presented. For all continuous variables, mean differences (MDs) or standard MDs with 95% CIs were calculated. RESULTS: The 5 studies with a total of 652 patients were included in the data synthesis final meta-analysis. While a slight favorable effect was detected in 3 out of the 5 studies, the overall effects were not significant, even after adjusting for heterogeneity. CONCLUSIONS: This population-specific evaluation of the efficacy of early mobilization to reduce hospitalization duration suggests that intervention may not universally justify the labor barriers and resource costs in patients undergoing non-emergency cardiac surgery. PROSPERO RESEARCH REGISTRATION IDENTIFYING NUMBER: CRD42019135338.
Assuntos
Procedimentos Cirúrgicos Cardíacos/reabilitação , Deambulação Precoce/métodos , Deambulação Precoce/estatística & dados numéricos , Unidades de Terapia Intensiva/estatística & dados numéricos , Modalidades de Fisioterapia/estatística & dados numéricos , Humanos , Tempo de Internação/estatística & dados numéricos , Desempenho Físico Funcional , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Strain-adjusting the band gap of MoS2 using patterned substrates to improve the photoelectric performance of MoS2 has gradually become a research hotspot in recent years. However, there are still difficulties in obtaining high-quality two-dimensional materials and preparing photodetectors on patterned substrates. To overcome this, a continuous multilayer MoS2 film was transferred to a patterned gallium nitride substrate (PGS) for the fabrication of photodetectors, and density functional theory calculations showed that the band gap of the MoS2 film increased and that the electron effective mass decreased due to the introduction of PGS. In addition, finite difference time domain simulation showed that the electric field in the MoS2 area on the PGS is enhanced compared with that on the flat gallium nitride substrate due to the enhanced light scattering effect of the PGS. The photoresponse of the MoS2/PGS photodetector at 460 nm was also enhanced, with Iph increasing by 5 times, R increasing by 2 times, NEP decreasing to 3.88 × 10-13 W/Hz1/2, and D* increasing to 5.6 × 108 Jones. Our research has important guiding significance in adjusting the band gap of MoS2 and enhancing the photoelectric performance of MoS2 photodetectors.
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A tandem [3 + 2] cycloaddition/reductive cyclization of nitrochalcones with activated methylene isocyanides for the efficient synthesis of pyrrolo[2,3-b]quinolones is reported. In this reaction, the in situ generated dihydropyrroline acts as the internal reductant to convert the nitro into an electrophilic nitroso group, which undergoes subsequent C-N bond formation. Transition-metal-free, simple experimental procedure and ready accessibility of starting materials characterize the present transformation.