NextOne Player: A Music Recommendation System Based on User Behavior.

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Functional characterization of breast cancer using pathway profiles

BACKGROUND: The molecular characteristics of human diseases are often represented by a list of genes termed “signature genes”. A significant challenge facing this approach is that of reproducibility: signatures developed on a set of patients may fail to perform well on different sets of patients. As diseases are resulted from perturbed cellular functions, irrespective of the particular genes that contribute to the function, it may be more appropriate to characterize diseases based on these perturbed cellular functions. METHODS: We proposed a profile-based approach to characterize a disease using a binary vector whose elements indicate whether a given function is perturbed based on the enrichment analysis of expression data between normal and tumor tissues. Using breast cancer and its four primary clinically relevant subtypes as examples, this approach is evaluated based on the reproducibility, accuracy and resolution of the resulting pathway profiles. RESULTS: Pathway profiles for breast cancer and its subtypes are constructed based on data obtained from microarray and RNA-Seq data sets provided by The Cancer Genome Atlas (TCGA), and an additional microarray data set provided by The European Genome-phenome Archive (EGA). An average reproducibility of 68% is achieved between different data sets (TCGA microarray vs. EGA microarray data) and 67% average reproducibility is achieved between different technologies (TCGA microarray vs. TCGA RNA-Seq data). Among the enriched pathways, 74% of them are known to be associated with breast cancer or other cancers. About 40% of the identified pathways are enriched in all four subtypes, with 4, 2, 4, and 7 pathways enriched only in luminal A, luminal B, triple-negative, and HER2+ subtypes, respectively. Comparison of profiles between subtypes, as well as other diseases, shows that luminal A and luminal B subtypes are more similar to the HER2+ subtype than to the triple-negative subtype, and subtypes of breast cancer are more likely to be closer to each other than to other diseases. CONCLUSIONS: Our results demonstrate that pathway profiles can successfully characterize both common and distinct functional characteristics of four subtypes of breast cancer and other related diseases, with acceptable reproducibility, high accuracy and reasonable resolution

Mechanically manipulating glymphatic transport by ultrasound combined with microbubbles

The glymphatic system is a perivascular fluid transport system for waste clearance. Glymphatic transport is believed to be driven by the perivascular pumping effect created by the pulsation of the arterial wall caused by the cardiac cycle. Ultrasound sonication of circulating microbubbles (MBs) in the cerebral vasculature induces volumetric expansion and contraction of MBs that push and pull on the vessel wall to generate a MB pumping effect. The objective of this study was to evaluate whether glymphatic transport can be mechanically manipulated by focused ultrasound (FUS) sonication of MBs. The glymphatic pathway in intact mouse brains was studied using intranasal administration of fluorescently labeled albumin as fluid tracers, followed by FUS sonication at a deep brain target (thalamus) in the presence of intravenously injected MBs. Intracisternal magna injection, the conventional technique used in studying glymphatic transport, was employed to provide a comparative reference. Three-dimensional confocal microscopy imaging of optically cleared brain tissue revealed that FUS sonication enhanced the transport of fluorescently labeled albumin tracer in the perivascular space (PVS) along microvessels, primarily the arterioles. We also obtained evidence of FUS-enhanced penetration of the albumin tracer from the PVS into the interstitial space. This study revealed that ultrasound combined with circulating MBs could mechanically enhance glymphatic transport in the brain

Chemo-enzymatic synthesis of Neu5Gc-containing sialylated lactulose

Purpose: To synthesize novel sialylated lactuloses, namely, Neu5Gc-α2,3-lactulose and Neu5Gc-α2,6-lactulose.Methods: ManNGc was chemically synthesized from commercially available N-acetylmannosaime (ManNAc), which was used as the donor substrate to synthesize α-(2→3) linkage and α-(2→6) linkage sialyllactulose from lactulose via sialyltransferases-catalyzed one-pot multienzyme (OPME) approach. The sialylated products were purified by silica gel flash chromatography column. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) were used to confirm the purity and characterize the structure of the new compounds.Results: Sialyllactulose with α-(2→3) linkage (Neu5Gc-α2,3-lactulose) and α-(2→6) linkage (Neu5Gc- α2,6-lactulose) were efficiently synthesized by an efficient one-pot multienzyme sialylation approach from ManNGc, sodium pyruvate, CTP, and lactulose. The molecular weight of the two products, based on mass spectral data was 648 Da while NMR data indicated the formation of sialylated glycans.Conclusion: Novel sialylated oligosaccharides have been efficiently synthesized from lactulose using highly efficient OPME sialylation approaches. Further investigations are required to ascertain the probiotic activities for possible applications in pharmaceutical and food industries.Keywords: Neu5Gc, Chemo-enzymatic synthesis, Sialylation, Sialyllactulose, Lactulos

