Scalable synthesis of Cu clusters for remarkable selectivity control of intermediates in consecutive hydrogenation.

Subnanometric Cu clusters that contain only a small number of atoms exhibit unique and, often, unexpected catalytic behaviors compared with Cu nanoparticles and single atoms. However, due to the high mobility of Cu species, scalable synthesis of stable Cu clusters is still a major challenge. Herein, we report a facile and practical approach for scalable synthesis of stable supported Cu cluster catalysts. This method involves the atomic diffusion of Cu from the supported Cu nanoparticles to CeO2 at a low temperature of 200 °C to form stable Cu clusters with tailored sizes. Strikingly, these Cu clusters exhibit high yield of intermediate product (95%) in consecutive hydrogenation reactions due to their balanced adsorption of the intermediate product and dissociation of H2. The scalable synthesis strategy reported here makes the stable Cu cluster catalysts one step closer to practical semi-hydrogenation applications.

BMP4 enhances foam cell formation by BMPR-2/Smad1/5/8 signaling.

Atherosclerosis and its complications are characterized by lipid-laden foam cell formation. Recently, an obvious up-regulation of BMP4 was observed in atherosclerotic plaque, however, its function and the underlying mechanism remains unknown. In our study, BMP4 pretreatment induced macrophage foam cell formation. Furthermore, a dramatic increase in the ratio of cholesteryl ester (CE) to total cholesterol (TC) was observed in BMP4-treated macrophages, accompanied by the reduction of cholesterol outflow. Importantly, BMP4 stimulation inhibited the expression levels of the two most important cellular cholesterol transporters ABCA1 and ABCG1, indicating that BMP4 may induce formation of foam cells by attenuating transporters expression. Further mechanism analysis showed that BMPR-2, one of the BMP4 receptors, was significantly increased in BMP4 treated macrophage foam cells. That blocking its expression using specific siRNA significantly increased ABCA1 and ABCG1 levels. Additionally, BMP4 treatment triggered the activation of Smad1/5/8 pathway by BMPR-2 signaling. After blocking the Smad1/5/8 with its inhibitor, ABCA1 and ABCG1 expression levels were up-regulated significantly, suggesting that BMP4 inhibited the expression of ABCA1 and ABCG1 through the BMPR-2/Smad1/2/8 signaling pathway. Therefore, our results will provide a new insight about how BMP4 accelerate the progressio of atherosclerosis, and it may become a potential target against atherosclerosis and its complications.

miR-21 attenuates lipopolysaccharide-induced lipid accumulation and inflammatory response: potential role in cerebrovascular disease.

BACKGROUND: Atherosclerosis constitutes the leading contributor to morbidity and mortality in cardiovascular and cerebrovascular diseases. Lipid deposition and inflammatory response are the crucial triggers for the development of atherosclerosis. Recently, microRNAs (miRNAs) have drawn more attention due to their prominent function on inflammatory process and lipid accumulation in cardiovascular and cerebrovascular disease. Here, we investigated the involvement of miR-21 in lipopolysaccharide (LPS)-induced lipid accumulation and inflammatory response in macrophages. METHODS: After stimulation with the indicated times and doses of LPS, miR-21 mRNA levels were analyzed by Quantitative real-time PCR. Following transfection with miR-21 or anti-miR-21 inhibitor, lipid deposition and foam cell formation was detected by high-performance liquid chromatography (HPLC) and Oil-red O staining. Furthermore, the inflammatory cytokines interleukin 6 (IL-6) and interleukin 10 (IL-10) were evaluated by Enzyme-linked immunosorbent assay (ELISA) assay. The underlying molecular mechanism was also investigated. RESULTS: In this study, LPS induced miR-21 expression in macrophages in a time- and dose-dependent manner. Further analysis confirmed that overexpression of miR-21 by transfection with miR-21 mimics notably attenuated lipid accumulation and lipid-laden foam cell formation in LPS-stimulated macrophages, which was reversely up-regulated when silencing miR-21 expression via anti-miR-21 inhibitor transfection, indicating a reverse regulator of miR-21 in LPS-induced foam cell formation. Further mechanism assays suggested that miR-21 regulated lipid accumulation by Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) pathway as pretreatment with anti-TLR4 antibody or a specific inhibitor of NF-κB (PDTC) strikingly dampened miR-21 silence-induced lipid deposition. Additionally, overexpression of miR-21 significantly abrogated the inflammatory cytokines secretion of IL-6 and increased IL-10 levels, the corresponding changes were also observed when silencing miR-21 expression, which was impeded by preconditioning with TLR4 antibody or PDTC. CONCLUSIONS: Taken together, these results corroborated that miR-21 could negatively regulate LPS-induced lipid accumulation and inflammatory responses in macrophages by the TLR4-NF-κB pathway. Accordingly, our research will provide a prominent insight into how miR-21 reversely abrogates bacterial infection-induced pathological processes of atherosclerosis, indicating a promising therapeutic prospect for the prevention and treatment of atherosclerosis by miR-21 overexpression.

Regulation of N-methyl-D-aspartate receptor subunit expression in the fetal guinea pig brain.

N-methyl-d-aspartate receptors (NMDARs) are critical for neuronal maturation and synaptic formation as well as for the onset of long-term potentiation, a process critical to learning and memory in postnatal life. In the current study, we demonstrated that NMDAR subunits undergo spatial, temporal, and sex-specific regulation. During development, we observed increasing NR1 and NR2A expression at the same time as levels of NR2B subunits decreased in the hippocampus and cortex in the fetal guinea pig. We have also shown that glucocorticoids can modulate fetal NMDAR subunit expression in a sex-specific fashion. This is clinically important because synthetic glucocorticoids are administered to pregnant women at risk of preterm labor. Repeated exposure to exogenous glucocorticoids caused a dose-dependent decrease in NR1 mRNA levels and increased NR2A mRNA expression in the female hippocampus at Gestational Day 62. There are significant changes in NMDAR subunit expression in late gestation. It is possible that these alter NMDA-dependent signaling at this time. Prenatal exposure to exogenous glucocorticoids modifies the trajectory of NMDAR subunit expression in females but not in males.