Study on SBS Optimal Block Ratio Based on Molecular Simulation.

The block ratio of SBS is an important factor influencing the swelling effect of modified asphalt, but the effect of the block ratio in the swelling process cannot be accurately studied by macro testing. In order to solve this problem and screen out the optimal SBS block ratio, molecular models of asphalt and SBS with different block ratios were established by molecular simulation technology at the microscopic level, and an asphalt-SBS interaction layer system was established on this basis. The diffusion and adhesion effects of SBS with different block ratios were evaluated by calculating the immersion depth, diffusion coefficient, and adhesion work of SBS in asphalt. The results show that SBS has a physical cross-linking reaction with asphalt during swelling, and SBS with a higher butadiene block ratio exhibits a deeper immersion depth; thus, SBS with a 3/7 block ratio has the best performance in the modification process, which is superior to SBS with other block ratios, in terms of both the diffusion and adhesion effect. The performance of asphalt modified by SBS with different block ratios was tested using penetration, softening point, and ductility, and the results were consistent with the simulation results, which proved the reliability of the microscopic conclusions from a macro perspective.

Maternal rodent exposure to di-(2-ethylhexyl) phthalate decreases muscle mass in the offspring by increasing myostatin.

BACKGROUND: Di-(2-ethylhexyl) phthalate (DEHP) and its metabolites can cross the placenta and may cause birth defects and developmental disorders. However, whether maternal DEHP exposure affects skeletal muscle development in the offspring and the pathways involved are unknown. This study investigated the effects of maternal DEHP exposure and the contribution of myostatin (MSTN) to skeletal muscle development in the offspring. METHODS: Pregnant wild-type and muscle-specific myostatin knockout (MSTN KO) C57BL/6 mice were randomized to receive vehicle (corn oil) or 250 mg/kg DEHP by gavage every other day until their pups were weaned (postnatal day 21 [PND21]). Body weights of the offspring mice were measured longitudinally, and their hindleg muscles were harvested at PD21. Also, C2C12 cells were treated with mono-2-ethylhexyl phthalate (MEHP), the primary metabolite of DEHP, and proteolysis, protein synthesis, and myogenesis markers were measured. The contribution of myostatin to maternal DEHP exposure-induced muscle wasting in the offspring was determined. RESULTS: Maternal DEHP exposure reduced body weight growth, myofibre size, and muscle mass in the offspring compared to controls (Quad: 2.70 ± 0.1 vs. 3.38 ± 0.23, Gastroc: 2.29 ± 0.09 vs. 2.81 ± 0.14, Tibialis: 1.01 ± 0.07 vs. 1.25 ± 0.11, mg/tibial length in mm, all P < 0.01, n = 35). Maternal DEHP exposure significantly increased Myostatin expression (2.45 ± 0.41 vs. 0.03 ± 0.00 DEHP vs. controls, P < 0.01, n = 5), Atrogin-1(2.68 ± 0.65 vs. 0.63 ± 0.01, P < 0.05, n = 5), MuRF1 (1.56 ± 0.51 vs. 0.31 ± 0.01, P < 0.05, n = 5), and Smad2/3 phosphorylation (4.12 ± 0.35 vs. 0.49 ± 0.18, P < 0.05), and decreased MyoD (0.27 ± 0.01 vs. 1.52 ± 0.01, P < 0.05, n = 5), Myogenin (0.25 ± 0.03 vs. 1.95 ± 0.56, P < 0.05, n = 5), and AKT phosphorylation (4.12 ± 0.35 vs. 1.00 ± 0.06, P < 0.05, n = 5), in skeletal muscle of the offspring in MSTNflox/flox , but not in MSTN KO mice. Maternal DEHP exposure resulted in up-regulation of CCAAT/enhancer-binding protein δ (C/EBPδ, 4.12 ± 0.35 vs. 1.00 ± 0.19, P < 0.05, n = 5) in skeletal muscle of the offspring in MSTNflox/flox and MSTN KO mice (4.12 ± 0.35 vs. 4.35 ± 0.28, P > 0.05, n = 5). In vitro, C/EBPδ silencing abrogated the MEHP-induced increases in Myostatin, MuRF-1, and Atrogin-1 and decreases in MyoD and Myogenin expression. CONCLUSIONS: Maternal DEHP exposure impairs skeletal muscle development in the offspring by enhancing the C/EBPδ-myostatin pathway in mice.

Effect of 3-caffeoyl, 4-dihydrocaffeoylquinic acid from Salicornia herbacea on endothelial nitric oxide synthase activation via calcium signaling pathway.

