Eleutherococcus sessiliflorus Inhibits Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)-Induced Osteoclast Differentiation and Prevents Ovariectomy (OVX)-Induced Bone Loss

The aim of this study was to evaluate the effects of root bark of Eleutherococcus sessiliflorus (ES) on osteoclast differentiation and function in vitro and in vivo. In vitro, we found that ES significantly inhibited the RANKL-induced formation of TRAP-positive multinucleated osteoclasts and osteoclastic bone resorption without cytotoxic effects. ES markedly downregulated the expression of nuclear factor of activated T cells cytoplasmic 1 (NFATc1); c-Fos; and osteoclast-related marker genes, such as TRAP, osteoclast-associated receptor (OSCAR), matrix metalloproteinase-9 (MMP-9), calcitonin receptor, cathepsin K, the 38 kDa d2 subunit of the vacuolar H⁺-transporting lysosomal ATPase (Atp6v0d2), dendritic cell-specific transmembrane protein (DC-STAMP), and osteoclast-stimulatory transmembrane protein (OC-STAMP). These effects were achieved by inhibiting the RANKL-mediated activation of MAPK signaling pathway proteins, including p38, ERK, and JNK. In vivo, ES attenuated OVX-induced decrease in bone volume to tissue volume ratio (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), and bone mineral density, but increased trabecular separation (Tb.Sp) in the femur. Collectively, our findings showed that ES inhibited RANKL-activated osteoclast differentiation in bone marrow macrophages and prevented OVX-mediated bone loss in rats. These findings suggest that ES has the potential to be used as a therapeutic agent for bone-related diseases, such as osteoporosis.     

Rapid Clearance of IR783 and Methyl-β-cyclodextrin Complex for Improved Tumor Imaging

Near-infrared (NIR) fluorescence cancer imaging with targeted NIR fluorophores holds considerable promise for accurate detection and cancer diagnosis. Among the various NIR heptamethine cyanine dyes reported previously, IR783 as a single small molecule has been widely used for tumor-targeted imaging without the additional conjugation of targeting moieties. Despite the potential advantages of IR783, the major problems, such as its non-specific uptake in normal tissues/organs and slow clearance, remain to be solved. A key determinant of sensitivity and detectability in tumor imaging is the improvement of the tumor-to-background ratio (TBR). Herein, a simple and effective supramolecular complex self-assembled from IR783 and methyl-β-cyclodextrin is developed to improve tumor imaging accompanied by rapid clearance from the body. The IR783-cyclodextrin complex allowed for rapid whole body biodistribution, which remarkably reduced non-specific background uptake, and thus increased the TBR value within 24 h post-injection. Therefore, this strategy is applicable in combination with many different types of carbocyanine dyes for improved tumor imaging.     

Solving the deterministic and stochastic uncapacitated facility location problem: from a heuristic to a simheuristic

The uncapacitated facility location problem (UFLP) is a popular combinatorial optimization problem with practical applications in different areas, from logistics to telecommunication networks. While most of the existing work in the literature focuses on minimizing total cost for the deterministic version of the problem, some degree of uncertainty (e.g., in the customers’ demands or in the service costs) should be expected in real-life applications. Accordingly, this paper proposes a simheuristic algorithm for solving the stochastic UFLP (SUFLP), where optimization goals other than the minimum expected cost can be considered. The development of this simheuristic is structured in three stages: (i) first, an extremely fast savings-based heuristic is introduced; (ii) next, the heuristic is integrated into a metaheuristic framework, and the resulting algorithm is tested against the optimal values for the UFLP; and (iii) finally, the algorithm is extended by integrating it with simulation techniques, and the resulting simheuristic is employed to solve the SUFLP. Some numerical experiments contribute to illustrate the potential uses of each of these solving methods, depending on the version of the problem (deterministic or stochastic) as well as on whether or not a real-time solution is required.     

Phase-sensitive recombination of two bose-einstein condensates on an atom chip

The recombination of two split Bose-Einstein condensates on an atom chip is shown to result in heating which depends on the relative phase of the two condensates. This heating reduces the number of condensate atoms between 10% and 40% and provides a robust way to read out the phase of an atom interferometer without the need for ballistic expansion. The heating may be caused by the dissipation of dark solitons created during the merging of the condensates.     

