Associations of plasma very-long-chain SFA and the metabolic syndrome in adults

Plasma levels of very-long-chain SFA (VLCSFA) are associated with the metabolic syndrome (MetS). However, the associations may vary by different biological activities of individual VLCSFA or population characteristics. We aimed to examine the associations of VLCSFA and MetS risk in Chinese adults. Totally, 2008 Chinese population aged 35–59 years were recruited and followed up from 2010 to 2012. Baseline MetS status and plasma fatty acids data were available for 1729 individuals without serious diseases. Among 899 initially metabolically healthy individuals, we identified 212 incident MetS during the follow-up. Logistic regression analysis was used to estimate OR and 95 % CI. Cross-sectionally, each VLCSFA was inversely associated with MetS risk; comparing with the lowest quartile, the multivariate-adjusted OR for the highest quartile were 0·18 (95 % CI 0·13, 0·25) for C20 : 0, 0·26 (95 % CI 0·18, 0·35) for C22 : 0, 0·19 (95 % CI 0·13, 0·26) for C24 : 0 and 0·16 (0·11, 0·22) for total VLCSFA (all Pfor trend<0·001). The associations remained significant after further adjusting for C16 : 0, C18 : 0, C18 : 3n-3, C22 : 6n-3, n-6 PUFA and MUFA, respectively. Based on follow-up data, C20 : 0 or C22 : 0 was also inversely associated with incident MetS risk. Among the five individual MetS components, higher levels of VLCSFA were most strongly inversely associated with elevated TAG (≥1·7 mmol/l). Plasma levels of VLCSFA were significantly and inversely associated with MetS risk and individual MetS components, especially TAG. Further studies are warranted to confirm the findings and explore underlying mechanisms

One-Shot Full-Range Quantification of Multi-Biomarkers With Different Abundance by a Tandem Giant Magnetoresistance Assay

In this study, we reported a tandem giant magnetoresistance (GMR) assay that realized the one-shot quantification of multi-biomarkers of infection, C-reactive protein (CRP) with procalcitonin (PCT), and neutrophil gelatinase-associated lipocalin (NGAL), all of which could cover their clinically relevant concentration ranges under a different principle. In the presence of co-determined assay, we quantified these three biomarkers in undiluted human blood serum in a single test. The tandem principle, based on which quantification of CRP occurs, combines a sandwich assay and an indirect competitive assay, which allows for the discrimination of the concentration values resulting from the multivalued dose-response curve (\u27Hook\u27 effect), which characterizes the one-step sandwich assay at high CRP concentrations. However, the entire diagnostically dynamic range, in the quantification of PCT and NGAL, was achieved by differential coating of two identical GMR sensors operated in tandem and by combining two standard curves. The sensor quantified low detection limits and a broader dynamic range for the detection of infection biomarkers. The noticeable features of the assay are its dynamic range and small sample volume requirement (50 mu L), and the need for a short measurement time of 15 min. These figures of merit render it a prospective candidate for practical use in point-of-care analysis

Seismic Azimuthal Anisotropy Beneath the Eastern United States and its Geodynamic Implications

Systematic spatial variations of anisotropic characteristics are revealed beneath the eastern U.S. using seismic data recorded between 1988 and 2016 by 785 stations. The resulting fast polarization orientations of the 5613 measurements are generally subparallel to the absolute plate motion (APM) and are inconsistent with the strike of major tectonic features. This inconsistency, together with the results of depth estimation using the spatial coherency of the splitting parameters, suggests a mostly asthenospheric origin of the observed azimuthal anisotropy. The observations can be explained by a combined effect of APM-induced mantle fabric and a flow system deflected horizontally around the edges of the keel of the North American continent. Beneath the southern and northeastern portions of the study area, the E-W keel-deflected flow enhances APM-induced fabric and produces mostly E-W fast orientations with large splitting times, while beneath the southeastern U.S., anisotropy from the N-S oriented flow is weakened by the APM

Dynamic Range Expansion of the C-Reactive Protein Quantification with a Tandem Giant Magnetoresistance Biosensor

In this study, we report a convenient analytical method for a full-range quantification of the C-reactive protein (CRP), a blood biomarker of infection and cardiovascular events. We determine CRP over the entire diagnostically relevant concentration range in undiluted human blood serum in a single test, using a tandem giant magnetoresistance (GMR) sensor. The tandem principle combines a sandwich assay and a competitive assay, which allows for the discrimination of the concentration values resulting from the multivalued dose-response curve ("Hook"effect), which characterizes the one-step sandwich assay at high CRP concentrations. The sensor covers a linear detection range for CRP concentration from 3 ng/mL to 350 μg/mL, the detection limit (s/n = 3) is 1 ng/mL. The prominent features of the chip-based method are its expanded dynamic range and low sample volume (50 μL), and the need for a short measurement time of 15 min. These figures of merit, in addition to the low detection limit equal to the established assay instrumentation, make it a viable candidate for use in point-of-care diagnostics

Silicon-based Integrated Microarray Biochips for Biosensing and Biodetection Applications

The silicon-based integrated microarray biochip (IMB) is an inter-disciplinary research direction of microelectronics and biological science. It has caught the attention of both industry and academia, in applications such as deoxyribonucleic acid (DNA) and immunological detection, medical inspection and point-of-care (PoC) diagnosis, as well as food safety and environmental surveillance. Future biodetection strategies demand biochips with high sensitivity, miniaturization, integration, parallel, multi-target and even intelligence capabilities. In this chapter, a comprehensive investigation of current research on state-of-the-art silicon-based integrated microarray biochips is presented. These include the electrochemical biochip, magnetic tunnelling junction (MTJ) based biochip, giant magnetoresistance (GMR) biochip and integrated oscillator-based biochip. The principles, methodologies and challenges of the aforementioned biochips will also be discussed and compared from all aspects, e.g., sensitivity, fabrication complexity and cost, compatibility with silicon-based complementary metal-oxide-semiconductor (CMOS) technology, multi-target detection capabilities, signal processing and system integrations, etc. In this way, we discuss future silicon-based fully integrated biochips, which could be used for portable medical detection and low cost PoC diagnosis applications

