The exonuclease activity of Apurinic/apyrimidinic endonuclease 1 (APE1) is responsible for processing matched/mismatched terminus in various DNA repair pathways and for removing nucleoside analogs associated with drug resistance. To fill in the gap of structural basis for exonucleolytic cleavage, we determine the APE1-dsDNA complex structures displaying end-binding. As an exonuclease, APE1 does not show base preference but can distinguish dsDNAs with different structural features. Integration with assaying enzyme activity and binding affinity for a variety of substrates reveals for the first time that both endonucleolytic and exonucleolytic cleavage can be understood by an induced space-filling model. Binding dsDNA induces RM (Arg176 and Met269) bridge that defines a long and narrow product pocket for exquisite machinery of substrate selection. Our study paves the way to comprehend end-processing of dsDNA in the cell and the drug resistance relating to APE1.
The novel coronavirus (COVID-19) has become a global pandemic outbreak. Patients with COVID-19 are prone to progress to acute respiratory distress syndrome (ARDS), and even severe ARDS with ineffective mechanical ventilation, and an extremely high mortality. Extracorporeal membrane oxygenation (ECMO) provides effective respiratory support and saves time for the treatment of severe COVID-19. The present study reports that a 31-year-old pregnant female infected by COVID-19, who suffered from fever, dyspnea, and rapid ARDS. The patient's pulmonary function gradually recovered by combining early mechanical ventilation and ECMO, and finally, this patient was successfully weaned from ECMO and the ventilator. No fibrosis lesions were found in the chest CT, and the patient recovered very well after leaving from the hospital for one month.
PurposeBoth chronic mass-forming pancreatitis (CMFP) and pancreatic ductal adenocarcinoma (PDAC) are focal pancreatic lesions and share very similar clinical symptoms and imaging performance. There is great clinical value in preoperative differentiation of those two lesions. The purpose of this study was to investigate the value of computed tomography (CT) features in discriminating CMFP from PDAC.Patients and methodsForty-seven patients with pathologically confirmed PDAC and 21 patients with CMFP were included in this study. Demographic and CT features, including tumor location, size, margin, pancreatic or bile duct dilatation, vascular invasion, cystic necrosis, pancreatic atrophy, calcification, and tumor contrast enhancement, were retrospectively analyzed and compared. Multivariate logistic regression analyses were adopted to identify relevant CT imaging features to discriminate CMFP from PDAC.ResultsThere were significant differences between CMFP and PDAC with respect to main pancreatic duct dilatation, vascular invasion, cystic necrosis, pancreatic atrophy, calcification, and tumor contrast enhancement. Delayed contrast enhancement (>70.5 Hounsfield units) showed high sensitivity and specificity of 84.2% and 84.7%. The areas under the curve (AUCs) of the predicting models based on qualitative and quantitative variables were 0.770 (95% CI: 0.660–0.880) and 0.943 (95% CI: 0.888–0.999), respectively. When all significant variables were used in combination to build a predicting model, the AUC was 0.969 (95% CI: 0.930–1.000) with 84.2% sensitivity and 94.7% specificity.ConclusionMain pancreatic duct dilatation, vascular invasion, cystic necrosis, pancreatic atrophy, calcification, tumor size, and tumor contrast enhancement were shown to be useful CT imaging features in discriminating CMFP from PDAC.
Microbial synthesis of functional polymers has become increasingly important for industrial biotechnology. For the first time, it became possible to synthesize controllable composition of poly(3-hydroxyalkanoate) (P3HA) consisting of 3-hydroxydodecanoate (3HDD) and phenyl group on the side-chain when chromosome of Pseudomonas entomophila was edited to weaken its β-oxidation. Cultured in the presence of 5-phenylvaleric acid (PVA), the edited P. entomophila produced only homopolymer poly(3-hydroxy-5-phenylvalerate) or P(3HPhV). While copolyesters P(3HPhV-co-3HDD) of 3-hydroxy-5-phenylvalerate (3HPhV) and 3-hydroxydodecanoate (3HDD) were synthesized when the strain was grown on mixtures of PVA and dodecanoic acid (DDA). Compositions of 3HPhV in P(3HPhV-co-3HDD) were controllable ranging from 3% to 32% depending on DDDA/PVA ratios. Nuclear magnetic resonance (NMR) spectra clearly indicated that the polymers were homopolymer of P(3HPhV) and random copolymers of 3HPhV and 3HDD. Their mechanical and thermal properties varied dramatically depending on the monomer ratios. Our results demonstrated the possibility to produce tailor-made, novel functional PHA using the chromosome edited P. entomophila.
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