Deletion of BACH1 Attenuates Atherosclerosis by Reducing Endothelial Inflammation.

BACKGROUND: The transcription factor BACH1 (BTB and CNC homology 1) suppressed endothelial cells (ECs) proliferation and migration and impaired angiogenesis in the ischemic hindlimbs of adult mice. However, the role and underlying mechanisms of BACH1 in atherosclerosis remain unclear. METHODS: Mouse models of atherosclerosis in endothelial cell (EC)-specific-Bach1 knockout mice were used to study the role of BACH1 in the regulation of atherogenesis and the underlying mechanisms. RESULTS: Genetic analyses revealed that coronary artery disease-associated risk variant rs2832227 was associated with BACH1 gene expression in carotid plaques from patients. BACH1 was upregulated in ECs of human and mouse atherosclerotic plaques. Endothelial Bach1 deficiency decreased turbulent blood flow- or western diet-induced atherosclerotic lesions, macrophage content in plaques, expression of endothelial adhesion molecules (ICAM1 [intercellular cell adhesion molecule-1] and VCAM1 [vascular cell adhesion molecule-1]), and reduced plasma TNF-α (tumor necrosis factor-α) and IL-1ß levels in atherosclerotic mice. BACH1 deletion or knockdown inhibited monocyte-endothelial adhesion and reduced oscillatory shear stress or TNF-α-mediated induction of endothelial adhesion molecules and/or proinflammatory cytokines in mouse ECs, human umbilical vein ECs, and human aortic ECs. Mechanistic studies showed that upon oscillatory shear stress or TNF-α stimulation, BACH1 and YAP (yes-associated protein) were induced and translocated into the nucleus in ECs. BACH1 upregulated YAP expression by binding to the YAP promoter. BACH1 formed a complex with YAP inducing the transcription of adhesion molecules. YAP overexpression in ECs counteracted the antiatherosclerotic effect mediated by Bach1-deletion in mice. Rosuvastatin inhibited BACH1 expression by upregulating microRNA let-7a in ECs, and decreased Bach1 expression in the vascular endothelium of hyperlipidemic mice. BACH1 was colocalized with YAP, and the expression of BACH1 was positively correlated with YAP and proinflammatory genes, as well as adhesion molecules in human atherosclerotic plaques. CONCLUSIONS: These data identify BACH1 as a mechanosensor of hemodynamic stress and reveal that the BACH1-YAP transcriptional network is essential to vascular inflammation and atherogenesis. BACH1 shows potential as a novel therapeutic target in atherosclerosis.

The Impact of Balloon Pre-dilatation Techniques on Drug-Coated Balloon Therapy for Femoropopliteal Artery Disease: Six-Month Results From the CIVILIAN Registry.

OBJECTIVE: The purpose of this study is to compare the initial outcomes of using the Chocolate balloon pre-dilatation (CLP) and sequential enlarging angioplasty pre-dilatation (sequential balloon pre-dilation [SP]) techniques versus the conventional balloon pre-dilatation (CP) method prior to drug-coated balloon (DCB) treatment for femoropopliteal (FP) lesions. METHODS: This was a retrospective analysis of prospectively collected data from the CIVILIAN (Clinical InVestigation of different lesIon preparation modaLIty followed by DCB in femoropopliteal Artery occlusioN disease) registry. Between March 2021 and November 2022, 3 pre-dilation techniques used prior to the DCB angioplasty were included. The study endpoint included intraoperative finial severe dissection after provisional stent placement, bailout stenting rate, the diameter of the largest pre-dilation balloon and DCB, as well as major adverse events (MAEs), including death, major limb amputation, or target vessel revascularization at 6 months. RESULTS: During the study period, 435 limbs (429 patients) were pre-dilated before DCB treatment in FP lesions, 166 limbs were pre-dilated with Chocolate balloons, 93 limbs with sequential enlarging balloon pre-dilation technique, and 176 limbs with CP. The largest pre-dilation balloon was significantly larger in CLP and SP groups than that in the CP group (CLP 4.74±0.52 mm vs CP 4.36±0.64 mm, p<0.001; SP 4.82±0.69 mm vs CP 4.36±0.63 mm, p<0.001). A consistent result was shown in DCB diameter (CLP 4.86±0.44 mm vs CP 4.71±0.51 mm, p=0.003; SP 4.90±0.58 mm vs CP 4.71±0.51 mm, p=0.006). The bailout stenting rate was significantly lower in the CLP group than that in the CP group (18.1% vs 30.1%, p=0.011). The rates of MAEs at 6 months in the CLP and SP groups were comparable to those in the CP group (7.2% and 8.6% vs 6.3%, p>0.05). The risk for intraoperative bailout stenting rate was related to TASC D classification (3.59, 95% CI: 1.83-7.05, p<0.001), chronic total occlusion (CTO) lesion (1.82, 95% CI: 1.07-3.10, p=0.028), as well as pre-dilated with the conventional balloon (1.64, 95% CI: 1.00-2.69, p=0.048). CONCLUSIONS: By utilizing chocolate balloon and sequential enlarging angioplasty, it becomes possible to use larger pre-dilation balloons and DCBs. In addition, the use of the chocolate balloon can significantly reduce the need for bailout stenting when compared with conventional balloons. CLINICAL IMPACT: The utilization of a chocolate balloon and sequential enlarging angioplasty has emerged as a promising technique for angioplasty procedures. This approach allows for the use of larger pre-dilation balloons and drug-coated balloons. The use of the chocolate balloon can significantly reduce the need for bail-out stenting when compared to conventional balloons. Further research is required to determine the impact of vessel preparation techniques on the primary patency.

