CircHAT1 regulates the proliferation and phenotype switch of vascular smooth muscle cells in lower extremity arteriosclerosis obliterans through targeting SFRS1.

This study aimed to decipher the mechanism of circular ribonucleic acids (circRNAs) in lower extremity arteriosclerosis obliterans (LEASO). First, bioinformatics analysis was performed for screening significantly down-regulated cardiac specific circRNA-circHAT1 in LEASO. The expression of circHAT1 in LEASO clinical samples was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of splicing factor arginine/serine-rich 1 (SFRS1), α-smooth muscle actin (α-SMA), Calponin (CNN1), cyclin D1 (CNND1) and smooth muscle myosin heavy chain 11 (SMHC) in vascular smooth muscle cells (VSMCs) was detected by Western blotting. Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) and Transwell assays were used to evaluate cell proliferation and migration, respectively. RNA immunoprecipitation (RNA-IP) and RNA pulldown verified the interaction between SFRS1 and circHAT1. By reanalyzing the dataset GSE77278, circHAT1 related to VSMC phenotype conversion was screened, and circHAT1 was found to be significantly reduced in peripheral blood mononuclear cells (PBMCs) of LEASO patients compared with healthy controls. Knockdown of circHAT1 significantly promoted the proliferation and migration of VSMC cells and decreased the expression levels of contractile markers. However, overexpression of circHAT1 induced the opposite cell phenotype and promoted the transformation of VSMCs from synthetic to contractile. Besides, overexpression of circHAT1 inhibited platelet-derived growth factor-BB (PDGF-BB)-induced phenotype switch of VSMC cells. Mechanistically, SFRS1 is a direct target of circHAT1 to mediate phenotype switch, proliferation and migration of VSMCs. Overall, circHAT1 regulates SFRS1 to inhibit the cell proliferation, migration and phenotype switch of VSMCs, suggesting that it may be a potential therapeutic target for LEASO.

Novel Association of KLRC4-KLRK1 Gene Polymorphisms with Susceptibility and Progression of Antithyroid Drug-Induced Agranulocytosis.

OBJECTIVE: Antithyroid drug (ATD)-induced agranulocytosis (TIA) is the most serious adverse effect during ATD treatment of Graves' disease (GD). Previously, the MICA gene was reported to be associated with TIA. MICA protein is an important ligand for the NKG2D protein, which is encoded by the KLRK1 gene and KLRC4-KLRK1 read-through transcription. This study further investigated the association between KLRC4-KLRK1 gene polymorphisms and susceptibility to TIA. METHODS: Twenty-eight candidate single nucleotide polymorphisms (SNPs) on KLRC4-KLRK1 read-through transcription were evaluated by the iPLEX MassARRAY system in 209 GD control patients and 38 TIA cases. RESULTS: A significant association of rs2734565 polymorphism with TIA was found (p=0.02, OR=1.80, 95% CI=1.09-2.96). The haplotype C-A-A-C-G, including rs2734565-C, was associated with a significantly higher risk of TIA (p=4.79E-09, OR=8.361, 95% CI=3.737-18.707). In addition, the interval time from hyperthyroidism to agranulocytosis onset was shorter in patients carrying the rs2734565-C allele than in non-carrying groups (45.00 (14.00-6570.00) d vs. 1080.00 (30.00-3600.00) d, p=0.046), and the interval from ATD treatment to agranulocytosis onset was also shorter in patients carrying rs2734565-C allele (29.00 (13.00-75.00) d vs. 57.50 (21.00-240.00) d, p=0.023). CONCLUSIONS: The findings suggest that the KLRC4-KLRK1 gene polymorphism is associated with susceptibility and progression of ATD-induced agranulocytosis. Patients carrying the rs2734565-C allele had a higher susceptibility and faster onset time of TIA.

ReIPS: A Secure Cloud-Based Reputation Evaluation System for IoT-Enabled Pumped Storage Power Stations.

