Biology subjects

chen, d.

Publications and source records attributed to chen, d..

3 recordsLinked to original sources

bioRxiv2024

A Novel Computational Pre-Procedural Planning Model for Coronary Interventions Based on Coronary CT Angiography

In percutaneous coronary intervention (PCI), the ability to predict post-PCI fractional flow reserve (FFR) and stented vessel informs procedural planning. However, highly precise and effective methods to quantitatively simulate coronary intervention are lacking. This study developed a validated virtual coronary intervention (VCI) technique for non-invasive physiological and anatomical assessment of PCI. In this study, patients with substantial lesions (pre-PCI FFR of less than 0.80) were enrolled. VCI framework was used to predict vessel reshape and post-PCI FFR. The accuracy of predicted post-VCI FFR, luminal cross-sectional area (CSA) and centreline curvature was validated with post-PCI computed tomography (CT) angiography datasets. Overall, 21 patients were selected for the study, of which 9 patients (9 vessels) were included in the analysis. The average time for PCI simulation was 24.92 {+/-} 1.00 s on a single processor. The calculated post-PCI FFR was 0.92 {+/-} 0.09 and the predicted post-VCI FFR was 0.90 {+/-} 0.08 (mean difference: -0.02 {+/-} 0.05 FFR unit; limits of agreement: -0.08 to 0.05). Morphologically, the predicted CSA is 16.36 {+/-} 4.41 mm2 and post-CSA is 17.91 {+/-} 4.84 mm2 (mean difference: -1.55 {+/-} 1.89 mm2; limits of agreement: -5.22 to 2.12), the predicted centreline curvature of stented region is 0.15 {+/-} 0.04 mm{square}1 and post-PCI centreline curvature is 0.17 {+/-} 0.03 mm{square}1 (mean difference: -0.02 {+/-} 0.06 mm{square}1; limits of agreement: -0.12 to 0.09). The proposed VCI technique achieves non-invasive pre-procedural anatomical and physiological assessment of coronary intervention. The proposed model has the potential to optimize PCI pre-procedural planning and improve the safety and efficiency of PCI. HighlightsO_LIPresent a computational pre-procedural planning model for coronary interventions. C_LIO_LIDevelop a computational framework to predict post-PCI FFR. C_LIO_LIValidation of the model with post-PCI CT angiography datasets. C_LIO_LIThe proposed model has the potential to optimize PCI pre-procedural planning. C_LI

bioengineering↗

bioRxiv2023

Ensemble-based design of tau to inhibit aggregation while preserving biological activity.

The microtubule-associated protein tau is implicated in neurodegenerative diseases characterized by amyloid formation. Mutations associated with frontotemporal dementia increase tau aggregation propensity and disrupt its endogenous microtubule-binding activity. However, the structural relationship between aggregation propensity and biological activity remains unclear. We employed a multi-disciplinary approach, including computational modeling, NMR, cross-linking mass spectrometry, and cell models to engineer tau sequences that modulate its structural ensemble. Our findings show that substitutions near the conserved PGGG {beta}-turn motif informed by tau isoform context reduce tau aggregation in vitro and cells and can even counteract aggregation induced by turn destabilizing disease-associated proline-to-serine mutations. Engineered tau sequences maintain microtubule binding and explain why 3R isoforms exhibit reduced pathogenesis compared to 4R. We propose a simple mechanism to reduce the formation of pathogenic species while preserving biological function, thus offering insights for therapeutic strategies aimed at reducing tau protein misfolding in neurodegenerative diseases. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=88 SRC="FIGDIR/small/571598v2_ufig1.gif" ALT="Figure 1"> View larger version (16K): org.highwire.dtl.DTLVardef@178a79org.highwire.dtl.DTLVardef@1842dc7org.highwire.dtl.DTLVardef@d9a32borg.highwire.dtl.DTLVardef@676dec_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2020

Allantoin induces pruritus by activating MrgprD in chronic kidney disease

Chronic kidney disease is a disease with decreased, irreversible renal function. Pruritus is the most common skin symptom in patients with chronic kidney disease, especially in end-stage renal disease (AKA chronic kidney disease-associated pruritus [CKD-aP]); however, the underlying molecular and neural mechanism of the CKD-aP in patients remains obscure. Our data show that the level of allantoin increases in the serum of CKD-aP and CKD model mice. Allantoin could induce scratching behavior in mice and active DRG neurons; the calcium influx and the action potential were significantly reduced in DRG neurons of MrgprD KO or TRPV1 KO mice. U73122, an antagonist of PLC, could also block calcium influx in DRG neurons induced by allantoin. Thus, our results concluded that allantoin plays an important role in CKD-aP, mediated by MrgprD and TrpV1, in CKD patients.

pathology↗