Circ_0003423 Alleviates ox-LDL-Induced Human Brain Microvascular Endothelial Cell Injury via the miR-589-5p/TET2 Network.

Brain microvascular endothelial cells (BMECs) injury is one of the main causes of cerebrovascular diseases. Circular RNA (circRNA) has been found to be involved in the regulation of cerebrovascular diseases progression. However, the role and mechanism of circ_0003423 in cerebrovascular diseases is still unclear. In our study, oxidized low density lipoprotein (ox-LDL)-induced HBMEC-IM cells were used to construct cerebrovascular cell injury model in vitro. Quantitative real-time PCR was used to determine the expression levels of circ_0003423, miR-589-5p and Ten-eleven translocation 2 (TET2). The interactions between miR-589-5p and circ_0003423 or TET2 were confirmed by dual-luciferase reporter assay, RIP assay and RNA pull-down assay. Cell viability, angiogenesis and apoptosis were measured using cell counting kit 8 assay, tube formation assay and flow cytometry. Cell oxidative stress was evaluated by detecting the levels of reactive oxygen species and lactate dehydrogenase. The protein levels were examined by western blot analysis. Our results showed that circ_0003423 was a downregulated circRNA in ox-LDL-induced HBMEC-IM cells. In the terms of mechanism, circ_0003423 was found to be a sponge of miR-589-5p. Function analysis showed that circ_0003423 overexpression could relieve ox-LDL-induced HBMEC-IM cell injury, and this effect could be reversed by miR-589-5p mimic. In addition, TET2 was confirmed to be a target of miR-589-5p, and its overexpression could alleviate ox-LDL-induced HBMEC-IM cell injury. Moreover, the rescue experiments also confirmed that TET2 silencing could abolish the inhibition effect of anti-miR-589-5p on ox-LDL-induced HBMEC-IM cell injury. In summary, our data showed that circ_0003423 alleviated ox-LDL-induced HBMEC-IM cells injury through regulating the miR-589-5p/TET2 axis.

Transcatheter closure of doubly committed subarterial ventricular septal defects with the Amplatzer ductal occluder: initial experience.

BACKGROUND: There is limited experience about transcatheter closure of doubly committed subarterial ventricular septal defects with Amplatzer ductal occluder. METHODS: Between March, 2015 and July, 2017, a total of 22 patients with doubly committed subarterial ventricular septal defects received transcatheter closure using Amplatzer ductal occluder and underwent clinical follow-up for at least 6 months. RESULTS: Device implantation was finally successful in 21 (95.4%) patients despite failed occlusion in one patient and intra-procedural replacement of unsuitable occluders in four (19.0%) patients. In mean 12.3 months of follow-up, there were no major complications (death, aortic valve or sinus rupture, device dislocation or embolisation, grade 2 new-onset aortic regurgitation, etc.), resulting in clinical occlusion success of 95.4%. Mechanical haemolysis occurred in one patient and resolved with medication. Residual shunt was observed in 11 (52.4%) patients (9 mild, 2 moderate-severe) post-procedurally, 14 (66.7%) patients (12 mild, 2 moderate-severe) in hospital stay, and 2 (9.5%) patients (2 mild, 0 moderate-severe) at the last follow-up. Device-induced new-onset aortic regurgitation was found in nine (42.8%) patients (9 mild, 0 moderate-severe) post-procedurally and in hospital stay, which was resolved in two (9.5%) patients and unchanged in seven (33.3%) patients at the last follow-up. Another four (19.0%) patients newly developed mild aortic regurgitation during follow-up. CONCLUSIONS: Transcatheter closure of doubly committed subarterial ventricular septal defects with Amplatzer ductal occluder is technically feasible in the selected patients. However, further study is needed to confirm its long-term clinical outcomes.

Oxidized high density lipoprotein induces macrophage apoptosis via toll-like receptor 4-dependent CHOP pathway.

Oxidized HDL (ox-HDL), unlike native HDL that exerts antiatherogenic effects, plays a proatherogenic role. However, the underlying mechanisms are not completely understood. This study was designed to explore the inductive effect of ox-HDL on endoplasmic reticulum (ER) stress-CCAAT-enhancer-binding protein homologous protein (CHOP)-mediated macrophage apoptosis and its upstream mechanisms. Our results showed that ox-HDL could be ingested by macrophages, causing intracellular lipid accumulation. As with tunicamycin (an ER stress inducer), ox-HDL induced macrophage apoptosis with concomitant activation of ER stress pathway, including nuclear translocation of activating transcription factor 6, phosphorylation of protein kinase-like ER kinase and eukaryotic translation initiation factor 2α, and upregulation of glucose-regulated protein 78 and CHOP, which were inhibited by 4-phenylbutyric acid (PBA, an ER stress inhibitor) and CHOP gene silencing. Additionally, diphenyleneiodonium (DPI, an oxidative stress inhibitor), probucol (a reactive oxygen species scavenger), and toll-like receptor 4 (TLR4) silencing reduced ox-HDL-induced macrophage apoptosis, oxidative stress, and CHOP upregulation. Moreover, HDL isolated from patients with metabolic syndrome induced macrophage apoptosis, oxidative stress, and CHOP upregulation, which were blocked by PBA and DPI. These data indicate that ox-HDL may activate ER stress-CHOP-induced apoptotic pathway in macrophages via enhanced oxidative stress and that this pathway may be mediated by TLR4.

