The zinc finger transcription factor,KLF2,protects against COVID-19 associated endothelial dysfunction

Coronavirus disease 2019(COVID-19)is regarded as an endothelial disease(endothelialitis)with its patho-mechanism being incompletely understood.Emerging evidence has demonstrated that endothelial dysfunction precipitates COVID-19 and its accompanying multi-organ injuries.Thus,pharmacotherapies targeting endothelial dysfunction have potential to ameliorate COVID-19 and its cardiovascular complications.The objective of the present study is to evaluate whether kruppel-like factor 2(KLF2),a master regulator of vascular homeostasis,represents a therapeutic target for C0VID-19-induced endothelial dysfunction.Here,we demonstrate that the expression of KLF2 was reduced and monocyte adhesion was increased in endothelial cells treated with COVID-19 patient serum due to elevated levels of pro-adhesive molecules,ICAM1 and VCAM1.IL-1β and TNF-α;two cytokines elevated in cytokine release syndrome in COVID-19 patients,decreased KLF2 gene expression.Pharmacologic(atorvastatin and tannic acid)and genetic(adenoviral overexpression)approaches to augment KLF2 levels attenuated COVID-19-serum-induced increase in endothelial inflammation and monocyte adhesion.Next-generation RNA-sequencing data showed that atorvastatin treatment leads to a cardiovascular protective transcriptome associated with improved endothelial function(vasodilation,antiinflammation,antioxidant status,anti-thrombosis/-coagulation,anti-fibrosis,and reduced angiogenesis).Finally,knockdown of KLF2 partially reversed the ameliorative effect of atorvastatin on COVID-19-serum-induced endothelial inflammation and monocyte adhesion.Collectively,the present study implicates loss of KLF2 as an important molecular event in the development of COVID-19-induced vascular disease and suggests that efforts to augment KLF2 levels may be therapeutically beneficial.

Conservation laws of the complex short pulse equation and coupled complex short pulse equations

In this paper, the complex short pulse equation and the coupled complex short pulse equations that can describe the ultra-short pulse propagation in optical fibers are investigated. The two complex nonlinear models are turned into multi-component real models by proper transformations. Lie symmetries are obtained via the classical Lie group method, and the results for the coupled complex short pulse equations contain the existing results as particular cases.Based on the linearizing operator and adjoint linearizing operator for the two real systems,adjoint symmetries can be obtained. Explicit conservation laws are constructed using the symmetry/adjoint symmetry pair(SA) method. Relationships between the nonlinear selfadjointness method and the SA method are investigated.