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Stent-grafts are bringing new life to aortic dissection patients through thoracic endovascular aortic repair (TEVAR). However, various postoperative complications are threatening the recovery of patients and even require clinical reintervention. The objective of the present study is to reveal the biomechanical mechanism of distal stent-graft-induced new entry (dSINE) deterioration after TEVAR. Six patients treated by TEVAR were collected from the clinical hospital, and dSINE was observed in the follow-up of all patients, which are evenly divided into two groups. The dSINE in the control group was stable while the patients in the experimental group continued to deteriorate and experienced reintervention. Computational fluid-structure interaction hemodynamics were performed in the above patients based on clinical images of early dSINE. The results show that time-averaged wall shear stress or oscillatory shear index alone fails to accurately forecast the deterioration of dSINE. While relative residence time and endothelial cell activation potential demonstrate stronger predictive power and the former seems to be better. Additionally, the region exposed to high von Mises stress and significant wall deformation is also associated with further dSINE deterioration. In conclusion, this study highlights that the postoperative biomechanical environment can predict the further development of dSINE, which is conducive to assisting physicians in improving the risk stratification of dSINE and customizing a follow-up plan. [ABSTRACT FROM AUTHOR]

Thrombosis seriously threatens human cardiovascular health and the safe operation of medical devices. The Food and Drug Administration's (FDA) benchmark nozzle model was designed to include the typical structure of medical devices. However, the thrombosis in the FDA nozzle has yet not been investigated. The objective of this study is to predict the thrombus formation process in the idealized medical device by coupling computational fluid dynamics and a macroscopic hemodynamic-based thrombus model. We developed the hemodynamic-based thrombus model by considering the effect of platelet consumption. The thrombus model was quantitatively validated by referring to the latest thrombosis experiment, which was performed in a backward-facing step with human blood flow. The same setup was applied in the FDA nozzle to simulate the thrombus formation process. The thrombus shaped like a ring was firstly observed in the FDA benchmark nozzle. Subsequently, the accuracy of the shear-stress transport turbulence model was confirmed in different turbulent flow conditions. Five scenarios with different Reynolds numbers were carried out. We found that turbulence could change the shape of centrosymmetric thrombus to axisymmetric and high Reynolds number blood flow would delay or even prevent thrombosis. Overall, the present study reports the thrombosis process in the FDA benchmark nozzle using the numerical simulation method, and the primary findings may shed light on the effect of turbulence on thrombosis. [ABSTRACT FROM AUTHOR]

Objectives: The left subclavian artery during thoracic endovascular aortic repair could be reconstructed by in situ fenestration. This study aims to evaluate the effects of thoracic endovascular aortic repair with in situ fenestration thoracic endovascular aortic repair on the hemodynamics. Methods: A male patient suffering from aortic dissection is treated by in situ fenestration thoracic endovascular aortic repair and the fenestration stent implanted in the left subclavian artery is partially protruding in the aortic arch for the stability. Two-phase non-Newtonian blood model is applied and three-element Windkessel model is implemented to reproduce physiological pressure waves. Simulations are carried out in three postoperative models to analyze different in situ fenestration thoracic endovascular aortic repair strategies; Case A: the protrusion length of fenestration stent is 23.2 mm representing the clinical postthoracic endovascular aortic repair aorta; Case B: the protrusion length is reduced by half simulating the improved surgery; Case C: the protruding portion is removed to simulate the ideal fenestration. Results: In Case A, a pressure difference is found on the fenestration stent surface and a blood acceleration phenomenon around the stent is observed. Only 2.36% of the inlet blood flow is assigned to the left subclavian artery. In the improved surgery, the blood supply to the left subclavian artery is elevated to 4.01%. As for the ideal fenestration, a further improvement is observed (6.14%). Moreover, the aortic arch surface exposed to low time-averaged wall shear stress expands significantly when the protrusion length is shortened. Conclusions: Overall, we conclude that appropriately shortening the protrusion length of the stent-graft may improve the efficacy of in situ fenestration thoracic endovascular aortic repair from the perspective of hemodynamics. [ABSTRACT FROM AUTHOR]

