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In order to ascertain the influencing factors and rules of the inner corrosion on the insulating joint unprotected side of the buried pipelines, a model of the buried pipeline’s insulating joint protected side and unprotected side cathodic protection system was established using the BEASY software with the help of the coupling calculation method for finite element and boundary element. The influences of different internal dielectric conductivity, potential difference between the protected side and the unprotected side as well as the damage rate of the inner coating on the internal corrosion of the unprotected side of the insulating joint were studied by numerical simulations, and the influence laws of various factors on the internal corrosion of the non - protected side of the insulating joint were analyzed with the help of analytical method. Results showed that the main factors affecting the internal corrosion of the unprotected side of the insulating joint were potential difference between the protected side and unprotected side, dielectric conductivity and the damage rate of the internal coating on the unprotected side. Furthermore, the corrosion rate was proportional to the potential difference between the protected side and the unprotected side, and to the dielectric conductivity, and were inversely proportional to the damage rate of the inner coating on the non - protected side.

BackgroundAs the second primary type of cognitive impairment worldwide, vascular cognitive impairment (VCI) is closely associated with cerebrovascular risks, which imposes a heavy burden on the society and families. Early diagnosis and treatment are important for intervening and reversing VCI. And formulating high-quality clinical guidelines is an effective way to improve diagnosis and treatment levels of VCI.ObjectiveTo assess the quality of guidelines for VCI, aiming at offering support for making clinical decisions for VCI.MethodsFrom August to November 2021, we searched literature databases and websites in China and abroad to identify guidelines for VCI, and assessed them using the Appraisal of Guidelines for Research & Evaluation (AGREE) Ⅱ.ResultsA total of 18 guidelines were enrolled, 12 of which are Chinese guidelines and 6 are foreign guidelines; 9 of which are evidence-based guidelines, and the other 9 are not. The intraclass correlation coefficient was 0.935, indicating a high degree of agreement between raters. The overall quality of these guidelines was relatively low, since in the six domains, only the average score of Clarity of Presentation was greater than 60% (64.04%) , and the average scores of Scope and Purpose (52.31%) and Editorial Independence (42.01%) were between 30% and 60%, and those for other three domains, Stakeholder Involvement (27.24%) , Rigor of Development (20.05%) and Applicability (13.83%) , were all less than 30%. The grade of recommendation for 6 guidelines was B, and that for other 12 guidelines was C.ConclusionThe overall quality of the included guidelines was rated relatively low, especially their average score for each of the three domains, Stakeholder Involvement, Rigor of Development, and Applicability, was below the average level. It is suggested to enhance the quality of VCI guidelines via improving the details of guidelines strictly under the evidence-based principle.

WD repeat‐containing protein 5 (WDR5) and mixed lineage leukemia (MLL) are critical for maintaining tumorigenesis in human cancers. Disruption of the MLL1–WDR5 interaction has been viewed as a promising therapeutic strategy for the treatment of leukemia. Here, we report a series of protein–protein binding interaction modes targeting MLL1‐WDR5 inhibitors using 3D‐QSAR, and molecular docking. CoMFA with q2 = 0.724, r2 = 0.957, rpred2 = 0.874 and CoMSIA with q2 = 0.826, r2 = 0.995, rpred2 = 0.827. Topomer CoMFA results show q2 = 0.807, r2 = 0.976, rpred2 = 0.789, and HQSAR results show q2 = 0.873, r2 = 0.982, rpred2 = 0.794. The 3D‐QSAR model with high validation and prediction performance is successfully constructed. Contour maps and molecular docking results according to the four models, 26 new compounds are finally designed on the computer after molecular screening. Further molecular dynamics simulations (MD) of compounds G01, G04, G09, G43, and G44 with high predicted activity are carried out to explore their possible binding modes. ILE305, PHE133, CYS261, and ALA176 are found to play crucial roles in stabilizing the inhibitor. ADMET predictions are also performed for these 26 new compounds. These results serve as references for the design of effective WDR5‐MLL1 inhibitors in the future. [ABSTRACT FROM AUTHOR]