As new biomarkers of coronary artery diseases (CAD) emerge via metabolomics, the underlying functional mechanisms remain to be elucidated. Functional metabolomics aims to translate ...metabolomics-derived biomarkers to disease mechanisms.
A cohort of 2324 patients who underwent coronary angiography from 4 independent centers was studied. A combination of ultra-performance liquid chromatography and quadrupole time-of-flight mass spectrometry in the negative ion mode was used for untargeted analysis of metabolites in plasma. Significant differential metabolites were identified by cross-comparisons with and within CAD types, including normal coronary artery, nonobstructvie coronary atherosclerosis, stable angina, unstable angina, and acute myocardial infarction. A tandem liquid chromatography-mass spectrometry-based approach using isotope-labeled standard addition was subsequently performed for targeted analysis of the metabolic marker
-acetylneuraminic acid (Neu5Ac). A functional metabolomics strategy was proposed to investigate the role of Neu5Ac in the progression of CAD by using in vitro and in vivo models.
We identified a total of 36 differential metabolites, 35 of which were confirmed with reference compounds. Elevation of Neu5Ac was observed in plasma during CAD progression in center 1 (
=4.0e-64, n=2019) and replicated in 3 independent centers (n=305). The increased level of Neu5Ac in plasma was confirmed by accurate targeted quantification. Mechanistically, Neu5Ac was able to trigger myocardial injury in vitro and in vivo by activation of the Rho/Rho-associated coiled-coil containing protein kinase signaling pathway through binding to RhoA and Cdc42, but not Rac1. Silencing neuraminidase-1, the enzyme that regulates Neu5Ac generation, ameliorated oxygen-glucose deprivation-induced injury in cardiomyocytes and ligation/isoprenaline-induced myocardial ischemia injury in rats. Pharmacological inhibition of neuraminidase by anti-influenza drugs, oseltamivir and zanamivir, also protected cardiomyocytes and the heart from myocardial injury.
Functional metabolomics identified a key role for Neu5Ac in acute myocardial infarction, and targeting neuraminidase-1 may represent an unrecognized therapeutic intervention for CAD.
Hypoxia is a major contributor to global kidney diseases. Targeting hypoxia is a promising therapeutic option against both acute kidney injury and chronic kidney disease; however, an effective ...strategy that can achieve simultaneous targeted kidney hypoxia imaging and therapy has yet to be established. Herein, we fabricated a unique nano-sized hypoxia-sensitive coassembly (Pc/C5A@EVs) via molecular recognition and self-assembly, which is composed of the macrocyclic amphiphile C5A, the commercial dye sulfonated aluminum phthalocyanine (Pc) and mesenchymal stem cell-excreted extracellular vesicles (MSC-EVs).
In murine models of unilateral or bilateral ischemia/reperfusion injury, MSC-EVs protected the Pc/C5A complex from immune metabolism, prolonged the circulation time of the complex, and specifically led Pc/C5A to hypoxic kidneys via surface integrin receptor α
β
and α
β
, where Pc/C5A released the near-infrared fluorescence of Pc and achieved enhanced hypoxia-sensitive imaging. Meanwhile, the coassembly significantly recovered kidney function by attenuating cell apoptosis, inhibiting the progression of renal fibrosis and reducing tubulointerstitial inflammation. Mechanistically, the Pc/C5A coassembly induced M1-to-M2 macrophage transition by inhibiting the HIF-1α expression in hypoxic renal tubular epithelial cells (TECs) and downstream NF-κB signaling pathway to exert their regenerative effects.
This synergetic nanoscale coassembly with great translational potential provides a novel strategy for precise kidney hypoxia diagnosis and efficient kidney injury treatment. Furthermore, our strategy of coassembling exogenous macrocyclic receptors with endogenous cell-derived membranous structures may offer a functional platform to address multiple clinical needs.
