Temperature Dependence of Rubber Hyper-Elasticity Based on Different Constitutive Models and Their Prediction Ability

Based on the electronic universal testing machine with a temperature chamber, this paper investigated the temperature and filler effects on the hyper-elastic behavior of reinforced rubbers and revealed the regulation of the stress and strain of the natural rubber and filled rubber with temperature. The experimental results showed that the hyper-elastic behavior of the filled rubber was temperature-dependent in a wide range. Comparing the adaptability of different models to the stress–strain variation with temperature, the Yeoh model was proven to reasonably characterize the experimental data at different temperatures. Based on the Yeoh model, an explicit temperature-dependent constitutive model was developed to describe the stress–strain response of the filled rubber in a relatively large temperature range. The prediction data of this proposed constitutive model fit well with the test data of the mechanical experiments, indicating that the model is suitable to characterize the large deformation behavior of filled rubbers at different temperatures to a certain degree. The proposed model can be used to obtain the material parameters and has been successfully applied to finite element analysis (FEA), suggesting a high application value. Notably, the model has a simple form and can be conveniently applied in related performance tests of actual production or finite element analysis

Molecular Dynamics Simulation of the Thermomechanical and Tribological Properties of Graphene-Reinforced Natural Rubber Nanocomposites

The thermomechanical and tribological properties of graphene (GNS)-reinforced NR were investigated using molecular dynamics (MD) simulations. The amorphous molecular dynamics models of two nanocomposites, i.e., natural rubber (pure NR) and graphene/natural rubber (GNS/NR), were established. In addition, the thermodynamic properties of the two materials, before and after the incorporation of graphene into the natural rubber matrix, were investigated through analytical comparison. The results showed that after the graphene was added to the rubber matrix as a reinforcing material, the elastic modulus and shear modulus were increased by 110% and 94.8%, respectively, the tensile property was increased by 178%, the overall thermal conductivity of the composite system was increased by 59%, the glass transition temperature increased from 223 K to 236 K, and the rigidity of the material matrix was significantly improved. The inherent interactions and wear mechanisms of the polymer nanocomposites were discussed at the atomic scale by analyzing the changes in temperature, atomic velocity, relative atomic concentration, and radial distribution functions at the friction interface in the thickness direction

Decrotonylation of AKT1 promotes AKT1 phosphorylation and activation during myogenic differentiation

Introduction: Myogenic differentiation plays an important role in pathophysiological processes including muscle injury and regeneration, as well as muscle atrophy. A novel type of posttranslational modification, crotonylation, has been reported to play a role in stem cell differentiation and disease. However, the role of crotonylation in myogenic differentiation has not been clarified. Objectives: This study aims to find the role of crotonylation during myogenic differentiation and explore whether it is a potential target in myogenic dysfunction disease. Methods: C2C12 cell line and skeletal muscle mesenchymal progenitors of Mus musculus were used for myogenic process study in vitro, while muscle injury model of mice was used for in vivo muscle regeneration study. Mass spectrometry favored in discovery of potential target protein of crotonylation and its specific sites. Results: We confirmed the gradual decrease in total protein crotonylation level during muscle differentiation and found decreased crotonylation of AKT1, which facilitated an increase in AKT1 phosphorylation. Then we verified that crotonylation of AKT1 at specific sites weakened its binding with PDK1 and impaired its phosphorylation. In addition, we found that increased expression of the crotonylation eraser HDAC3 decreased AKT1 crotonylation levels during myogenic differentiation, jointly promoting myogenic differentiation. Conclusion: Our study highlights the important role of decrotonylation of AKT1 in the process of muscle differentiation, where it aids the phosphorylation and activation of AKT1 and promotes myogenic differentiation. This is of great significance for exploring the pathophysiological process of muscle injury repair and sarcopenia

Super enhancers targeting ZBTB16 in osteogenesis protect against osteoporosis

Abstract As the major cell precursors in osteogenesis, mesenchymal stem cells (MSCs) are indispensable for bone homeostasis and development. However, the primary mechanisms regulating osteogenic differentiation are controversial. Composed of multiple constituent enhancers, super enhancers (SEs) are powerful cis-regulatory elements that identify genes that ensure sequential differentiation. The present study demonstrated that SEs were indispensable for MSC osteogenesis and involved in osteoporosis development. Through integrated analysis, we identified the most common SE-targeted and osteoporosis-related osteogenic gene, ZBTB16. ZBTB16, positively regulated by SEs, promoted MSC osteogenesis but was expressed at lower levels in osteoporosis. Mechanistically, SEs recruited bromodomain containing 4 (BRD4) at the site of ZBTB16, which then bound to RNA polymerase II-associated protein 2 (RPAP2) that transported RNA polymerase II (POL II) into the nucleus. The subsequent synergistic regulation of POL II carboxyterminal domain (CTD) phosphorylation by BRD4 and RPAP2 initiated ZBTB16 transcriptional elongation, which facilitated MSC osteogenesis via the key osteogenic transcription factor SP7. Bone-targeting ZBTB16 overexpression had a therapeutic effect on the decreased bone density and remodeling capacity of Brd4 fl/fl Prx1-cre mice and osteoporosis (OP) models. Therefore, our study shows that SEs orchestrate the osteogenesis of MSCs by targeting ZBTB16 expression, which provides an attractive focus and therapeutic target for osteoporosis. Without SEs located on osteogenic genes, BRD4 is not able to bind to osteogenic identity genes due to its closed structure before osteogenesis. During osteogenesis, histones on osteogenic identity genes are acetylated, and OB-gain SEs appear, enabling the binding of BRD4 to the osteogenic identity gene ZBTB16. RPAP2 transports RNA Pol II from the cytoplasm to the nucleus and guides Pol II to target ZBTB16 via recognition of the navigator BRD4 on SEs. After the binding of the RPAP2-Pol II complex to BRD4 on SEs, RPAP2 dephosphorylates Ser5 at the Pol II CTD to terminate the transcriptional pause, and BRD4 phosphorylates Ser2 at the Pol II CTD to initiate transcriptional elongation, which synergistically drives efficient transcription of ZBTB16, ensuring proper osteogenesis. Dysregulation of SE-mediated ZBTB16 expression leads to osteoporosis, and bone-targeting ZBTB16 overexpression is efficient in accelerating bone repair and treating osteoporosis

