Acute liver injury (ALI) is a severe disorder resulting from excessive hepatocyte cell death, and frequently caused by acetaminophen intoxication. Clinical management of ALI progression is hampered by the dearth of blood biomarkers available. In this study, a bioinformatics workflow was developed to screen omics databases and identify potential biomarkers for hepatocyte cell death. Then, discovery proteomics was harnessed to select from among these candidates those that were specifically detected in the blood of acetaminophen-induced ALI patients. Among these candidates, the isoenzyme alcohol dehydrogenase 1B (ADH1B) was massively leaked into the blood. To evaluate ADH1B, we developed a targeted proteomics assay and quantified ADH1B in serum samples collected at different times from 17 patients admitted for acetaminophen-induced ALI. Serum ADH1B concentrations increased markedly during the acute phase of the disease, and dropped to undetectable levels during recovery. In contrast to alanine aminotransferase activity, the rapid drop in circulating ADH1B concentrations was followed by an improvement in the international normalized ratio (INR) within 10–48 h, and was associated with favorable outcomes. In conclusion, the combination of omics data exploration and proteomics revealed ADH1B as a new blood biomarker candidate that could be useful for the monitoring of acetaminophen-induced ALI. 相似文献
A main characteristic of sphingolipids is the presence of a very long chain fatty acid (VLCFA) whose function in cellular processes is not yet fully understood. VLCFAs of sphingolipids are involved in the intracellular traffic to the vacuole and the maturation of early endosomes into late endosomes is one of the major pathways for vacuolar traffic. Additionally, the anionic phospholipid phosphatidylinositol-3-phosphate (PtdIns (3)P or PI3P) is involved in protein sorting and recruitment of small GTPase effectors at late endosomes/multivesicular bodies (MVBs) during vacuolar trafficking. In contrast to animal cells, PI3P mainly localizes to late endosomes in plant cells and to a minor extent to a discrete sub-domain of the plant’s early endosome (EE)/trans-Golgi network (TGN) where the endosomal maturation occurs. However, the mechanisms that control the relative levels of PI3P between TGN and MVBs are unknown. Using metazachlor, an inhibitor of VLCFA synthesis, we found that VLCFAs are involved in the TGN/MVB distribution of PI3P. This effect is independent from either synthesis of PI3P by PI3-kinase or degradation of PI(3,5)P2 into PI3P by the SUPPRESSOR OF ACTIN1 (SAC1) phosphatase. Using high-resolution live cell imaging microscopy, we detected transient associations between TGNs and MVBs but VLCFAs are not involved in those interactions. Nonetheless, our results suggest that PI3P might be transferable from TGN to MVBs and that VLCFAs act in this process. 相似文献
Syntheses of eight novel methacrylates bearing phosphonic acid groups were synthesized in three to five steps. The interaction of these monomers with hydroxyapatite was investigated using 13C‐NMR spectroscopy. Free radical homopolymerizations were carried out in a mixture ethanol/water (2.5/1, v/v) using 2,2′azo(2‐methylpropionamidine) dihydrochloride as initiator. The copolymerization of these monomers with a mixture HEMA/GDMA (5/3, mol/mol) was investigated by photo‐DSC. Dentin shear bond strength measurements showed that 2‐methacryloyloxy‐3‐(1,1,2,2‐tetrafluoroethoxy)propylphosphonic acid 4b , 2,3‐dimethacryloyloxypropylphosphonic acid 18 and 3‐(methacryloyloxy)‐2,2‐(di[(dihydroxyphosphoryl)methyl])propyl methacrylate 23 are promising candidates for dental adhesives.
In this paper, a novel phase-locked loop (PLL) architecture with multiple charge pumps, which is used to design a fast-locking
PLL and a low-phase-noise PLL, is proposed. The effective capacitance and resistance of the loop filter in terms of voltage
is scaled up/down according to the locking status by controlling the magnitude and direction of the charge pump current. Two
PLLs, one with a fast-locking characteristic and the other with a low-phase-noise characteristic, are designed and fabricated
in a 0.35-μm CMOS process based on the proposed architecture. The fast-locking PLL has a locking time of less than 6 μs and
a phase noise of −90.45 dBc/Hz at 1 MHz offset. The low-phase-noise PLL has a locking time of 25 μs, a phase noise of −105.37 dBc/Hz
at 1 MHz offset, and a reference spur of −50 dBc. Both PLLs have an 851.2 MHz output frequency. 相似文献
Although a variety of stretchable strain sensors based on electrical percolation have been reported, stretchable sensors detecting low strains have been rarely demonstrated. This is because large stretchability of a strain sensor conflicts with high strain resolution at low strains. Here, the electrical percolation into 2D is confined and a strain sensor that is highly sensitive at low strains and simultaneously highly stretchable is presented. The 2D confinement of the electrical percolation is accomplished by a close‐packed monolayer assembly of conductive microparticles (MPs) on an elastomer substrate. The current profiles of the MP monolayer at low strains are in situ visualized using conductive atomic force microscopy. When the lattice of the MP monolayer is aligned vertically to the strain direction, the resistance is highly sensitive to low‐strain deformations (ε = 0 – 0.05), but the sensor has reasonable stretchability (ε = 0.3). The simultaneous achievement of the high sensitivity at low strains and the reasonable stretchability is explained by the relationship between the strain‐dependent current profile and the relative position changes of the MPs. A high‐precision pulse sensor clearly showing the representative peaks is demonstrated. 相似文献