A novel digital design methodology that combines computational fluid dynamics (CFD) modelling and Taguchi-Grey relational analysis method was presented for a single-strand tundish. The present study ...aimed at optimizing the flow control device in the tundish with an emphasis on maximizing the inclusion removal rate and minimizing the dead volume fraction. A CFD model was employed to calculate the fluid flow and the residence-time distribution of liquid steel in the tundish. The Lagrangian approach was applied to investigate the behavior of non-metallic inclusions in the system. The calculated residence-time distribution curves were used to analyze the dead volume fraction in the tundish. A Taguchi orthogonal array L9(3^4) was used to analyze the effects of design factors on both single and multiple responses. Moreover, for the purpose of meeting the multi-objective target functions, grey relational analysis and analysis of variance were used. The optimum positions of the weir and the dam were obtained based on the design targets. A special focus of this study was to demonstrate the capabilities of the Taguchi-Grey relational analysis method as a powerful means of increasing the effectiveness of CFD simulation.
Seabed instability around a pipeline is one of the primary concerns in offshore pipeline projects. To date, most studies focus on investigating the wave/current-induced response within a porous ...seabed around either a fully buried pipeline or a thoroughly exposed one. In this study, unlike previous investigations, a series of comprehensive laboratory experiments are carried out in a wave flume to investigate the wave-induced pore pressures around a partially embedded pipeline in a trench layer. Measurements show that the presence of the partially buried pipeline can significantly affect the excess pore pressure in a partially backfilled trench layer, which deviates considerably from that predicted by the theoretical approach. The morphology of the trench layer accompanied with the backfill sediments, especially the deeper trench and thicker backfill (i.e., b≥1D,e≥0.5D), provides a certain degree of resistance to seabed instability. The amplitude of excess pore pressure around the trench layer roughly exhibits a left-right asymmetric distribution along the periphery of the pipeline, and decays sharply from the upper layer of the trench to the lower region. Deeper trench depth and thicker buried layer significantly weaken the pore-water pressures in the whole trench area, thus sheltering and protecting the submarine pipeline against the transient seabed liquefaction.
•First comprehensive experimental data for wave-induced pore pressure around buried pipeline in a trench layer.•Investigate effect of wave characteristics on transient pore-water response near the partial-buried pipeline.•Examine effect of trench depth and backfill thickness on oscillatory pore-water pressure around the partial-buried pipeline.
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•Zirconia-supported CuO catalysts were prepared.•These catalysts catalytically converted glycerol to lactic acid.•Up to 95% yields of lactic acid were obtained.•Cu0 promoted both ...dehydrogenation and hydrogenolysis.
Zirconia-supported copper oxide catalysts with various compositions were prepared and characterized by atomic absorption spectroscopy, N2 physical adsorption, temperature programmed reduction, powder X-ray diffraction and X-ray photoelectron spectroscopy. These catalysts were evaluated for the conversion of glycerol to lactic acid in aqueous solution in the presence of a base and under an inert atmosphere. The results showed that CuO/ZrO2 with ∼30% Cu loading exhibited the highest activity for the conversion of glycerol. Under optimum conditions, 100% glycerol conversion and 94.6% selectivity for lactic acid were obtained over 30%CuO/ZrO2 when reacting 10mL of glycerol solution (1.4M), using 0.2g catalyst in the presence of NaOH (1:1 NaOH/glycerol molar ratio) at 453K and 1.4MPaN2 for 8h. Moreover, the reusability of 30%CuO/ZrO2 was investigated, and a reaction mechanism for the conversion of glycerol is proposed.
Polarization entangled photon pair source is widely used in many quantum information processing applications such as teleportation, quantum communications, quantum computation and high precision ...quantum metrology. We report on the generation of a continuous-wave pumped 1550 nm polarization entangled photon pair source at telecom wavelength using a type-II periodically poled KTiOPO(4) (PPKTP) crystal in a Sagnac interferometer. Hong-Ou-Mandel (HOM) interference measurement yields signal and idler photon bandwidth of 2.4 nm. High quality of entanglement is verified by various kinds of measurements, for example two-photon interference fringes, Bell inequality and quantum states tomography. The source can be tuned over a broad range against temperature or pump power without loss of visibilities. This source will be used in our future experiments such as generation of orbital angular momentum entangled source at telecom wavelength for quantum frequency up-conversion, entanglement based quantum key distributions and many other quantum optics experiments at telecom wavelengths.