Targeting macrophage M1 polarization suppression through PCAF inhibition alleviates autoimmune arthritis via synergistic NF-κB and H3K9Ac blockade

Abstract Sustained inflammatory invasion leads to joint damage and progressive disability in several autoimmune rheumatic diseases. In recent decades, targeting M1 macrophage polarization has been suggested as a promising therapeutic strategy for autoimmune arthritis. P300/CBP-associated factor (PCAF) is a histone acetyltransferase (HAT) that exhibits a strong positive relationship with the proinflammatory microenvironment. However, whether PCAF mediates M1 macrophage polarization remains poorly studied, and whether targeting PCAF can protect against autoimmune arthritis in vivo remains unclear. Commonly used drugs can cause serious side effects in patients because of their extensive and nonspecific distribution in the human body. One strategy for overcoming this challenge is to develop drug nanocarriers that target the drug to desirable regions and reduce the fraction of drug that reaches undesirable targets. In this study, we demonstrated that PCAF inhibition could effectively inhibit M1 polarization and alleviate arthritis in mice with collagen-induced arthritis (CIA) via synergistic NF-κB and H3K9Ac blockade. We further designed dextran sulfate (DS)-based nanoparticles (DSNPs) carrying garcinol (a PCAF inhibitor) to specifically target M1 macrophages in inflamed joints of the CIA mouse model via SR-A–SR-A ligand interactions. Compared to free garcinol, garcinol-loaded DSNPs selectively targeted M1 macrophages in inflamed joints and significantly improved therapeutic efficacy in vivo. In summary, our study indicates that targeted PCAF inhibition with nanoparticles might be a promising strategy for treating autoimmune arthritis via M1 macrophage polarization inhibition

Localized‐domains staging structure and evolution in lithiated graphite

Abstract Intercalation provides to the host materials a means for controlled variation of many physical/chemical properties and dominates the reactions in metal‐ion batteries. Of particular interest is the graphite intercalation compounds with intriguing staging structures, which however are still unclear, especially in their nanostructure and dynamic transition mechanism. Herein, the nature of the staging structure and evolution of the lithium (Li)‐intercalated graphite was revealed by cryogenic‐transmission electron microscopy and other methods at the nanoscale. The intercalated Li‐ions distribute unevenly, generating local stress and dislocations in the graphitic structure. Each staging compound is found macroscopically ordered but microscopically inhomogeneous, exhibiting a localized‐domains structural model. Our findings uncover the correlation between the long‐range ordered structure and short‐range domains, refresh the insights on the staging structure and transition of Li‐intercalated/deintercalated graphite, and provide effective ways to enhance the reaction kinetic in rechargeable batteries by defect engineering

Additional file 10 of LncRNA MRF drives the regulatory function on monocyte recruitment and polarization through HNRNPD-MCP1 axis in mesenchymal stem cells

Additional file 10: Fig. S7. The gating strategy for assessment of in vivo human monocyte recruitment via flow cytometry analysis. (A) The gating strategy for human CFSE-labeled monocytes in peritoneal lavage fluid. (B) The gating strategy for identification of human CFSE-labeled monocytes among spleen cells

Additional file 5 of LncRNA MRF drives the regulatory function on monocyte recruitment and polarization through HNRNPD-MCP1 axis in mesenchymal stem cells

Additional file 5: Fig. S4. The dot-plot analysis and the expression of signature genes of macrophage polarization upon MRF knockdown. (A) The dot-plots of M1 macrophage polarization. (B) The dot-plots of M2 macrophage polarization. (C) The ratio of CD68+/HLA-DR+ cells. (D) The ratio of CD68+/CD206+ cells. (E-G) The expression of the M1 signature genes CCL5, NLRP3 and IDO1 was measured via qRT‒PCR. (H-J) The expression of the M2 signature genes CCL17, CD206 and CCL22 was measured via qRT‒PCR. The data are presented as the mean ± SD; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns= not significant. n=3, all experiments were independently repeated three times