158 research outputs found

    Heparinization and hybridization of electrospun tubular graft for improved endothelialization and anticoagulation

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    Supplementary data to this article can be found online at https://doi.org/10.1016/j.msec.2020.111861.Constructing biomimetic structure and immobilizing antithrombus factors are two effective methods to ensure rapid endothelialization and long-term anticoagulation for small-diameter vascular grafts. However, few literatures are available regarding simultaneous implementation of these two strategies. Herein, a nano-micro-fibrous biomimetic graft with a heparin coating was prepared via a step-by-step in situ biosynthesis method to improve potential endothelialization and anticoagulation. The 4-mm-diameter tubular graft consists of electrospun cellulose acetate (CA) microfibers and entangled bacterial nanocellulose (BNC) nanofibers with heparin coating on dual fibers. The hybridized and heparinized graft possesses suitable pore structure that facilitates endothelia cells adhesion and proliferation but prevents infiltration of fibrous tissue and blood leakage. In addition, it shows higher mechanical properties than those of bare CA and hybridized CA/BNC grafts, which match well with native blood vessels. Moreover, this dually modified graft exhibits improved blood compatibility and endothelialization over the counterparts without hybridization or heparinization according to the testing results of platelet adhesion, cell morphology, and protein expression of von Willebrand Factor. This novel graft with dual modifications shows promising as a new small-diameter vascular graft. This study provides a guidance for promoting endothelialization and blood compatibility by dual modifications of biomimetic structure and immobilized bioactive molecules.This work was supported by the National Natural Science Foundation of China (grant nos. 51973058 and 31870963), the Key Research and Development Program of Jiangxi Province (No. 20192ACB80008), and the Key Project of Natural Science Foundation of Jiangxi Province (20202ACBL204013).info:eu-repo/semantics/publishedVersio

    TPST2-mediated receptor tyrosine sulfation enhances leukocidin cytotoxicity and S. aureus infection

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    BackgroundAn essential fact underlying the severity of Staphylococcus aureus (S. aureus) infection is the bicomponent leukocidins released by the pathogen to target and lyse host phagocytes through specific binding cell membrane receptors. However, little is known about the impact of post-transcriptional modification of receptors on the leukocidin binding.MethodIn this study, we used small interfering RNA library (Horizon/Dharmacon) to screen potential genes that affect leukocidin binding on receptors. The cell permeability was investigated through flow cytometry measuring the internalization of 4′,6-diamidino-2-phenylindole. Expression of C5a anaphylatoxin chemotactic receptor 1 (C5aR1), sulfated C5aR1 in, and binding of 6x-His–tagged Hemolysin C (HlgC) and Panton-Valentine leukocidin (PVL) slow-component to THP-1 cell lines was detected and analyzed via flow cytometry. Bacterial burden and Survival analysis experiment was conducted in WT and myeloid TPST-cko C57BL/6N mice.ResultsAfter short hairpin RNA (shRNA) knockdown of TPST2 gene in THP-1, HL-60, and RAW264.7, the cytotoxicity of HlgAB, HlgCB, and Panton–Valentine leukocidin on THP-1 or HL-60 cells was decreased significantly, and the cytotoxicity of HlgAB on RAW264.7 cells was also decreased significantly. Knockdown of TPST2 did not affect the C5aR1 expression but downregulated cell surface C5aR1 tyrosine sulfation on THP-1. In addition, we found that the binding of HlgC and LukS-PV on cell surface receptor C5aR1 was impaired in C5aR1+TPST2− and C5aR1−TPST2− cells. Phagocyte knockout of TPST2 protects mice from S. aureus infection and improves the survival of mice infected with S. aureus.ConclusionThese results indicate that phagocyte TPST2 mediates the bicomponent leukocidin cytotoxicity by promoting cell membrane receptor sulfation modification that facilitates its binding to leukocidin S component

    Underestimated ecosystem carbon turnover time and sequestration under the steady state assumption: a perspective from long‐term data assimilation

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    It is critical to accurately estimate carbon (C) turnover time as it dominates the uncertainty in ecosystem C sinks and their response to future climate change. In the absence of direct observations of ecosystem C losses, C turnover times are commonly estimated under the steady state assumption (SSA), which has been applied across a large range of temporal and spatial scales including many at which the validity of the assumption is likely to be violated. However, the errors associated with improperly applying SSA to estimate C turnover time and its covariance with climate as well as ecosystem C sequestrations have yet to be fully quantified. Here, we developed a novel model-data fusion framework and systematically analyzed the SSA-induced biases using time-series data collected from 10 permanent forest plots in the eastern China monsoon region. The results showed that (a) the SSA significantly underestimated mean turnover times (MTTs) by 29%, thereby leading to a 4.83-fold underestimation of the net ecosystem productivity (NEP) in these forest ecosystems, a major C sink globally; (b) the SSA-induced bias in MTT and NEP correlates negatively with forest age, which provides a significant caveat for applying the SSA to young-aged ecosystems; and (c) the sensitivity of MTT to temperature and precipitation was 22% and 42% lower, respectively, under the SSA. Thus, under the expected climate change, spatiotemporal changes in MTT are likely to be underestimated, thereby resulting in large errors in the variability of predicted global NEP. With the development of observation technology and the accumulation of spatiotemporal data, we suggest estimating MTTs at the disequilibrium state via long-term data assimilation, thereby effectively reducing the uncertainty in ecosystem C sequestration estimations and providing a better understanding of regional or global C cycle dynamics and C-climate feedback
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