ABSTRACT
Accurate determination of cerium (Ce) valence state is important for interpreting the Ce anomaly in geological archives for (paleo)redox reconstruction. However, the routine application of Ce L3-edge X-ray absorption near-edge structure (XANES) spectroscopy for detecting trace Ce in geological samples can often be restricted by coexisting titanium (Ti) due to the proximity of their fluorescence emission lines. Therefore, the signal-to-noise ratio of Ce L3-edge XANES spectra may not be sufficiently high for high-quality spectroscopic analysis. This study introduces a semi-quantitative approach appropriate for Ti-rich, Ce-dilute geological materials by synchrotron-based X-ray measurement at the Ce L2-edge. First, the results confirm that Ce L2-edge XANES spectra are able to avoid overlapping Ti Kß emissions and provide more reliable information on the Ce valence state in Ti-rich materials relative to L3-edge XANES. Moreover, the application of transition-edge sensor (TES) could reach the higher sensitivity with better energy resolution than conventional silicon drift detector (SDD) to detect fluorescence X-ray (Ce Lß1). The investigation on bauxites developed from the Columbia River Basalts shows that combining Ce L2-edge XANES and TES allows for resolving weak Ce fluorescence lines at the L2-edge from Ti-rich, Ce-dilute samples (Ti/Ce mass ratio up to â¼6000, tens of ppm Ce). The outcome emphasizes the practical possibility of investigating Ce redox state in Ti-rich geological samples.
Subject(s)
Cerium , Cerium/chemistry , Titanium , Aluminum Oxide , X-Ray Absorption Spectroscopy , Oxidation-ReductionABSTRACT
Synergizing the sensitive circulating tumor cell (CTC) capture, detection, release and the specific magnetic resonance/fluorescence (MR/FL) imaging for accurate cancer diagnosis is of great importance for cancer treatment. Herein, EcoR1-responsive complementary pairing of two ssDNA with a fluorescent P0 aptamer, which can specifically bind with the overexpressed MUC1 protein on cancer cells, was covalently modified to SiO2@C-coated magnetic nanoparticles for preparing a special nanoparticle-mediated FL turn-on aptasensor (FSC-D-P0). This aptasensor can selectively capture/enrich CTC and thus achieve sensitive CTC detection/imaging in even the blood due to its stable targeting, unique magnetic properties and the regulated interactions between the quencher and the fluorescent groups. Meanwhile, FSC-D-P0 can release the captured CTC for further downstream analysis upon the EcoR1 enzyme-triggered cleavage of the double-stranded DNA (dsDNA). Most importantly, this aptasensor can distinctly avoid false positivity of MRI via multiple targeting mechanisms. Thus, the sensitive CTC capture, detection, release and accurate MR/FL imaging were synergistically combined into a single platform with good biocompatibility, promising a robust pattern for clinical tumor diagnosis in vitro and in vivo.
Subject(s)
Aptamers, Nucleotide , Biosensing Techniques , Biosensing Techniques/methods , Limit of Detection , Magnetic Resonance Imaging , Silicon DioxideABSTRACT
The alteration of the enteric nervous system (ENS) and its role in neuroimmune modulation remain obscure in the pathogenesis of inflammatory bowel diseases (IBDs). Here, by using the xCell tool and the latest immunolabeling-enabled three-dimensional (3D) imaging of solvent-cleared organs technique, we found severe pathological damage of the entire ENS and decreased expression of choline acetyltransferase (ChAT) in IBD patients. As a result, acetylcholine (ACh), a major neurotransmitter of the nervous system synthesized by ChAT, was greatly reduced in colon tissues of both IBD patients and colitis mice. Importantly, administration of ACh via enema remarkably ameliorated colitis, which was proved to be directly dependent on monocytic myeloid-derived suppressor cells (M-MDSCs). Furthermore, ACh was demonstrated to promote interleukin-10 secretion of M-MDSCs and suppress the inflammation through activating the nAChR/ERK pathway. The present data reveal that the cholinergic signaling pathway in the ENS is impaired during colitis and uncover an ACh-MDSCs neuroimmune regulatory pathway, which may offer promising therapeutic strategies for IBDs.
Subject(s)
Acetylcholine/administration & dosage , Enteric Nervous System/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Inflammatory Bowel Diseases/therapy , Interleukin-10/metabolism , Monocytes/metabolism , Myeloid-Derived Suppressor Cells/metabolism , Receptors, Nicotinic/metabolism , Acetylcholine/pharmacology , Animals , Choline O-Acetyltransferase/metabolism , Enteric Nervous System/physiopathology , Female , Humans , Inflammatory Bowel Diseases/physiopathology , Mice , Mice, Inbred C57BL , Neurons/metabolismABSTRACT
Accumulating evidence indicated that oxymatrine (OMT), an alkaloid compound from the Chinese medicinal herb Sophora flavescens, exhibits activity against hepatic fibrosis. The present study attempted to explore the underlying mechanisms of OMTmediated inhibition of collagen production. For this, the LX2 human hepatic stellate cell line was treated with OMT (240, 480 or 960 mg/l) for 35 days. The endogenic expression of procollagen I was decreased by OMT in a dose and timedependent manner, accompanied with the downregulation of Ybox binding protein 1 (YB1), a vital transcription factor, particularly on the fourth day of incubation with a high concentration of OMT. To further explore the intracellular changes in YB1 levels, nuclear/cytoplasmic proteins were extracted separately, and subsequent western blot analysis revealed a significant upregulation of YB1 in the nucleus in parallel with its downregulation in the cytoplasm, indicating the nuclear translocation of YB1 induced by OMT treatment. In another experiment, knockdown of YB1 using small interfering RNA led to elevated mRNA levels of collagen I, thereby reversing the effects of OMT treatment. In conclusion, these present study suggested that the attenuation of procollagen I expression caused by OMT was, to a certain extent, mediated via nuclear translocation of YB1.