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

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

Controllable synthesis of biomimetic nano/submicro-fibrous tubes for potential small-diameter vascular grafts

Mimicking the morphological structure of native blood vessels is critical for the development of vascular grafts. Herein, small-diameter composite vascular grafts that integrate the nanofibrous bacterial cellulose (BC) and submicrofibrous cellulose acetate (CA) were fabricated via a combined electrospinning and step-by-step in situ biosynthesis. Scanning electron microscopy (SEM) observation shows the nano/submicro-fibrous morphology and well-interconnected porous structure of the BC/CA grafts. It is found that the BC/CA graft with a suitable BC content demonstrates lower potential of thrombus formation and enhanced endothelialization as compared to the BC and CA counterparts. Western blotting and RT-qPCR results suggest that the BC/CA-2 graft promotes endothelialization by improving expressions of genes vWF-1 and CD31 and protein CD31. The in vivo tests demonstrate much lower inflammatory response to the BC/CA graft. These results suggest that the BC/CA graft shows a great potential as an artificial graft for rapid formation of an endothelial cell monolayer.National Natural Science Foundation of China (Grant no. 51973058, 31870963, 31760265) and Key Research and Development Program of Jiangxi Province (No. 20192ACB80008)info:eu-repo/semantics/publishedVersio

Intermediate-Length GGC Repeat Expansion in NOTCH2NLC Was Identified in Chinese Patients with Amyotrophic Lateral Sclerosis

GGC repeat expansions in the 5’ untranslated region (5’UTR) of the Notch Homolog 2 N-terminal-like C gene (NOTCH2NLC) have been reported to be the genetic cause of neuronal intranuclear inclusion disease (NIID). However, whether they exist in other neurodegenerative disorders remains unclear. To determine whether there is a medium-length amplification of NOTCH2NLC in patients with amyotrophic lateral sclerosis (ALS), we screened 476 ALS patients and 210 healthy controls for the presence of a GGC repeat expansion in NOTCH2NLC by using repeat-primed polymerase chain reaction (RP-PCR) and fragment analysis. The repeat number in ALS patients was 16.11 ± 5.7 (range 7–46), whereas the repeat number in control subjects was 16.19 ± 3.79 (range 10–29). An intermediate-length GGC repeat expansion was observed in two ALS patients (numbers of repeats: 45, 46; normal repeat number ≤ 40) but not in the control group. The results suggested that the intermediate NOTCH2NLC GGC repeat expansion was associated with Chinese ALS patients, and further functional studies for intermediate-length variation are required to identify the mechanism

Migraine and white matter lesions: a mendelian randomization study

Abstract Previous studies have found that migraine patients are associated with white matter lesions (WMLs), but the causal relationship between the two remains unclear. We intend to explore the bidirectional causal relationship between migraine and WMLs using a two-sample mendelian randomization (MR) method. We employed summary-level data from a recent large-scale genome-wide association study (GWAS) that characterized three white matter (WM) phenotypes: white matter hyperintensities (WMH, N = 18,381), fractional anisotropy (FA, N = 17,673), and mean diffusivity (MD, N = 17,467), as well as migraine (N = 589,356). The inverse variance-weighted (IVW) method was used as the main approach for analyzing causality. Weighted median analysis, simple median analysis, and MR-Egger regression served as complementary methods. The bidirectional MR study affords no support for causality between WMLs and migraine. In all MR methods, there was no obvious causal evidence between them. In our bidirectional MR study, we didn't reach this conclusion that WMLs can cause migraine, migraine wouldn’t increase the risk of WMLs, either

Artificial neural network identified the significant genes to distinguish Idiopathic pulmonary fibrosis

Abstract Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease that causes irreversible damage to lung tissue characterized by excessive deposition of extracellular matrix (ECM) and remodeling of lung parenchyma. The current diagnosis of IPF is complex and usually completed by a multidisciplinary team including clinicians, radiologists and pathologists they work together and make decision for an effective treatment, it is imperative to introduce novel practical methods for IPF diagnosis. This study provided a new diagnostic model of idiopathic pulmonary fibrosis based on machine learning. Six genes including CDH3, DIO2, ADAMTS14, HS6ST2, IL13RA2, and IGFL2 were identified based on the differentially expressed genes in IPF patients compare to healthy subjects through a random forest classifier with the existing gene expression databases. An artificial neural network model was constructed for IPF diagnosis based these genes, and this model was validated by the distinctive public datasets with a satisfactory diagnostic accuracy. These six genes identified were significant correlated with lung function, and among them, CDH3 and DIO2 were further determined to be significantly associated with the survival. Putting together, artificial neural network model identified the significant genes to distinguish idiopathic pulmonary fibrosis from healthy people and it is potential for molecular diagnosis of IPF

ADRB2 inhibition combined with antioxidant treatment alleviates lung fibrosis by attenuating TGFβ/SMAD signaling in lung fibroblasts

Abstract Idiopathic pulmonary fibrosis is a progressive and fatal interstitial lung disease with a poor prognosis and limited therapeutic options, which is characterized by aberrant myofibroblast activation and pathological remodeling of the extracellular matrix, while the mechanism remains elusive. In the present investigation, we observed a reduction in ADRB2 expression within both IPF and bleomycin-induced fibrotic lung samples, as well as in fibroblasts treated with TGF-β1. ADRB2 inhibition blunted bleomycin-induced lung fibrosis. Blockage of the ADRB2 suppressed proliferation, migration, and invasion and attenuated TGF-β1-induced fibroblast activation. Conversely, the enhancement of ADRB2 expression or functionality proved capable of inducing fibroblast-to-myofibroblast differentiation. Subsequent mechanistic investigation revealed that inhibition of ADRB2 suppressed the activation of SMAD2/3 in lung fibroblasts and increased phos-SMAD2/3 proteasome degradation, and vice versa. Finally, ADRB2 inhibition combined with antioxidants showed increased efficacy in the therapy of bleomycin-induced lung fibrosis. In short, these data indicate that ADRB2 is involved in lung fibroblast differentiation, and targeting ADRB2 could emerge as a promising and innovative therapeutic approach for pulmonary fibrosis

Progress in utilisation of waste cooking oil for sustainable biodiesel and biojet fuel production

The increase in human consumption of plant and animal oils has led to the rise in waste cooking oil (WCO) production. Instead of disposing the used cooking oil as waste, recent technological advance has enabled the use of WCO as a sustainable feedstock for biofuels production, thereby maximising the value of biowastes via energy recovery while concomitantly solving the disposal issue. The current regulatory frameworks for WCO collection and recycling practices imposed by major WCO producing countries are reviewed, followed by the overview of the progress in biodiesel conversion techniques, along with novel methods to improve the feasibility for upscaling. The factors which influence the efficiency of the reactions such as properties of feedstock, heterogenous catalytic processes, cost effectiveness and selectivity of reaction product are discussed. Ultrasonic-assisted transesterification is found to be the least energy intensive method for producing biodiesel. The production of bio-jet fuels from WCO, while scarce, provide diversity in waste utilisation if problems such as carbon chain length, requirements of bio-jet fuel properties, extreme reaction conditions and effectiveness of selected catalyst-support system can be solved. Technoeconomic studies revealed that WCO biofuels is financially viable with benefit of mitigating carbon emissions, provided that the price gap between the produced fuel and commercial fuels, sufficient supply of WCO and variation in the oil properties are addressed. This review shows that WCO is a biowaste with high potential for advanced transportation fuel production for ground and aviation industries. The advancement in fuel production technology and relevant policies would accelerate the application of sustainable WCO biofuels.N/