Residual Interactions of LL-37 with POPC and POPE:POPG Bilayer Model Studied by All-Atom Molecular Dynamics Simulation

LL-37 is a membrane-active antimicrobial peptide (AMP) that could disrupt the integrity of bacterial membranes due to its inherent cationic and amphipathic nature. Developing a shorter derivative of a long peptide such as LL-37 is of great interest, as it can reduce production costs and cytotoxicity. However, more detailed information about the residual interaction between LL-37 and the membrane is required for further optimization. Previously, molecular dynamics simulation using mixed all-atom and united-atom force fields showed that LL-37 could penetrate the bilayer membrane. This study aimed to perform all-atom molecular dynamics simulations, highlighting the residual interaction of LL-37 with the simplest model of the bacterial membrane, POPE:POPG (2:1), and compare its interaction with the POPC, which represents the eukaryotic membrane. The result showed leucine–leucine as the leading residues of LL-37 that first contact the membrane surface. Then, the cationic peptide of LL-37 started to penetrate the membrane by developing salt bridges between positively charged amino acids, Lys–Arg, and the exposed phosphate group of POPE:POPG, which is shielded in POPC. Residues 18 to 29 are suggested as the core region of LL-37, as they actively interact with the POPE:POPG membrane, not POPC. These results could provide a basis for modifying the amino acid sequence of LL-37 and developing a more efficient design for LL-37 derivatives.     

Targeting of Glycosaminoglycans in Genetic and Inflammatory Airway Disease

In the lung, glycosaminoglycans (GAGs) are dispersed in the extracellular matrix (ECM) occupying the interstitial space between the capillary endothelium and the alveolar epithelium, in the sub-epithelial tissue and in airway secretions. In addition to playing key structural roles, GAGs contribute to a number of physiologic processes ranging from cell differentiation, cell adhesion and wound healing. Cytokine and chemokine–GAG interactions are also involved in presentation of inflammatory molecules to respective receptors leading to immune cell migration and airway infiltration. More recently, pathophysiological roles of GAGs have been described. This review aims to discuss the biological roles and molecular interactions of GAGs, and their impact in the pathology of chronic airway diseases, such as cystic fibrosis and chronic obstructive pulmonary disease. Moreover, the role of GAGs in respiratory disease has been heightened by the current COVID-19 pandemic. This review underlines the essential need for continued research aimed at exploring the contribution of GAGs in the development of inflammation, to provide a better understanding of their biological impact, as well as leads in the development of new therapeutic agents.     

Crosstalk between β-Catenin and CCL2 Drives Migration of Monocytes towards Glioblastoma Cells

Isocitrate dehydrogenase (IDH)-wildtype glioblastoma (GBM) is a fast growing and highly heterogeneous tumor, often characterized by the presence of glioblastoma stem cells (GSCs). The plasticity of GSCs results in therapy resistance and impairs anti-tumor immune response by influencing immune cells in the tumor microenvironment (TME). Previously, β-catenin was associated with stemness in GBM as well as with immune escape mechanisms. Here, we investigated the effect of β-catenin on attracting monocytes towards GBM cells. In addition, we evaluated whether CCL2 is involved in β-catenin crosstalk between monocytes and tumor cells. Our analysis revealed that shRNA targeting β-catenin in GBMs reduces monocytes attraction and impacts CCL2 secretion. The addition of recombinant CCL2 restores peripheral blood mononuclear cells (PBMC) migration towards medium (TCM) conditioned by shβ-catenin GBM cells. CCL2 knockdown in GBM cells shows similar effects and reduces monocyte migration to a similar extent as β-catenin knockdown. When investigating the effect of CCL2 on β-catenin activity, we found that CCL2 modulates components of the Wnt/β-catenin pathway and alters the clonogenicity of GBM cells. In addition, the pharmacological β-catenin inhibitor MSAB reduces active β-catenin, downregulates the expression of associated genes and alters CCL2 secretion. Taken together, we showed that β-catenin plays an important role in attracting monocytes towards GBM cells in vitro. We hypothesize that the interactions between β-catenin and CCL2 contribute to maintenance of GSCs via modulating immune cell interaction and promoting GBM growth and recurrence.     

基于BERT及双向GRU模型的慕课用户评论情感倾向性分析

以实现慕课网用户评论的情感倾向性分析为目的,本文提出一种基于BERT和双向GRU模型的用户评论情感倾向性分类方法。首先使用BERT模型提取课程评论文本的特征表示,其次将获取的词语特征输入BiGRU网络实现用户评论的情感特征的提取,最后用Softmax逻辑回归的方式进行情感倾向性分类。实验结果表明基于BERT和双向GRU模型的评论情感倾向性分类模型的F1值达到92.5%,提高了用户情感倾向性分析的准确率,从而验证了方法的有效性。     

Modification of polybutadienes by catalytic and photochemical decomposition of dimethyldiazomalonate

Modifications of polybutadienes via catalytic and photolytic decomposition of dimethyldiazomalonate (dmdm) are described. This method pertains to the generation of highly reactive carbenes which give rise to the formation of addition and insertion products. Chemical structures of the modified polymers were confirmed by NMR spectroscopy. It was found that carbene dimers were also formed in a significant extent depending on the molecular weight and microstructure of the initial polymers.     

Polymers with acyloxime ester groups in the main chain. 2. Photochemical synthesis of block copolymers

Block copolymers of styrene and methyl methacrylate (MMA) were prepared in a two-stage free-radical polymerization by means of an azo-acyloxime ester (AOE) initiator. In the first stage, photosensitive styrene prepolymers were synthesized by using AOE initiator. These polymers were photolysed in the presence of MMA in the second stage to form block copolymers. The block copolymer structure was elucidated by means of extraction by appropriate solvents, GPC analysis and IR and NMR spectral measurements.