The behavior of blood cells and vessel compliance significantly influence hemodynamic parameters, which are closely related to the development of aortic dissection. Here the two-phase non-Newtonian model and the fluid-structure interaction (FSI) method are coupled to simulate blood flow in a patient-specific dissected aorta. Moreover, three-element Windkessel model is applied to reproduce physiological pressure waves. Important hemodynamic indicators, such as the spatial distribution of red blood cells (RBCs) and vessel wall displacement, which greatly influence the hemodynamic characteristics are analyzed. Results show that the proximal false lumen near the entry tear appears to be a vortex zone with a relatively lower volume fraction of RBCs, a low time-averaged wall shear stress (TAWSS) and a high oscillatory shear index (OSI), providing a suitable physical environment for the formation of atherosclerosis. The highest TAWSS is located in the narrow area of the distal true lumen which might cause further dilation. TAWSS distributions in the FSI model and the rigid wall model show similar trend, while there is a significant difference for the OSI distributions. We suggest that an integrated model is essential to simulate blood flow in a more realistic physiological environment with the ultimate aim of guiding clinical treatment. [ABSTRACT FROM AUTHOR]

The five anthraquinones compounds (including aloe-emodin, emodin, physcion, chrysophanol, and rhein) are regarded as the main effective ingredients in rhubarb (Dahuang in Chinese, one of the commonly used Chinese herbal medicines). In this work, a simple and effective solid phase extraction (SPE) method based on bis(tetraoxacalix[2]arene[2]triazine) modified silica gel as adsorbent was developed. Coupled with UHPLC-FLD, the developed method was successfully applied for the measuring of main anthraquinones in human urine after oral administration of the extracts of rhubarb. To obtain the highest recoveries of the five anthraquinones in the SPE process, the main parameters which may affect extraction efficiency were optimized. The optimized sorbent amount, sample loading pH, sample loading rate, washing solution, and eluent condition were obtained. The developed method showed good linearity in 0.012–1.800 μg mL−1 for the five anthraquinones with correlation coefficients more than 0.9993. The investigated LOD values ranged from 3.9 to 5.7 ng mL−1, while the LOQs were between 12.0 and 18.2 ng mL−1. The recoveries of the method were also investigated, which were in the range of 94.8–106.6%. The application of the mixed-mode SPE materials in the proposed method was feasible and simple, and suitable for the enrichment of anthraquinones in urine samples. [ABSTRACT FROM AUTHOR]

Sclerotinia rot infected by cosmopolitan fungi Sclerotinia sclerotiorum is a serious and destructive disease in carrot production, especially during their postharvest storage. Natural products with the advantages of environmentally friendly and safety have been widely concerned. This research estimated the impact of hinokitiol against S. sclerotiorum and on the quality of carrots. In vitro and in vivo tests demonstrated that hinokitiol had promising antifungal activities against both carbendazim-susceptible and -resistant isolates of S. sclerotiorum. Importantly, it effectively kept the quality and prolonged the shelf life of carrot by declining the loss of weight, ascorbic acid, carotenoid, and total phenolics content, preventing the formation of malondialdehyde, and enhancing the activities of antioxidant enzymes. Further study found that hinokitiol inhibited the formation of sclerotia by destroying the morphology and the integrality of cell membrane, reduced the pathogenicity by suppressing the synthesis of oxalic acid and exopolysaccharide, declined the activities of enzymes and the gene expression related to sclerotia development in S. sclerotiorum. These information evidenced the great potential of hinokitiol as a natural fresh-keeping agent for the management of postharvest decay infected by S. sclerotiorum. • Hinokitiol had promising antimicrobial activities against S. sclerotiorum. • It maintained the quality and extend the shelf life of carrots. • It inhibited the myceliogenic and carpogenic germination of sclerotia. • Hinokitiol prevented the development of sclerotia might the main action mechanism. [ABSTRACT FROM AUTHOR]

