2-(4-Bromo­phen­yl)quinoxaline

In the title compound, C14H9BrN2, the benzene and quinoxaline rings are almost coplanar [r.m.s. deviation = 0.0285 (3) Å and dihedral angle = 2.1 (2)°]

HSF-1 attenuates isoflurane-induced cognitive dysfunction by inhibiting TLR2 expression

Purpose: To investigate the regulatory effects of heat shock factor 1 (HSF-1) in the progression of postoperative cognitive dysfunction (POCD). Methods: Isoflurane (ISO)-induced POCD model in rats was established to determine the role of HSF-1 in POCD. Morris water maze test was used to evaluate the learning and memory abilities of the POCD rats while mRNA and protein levels of HSF-1 were determined by RNA extraction/quantitative real-time polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. Results: The mRNA and protein levels of HSF-1 were significantly reduced in ISO model, but OE-HSF-1 treatment significantly elevated HSF-1 level (p < 0.05). ISO treatment also significantly decreased escape latency but increased the decreased target quadrant of the rats, while HSF-1 upregulation reversed these effects (p < 0.05). Additionally, HSF-1 alleviated ISO-induced hippocampal injury, improved ISO-induced hippocampal inflammation, and inhibited ISO-induced hippocampal apoptosis. Furthermore, HSF-1 was modulated by POCD via TLR2/NF-κB pathway (p < 0.05). Conclusion: HSF-1 attenuates ISO-induced cognitive dysfunction by suppressing TLR2 expression. This activity provides a potential strategy to prevent POCD via HSF-1

Potential Metabolite Markers of Schizophrenia

Schizophrenia is a severe mental disorder that affects 0.5–1% of the population worldwide. Current diagnostic methods are based on psychiatric interviews, which are subjective in nature. The lack of disease biomarkers to support objective laboratory tests has been a long-standing bottleneck in the clinical diagnosis and evaluation of schizophrenia. Here we report a global metabolic profiling study involving 112 schizophrenic patients and 110 healthy subjects, who were divided into a training set and a test set, designed to identify metabolite markers. A panel of serum markers consisting of glycerate, eicosenoic acid, ß-hydroxybutyrate, pyruvate and cystine was identified as an effective diagnostic tool, achieving an area under the receiver operating characteristic curve (AUC) of 0.945 in the training samples (62 patients and 62 controls) and 0.895 in the test samples (50 patients and 48 controls). Furthermore, a composite panel by the addition of urine ß-hydroxybutyrate to the serum panel achieved a more satisfactory accuracy, which reached an AUC of 1 in both the training set and the test set. Multiple fatty acids and ketone bodies were found significantly (P<0.01) elevated in both the serum and urine of patients, suggesting an upregulated fatty acid catabolism, presumably resulting from an insufficiency of glucose supply in the brains of schizophrenia patients

An Optimized Procedure for Metabonomic Analysis of Rat Liver Tissue Using Gas Chromatography/Time-of-Flight Mass Spectrometry

In this paper, we present a tissue metabonomic method with an optimized extraction procedure followed by instrumental analysis with gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) and spectral data analysis with multivariate statistics. Metabolite extractions were carried out using three solvents: chloroform, methanol, and water, with design of experiment (DOE) theory and multivariate statistical analysis. A two-step metabolite extraction procedure was optimized using a mixed solvent of chloroform–methanol–water (1:2:1, v/v/v) and then followed by methanol alone. This approach was subsequently validated using standard compounds and liver tissues. Calibration curves were obtained in the range of 0.50–125.0 µg/mL for standards and 0.02–0.25 g/mL acceptable for liver tissue samples. For most of the metabolites investigated, relative standard deviations (RSD) were below 10% within a day (reproducibility) and below 15% within a week (stability). Rat liver tissues of carbon tetrachloride-induced acute liver injury models (n = 10) and healthy control rats (n = 10) were analyzed which demonstrated the applicability of the developed procedure for the tissue metabonomic study

GC/MS-Based Urinary Metabolomics Reveals Systematic Differences in Metabolism and Ethanol Response between Sprague–Dawley and Wistar Rats

