Prognostic impact of c-Rel nuclear expression and REL amplification and crosstalk between c-Rel and the p53 pathway in diffuse large B-cell lymphoma

Dysregulated NF-κB signaling is critical for lymphomagenesis. The regulation, function, and clinical relevance of c-Rel/NF-κB activation in diffuse large B-cell lymphoma (DLBCL) have not been well studied. In this study we analyzed the prognostic significance and gene-expression signature of c-Rel nuclear expression as surrogate of c-Rel activation in 460 patients with de novo DLBCL. Nuclear c-Rel expression, observed in 137 (26.3%) DLBCL patients frequently associated with extranoal origin, did not show significantly prognostic impact in the overall- or germinal center B-like-DLBCL cohort, likely due to decreased pAKT and Myc levels, up-regulation of FOXP3, FOXO3, MEG3 and other tumor suppressors coincided with c-Rel nuclear expression, as well as the complicated relationships between NF-κB members and their overlapping function. However, c-Rel nuclear expression correlated with significantly poorer survival in p63+ and BCL-2− activated B-cell-like-DLBCL, and in DLBCL patients with TP53 mutations. Multivariate analysis indicated that after adjusting clinical parameters, c-Rel positivity was a significantly adverse prognostic factor in DLBCL patients with wild type TP53. Gene expression profiling suggested dysregulations of cell cycle, metabolism, adhesion, and migration associated with c-Rel activation. In contrast, REL amplification did not correlate with c-Rel nuclear expression and patient survival, likely due to co-amplification of genes that negatively regulate NF-κB activation. These insights into the expression, prognostic impact, regulation and function of c-Rel as well as its crosstalk with the p53 pathway underscore the importance of c-Rel and have significant therapeutic implications

A three-dimensional ant colony algorithm for multi-objective ice routing of a ship in the Arctic area

| openaire: EC/H2020/730888/EU//RESET Funding Information: This study was supported by the National Science Foundation of China (NSFC) under Grant No. 52071247 and 51779202; Hubei Provincial Natural Science Foundation of China under Grant No. 2019CFA039 and 2021EHB007; Innovation and entrepreneurship team import project of Shaoguan city under Grant No. 201208176230693; the European Union's Horizon 2020 Research and Innovation Programme RISE under grant agreement No. 730888 (RESET). The first author would like to thank the China Scholarship Council (CSC) No. 202006950053. Funding Information: This study was supported by the National Science Foundation of China (NSFC) under Grant No. 52071247 and 51779202 ; Hubei Provincial Natural Science Foundation of China under Grant No. 2019CFA039 and 2021EHB007 ; Innovation and entrepreneurship team import project of Shaoguan city under Grant No. 201208176230693 ; the European Union’s Horizon 2020 Research and Innovation Programme RISE under grant agreement No. 730888 (RESET). The first author would like to thank the China Scholarship Council (CSC) No. 202006950053 . Publisher Copyright: © 2022 Elsevier LtdThe increasing shipping activities in the Arctic area pose challenges to a ship's safety and fuel saving in ice-covered waters. The optimal ship route planning can reduce the fuel consumption and navigation risk for ice-going ships in the Northeast Route. In this paper, a multi-objective ice routing model has been developed for searching optimal routes with two objectives, i.e., minimization of the fuel consumption and the total risk along a voyage, considering the time-varying ice data. Navigation risk is considered by applying a risk assessment model for Arctic navigation. A 3D-ACA (Three-Dimensional Ant Colony Algorithm) has been proposed and implemented in the developed ice routing model to make decisions on a ship's passing waypoints and sailing speeds along each waypoint. Finally, several case studies with different route planning objectives have been conducted to demonstrate the performance of the proposed model.Peer reviewe

Prognostic impact of c-Rel nuclear expression and REL amplification and crosstalk between c-Rel and the p53 pathway in diffuse large B-cell lymphoma

Dysregulated NF-\u3baB signaling is critical for lymphomagenesis. The regulation, function, and clinical relevance of c-Rel/NF-\u3baB activation in diffuse large B-cell lymphoma (DLBCL) have not been well studied. In this study we analyzed the prognostic significance and gene-expression signature of c-Rel nuclear expression as surrogate of c-Rel activation in 460 patients with de novo DLBCL. Nuclear c-Rel expression, observed in 137 (26.3%) DLBCL patients frequently associated with extranoal origin, did not show significantly prognostic impact in the overall- or germinal center B-like-DLBCL cohort, likely due to decreased pAKT and Myc levels, up-regulation of FOXP3, FOXO3, MEG3 and other tumor suppressors coincided with c-Rel nuclear expression, as well as the complicated relationships between NF-\u3baB members and their overlapping function. However, c-Rel nuclear expression correlated with significantly poorer survival in p63+ and BCL-2- activated B-cell-like-DLBCL, and in DLBCL patients with TP53 mutations. Multivariate analysis indicated that after adjusting clinical parameters, c-Rel positivity was a significantly adverse prognostic factor in DLBCL patients with wild type TP53. Gene expression profiling suggested dysregulations of cell cycle, metabolism, adhesion, and migration associated with c-Rel activation. In contrast, REL amplification did not correlate with c-Rel nuclear expression and patient survival, likely due to co-amplification of genes that negatively regulate NF-\u3baB activation. These insights into the expression, prognostic impact, regulation and function of c-Rel as well as its crosstalk with the p53 pathway underscore the importance of c-Rel and have significant therapeutic implications