Anthracnose caused by Colletotrichum musae is a devastating post-harvest disease on bananas, and it leads to serious economic losses. Exploring environmentally friendly natural compounds to manage anthracnose in fruit has been attracting more attention. In the current study, the effect of hinokitiol against C. musae and on banana quality was investigated. Our results showed that hinokitiol exhibited promising antifungal activities both in vitro and in vivo. Importantly, it effectively delayed banana ripening by maintaining weight, color, firmness, and TSS content, and it dramatically reduced the release of ethylene, the respiration rate, and the expression of genes involved in releasing ethylene. Moreover, the activities of defense-related enzymes including SOD, POD, and APX were enhanced by hinokitiol. The mechanism of hinokitiol against C. musae may be attributed to the destruction on the integrity of the plasma membrane, which leads to the leakage of cellular constituents and eventually the cell death of C. musae. Taken together, this study provided substantial evidence that hinokitiol had great potential to be developed as a natural antifungal agent against C. musae, prolonging the storage period of postharvest bananas. • Hinokitiol exhibited promising activity against C. musae both in vitro and in vivo. • Hinokitiol delayed banana ripening and enhanced the antioxidant enzyme activities.s • Hinokitiol destroyed the morphology and the cell membranes integrity of C. musae. [ABSTRACT FROM AUTHOR]

The transfers of potassium ion (K+) facilitated by 3,3′,6,6′-tetrakis[ p-( n-dodecyloxy)benzoyloxymethyl]dibenzo-18-crown-6 (L1) and of sodium ion (Na+) facilitated by 3′,6′-bis{3′′,4′′,5′′-tris[ p-( n-dodecyloxy)benzyloxy]benzoyloxymethyl}benzo-15-crown-5 (L2) have been investigated at the micro-water/1.2-dichloroethane (micro-W/DCE) interface supported at the tip of a micropipette by cyclic voltammetry and chronoamperometry. The experimental results demonstrate that the mechanisms of both facilitated ion transfer (FIT) processes correspond to the transfer by an interfacial complexation (TIC) and the transfer by an interfacial dissociation (TID) processes. Some thermodynamic parameters, such as, stoichiometry, diffusion coefficient and the association constants are evaluated by cyclic voltammetry. Furthermore, the chronoamperometry has been employed to explore the roughness of the interface supported at the micropipette by analysis of the current-time curves based on the system of facilitated Na+ transfer by L2 at the water/DCE interface. [ABSTRACT FROM AUTHOR]

In the present study, a total of 21 natural or synthetic small-molecule organic acids were selected and determined for their activity against postharvest gray mold caused by B. cinerea. Overall, cuminic acid, which was extracted from the seed of Cuminum cyminum L, showed the most promising antifungal activity against B. cinerea both in vitro and in vivo. The study on action mechanism showed that cuminic acid could inhibit the development of sclerotia and the secretion of oxalic acid, destroy the cell membrane integrity, and down regulate the expression of several key genes involved in sclerotia development and pathogenicity of B. cinerea. Furthermore, cuminic acid could potentially reduce the degradation of TSS and TA content, while it had no significant effect on the weight loss, firmness, and VC content of apple and tomato. Importantly, cuminic acid could enhance the antioxidant enzyme activities of the fruits. All these results demonstrate the antifungal activity and highlight the great potential of cuminic acid as an alternative environmental-friendly agent for the control of postharvest gray mold both on fruits and vegetables. [Display omitted] • Systematic investigated the activity of small-molecule organic acids against B. cinerea. • Explored the potential action mechanism of cuminic acid against B. cinerea. • Evaluated the effect of cuminic acid on the quality of apple and tomato fruits. [ABSTRACT FROM AUTHOR]

