Y. J. Cui

Low Expression of lncRNA-GAS5 Is Implicated in Human Primary Varicose Great Saphenous Veins

The cellular mechanisms of primary varicose great saphenous veins (GSVs) involve inflammation, apoptosis, and proliferation of local cells and extracellular matrix degradation. Long non-coding RNAs (lncRNAs) play important roles in these cellular processes; however, which and how lncRNAs related to these mechanisms take effect on GSVs remain unclear. By screening lncRNAs that might experience changes in GSV varicosities, we selected the lower expressed lncRNA-GAS5 (growth arrest specific transcript 5) for functional assessments. Silencing of lncRNA-GAS5 promoted cell proliferation and migration, and cell cycle of the human saphenous vein smooth muscle cells (HSVSMCs), whereas overexpressing it inhibited these cellular behaviors and reduced apoptosis of HSVSMCs. RNA pull-down experiment revealed a direct bind of lncRNA-GAS5 to a Ca2+-dependent RNA-binding protein, Annexin A2. Further experiments showed that silencing of Annexin A2 reduced the HSVSMCs proliferation and vice versa. In the context of lncRNA-GAS5 knockdown, silencing of Annexin A2 reduced the proliferation of HSVSMCs while overexpression of Annexin A2 increased the proliferation. Thus, the low expression of lncRNA-GAS5 may facilitate HSVSMCs proliferation and migration through Annexin A2 and thereby the pathogenesis of GSV varicosities.

SNX13 reduction mediates heart failure through degradative sorting of apoptosis repressor with caspase recruitment domain

Heart failure (HF) is associated with complicated molecular remodelling within cardiomyocytes; however, the mechanisms underlying this process remain unclear. Here we show that sorting nexin-13 (SNX13), a member of both the sorting nexin and the regulator of G protein signalling (RGS) protein families, is a potent mediator of HF. Decreased levels of SNX13 are observed in failing hearts of humans and of experimental animals. SNX13-deficient zebrafish recapitulate HF with striking cardiomyocyte apoptosis. Mechanistically, a reduction in SNX13 expression facilitates the degradative sorting of apoptosis repressor with caspase recruitment domain (ARC), which is a multifunctional inhibitor of apoptosis. Consequently, the apoptotic pathway is activated, resulting in the loss of cardiac cells and the dampening of cardiac function. The N-terminal PXA structure of SNX13 is responsible for mediating the endosomal trafficking of ARC. Thus, this study reveals that SNX13 profoundly affects cardiac performance through the SNX13-PXA-ARC-caspase signalling pathway.

Cardiac Nav1.5 is modulated by ubiquitin protein ligase E3 component n-recognin UBR3 and 6

The voltage‐gated Na+ channel Nav1.5 is essential for action potential (AP) formation and electrophysiological homoeostasis in the heart. The ubiquitin–proteasome system (UPS) is a major degradative system for intracellular proteins including ion channels. The ubiquitin protein ligase E3 component N‐recognin (UBR) family is a part of the UPS; however, their roles in regulating cardiac Nav1.5 channels remain elusive. Here, we found that all of the UBR members were expressed in cardiomyocytes. Individual knockdown of UBR3 or UBR6, but not of other UBR members, significantly increased Nav1.5 protein levels in neonatal rat ventricular myocytes, and this effect was verified in HEK293T cells expressing Nav1.5 channels. The UBR3/6‐dependent regulation of Nav1.5 channels was not transcriptionally mediated, and pharmacological inhibition of protein biosynthesis failed to counteract the increase in Nav1.5 protein caused by UBR3/6 reduction, suggesting a degradative modulation of UBR3/6 on Nav1.5. Furthermore, the effects of UBR3/6 knockdown on Nav1.5 proteins were abolished under the inhibition of proteasome activity, and UBR3/6 knockdown reduced Nav1.5 ubiquitylation. The double UBR3–UBR6 knockdown resulted in comparable increases in Nav1.5 proteins to that observed for single knockdown of either UBR3 or UBR6. Electrophysiological recordings showed that UBR3/6 reduction‐mediated increase in Nav1.5 protein enhanced the opening of Nav1.5 channels and thereby the amplitude of the AP. Thus, our findings indicate that UBR3/6 regulate cardiomyocyte Nav1.5 channel protein levels via the ubiquitin–proteasome pathway. It is likely that UBR3/6 have the potential to be a therapeutic target for cardiac arrhythmias.

