The influenza virus nucleoprotein (NP) is an emerging target for anti-influenza drug development. Nucleozin (1) and its closely related derivatives had been identified as NP inhibitors displaying anti-influenza activity. Utilizing 1 as a lead molecule, we successfully designed and synthesized a series of 1H-1,2,3-triazole-4-carboxamide derivatives as new anti-influenza A agents. One of the most potent compounds, 3b, inhibited the replication of various H3N2 and H1N1 influenza A virus strains with IC(50) values ranging from 0.5 to 4.6 μM. Compound 3b also strongly inhibited the replication of H5N1 (RG14), amantidine-resistant A/WSN/33 (H1N1), and oseltamivir-resistant A/WSN/1933 (H1N1, 274Y) virus strains with IC(50) values in sub-μM ranges. Further computational studies and mechanism investigation suggested that 3b might directly target influenza virus A nucleoprotein to inhibit its nuclear accumulation. 相似文献
The purpose of our study was to retrospectively evaluate and categorize temporal changes in MRI appearances of the prostate in patients who underwent focal therapy with MRI follow-up.
Methods
The Institutional Review Board approved this retrospective study and waived the requirement for informed consent. Thirty-seven patients (median age 61; 48–70 years) with low-to-intermediate-risk, clinically organ-confined prostate cancer underwent focal ablation therapy from 2009 to 2014. Two radiologists reviewed post-treatment MRIs (n = 76) and categorized imaging features blinded to the time interval between the focal therapy and the follow-up MRI. Inter-reader agreement was assessed (kappa) and generalized linear regression was used to examine associations between an imaging feature being present/absent and days between ablation and MRI.
Results
Inter-reader agreement on MRI features ranged from fair to substantial. Edema was found present at earlier times after ablation (median 16–25 days compared to MRIs without edema, median 252–514 days), as was rim enhancement of the ablation zone (18–22.5 days vs. 409–593 days), a hypointense rim around the ablation zone on T2-weighted images (53-57.5 days vs. 279–409 days) and the presence of an appreciable ablation cavity (48.5–60 days vs. 613–798 days, all p < 0.05). Enhancement of the ablation zone/scar (553–731 days vs. 61.5–162 days) and the formation of a T2-hypointense scar were found to be present on later MRI scans (514–553 days vs. 29–32 days, one reader).
Conclusions
The MRI appearance of the prostate after focal ablation changes substantially over time. Identification of temporal patterns in the appearance of imaging features should help reduce image interpretation variability and errors when assessing post-therapeutic scans.
Abdominal Radiology - To evaluate the role of diffusion kurtosis and diffusivity as potential imaging biomarkers to predict response to neoadjuvant chemoradiation therapy (CRT) from baseline... 相似文献