To study the effect of quercetin (QUR) on modulating immune effects, enhancing anti-tumor activity, and reducing drug related side effects, three QUR nanosuspensions (QUR-NPs) with different particle sizes were prepared by a microprecipitation-high pressure homogenization method using mPEG-DCA as a stabilizer. Dynamic light scattering was used to analyze the particle sizes of the three QUR-NPs. The results of stability tests showed that the three QUR-NPs had good storage and plasma stability. It was confirmed that plasma protein adsorption occurred for all three QUR-NPs. The results of DSC, DTG, XRPD, and Raman spectroscopy showed that there was no significant change in the crystal form of QUR for any of the three QUR-NPs compared with the commercial QUR. The in vitro dissolution rate of the three QUR-NPs was significantly faster than that of the micronized QUR, with the dissolution rate increasing as particle size decreased. All three QUR-NPs showed stronger in vitro inhibitory activity on MCF-7 cells than the pure QUR solution, with the largest NPs having the strongest inhibitory effect. The pharmacokinetic parameters in rats showed that the MRT and t 1/2 of the QUR-NPs increased as particle size increased. QUR-NPs and the pure QUR solution showed obvious anti-tumor effects against murine hepatic carcinoma H22 model in vivo, although they were not as effective as cyclophosphamide (CTX). However, the anti-tumor effect of the large QUR-NPs combined with CTX was the strongest among all the tested groups. From the results of the thymus and spleen index, it was found that the QUR-NPs could not only regulate the immunity of tumor-bearing mice, but also alleviate the immunosuppression caused by CTX and protect normal tissues, all while enhancing the anti-tumor effect. The immunomodulatory effect of the QUR-NPs on tumor-bearing mice was significantly better than that of the pure QUR solution. Therefore, nanosuspensions can be used as a new drug delivery system for QUR to assist tumor therapy and regulate immunity. [ABSTRACT FROM AUTHOR]

Bioactive peptides are attractive candidates for drug development. QAW is a tripeptide that is obtained from an anti-inflammatory protein-Annexin A1 (ANXA1). Previous studies showed that QAW alleviated inflammation in experimental colitis and inflammatory bowel disease via NF-κB inhibition. This study establishes adjuvant-induced arthritis (AIA) mouse models and explores the anti-inflammatory efficacy of QAW in AIA mice. To enhance the targeting, responsiveness, and efficacy of QAW to inflammation, QAW (Q) is modified with a cell penetrating peptide (T), a matrix metalloproteases-2/9 (MMP-2/9) digestive peptide (M), and an inflammation targeting peptide-RGD (R). The designed RMTQ demonstrates enhanced delivery to cytoplasm, higher reduction of pro-inflammatory factors, and better efficacy than QAW. The anti-inflammatory efficacy of RMTQ is similar to that of DEX in this study whereas RMTQ treatment shows a higher safety than that of DEX. In sum, this study demonstrates that RMTQ can be a potential therapeutic for inflammatory arthritis. [ABSTRACT FROM AUTHOR]

Abstract: A highly sensitive electrochemical sensor made of a glassy carbon electrode (GCE) coated with a Langmuir–Blodgett film (LB) containing polyaniline (PAn) doped with p-toluenesulfonic acid (PTSA) (LB/PAn-PTSA/GCE) has been used for the detection of trace concentrations of Ag+. UV–vis absorption spectra indicated that the PAn was doped by PTSA. The surface morphology of the PAn LB film was characterized by atomic force microscopy (AFM). The electrochemical properties of this LB/PAn-PTSA/GCE were studied using electrochemical impedance spectroscopy (EIS) and cyclic voltammetry. The LB/PAn-PTSA/GCE was used as a voltammetric sensor for determination of trace Ag+ at pH 5.0 using linear scanning stripping voltammetry. Under the optimal experimental conditions, the stripping current was proportional to the Ag+ concentration over the range from 6.0×10−10 molL−1 to 1.0×10−6 molL−1, with a detection limit of 4.0×10−10 molL−1. The high sensitivity, selectivity, and stability of this LB/PAn-PTSA/GCE also demonstrated its practical utility for simple, rapid and economical determination of Ag+ in water samples. [Copyright &y& Elsevier]

[Display omitted] Tumor multidrug resistance (MDR) is one of the main reasons for the failure of clinical chemotherapy. Here, a bio-responsive anti-drug-resistant polymer micelle that can respond to the reductive GSH in the tumor microenvironment (TME) for delivery of HCPT was designed. A new type of polymer with anti-drug resistance and anti-tumor effect was synthesized and used to encapsulated HCPT to form reduction-sensitive micelles (PDSAH) by a thin-film dispersion method. It is demonstrated that the micelle formulation improves the anti-tumor activity and biosafety of HCPT, and also plays a significant role in reversing the drug resistance, which contributes to inhibiting the tumor growth and prolonging the survival time of H22 tumor-bearing mice. The results indicate that this nanoplatform can serve as a flexible and powerful system for delivery of other drugs that are tolerated by tumors or bacteria. [ABSTRACT FROM AUTHOR]