Investigation on swelling-shrinkage behavior of unsaturated compacted GMZ bentonite on wetting-drying cycles

It is generally recognized that swelling/shrinkage deformation and accumulative deformation of compacted expansive soil on wetting-drying cycles are strongly influenced by the specimen’s dry density and the net stress applied. However, investigations on the coupling effects of dry density and vertical net stress on the swelling/shrinkage deformation and accumulative deformation are limited. Cyclical wetting-drying tests were conducted on unsaturated compacted GMZ bentonite specimens with three dry densities under five vertical net stresses. The influence of vertical stress on accumulative deformation was analyzed. Then, the critical vertical stress was proposed for specimens with different dry densities. The effect of dry density on accumulative deformation was studied and the critical dry density was determined for different vertical stresses. Based on these, the concept of critical swelling-shrinkage line is proposed in the e-p space. According to the relationship between the initial state of specimen and the critical swelling-shrinkage line, a state parameter is proposed for determination of the accumulative strain on wetting-drying cycles.

Adsorption, Desorption and Competitive Adsorption of Heavy Metal Ions from Aqueous Solution onto GMZ01 Bentonite

The geochemical processes of adsorption, desorption and competitive adsorption on bentonite are important for the long-term safety assessment of high-level nuclear waste (HLW) repositories. In this paper, batch adsorption, desorption experiments of Cr(III) and the competitive adsorption experiment with Cu(II) were performed in aqueous solutions on Gao-miao-zi (GMZ) bentonite. Results show that the pH value significantly affect the Cr(III) adsorption/desorption on GMZ bentonite. Both adsorption and desorption isotherms are consistent with the Freundlich equation. The distribution coefficients (K d ) were calculated from the competitive adsorption test; Higher K d values of Cr(III) were obtained than that of Cu(II), indicating the stronger retention capacity of Cr(III) on GMZ bentonite in a binary metal system.

Unsaturated Hydraulic Conductivity of Highly Compacted Sand-GMZ01 Bentonite Mixtures Under Confined Conditions

Highly compacted sand-bentonite mixtures are commonly recognized as potential buffer/backfill materials using in deep geological repository for high-level radioactive waste disposals. After water retention curve was determined, instantaneous profile method was employed in this paper for measuring unsaturated hydraulic conductivity of highly compacted GMZ01 bentonite and quartz sand mixture (7:3), with a dry density of 1.90 g/cm3, under confined conditions. Results show that, as suction decreased from 60 MPa to zero, the measured unsaturated hydraulic conductivity firstly decreased and then turned to increase. This phenomenon can be explained in terms of microstructure changes during hydration under constant-volume conditions.

The research status of the Sorting Nexins Family

Sorting nexins (SNXs) is a general term for a large family of proteins containing a phox-homology (PX) domain. This family consists of 33 members in the mammalian proteome, whose PX domain efficiently binds phosphatidylinositol-3-phosphate, and is therefore recruited by early endosomal membranes. The PX domain is also involved in important protein-protein interactions, including the trafficking of cargo-adaptors and membrane-associated scaffolds in regulating cell signaling. Therefore, SNXs may play important roles in endocytosis, endosomal sorting, cell signaling, membrane trafficking, membrane remodeling and organelle motility. In the present article, we propose a classification of the SNX proteins into three distinct subfamilies on the basis of their structural differences. We also examine the evidence linking SNXs to various disorders, with a particular focus on cancer, Alzheimers disease, neurological disorders, and cardiovascular disease. This review aims to summarize SNX protein discovery, genetic mapping, construction, classification, and role in disease.