In order to explore one truly green and environment-friendly gel polymer electrolyte (GPE), the natural biopolymer of lignin is firstly all over the world used as matrix to prepare GPE. The ...electrolyte membrane based on lignin can be easily fabricated just with lignin, liquid electrolyte and distilled water. Through comprehensive investigation of obtained GPE, it is found that the liquid electrolyte uptake reaches up to 230 wt.%; before 100 °C, GPE does not lose any weight and is thermal stable; at room temperature the ion conductivity is 3.73 mS cm−1; the amazing property of lithium ion transference number is high up to 0.85; GPE expresses complete electrochemical stability before 7.5 V and favorable compatibility with lithium anode; the outstanding cell performance of C-rate and cycle capacity. All these remarkably excellent performances endow lignin with application potential in GPE used in lithium ion batteries (LIBs) with higher performances.
In order to explore one true green and environment-friendly gel polymer electrolyte (GPE), the natural biopolymer of lignin is firstly all over the world used as matrix to prepare GPE. Both super simple preparation technology of electrolyte membrane and unbelievable outstanding comprehensive performances open one bran-new direction and perspective to develop lithium ion batteries with true zero environmental impact. Display omitted
•One kind of natural polymer lignin is firstly explored for gel polymer electrolyte.•The obtained GPE presents the outstanding comprehensive performances.•The super simple film formation technology demonstrates the potential application.•It is a realistic milestone for lithium ion battery with zero environmental impact.
Introduction
Ophiocordyceps gracilis, a type of edible and medicinal fungus, exhibits multiple health‐promoting effects. Due to the scarcity of natural O. gracilis, artificial cultures have been ...developed as its substitutes. However, lacking comprehension of the metabolite composition of cultures limits its utilisation.
Objective
This research aimed to evaluate the nutritional and medicinal value of four cultures of O. gracilis by analysing their metabolite composition. In addition, metabolic pathways in mycelia and fruiting bodies were analysed to explore fruiting body formation mechanism at metabolic level.
Method
The mycelia, fermentation broth, spore powder and fruiting bodies of O. gracilis were cultivated in this study. Their metabolite composition was compared using an untargeted metabolomics approach based on liquid chromatography–tandem mass spectrometry (LC–MS/MS).
Results
Principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS‐DA) showed that the four cultures have noticeable differences in metabolite composition. A total of 612 metabolites were identified, among which 159 metabolites showed significant differences, and these differential metabolites were classified into 13 categories. The metabolites in the fruiting bodies were the most abundant compared with other cultures. However, each culture had its own advantages and significantly accumulates some active metabolites respectively. Pearson's correlation analysed the mutual relationship among metabolites. In addition, seven metabolic pathways were closely related to fruiting body formation, such as “Biosynthesis of plant secondary metabolites”, “amino acids metabolism”, “tricarboxylic acid (TCA) cycle”.
Conclusion
This study offered a reference to mycelia, fermentation broth, spore powder and fruiting bodies of O. gracilis as health‐promoting functional foods and medicine.
Ophiocordyceps gracilis is a precious edible and medicinal fungus. The metabolites composition of mycelia, fermentation broth, spore powder, and fruiting bodies of O. gracilis were compared. There were 159 differential metabolites, each culture had its own advantages and significantly accumulated some active metabolites respectively. Additionally, the relationship between metabolites and the formation mechanism of the fruiting bodies were preliminarily investigated. This study provides a reference to cultures of O. gracilis as health‐promoting functional foods and medicine development.
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