Type B aortic dissection is a major aortic catastrophe that can be acutely complicated by rapid expansion, rupture, and malperfusion syndromes. The separation of the intima from aortic walls will form a second blood-filled lumen defined as "false lumen (FL)", where the thrombus is more likely to form due to the local stasis hemodynamic conditions. Complete thrombosis of FL is associated with a beneficial outcome while patency and partial thrombosis will lead to later complications. However, the thrombosis mechanism is still unclear and little is known about the impact of chemical species transported by blood flow on this process. The proteins involved in the coagulation cascade (CC) may play an important role in the process of thrombosis, especially in the activation and stabilization of platelets. Based on this hypothesis, a reduced-order fluid-chemical model was established to simulate CC in an aortic dissection phantom with two tears. A high level of fibrin is continuously observed at the top of the FL and some time-varying areas between two tears, indicating a high likelihood of thrombus formation there. This finding is consistent with the clinical observation. The time evolution of coagulation factors is greatly affected by local hemodynamics, especially in the high disturbance zone where the evolution has characteristics of periodic changes consistent with the flow field. The ability of the proposed model to reproduce the CC response provides a potential application to integrate with a model that can simulate platelet activities, forming a biochemical-based model which would help unveil the mechanisms of thrombosis in FL and the clinical decision of appropriate treatment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The impact of left subclavian artery (LSA) coverage during thoracic endovascular aortic repair (TEVAR) on the circulatory system is not fully understood. Here, we coupled a single-phase non-Newtonian model with fluid-structure interaction (FSI) technique to simulate blood flow in an acute type B aortic dissection. Three-element Windkessel model was implemented to reproduce physiological pressure waves, where a new workflow was designed to determine model parameters with the absence of measured data. Simulations were carried out in three geometric models to demonstrate the consequence of TEVAR with the LSA coverage; case A: pre-TEVAR aorta; case B: post-TEVAR aorta with the disappearance of LSA; case C: post-TEVAR aorta with virtually adding LSA. Results show that the blood flow through the compressed true lumen is only 8.43%, which may lead to ischemia in related organs. After TEVAR, the wall pressure on the stented segment increases and blood flow in the supra-aortic branches and true lumen is improved. Meantime, the average deformation of the aorta is obviously reduced due to the implantation of the stent graft. After virtually adding LSA, significant changes in the distribution of blood flow and two indices based on wall shear stress are observed. Moreover, the movement of residual false lumen becomes stable, which could contribute to patient recovery. Overall, this study quantitatively evaluates the efficacy of TEVAR for acute type B aortic dissection and demonstrates that the coverage of LSA has a considerable impact on the important hemodynamic parameters., (Copyright © 2019 by ASME.)

Despite great improvements in the past decades, the controllable fabrication of metal nanoelectrodes still remains very challenging. In this work, a simple and general way to fabricate metal nanoelectrodes (Ag, Au, and Pt) is developed. On the basis of interfacial reactions at nano-liquid/liquid interfaces supported at nanopipettes, the nanoparticles can be formed in situ and have been used to block the orifices of pipettes to make nanoelectrodes. The effect of the driving force for interfacial reaction at the liquid/liquid interface, the ratio of redox species in organic and aqueous phases, and the surface charge of the inner wall of a pipette have been studied. The fabricated nanoelectrodes have been characterized by scanning electron microscopy (SEM) and electrochemical techniques. A silver electrode with about 10 nm in radius has been employed as the scanning electrochemical microscopy (SECM) probe to explore the thickness of a water/nitrobenzene (W/NB) interface, and this value is equal to 0.8 ± 0.1 nm (n = 5). This method of fabrication of nanoelectrodes can be extended to other metal or semiconductor electrodes.