Metabolic differences of experimental animals contribute to pharmacological variations. Sprague–Dawley (SD) and Wistar rats are commonly used experimental rats with similar genetic background, and considered interchangeable in practical researches. In this study, we present the urinary metabolomics results, based on gas chromatography coupled to mass spectrometry (GC/MS), which reveal the systematic metabolic differences between SD and Wistar rats under different perturbations such as fasting, feeding, and consecutive acute ethanol interventions. The different metabotypes between the two strains of rats involve a number of metabolic pathways and symbiotic gut microflora. SD rats exhibited higher individualized metabolic variations in the fasting and feeding states, and a stronger ability to recover from an altered metabolic profile with less hepatic injury from the consecutive ethanol exposure, as compared to Wistar rats. In summary, the GC/MS-based urinary metabolomics studies demonstrated an intrinsic metabolic difference between SD and Wistar rats, which warrants consideration in experimental design using these animal strains

An Ultrasonication-Assisted Extraction and Derivatization Protocol for GC/TOFMS-Based Metabolite Profiling

Conventional chemical derivatization of metabolites in biological specimens is time-consuming, which limits the throughput and efficiency of metabolite profiling using a gas chromatography/time-of-flight mass spectrometry (GC/TOFMS) platform. We report an ultrasonication-assisted protocol which reduces the derivatization time from hours to about 30 min and significantly enhances the derivatization efficiency prior to a GC/TOFMS analysis. The protocol was evaluated using 40 compounds representing different classes of human metabolites, and demonstrated good analytical precision and accuracy. In comparison with the conventional method, the new protocol was able to increase the intensity of most of the identified peaks (71.0%) in the GC/TOFMS chromatograms of human serum samples. The detected compounds with increased intensity include most amino acids, keto-containing organic acids, carbonyl-containing carbohydrates, and unsaturated fatty acids. We applied this protocol in a metabolomic study of human serum samples obtained from 34 patients diagnosed with hypertension and 29 age- and gender-matched healthy subjects. Metabolite markers associated with hypertension, including glucosamine, D-sorbitol, 1-stearoylglycerol, and homocysteine, were identified and validated by statistical methods and use of reference standards. Our work highlights the potential of this novel approach for the large-scale metabolite profiling of samples generated from plant, animal, and clinical and epidemiological studies

Fibre tapering using plasmonic microheaters and deformation-induced pull

Optical fibres with diameters at micro- or sub-micrometre scale are widely adopted as a convenient tool for studying light–matter interactions. To prepare such devices, two elements are indispensable: a heat source and a pulling force. In this paper, we report a novel fibre-tapering technique in which micro-sized plasmonic heaters and elaborately deformed optical fibres are compactly combined, free of flame and bulky pulling elements. Using this technique, micro-nano fibres with abrupt taper and ultra-short transition regions were successfully fabricated, which would otherwise be a challenge for traditional techniques. The compactness of the proposed system enabled it to be further transferred to a scanning electron microscope for in-situ monitoring of the tapering process. The essential dynamics of “heat and pull” was directly visualised with nanometre precision in real time and theoretically interpreted, thereby establishing an example for future in-situ observations of micro and nanoscale light-matter interactions

Inhibition of SREBP by a Small Molecule, Betulin, Improves Hyperlipidemia and Insulin Resistance and Reduces Atherosclerotic Plaques

SummarySterol regulatory element-binding proteins (SREBPs) are major transcription factors activating the expression of genes involved in biosynthesis of cholesterol, fatty acid and triglyceride. In this study, we identified a small molecule, betulin, that specifically inhibited the maturation of SREBP by inducing interaction of SREBP cleavage activating protein (SCAP) and Insig. Inhibition of SREBP by betulin decreased the biosynthesis of cholesterol and fatty acid. In vivo, betulin ameliorated diet-induced obesity, decreased the lipid contents in serum and tissues, and increased insulin sensitivity. Furthermore, betulin reduced the size and improved the stability of atherosclerotic plaques. Our study demonstrates that inhibition SREBP pathway can be employed as a therapeutic strategy to treat metabolic diseases including type II diabetes and atherosclerosis. Betulin, which is abundant in birch bark, could be a leading compound for development of drugs for hyperlipidemia