Hydrazyl hydroxycoumarins as new potential conquerors towards Pseudomonas aeruginosa.

A class of unique hydrazyl hydroxycoumarins (HHs) as novel structural scaffold was developed to combat dreadful bacterial infections. Some HHs could effectively suppress bacterial growth at low concentrations, especially, pyridyl HH 7 exhibited a good inhibition against Pseudomonas aeruginosa 27853 with a low MIC value of 0.5 µg/mL, which was 8-fold more active than norfloxacin. Furthermore, pyridyl HH 7 with low hemolytic activity and low cytotoxicity towards NCM460 cells showed much lower trend to induce the drug-resistant development than norfloxacin. Preliminarily mechanism exploration indicated that pyridyl HH 7 could eradicate the integrity of bacterial membrane, result in the leakage of intracellular proteins, and interact with bacterial DNA gyrase via non-covalent binding, and ADME analysis manifested that compound 7 gave good pharmacokinetic properties. These results suggested that the newly developed hydrazyl hydroxycoumarins as potential multitargeting antibacterial agents should be worthy of further investigation for combating bacterial infection.

Loss of PR55α promotes proliferation and metastasis by activating MAPK/AKT signaling in hepatocellular carcinoma.

BACKGROUND: PR55α plays important roles in oncogenesis and progression of numerous malignancies. However, its role in hepatocellular carcinoma (HCC) is unclear. This study aims to characterize the functions of PR55α in HCC. METHODS: PR55α expressions in HCC tissues and paired healthy liver samples were evaluated using Western blot and tissue microarray immunohistochemistry. We knocked down the expression of PR55α in SMMC-7721 and LM3 cell lines via small interfering and lentivirus. In vitro cell counting, colony formation, migration and invasion assays were performed along with in vivo xenograft implantation and lung metastases experiments. The potential mechanisms involving target signal pathways were investigated by RNA-sequencing. RESULTS: PR55α expression level was suppressed in HCC tissues in comparison to healthy liver samples. Decreased PR55α levels were correlated with poorer prognosis (P = 0.0059). Knockdown of PR55α significantly promoted cell proliferation and migration, induced repression of the cell cycle progression and apoptosis in vitro while accelerating in vivo HCC growth and metastasis. Mechanistic analysis indicated that PR55α silencing was involved with MAPK/AKT signal pathway activation and resulted in increased phosphorylation of both AKT and ERK1/2. CONCLUSIONS: This study identifies PR55α to be a candidate novel therapeutic target in the treatment of HCC.

Automatic Detection of Coronary Metallic Stent Struts Based on YOLOv3 and R-FCN.

An artificial stent implantation is one of the most effective ways to treat coronary artery diseases. It is vital in vascular medical imaging, such as intravascular optical coherence tomography (IVOCT), to be able to track the position of stents in blood vessels effectively. We trained two models, the "You Only Look Once" version 3 (YOLOv3) and the Region-based Fully Convolutional Network (R-FCN), to detect metal support struts in IVOCT, respectively. After rotating the original images in the training set for data augmentation, and modifying the scale of the conventional anchor box in both two algorithms to fit the size of the target strut, YOLOv3 and R-FCN achieved precision, recall, and AP all above 95% in 0.4 IoU threshold. And R-FCN performs better than YOLOv3 in all relevant indicators.