BCL6 attenuates hyperoxia-induced lung injury by inhibiting NLRP3-mediated inflammation in fetal mouse.

BACKGROUND: The transcriptional repressor B-cell lymphoma 6 (BCL6) has been reported to inhibit inflammation. So far, experimental evidence for the role of BCL6 in bronchopulmonary dysplasia (BPD) is lacking. Our study investigated the roles of BCL6 in the progression of BPD and its downstream mechanisms. METHODS: Hyperoxia or lipopolysaccharide (LPS) was used to mimic the BPD mouse model. To investigate the effects of BCL6 on BPD, recombination adeno-associated virus serotype 9 expressing BCL6 (rAAV9-BCL6) and BCL6 inhibitor FX1 were administered in mice. The pulmonary pathological changes, inflammatory chemokines and NLRP3-related protein were observed. Meanwhile, BCL6 overexpression plasmid was used in human pulmonary microvascular endothelial cells (HPMECs). Cell proliferation, apoptosis, and NLRP3-related protein were detected. RESULTS: Either hyperoxia or LPS suppressed pulmonary BCL6 mRNA expression. rAAV9-BCL6 administration significantly inhibited hyperoxia-induced NLRP3 upregulation and inflammation, attenuated alveolar simplification and dysregulated angiogenesis in BPD mice, which were characterized by decreased mean linear intercept, increased radical alveolar count and alveoli numbers, and the upregulated CD31 expression. Meanwhile, BCL6 overexpression promoted proliferation and angiogenesis, inhibited apoptosis and inflammation in hyperoxia-stimulated HPMECs. Moreover, administration of BCL6 inhibitor FX1 arrested growth and development. FX1-treated BPD mice exhibited exacerbation of alveolar pathological changes and pulmonary vessel permeability, with upregulated mRNA levels of pro-inflammatory cytokines and pro-fibrogenic factors. Furthermore, both rAAV9-BCL6 and FX1 administration exerted a long-lasting effect on hyperoxia-induced lung injury (≥4 wk). CONCLUSIONS: BCL6 inhibits NLRP3-mediated inflammation, attenuates alveolar simplification and dysregulated pulmonary vessel development in hyperoxia-induced BPD mice. Hence, BCL6 may be a target in treating BPD and neonatal diseases.

Bio-based epoxy vitrimer with inherent excellent flame retardance and recyclability via molecular design.

The development of biobased fire-safe thermosets with recyclability heralds the switch for a transition towards a circular economy. In this framework, we introduced a novel high-performance bio-epoxy vitrimer (named GVD), which was fabricated by forming a crosslinking network between bio-epoxy glycerol triglycidyl ether (Gte), varying amounts of reactive flame-retardant agent 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) (0-7 wt%) and a vanillin-based hardener (VA) with imine bonds. For instance, the epoxy vitrimer GVD5, featuring a DOPO content of 5 wt%, achieved a V-0 rating in the vertical burning test (UL-94) and obtained a limiting oxygen index (LOI) value of 31 %, surpassing the performance of pristine epoxy. Furthermore, the peak heat release rate and total heat release of GVD5 were reduced by 38.2 % and 26.3 %, respectively, compared to pristine epoxy. The GVD vitrimers further demonstrated exceptional reprocessability and recyclability, attributed to the presence of dynamic imine bonds within the topological crosslinking network. Remarkably, the epoxy vitrimers maintained the mechanical properties of the parent epoxy. Therefore, this work provides a facile strategy for fabricating high-performance and multi-functional bio-epoxy thermosets.

Recent Progress on Multifunctional Thermally Conductive Epoxy Composite.

In last years, the requirements for materials and devices have increased exponentially. Greater competitiveness; cost and weight reduction for structural materials; greater power density for electronic devices; higher design versatility; materials customizing and tailoring; lower energy consumption during the manufacturing, transport, and use; among others, are some of the most common market demands. A higher operational efficiency together with long service life claimed. Particularly, high thermally conductive in epoxy resins is an important requirement for numerous applications, including energy and electrical and electronic industry. Over time, these materials have evolved from traditional single-function to multifunctional materials to satisfy the increasing demands of applications. Considering the complex application contexts, this review aims to provide insight into the present state of the art and future challenges of thermally conductive epoxy composites with various functionalities. Firstly, the basic theory of thermally conductive epoxy composites is summarized. Secondly, the review provides a comprehensive description of five types of multifunctional thermally conductive epoxy composites, including their fabrication methods and specific behavior. Furthermore, the key technical problems are proposed, and the major challenges to developing multifunctional thermally conductive epoxy composites are presented. Ultimately, the purpose of this review is to provide guidance and inspiration for the development of multifunctional thermally conductive epoxy composites to meet the increasing demands of the next generation of materials.

MiR-155-5p Attenuates Vascular Smooth Muscle Cell Oxidative Stress and Migration via Inhibiting BACH1 Expression.

The malfunction of vascular smooth muscle cells (VSMCs) is an initiating factor in the pathogenesis of pathological vascular remodeling, including hypertension-related vascular lesions. MicroRNAs (miRNAs) have been implicated in the pathogenesis of VSMC proliferation and migration in numerous cases of cardiovascular remodeling. The evidence for the regulatory role of miR-155-5p in the development of the cardiovascular system has been emerging. However, it was previously unclear whether miR-155-5p participated in the migration of VSMCs under hypertensive conditions. Thus, we aimed to define the exact role and action of miR-155-5p in VSMC migration by hypertension. Here, we detected that the level of miR-155-5p was lower in primary VSMCs from spontaneously hypertensive rats (SHRs). Its overexpression attenuated, while its depletion accelerated, the migration and oxidative damage of VSMCs from SHRs. Our dual-luciferase reporter assay showed that miRNA-155-5p directly targeted the 3'-untranslated region (3'-UTR) of BTB and CNC homology 1 (BACH1). The miR-155-5p mimic inhibited BACH1 upregulation in SHR VSMCs. By contrast, the deletion of miR-155-5p further elevated the upregulation of BACH1 in SHR-derived VSMCs. Importantly, the overexpression of miR-155-5p and knockdown of BACH1 had synergistic effects on the inhibition of VSMCs in hypertension. Collectively, miR-155-5p attenuates VSMC migration and ameliorates vascular remodeling in SHRs, via suppressing BACH1 expression.