A tandem giant magnetoresistance assay for one-shot quantification of clinically relevant concentrations of N-terminal pro-B-type natriuretic peptide in human blood

We report a microfluidic sandwich immunoassay constructed around a dual-giant magnetoresistance (GMR) sensor array to quantify the heart failure biomarker NT-proBNP in human plasma at the clinically relevant concentration levels between 15\ua0pg/mL and 40\ua0ng/mL. The broad dynamic range was achieved by differential coating of two identical GMR sensors operated in tandem, and combining two standard curves. The detection limit was determined as 5\ua0pg/mL. The assay, involving 53 plasma samples from patients with different cardiovascular diseases, was validated against the Roche Cobas e411 analyzer. The salient features of this system are its wide concentration range, low detection limit, small sample volume requirement (50\ua0μL), and the need for a short measurement time of 15\ua0min, making it a prospective candidate for practical use in point of care analysis

Structural Analysis of Alkaline β-Mannanase from Alkaliphilic Bacillus sp. N16-5: Implications for Adaptation to Alkaline Conditions

Significant progress has been made in isolating novel alkaline β-mannanases, however, there is a paucity of information concerning the structural basis for alkaline tolerance displayed by these β-mannanases. We report the catalytic domain structure of an industrially important β-mannanase from the alkaliphilic Bacillus sp. N16-5 (BSP165 MAN) at a resolution of 1.6 Å. This enzyme, classified into subfamily 8 in glycosyl hydrolase family 5 (GH5), has a pH optimum of enzymatic activity at pH 9.5 and folds into a classic (β/α)8-barrel. In order to gain insight into molecular features for alkaline adaptation, we compared BSP165 MAN with previously reported GH5 β-mannanases. It was revealed that BSP165 MAN and other subfamily 8 β-mannanases have significantly increased hydrophobic and Arg residues content and decreased polar residues, comparing to β-mannanases of subfamily 7 or 10 in GH5 which display optimum activities at lower pH. Further, extensive structural comparisons show alkaline β-mannanases possess a set of distinctive features. Position and length of some helices, strands and loops of the TIM barrel structures are changed, which contributes, to a certain degree, to the distinctly different shaped (β/α)8-barrels, thus affecting the catalytic environment of these enzymes. The number of negatively charged residues is increased on the molecular surface, and fewer polar residues are exposed to the solvent. Two amino acid substitutions in the vicinity of the acid/base catalyst were proposed to be possibly responsible for the variation in pH optimum of these homologous enzymes in subfamily 8 of GH5, identified by sequence homology analysis and pKa calculations of the active site residues. Mutational analysis has proved that Gln91 and Glu226 are important for BSP165 MAN to function at high pH. These findings are proposed to be possible factors implicated in the alkaline adaptation of GH5 β-mannanases and will help to further understanding of alkaline adaptation mechanism

Aptamer nucleotide analog drug conjugates in the targeting therapy of cancers

Aptamers are short single-strand oligonucleotides that can form secondary and tertiary structures, fitting targets with high affinity and specificity. They are so-called “chemical antibodies” and can target specific biomarkers in both diagnostic and therapeutic applications. Systematic evolution of ligands by exponential enrichment (SELEX) is usually used for the enrichment and selection of aptamers, and the targets could be metal ions, small molecules, nucleotides, proteins, cells, or even tissues or organs. Due to the high specificity and distinctive binding affinity of aptamers, aptamer–drug conjugates (ApDCs) have demonstrated their potential role in drug delivery for cancer-targeting therapies. Compared with antibodies which are produced by a cell-based bioreactor, aptamers are chemically synthesized molecules that can be easily conjugated to drugs and modified; however, the conventional ApDCs conjugate the aptamer with an active drug using a linker which may add more concerns to the stability of the ApDC, the drug-releasing efficiency, and the drug-loading capacity. The function of aptamer in conventional ApDC is just as a targeting moiety which could not fully perform the advantages of aptamers. To address these drawbacks, scientists have started using active nucleotide analogs as the cargoes of ApDCs, such as clofarabine, ara-guanosine, gemcitabine, and floxuridine, to replace all or part of the natural nucleotides in aptamer sequences. In turn, these new types of ApDCs, aptamer nucleotide analog drug conjugates, show the strength for targeting efficacy but avoid the complex drug linker designation and improve the synthetic efficiency. More importantly, these classic nucleotide analog drugs have been used for many years, and aptamer nucleotide analog drug conjugates would not increase any unknown druggability risk but improve the target tumor accumulation. In this review, we mainly summarized aptamer-conjugated nucleotide analog drugs in cancer-targeting therapies

Live cell imaging of DNA and RNA with fluorescent signal amplification and background reduction techniques

Illuminating DNA and RNA dynamics in live cell can elucidate their life cycle and related biochemical activities. Various protocols have been developed for labeling the regions of interest in DNA and RNA molecules with different types of fluorescent probes. For example, CRISPR-based techniques have been extensively used for imaging genomic loci. However, some DNA and RNA molecules can still be difficult to tag and observe dynamically, such as genomic loci in non-repetitive regions. In this review, we will discuss the toolbox of techniques and methodologies that have been developed for imaging DNA and RNA. We will also introduce optimized systems that provide enhanced signal intensity or low background fluorescence for those difficult-to-tag molecules. These strategies can provide new insights for researchers when designing and using techniques to visualize DNA or RNA molecules