Epac1 regulates cellular SUMOylation by promoting the formation of SUMO-activating nuclear condensates

Protein SUMOylation plays an essential role in maintaining cellular homeostasis when cells are under stress. However, precisely how SUMOylation is regulated, and a molecular mechanism linking cellular stress to SUMOylation remains elusive. Herein, we report that cAMP, a major stress-response second messenger, acts through Epac1 as a regulator of cellular SUMOylation. The Epac1-associated proteome is highly enriched with components of the SUMOylation pathway. Activation of Epac1 by intracellular cAMP triggers phase separation and the formation of nuclear condensates containing Epac1 and general components of the SUMOylation machinery to promote cellular SUMOylation. Furthermore, genetic knockout of Epac1 obliterates oxidized low-density lipoprotein induced cellular SUMOylation in macrophages, leading to suppression of foam cell formation. These results provide a direct nexus connecting two major cellular stress responses to define a molecular mechanism in which cAMP regulates the dynamics of cellular condensates to modulate protein SUMOylation.

The Effects of Core Machining Configurations on the Mechanical Properties of Cores and Sandwich Structures

Composite sandwich structures are widely used in the fields of aviation, marine, and energy due to their high specific stiffness and design flexibility. Improving the mechanical properties of the cores is significant to the strength, modulus, and stability of composite sandwich structures. Two kinds of core machining configurations were designed by combining thin grooves, perforated holes, and thick contour cuts as well as non-machining plain cores. The cores and sandwich structures with these configurations were fabricated using a vacuum-assistant infusion process. Static tensile, compressive, shear, and peeling tests were conducted on the infused cores and sandwich structures. The results showed that the tensile, compressive, and shear moduli, and compressive strength of the infused cores can be greatly improved. The tensile strength changed negligibly due to stress concentration induced by irregular foam cell and the shear-lag phenomenon of the resin column/foam interface. The shear strength of the infused cores increased slightly. The thick contour cuts and perforated holes can greatly improve the face sheet/core peel capacity of the sandwich structures, whereas the thin grooves can moderately improve the peel capacity. Both infused cores with the designed machining configurations exhibited positive effects on the compressive, tensile, and shear moduli, and compressive strength, considering the material costs. The study provides a comprehensive and quantitative insight into the effects of core machining configurations on mechanical properties of infused cores and composite sandwich structures.

The Roles and Associated Mechanisms of Adipokines in Development of Metabolic Syndrome

Metabolic syndrome is a cluster of metabolic indicators that increase the risk of diabetes and cardiovascular diseases. Visceral obesity and factors derived from altered adipose tissue, adipokines, play critical roles in the development of metabolic syndrome. Although the adipokines leptin and adiponectin improve insulin sensitivity, others contribute to the development of glucose intolerance, including visfatin, fetuin-A, resistin, and plasminogen activator inhibitor-1 (PAI-1). Leptin and adiponectin increase fatty acid oxidation, prevent foam cell formation, and improve lipid metabolism, while visfatin, fetuin-A, PAI-1, and resistin have pro-atherogenic properties. In this review, we briefly summarize the role of various adipokines in the development of metabolic syndrome, focusing on glucose homeostasis and lipid metabolism.

Phage Display Preparation of Specific Polypeptides in Atherosclerotic Foam Cells

Atherosclerosis and related complications are the most common causes of death in modern societies. Macrophage-derived foam cells play critical roles in the initiation and progression of atherosclerosis. Effective, rapid, and instrument-independent detection in the early stage of chronic atherosclerosis progression could provide an opportunity for early intervention and treatment. Therefore, as a starting point, in this study, we aimed to isolate and prepare foam cell-specific polypeptides using a phage display platform. The six target polypeptides, which were acquired in this study, were evaluated by ELISA and showed strong specificity with foam cells. Streptavidin coupled quantum dots (QDs) were used as fluorescence developing agents, and images of biotin-modified polypeptides specifically binding with foam cells were clearly observed. The polypeptides obtained in this study could lay the foundation for developing a rapid detection kit for early atherosclerosis lesions and could provide new materials for research on the mechanisms of foam cell formation and the development of blocking drugs.

TMT-based quantitative proteomic profiling of human monocyte-derived macrophages and foam cells

Background Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide, most of which are caused by atherosclerosis. Discerning processes that participate in macrophage-to-foam cell formation are critical for understanding the basic mechanisms underlying atherosclerosis. To explore the molecular mechanisms of foam cell formation, differentially expressed proteins were identified. Methods Human peripheral blood mononuclear cells were stimulated with macrophage colony-stimulating factor, and obtained macrophages were transformed into foam cells by oxidized low-density lipoprotein. Tandem mass tag (TMT) labeling combined with mass spectrometry was performed to find associations between foam cell transformation and proteome profiles. Results Totally, 5146 quantifiable proteins were identified, among which 1515 and 182 differentially expressed proteins (DEPs) were found in macrophage/monocyte and foam cell/macrophage, respectively. Subcellular localization analysis revealed that downregulated DEPs of macrophages/monocytes were mostly located in the nucleus, whereas upregulated DEPs of foam cells/macrophages were mostly extracellular or located in the plasma membrane. Functional analysis of DEPs demonstrated that cholesterol metabolism-related proteins were upregulated in foam cells, whereas immune response-related proteins were downregulated in foam cells. The protein interaction network showed that the DEPs with the highest interaction scores between macrophages and foam cells were mainly concentrated in lysosomes and the endoplasmic reticulum. Conclusions Proteomics analysis suggested that cholesterol metabolism was upregulated, while the immune response was suppressed in foam cells. KEGG enrichment analysis and protein-protein interaction analysis indicated that DEPs located in the endoplasmic reticulum and lysosomes might be key drivers of foam cell formation. These data provide a basis for identifying the potential proteins associated with the molecular mechanism underlying macrophage transformation to foam cells.

Exploring the Potential to Repurpose Flexible Moulded Polyurethane Foams as Acoustic Insulators

Polyurethane flexible foams are widely used for a variety of applications to improve comfort and durability. Their long-term frequent use inevitably leads to the generation of waste that needs to be treated. The recycling and reuse of polyurethane waste are essential to achieve an environmentally friendly economy. The present study investigates the potential to reuse and repurpose flexible polyurethane foam from automotive seat cushion waste materials. Flexible foams were prepared with different hardnesses using isocyanate–polyol ratios between 0.8 and 1.2 NCO-index. Dry heat aging tests were performed to mimic the long-term usage of the materials. The decrease in compressive strength was compared with the change in acoustic damping properties before and after the aging tests using an acoustic tube, and the change in foam cell structures was also analyzed by micro-CT. On the basis of the results obtained, although the foam systems are no longer suitable to be used as seat cushions due to aging, they can still be used as sound insulation materials within a given frequency range, as their sound absorption capacity is suitable for such purpose.