3-Caffeoyl-4-dicaffeoylquinic acid (CDCQ) is a natural chlorogenic acid isolated from Salicornia herbacea that protects against oxidative stress, inflammation, and cancer. Nitric oxide (NO) plays a physiologically beneficial role in the cardiovascular system, including vasodilation, protection of endothelial cell function, and anti-inflammation. However, the effect of CDCQ on NO production and eNOS phosphorylation in endothelial cells is unclear. We investigated the effect of CDCQ on eNOS phosphorylation and NO production in human endothelial cells, and the underlying signaling pathway. CDCQ significantly increased NO production and the phosphorylation of eNOS at Ser1177. Additionally, CDCQ induced phosphorylation of PKA, CaMKII, CaMKKß, and AMPK. Interestingly, CDCQ increased the intracellular Ca2+ level, and L-type Ca2+ channel (LTCC) blockade significantly attenuated CDCQ-induced eNOS activity and NO production by inhibiting PKA, CaMKII, CaMKKß, and AMPK phosphorylation. These results suggest that CDCQ increased eNOS phosphorylation and NO production by Ca2+-dependent phosphorylation of PKA, CaMKII, CaMKKß, and AMPK. Our findings provide evidence that CDCQ plays a pivotal role in the activity of eNOS and NO production, which is involved in the protection of endothelial dysfunction.

Rutaecarpine Increases Nitric Oxide Synthesis via eNOS Phosphorylation by TRPV1-Dependent CaMKII and CaMKKß/AMPK Signaling Pathway in Human Endothelial Cells.

Rutaecarpine (RUT) is a bioactive alkaloid isolated from the fruit of Evodia rutaecarpa that exerts a cellular protective effect. However, its protective effects on endothelial cells and its mechanism of action are still unclear. In this study, we demonstrated the effects of RUT on nitric oxide (NO) synthesis via endothelial nitric oxide synthase (eNOS) phosphorylation in endothelial cells and the underlying molecular mechanisms. RUT treatment promoted NO generation by increasing eNOS phosphorylation. Additionally, RUT induced an increase in intracellular Ca2+ concentration and phosphorylation of Ca2+/calmodulin-dependent protein kinase kinase ß (CaMKKß), AMP-activated protein kinase (AMPK), and Ca2+/calmodulin-dependent kinase II (CaMKII). Inhibition of transient receptor potential vanilloid type 1 (TRPV1) attenuated RUT-induced intracellular Ca2+ concentration and phosphorylation of CaMKII, CaMKKß, AMPK, and eNOS. Treatment with KN-62 (a CaMKII inhibitor), Compound C (an AMPK inhibitor), and STO-609 (a CaMKKß inhibitor) suppressed RUT-induced eNOS phosphorylation and NO generation. Interestingly, RUT attenuated the expression of ICAM-1 and VCAM-1 induced by TNF-α and inhibited the inflammation-related NF-κB signaling pathway. Taken together, these results suggest that RUT promotes NO synthesis and eNOS phosphorylation via the Ca2+/CaMKII and CaM/CaMKKß/AMPK signaling pathways through TRPV1. These findings provide evidence that RUT prevents endothelial dysfunction and benefit cardiovascular health.

Effects of Filler⁻Bitumen Ratio and Mineral Filler Characteristics on the Low-Temperature Performance of Bitumen Mastics.

This study analyzed the effects of the filler⁻bitumen interaction of the content and the meso powder characteristics of the mineral filler on the low-temperature performance of bitumen mastics. Control strategies for the mineral filler content (filler⁻bitumen ratio (RFB)) were also determined. Panjin #90 bitumen and styrene⁻butadiene⁻styrene polymer-modified bitumen were used in the experiment. Four kinds of limestone powder were used, all of which satisfy the Chinese standard for powder particle size but exhibit different meso characteristics. Each kind of limestone powder was used to prepare bitumen mastic samples under five different RFBs. The meso voids in the unit mass (Vg) of the four kinds of mineral filler were tested on the basis of the principle of the Rigden void ratio. The fixed bitumen⁻free bitumen ratio in the bitumen mastic samples was determined using Vg, bitumen density, and RFB. The low-temperature cohesive strength of the bitumen mastics was used as the control index for critical failure, whereas variation rates of bending creep stiffness at low temperature were used as the control index for fatigue failure. Results showed that the effects of the filler⁻bitumen interaction of the content and the meso characteristics of the mineral filler are significant and such effects are determined by the fixed bitumen⁻free bitumen ratio. The optimal fixed bitumen⁻free bitumen ratio in the bitumen mastics under two low-temperature conditions (−30 °C and −10 °C) can be determined on the basis of the influence of the fixed bitumen⁻free bitumen ratio on the critical and the failure control indices. Moreover, RFB can be obtained through reverse calculation. The mineral filler content can therefore be precisely controlled, which is crucial for the rational use of mineral filler and for the improvement of the pavement performance of bitumen mastics at low temperatures.