Long phase coherence time and number squeezing of two Bose-Einstein condensates on an atom chip

We measure the relative phase of two Bose-Einstein condensates confined in a radio frequency induced double-well potential on an atom chip. We observe phase coherence between the separated condensates for times up to approximately 200 ms after splitting, a factor of 10 longer than the phase diffusion time expected for a coherent state for our experimental conditions. The enhanced coherence time is attributed to number squeezing of the initial state by a factor of 10. In addition, we demonstrate a rotationally sensitive (Sagnac) geometry for a guided atom interferometer by propagating the split condensates.     

A model of the early mineralization process of mantle dentin

The aim of this study was to investigate the relationship between proteoglycans (PGs) and collagen fibrils at the early mineralization process of mantle dentin. Ten first molar dental germs of rats were removed and fixed in glutaraldehyde/formaldehyde in cacodylate buffer and post-fixed in osmium tetroxide. The samples were dehydrated and embedded in epoxy resin. Ultrathin sections were contrasted and analyzed in TEM before and after treatment with EDTA, chondroitinases AC and ABC. After EDTA treatment, a electrondense substance associated with collagen fibril was removed, and did not stain again. A high magnification of these areas showed globular structures with 15 nm diameter surrounding collagen fibrils. In advanced mineralization areas, collagen fibrils showed a banded pattern and at high magnification the fibrils presented a light 10 nm ring inside and a dark 10 nm ring outside. After chondroitinase treatment, the electrondense substance associated with collagen fibrils was removed, showing a banded pattern of clear and dark areas along them. From morphological data, the authors proposed a model of interaction between PGs and collagen fibrils, where glicosaminoglycans chains are inside the fibrils, while the protein core remains outside. That stereochemical arrangement would start the crystal nucleation.     

3alpha,4alpha-Epoxy-2-piperidone, a new minor derivative from leaves of Piper crassinervium Kunth (Piperaceae)

A new antifungal piperidone derivative 3alpha,4alpha-epoxy-2-piperidone, whose structure was determined by spectroscopic methods, was isolated from the MeOH extract from leaves of Piper crassinervium. This is the first occurrence of one amide in P. crassinervium.     

Synthesis and biological evaluation of potential bisubstrate inhibitors of protein farnesyltransferase. Design and synthesis of functionalized imidazoles

A novel series of compounds, derived from 2,5-functionalized imidazoles, have been synthesized as potential bisubstrate inhibitors of protein farnesyltransferase (FTase) using structure-based design. These compounds have a 1,4-diacid chain and a tripeptide connected by an imidazole ring. The synthetic strategy relies on the functionalization at the C-2 position of the heterocycle with the diacid side chain and peptide coupling at the C-5 position. Several new compounds were synthesized in good yields. Kinetic experiments on the most active compounds revealed different binding modes depending on the diacid chain length.     

Combination of COFRADIC and high temperature-extended column length conventional liquid chromatography: a very efficient way to tackle complex protein samples, such as serum

The previously reported COmbined FRActional DIagonal Chromatography (COFRA-DIC) methodology, in which a subset of peptides representative for their parent proteins are sorted, is particularly powerful for whole proteome analysis. This peptide-centric technology is built around diagonal chromatography, where peptide separations are crucial. This paper presents high efficiency peptide separations, in which four 250 x 2.1 mm, 5 microm Zorbax 300SB-C18 columns (total length 1 m) were coupled at operating temperatures of 60'C using a dedicated LC oven and conventional LC equipment. The high efficiency separations were combined with the COFRADIC procedure. This extremely powerful combination resulted, for the analysis of serum, in an increase in the uniquely identified peptide sequences by a factor of 2.6, compared to the COFRADIC procedure on a 25 cm column. This is a reflection of the increased peak capacity obtained on the 1 m column, which was calculated to be a factor 2.7 higher than on the 25 cm column. Besides more efficient sorting, less ion suppression was noticed.