Reputation evaluation is an effective measure for maintaining secure Internet of Things (IoT) ecosystems, but there are still several challenges when applied in IoT-enabled pumped storage power stations (PSPSs), such as the limited resources of intelligent inspection devices and the threat of single-point and collusion attacks. To address these challenges, in this paper we present ReIPS, a secure cloud-based reputation evaluation system designed to manage intelligent inspection devices' reputations in IoT-enabled PSPSs. Our ReIPS incorporates a resource-rich cloud platform to collect various reputation evaluation indexes and perform complex evaluation operations. To resist single-point attacks, we present a novel reputation evaluation model that combines backpropagation neural networks (BPNNs) with a point reputation-weighted directed network model (PR-WDNM). The BPNNs objectively evaluate device point reputations, which are further integrated into PR-WDNM to detect malicious devices and obtain corrective global reputations. To resist collusion attacks, we introduce a knowledge graph-based collusion device identification method that calculates behavioral and semantic similarities to accurately identify collusion devices. Simulation results show that our ReIPS outperforms existing systems regarding reputation evaluation performance, particularly in single-point and collusion attack scenarios.

Tailor-Made Dispersion and Distribution of Stereocomplex Crystallites in Poly(l-lactide)/Elastomer Blends toward Largely Enhanced Crystallization Rate and Impact Toughness.

Stereocomplex (SC) crystallites, formed between poly(l-lactide) (PLLA) and poly(d-lactide), exhibit great potential to substantially enhance crystallization rate of PLLA-based materials as an eco-friendly nucleating agent. However, the nucleation efficiency of the SC crystallites is still far below an expected level, mostly on account of their strong aggregation tendency in PLLA/PDLA melts. Herein, taking PLLA/poly(ethylene-methyl acrylate-glycidyl methacrylate) (E-MA-GMA) blends as an example, we report a unique and facile strategy to control the dispersion and distribution of SC crystallites within the PLLA matrix by using elastomeric E-MA-GMA as carrier for the incorporation of PDLA. To do this, PDLA was first blended with E-MA-GMA or chemically grafted onto the E-MA-GMA. During subsequent melt-blending of PLLA and the E-MA-GMA/PDLA master batch, the PDLA chain clusters predispersed in the E-MA-GMA phase can gradually migrate into PLLA matrix and then collaborate with the matrix chains to form large amounts of tiny and well-dispersed SC crystallites. Compared with the SC-crystallite agglomerates formed by the direct melt-blending of PLLA and PDLA components, such tiny SC crystallites are much more effective in accelerating PLLA matrix crystallization. More interestingly, when PDLA chains are grafted onto the EMA-GMA, the formed SC crystallites tend to preferentially distribute at the blend interface and thus induce not only optimal nucleation efficiency but also superior impact toughness because these interface-localized SC crystallites can also serve as bridges to enhance interface adhesion. This work could open a new avenue in designing heat-resistant and supertough PLLA blends via controllable construction of SC crystallites.

Safety and efficacy of degradable vs. permanent polymer drug-eluting stents: a meta-analysis of 18,395 patients from randomized trials.

BACKGROUND: Degradable polymer drug-eluting stents (DP-DES) represent a promising strategy to improve the delayed healing and hypersensitive reaction in the vessel. However, the efficacy and safety of DP-DES vs. permanent polymer drug-eluting stents (PP-DES) are less well defined. The aim of this meta-analysis was to compare the total, short (<30 days), mid (30 days-1 year) and long (>1 year) term outcomes of DP-DES vs. PP-DES METHODS: PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for randomized clinical trials to compare any of approved DP- and PP-DES. Efficacy endpoints were target-lesion revascularization (TLR) and in-stent late loss (ISLL). Safety endpoints were death, myocardial infarction (MI), and composite of definite and probable stent thrombosis (ST). RESULTS: The meta-analysis included 19 RCTs (n=18,395) with interesting results. As compared with DES, there was a significantly reduced very late ST (OR [95% CI]=0.42 [0.24-0.77], p=0.852) and ISLL (OR [95% CI]=-0.07 [-0.12-0.02], p=0.000) in DP-DES patients. However, there were no differences between DP-DES and PP-DES for other safety and efficiency outcomes, except that the stratified analysis showed a significant decreased TLR with DP-DES as compared to paclitaxel-eluting stent (OR [95% CI]=0.41 [0.20-0.81], p=0.457). CONCLUSIONS: DP-DES are more effective in reducing very late ST and ISLL, as well as comparable to PP-DES with regard to death, TLR and MI. Further large RCTs with long-term follow-up are warranted to better define the relative merits of DP-DES.