Effect of hydrogen sulfide on PC12 cell injury induced by high ATP concentration

Purpose: To investigate the potential protective effect of hydrogen sulfide against neural cell damage induced by a high-concentration of adenosine triphosphate (ATP).Methods: PC12 cells were incubated with ATP in order to induce cell damage. The extracellular level of H2S and protein expression of cystathionine-β-synthase (CBS) were determined. The PC12 cells pretreated with NaHS, aminooxyacetic acid (AOAA) and KN-62, prior to further incubation with ATP, and the effect of the treatments on cell viability was investigated.Results: High-concentration ATP induced cell death in PC12 cells, and this was accompanied by markedly increased contents of extracellular H2S and CBS expression (p < 0.05). The ATP-induced cytotoxicity was significantly compromised after pretreatment with H2S. (p < 0.05). The viability of PC12 cells pretreated with NaHS and AOAA was significantly higher than that of PC12 cells treated with ATP alone. In addition, the viability of ATP-treated PC12 cells was further markedly increased after pretreatment with NaHS and KN-62 (p < 0.05).Conclusion: ATP induced a concentration- and time-dependent cytotoxicity in PC12 cells via theendogenous H2S/CBS system. Supplementation with exogenous H2S mitigated the cell damageinduced by high concentration of ATP via a specific mechanism which may be specifically related to P2X7R

Metabolic Profiling of Pleurotus tuoliensis During Mycelium Physiological Maturation and Exploration on a Potential Indicator of Mycelial Maturation

Pleurotus tuoliensis is a valuable and rare edible fungus with extremely high nutritional and medicinal value. However, the relative immaturity of P. tuoliensis cultivation technology leads to fluctuating yields and quality. The main difficulty in P. tuoliensis cultivation is estimate of mycelial maturity. There is currently no measurable indicator that clearly characterizes the physiological maturation of mycelia. The aim of this study was to identify potential indicators of physiological maturation for P. tuoliensis mycelia by using metabolomics approach. A metabolite profiling strategy involving gas chromatography-mass spectrometry (GC/MS) was used to analyze changes to extracellular metabolites in mycelia collected at mycelium physiological maturation period (MPMP) day 0, MPMP day 35 at 17°C and MPMP day 35 at 29°C. 72 differential metabolites (37.8% up-regulated and 62.2% down-regulated) were identified based on the selected criteria [variable important in projection (VIP) greater than 1.0 and p < 0.01]. Metabolic pathways enrichment analysis showed that these metabolites are involved in glycolysis, organic acid metabolism, amino acid metabolism, tricarboxylic acid cycle (TCA), sugar metabolism, nicotinate and nicotinamide metabolism, and oxidative phosphorylation. In addition, the pyrimidine synthesis pathway was significantly activated during mycelium physiological maturation of P. tuoliensis. The abundance of N-carbamoyl-L-aspartate (CA-asp), a component of this pathway, was significantly increased at MPMP day 35, which motivated us to explore its potential as an indicator for physiological maturation of mycelia. The content of CA-asp in mycelia changed in a consistent manner during physiological maturation. The feasibility of using CA-asp as an indicator for mycelial maturation requires further investigation

The impact of electron anisotropy on the polarization of the X-ray emission from black hole accretion disks and implications for the black hole X-ray binary 4U 1630-47

The Imaging X-ray Polarimetry Explorer (IXPE) observations of the X-ray binary 4U 1630-47 in the high soft state revealed linear polarization degrees (PDs) rising from 6% at 2 keV to 10% at 8 keV. Explaining the results in the framework of the standard optically thick, geometrically thin accretion disk scenario requires careful fine-tuning of the relevant model parameters. We argue here that the emission of polarized Bremsstrahlung by anisotropic electrons in the accretion disk atmosphere can account for the overall high PDs and the increase of the PDs with energy. We discuss plasma and accretion effects that can generate electron anisotropies at a level required by the 4U 1630-47 results. We conclude by emphasizing that X-ray polarimetry affords us the opportunity to obtain information about the magnetization of the accretion disk atmosphere.Comment: 8 pages and 6 figures, submitted to the Astrophysical Journal Letter

Large-scale synthesis of high moment FeCo nanoparticles using modified polyol synthesis

Binary alloys of Fe and Co have among the highest magnetizations of any transition metal alloy systems, but their affinity to form oxides act to reduce the magnetization of nanoparticles as their size is reduced below ∼30 nm. Here, we demonstrate the synthesis of single phase, size-controlled FeCo nanoparticles having magnetization greater than 200 emu/g via a non-aqueous method in which ethylene glycol served as solvent and reducing agent as well as surfactant. Experiments indicated pure-phase FeCo nanoparticles, having saturationmagnetization up to 221 emu/g for sizes of 20–30 nm, in single batch processes resulting in \u3e 2 g/batch. Post-synthesis oxidation of nanoparticles was investigated until very stable nanoparticles were realized with constant magnetization over time