[Advanced glycated albumin induces macrophage apoptosis via activating caspase-12 pathway].

The purpose of the present study was to investigate the effect of advanced glycated albumin (AGE-alb) on the activation of caspase-12, a key molecule in endoplasmic reticulum stress (ERS)-associated apoptotic pathway, and to elucidate the underlying molecular mechanisms of macrophage apoptosis. RAW264.7 macrophages were treated with AGE-alb (2, 4 and 6 g/L), control albumin (C-alb, 4 g/L), tunicamycin (TM, 4 mg/L), or pretreated with 4-phenylbutyric acid (PBA, 5 mmol/L) for 1 h and then treated with AGE-alb (4 g/L). After incubation for 24 h, the cell viability and apoptosis were determined by using MTT assay and TUNEL detection kit, respectively. Lactate dehydrogenase (LDH) activity in media was determined by using an assay kit. The protein levels of caspase-12 were examined by Western blot analysis. The results showed that like TM (an ERS inducer), incubation with AGE-alb led to significant decrease in viability and increase in LDH activity in media and apoptotic rate in a dose-dependent manner. In addition, AGE-alb induced activation of caspase-12 especially at the concentration of 4 and 6 g/L (P < 0.01), which was similar to TM. However, PBA (an ERS inhibitor) protected RAW264.7 macrophages from AGE-alb-induced decrease in viability and increases in LDH activity and apoptosis. Moreover, PBA also inhibited the caspase-12 activation induced by AGE-alb (P < 0.05). These results suggest that AGE-alb may induce apoptosis in RAW 264.7 macrophages, and the mechanism may be related to the activation of ERS-associated apoptotic pathway mediated by caspase-12.

Transthoracic echocardiography as an alternative major guidance to angiography during transcatheter closure of patent ductus arteriosus: technical feasibility and clinical relevance.

The conventional transcatheter closure of patent ductus arteriosus (PDA) requires femoral artery puncture and angiography for duct anatomic and shunting estimation. If such estimation can be replaced by transthoracic echocardiography (TTE), the procedure will be further simplified, with fewer invasions. This study aimed to examine whether TTE can serve as an alternative to aorta angiography and as a major guidance for transcatheter duct closure. The study enrolled 298 consecutive patients (71 males and 227 females) with PDA. In the study, TTE with combined two-dimensional echocardiography (2DE) imaging and color-coded flow imaging (CDFI) was performed to measure the minimal shunting width (MSW) as the estimated minimal duct size for selection of an Amplatzer duct occluder (ADO) and to monitor the transcatheter duct closure intraprocedurally. The MSW was validated against the duct-stretched diameter (SDD), against the minimal waist diameter of the conical part of a released occluder measured by X-ray spot picture after successful duct closure (SDC), and against the size of the finally used ADO (SADO). Good correlation was found between MSW and SDD [SDD (mm) = 1.31 MSW; r = 0.89; p < 0.01] and between MSW and SADO [SADO (mm) = 1.71 MSW; r = 0.88; p < 0.01]. Of 296 patients who received occlusion using MSW as the reference for selection of the occluder, SDC was attained in 288 (97.3%), 5 (1.7%), and 2 (0.7%) patients, respectively, at the first, second (1 ADO replacement), and third (2 ADO replacements) occluding attempt. Acute occluder dislodgement occurred in one patient (0.3%). At the 12-month follow-up assessment, no major complications were found, and the total immediate or 12-month SDC was 99.7%. Echocardiography as an alternative major guidance to angiography for transcatheter duct closure is technically feasible, and TTE guidance can further simplify the procedure, with fewer invasions and potential complications.

[Changes of left ventricular remodeling in hypertension patients with carotid atherosclerosis of phlegm-dampness syndrome].

OBJECTIVE: To study changes of left ventricular remodeling (LVR) in hypertension patients with carotid atherosclerosis (CAS) of phlegm-dampness syndrome (PDS). METHODS: Doppler ultrasonography data of CAS were observed in 223 hypertension patients with CAS (as the hypertension group, including 119 patients of the PDS group and 104 of the non-PDS group), 81 CAS patients with non-hypertension, and 19 non-hypertension non-CAS patients (as the control group). The difference in the degree of LVR was compared among the above groups. RESULTS: The left ventricular posterior wall thickness (LVPWT), inter ventricular septum thickness (IVS), E/A were higher in the hypertension group than in the non-hypertension group (P < 0.05). The left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic diameter (LVESD), stroke volume (SV) were higher in the soft plaque hypertension group and the soft plaque non-hypertension group than in the hard plaque group, the thickening intimal group, and the normal intimal group (P < 0.01 , P < 0.05). The LVEDD, LVESD, and SV were higher, and the ejection fraction (EF) was lower in the PDS hypertension group than in the non-PDS hypertension group (all P < 0.05). Of them, LVEDD, LVESD, and SV were higher in the soft plaque group than in the hard plaque group (P < 0.01), the thickening intimal group (P < 0.01) and the normal intimal group (P < 0.05). There was no statistical difference in PDS hypertension between the soft plaque group and the hard plaque group (P > 0.05). CONCLUSION: The hypertension patients with CAS of PDS might be correlated to LVR, and LVR was more obviously in the soft plaque patients.

