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The as-fabricated nano-onion-incorporated graphene films exhibited a highly hydrophobic nature showing a water contact angle of up to 1290. The surface energies of these films were in the range of 41 to 35 mJ·m-2. Moreover, a chemiresistive sensor directly fabricated using C. sinensis-derived onion-structured graphene showed a p-type semiconductor nature and a promising response to acetone at room temperature. With its unique morphology, surface properties, and electrical characteristics, this material is expected to be useful for a wide range of applications.Recently developed high-throughput in vitro assays in combination with computational models could provide alternatives to animal testing. The purpose of the present study was to model the plasma, hepatic, and renal pharmacokinetics of approximately 150 structurally varied types of drugs, food components, and industrial chemicals after virtual external oral dosing in rats and to determine the relationship between the simulated internal concentrations in tissue/plasma and their lowest-observed-effect levels. The model parameters were based on rat plasma data from the literature and empirically determined pharmacokinetics measured after oral administrations to rats carried out to evaluate hepatotoxic or nephrotic potentials. To ensure that the analyzed substances exhibited a broad diversity of chemical structures, their structure-based location in the chemical space underwent projection onto a two-dimensional plane, as reported previously, using generative topographic mapping. A high-throughput in silico one-comue concentrations of drugs and chemicals after oral dosing, thereby facilitating estimates of nephrotoxic or hepatotoxic potential as a part of the risk assessment.Amyloid formation of full-length TTR involves dissociation of the native tetramers into misfolded monomers that self-assemble into amyloid. In addition to the full-length TTR, C-terminal fragments including residues 49-127 were also observed in vivo, implying the presence of additional misfolding pathways. It was previously proposed that a proteolytic cleavage might lead to the formation of the C-terminal fragment TTR amyloid. Here, we report mechanistic studies of misfolding and aggregation of a TTR variant (G53A) in the absence and presence of a serine protease. A proteolytic cleavage of G53A in the CD loop (K48 and T49) with agitation promoted TTR misfolding and aggregation, suggesting that the proteolytic cleavage may lead to the aggregation of the C-terminal fragment (residues 49-127). To gain more detailed insights into TTR misfolding promoted by proteolytic cleavage, we investigated structural changes in G53A TTR in the presence and absence of trypsin. Our combined biophysical analyses revealed that the proteolytic cleavage accelerated the formation of spherical small oligomers, which exhibited cytotoxic activities. However, the truncated TTR appeared to maintain native-like structures, rather than the C-terminal fragment (residues 49-127) being released and unfolded from the native state. In addition, our solid-state nuclear magnetic resonance and Fourier transform infrared structural studies showed that the two aggregates derived from the full-length and cleaved TTR exhibited nearly identical molecular structural features, suggesting that the proteolytic cleavage in the CD loop destabilizes the native tetrameric structure and accelerates oligomer formation through a common TTR misfolding and aggregation mechanism rather than through a distinct molecular mechanism.Collagen remodeling in normal and pathologic conditions releases numerous collagen fragments into biological fluids. Although a few collagen fragments have been tested as biomarkers for disease indication, most occur at trace levels, making them nearly impossible to detect even with modern analytical tools. Here we report a new way to enrich collagen fragments that allows complete peptidomic analysis of collagen fragments in urine. Enrichment is made possible by dimeric collagen hybridizing peptides (CHPs) that bind collagen fragments originating from the triple helical regions of all collagen types with minimal sequence bias. LC-MS/MS analysis of enriched mouse urine revealed an average of 383 collagenous peptide fragments per sample (compared to 34 for unenriched sample), which could be mapped to all types of mouse collagens in the SwissProt database including FACITs and MACITs. Hierarchical clustering of a selected panel of the detected fragments separated osteopenic mice from healthy mice. The results demonstrate dimeric CHP's ability to enrich collagen fragments from biological fluid and its potential to aid peptidomics-based disease detection and biomarker discovery.While currently available methods for peptide sample preparation are mostly suitable for ex situ analysis via exhaustive extraction techniques, these techniques do not allow for in situ extraction of peptides from biological samples, such as blood or plasma collected from patients for routine clinical applications. Biocompatible solid phase microextraction (Bio-SPME) has shown great potential in metabolomics for in situ extraction of metabolites including labile compounds from biological matrices in a biocompatible and non-exhaustive fashion, thus facilitating even in vivo sampling. However, the amounts of peptides extracted by such Bio-SPME chemical biopsy tools are deemed too low for quantification when porous polyacrylonitrile (PAN)-based biocompatible thin film sorbent coatings are used, since such materials have been commonly applied as means to restrict access of high molecular weight compounds such as proteins. Aiming to improve peptide extraction by the SPME sorbent while still preventing protein adsorption, thin films with nanoscale irregularities and mesopores were prepared by inclusion of the porogen lithium perchlorate in the slurries of the coatings. The novel thin film coating method significantly improved extraction of a range of angiotensins known to possess important roles in blood pressure regulation and electrolyte balance. Model low abundance peptides covering a wide range of hydrophobicities were successfully extracted from physiological buffers and human plasma using the increased porosity coating, while the SPME protocol on the tryptic digestion of a protein supported that enzymes were excluded during peptide extraction. ALK inhibitor cancer Surface rheological analysis, which displayed mesopores on the C18/PAN coatings, confirmed that the porosity of the coating facilitated the mass transport of peptides through the PAN layer, thus enabling extraction of high amounts of peptides by the new C18/PAN coating.
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