Ratiometric emission of Tb(III)-functionalized Cd-based layered MOFs for portable visual detection of trace amounts of diquat in apples, potatoes and corn.

Diquat (DQ) is a typical bipyridine herbicide widely used to control weeds in fields and orchards. The severe toxicity of diquat poses a serious threat to the environment and human health. Metal-organic frameworks (MOFs) have received widespread attention due to their unique physical and chemical properties and applications in the detection of toxic and harmful substances. In this work, a two-dimensional (2D) Tb(III) functionalized MOF Tb(III)@1 (1 = [Cd(HTATB)(bimb)]n·H2O (Cd-MOF), H3TATB = 4,4',4″-triazine-2,4,6-tribenzoicacid, bimb = 1,4-bis((1H-imidazol-1-yl)methyl)benzene) has been prepared and characterized. Tb(III)@1 has excellent optical properties and high water and chemical stability. After the Tb(III) is fixed by the uncoordinated -COO- in the 1 framework, Tb(III)@1 emits the typical green fluorescence of the lanthanide ion Tb(III) through the "antenna effect". It is worth noting that Tb(III)@1 can be used as a dual emission fluorescence chemical sensor for the ratio fluorescence detection of pesticide DQ, exhibiting a relatively low detection limit of 0.06 nM and a wide detection range of 0-50 nM. After the addition of DQ, a rapid color change of Tb(III)@1 fluorescence from green to blue was observed due to the combined effects of IFE, FRET and dynamic quenching. Therefore, a simple test paper box has been designed for direct on-site determination of pesticide DQ. In addition, the developed sensor has been successfully applied to the detection of DQ in real samples (fruits a Yin-Xia Sun and Bo-Tao Ji contributed equally to this work and should be considered co-first authors.nd vegetables) with satisfactory results. The results indicate that the probe developed in this study has broad application prospects in both real sample detection and actual on-site testing.

A highly selective and sensitive rhodamine B-based chemosensor for Sn4+ in water-bearing and biomaging and biosensing in zebrafish.

A novel colorimetric-fluorescent dual-mode chemosensor (JT5) based on rhodamine B has been produced for monitoring Sn4+ in the DMSO/H2O (4:1, v/v) medium. It has high sensitivity, a low detection limit, a short response time (1 s) and high stability, and can still be maintained after two weeks with the red dual fluorescence/ colorimetric response. Enhancement of red fluorescence (591 nm) and red colorimetric (567 nm) response of JT5 by Sn4+ addition. The electrostatic potential of the sensor JT5 molecule was simulated to speculate on the sensing mechanism, and the IR, mass spectrometry and 1H NMR titration were utilized to further demonstrate that JT5 was coordinated to Sn4+ with a 1:1 type, the rhodamine spironolactam ring of JT5 opens up to form a penta-membered ring with Sn4+, meanwhile, its system may have chelation enhanced fluorescence (CHEF) effect. In addition, theoretical calculations were carried out to give the energy gaps of JT5 and [JT5 + Sn4+] as well as to simulate the electronic properties of the maximal absorption peaks. Notably, the sensor JT5 was successfully applied to monitoring Sn4+ in zebrafish, and the JT5-loaded filter paper provided a solid-state platform for detecting Sn4+ by both naked eye and fluorescent methods. In summary, this work contributes to monitoring Sn4+ in organisms and solid-state materials and promotes understanding of Sn4+ functions in biological systems, environments, and solid-state materials.

Hot Crack Formation Mechanism and Inhibition of a Novel Cobalt-Based Alloy Coating during Laser Cladding.

Laser cladding provides advanced surface treatment capabilities for enhancing the properties of components. However, its effectiveness is often challenged by the formation of hot cracks during the cladding process. This study focuses on the formation mechanism and inhibition of hot cracks in a novel cobalt-based alloy (K688) coating applied to 304LN stainless steel via laser cladding. The results indicate that hot crack formation is influenced by liquid film stability, the stress concentration, and precipitation phases. Most hot cracks were found at 25°-45° high-angle grain boundaries (HAGBs) due to the high energy of these grain boundaries, which stabilize the liquid film. A flat-top beam, compared to a Gaussian beam, creates a melt pool with a lower temperature gradient and more mitigatory fluid flow, reducing thermal stresses within the coating and the fraction of crack-sensitive, high-angle grain boundaries (S-HAGBs). Finally, crack formation was significantly inhibited by utilizing a flat-top laser beam to optimize the process parameters. These findings provide a technical foundation for achieving high-quality laser cladding of dissimilar materials, offering insights into optimizing process parameters to prevent hot crack formation.

Research Progress in High-Performance Magnesium Alloy and Its Applications.

Magnesium is abundant in the Earth's crust and seawater [...].