Single-Cell Transcriptomics Reveals Crucial Cell Subsets and Functional Heterogeneity Associated With Carotid Atherosclerosis and Cerebrovascular Events.

BACKGROUND: Carotid atherosclerosis is a chronic inflammatory disorder and is responsible for the vast majority of ischemic strokes. Inappropriate innate and adaptive immune responses synergize with malfunctional vascular wall cells to cause atherosclerotic lesions. Yet, functional characteristics of specific immune and endothelial cell subsets associated with atherosclerosis and cerebrovascular events are poorly understood. METHODS: Here, using single-cell RNA sequencing, the unprecedentedly largest data set from 20 patients' carotid artery plaques and paired peripheral blood mononuclear cells was generated, with which an ultra-high-precision cellular landscape of the atherosclerotic microenvironment involving 372 070 cells was depicted. RESULTS: Compared with peripheral blood mononuclear cells, 3 plaque-specific T-cell subsets exhibiting proatherogenic features of both activation and exhaustion were identified. Strikingly, usually antiatherogenic, CD4+FOXP3+ regulatory T cells from plaques of patients with symptomatic disease acquired proinflammatory properties by probably converting to T helper 17 and T helper 9 cells, while CD4+NR4A1+/C0 and CD8+SLC4A10+ T cells related to cerebrovascular events possessed atherogenic attributes including proinflammation, polarization, and exhaustion. In addition, monocyte-macrophage dynamics dominated innate immune response. Two plaque-specific monocyte subsets performed diametrically opposed functions, EREG+ monocytes promoted cerebrovascular events while C3+ monocytes are anti-inflammatory. Similarly, IGF1+ and HS3ST2+ macrophages with classical proinflammatory M1 macrophage features were annotated and contributed to cerebrovascular events. Moreover, SULF1+ (sulfatase-1) endothelial cells were also found to participate in cerebrovascular events through affecting plaque vulnerability. CONCLUSIONS: This compendium of single-cell transcriptome data provides valuable insights into the cellular heterogeneity of the atherosclerotic microenvironment and the development of more precise cardiovascular immunotherapies.

Ambient RNAs removal of cortex-specific snRNA-seq reveals Apoe+ microglia/macrophage after deeper cerebral hypoperfusion in mice.

BACKGROUND: Ambient RNAs contamination in single-nuclei RNA sequencing (snRNA-seq) is a challenging problem, but the consequences of ambient RNAs contamination of damaged and/or diseased tissues are poorly understood. Cognitive impairments and white/gray matter injuries are characteristic of deeper cerebral hypoperfusion mouse models induced by bilateral carotid artery stenosis (BCAS), but the molecular mechanisms still need to be further explored. More importantly, the BCAS mice can also offer an excellent model to examine the signatures of ambient RNAs contamination in damaged tissues when performing snRNA-seq. METHODS: After the sham and BCAS mice were established, cortex-specific single-nuclei libraries were constructed. Single-nuclei transcriptomes were described informatically by the R package Seurat, and ambient RNA markers of were identified in each library. Then, after removing ambient RNAs in each sample using the in silico approaches, the combination of CellBender and subcluster cleaning, single-nuclei transcriptomes were reconstructed. Next, the comparison of ambient RNA contamination was performed using irGSEA analysis before and after the in silico approaches. Finally, further bioinformatic analyses were performed. RESULTS: The ambient RNAs are more predominant in the BCAS group than the sham group. The contamination mainly originated from damaged neuronal nuclei, but could be reduced largely using the in silico approaches. The integrative analysis of cortex-specific snRNA-seq data and the published bulk transcriptome revealed that microglia and other immune cells were the primary effectors. In the sequential microglia/immune subgroups analysis, the subgroup of Apoe+ MG/Mac (microglia/macrophages) was identified. Interestingly, this subgroup mainly participated in the pathways of lipid metabolism, associated with the phagocytosis of cell debris. CONCLUSIONS: Taken together, our current study unravels the features of ambient RNAs in snRNA-seq datasets under diseased conditions, and the in silico approaches can effectively eliminate the incorrected cell annotation and following misleading analysis. In the future, snRNA-seq data analysis should be carefully revisited, and ambient RNAs removal needs to be taken into consideration, especially for those diseased tissues. To our best knowledge, our study also offers the first cortex-specific snRNA-seq data of deeper cerebral hypoperfusion, which provides with novel therapeutic targets.

GATA6 Inhibits Neuronal Autophagy and Ferroptosis in Cerebral ischemia-reperfusion Injury Through a miR-193b/ATG7 axis-dependent Mechanism.

Ferroptosis is a newly described form of regulated necrotic cell death, which is engaged in the pathological cell death related to stroke, contributing to cerebral ischemia-reperfusion (I/R) injury. Therefore, we performed this study to clarify the role of GATA6 in neuronal autophagy and ferroptosis in cerebral I/R injury. The cerebral I/R injury-related differentially expressed genes (DEGs) as well as the downstream factors of GATA6 were predicted bioinformatically. Moreover, the relations between GATA6 and miR-193b and that between miR-193b and ATG7 were evaluated by chromatin immunoprecipitation and dual-luciferase reporter assays. Besides, neurons were treated with oxygen-glucose deprivation (OGD), followed by overexpression of GATA6, miR-193b, and ATG7 alone or in combination to assess neuronal autophagy and ferroptosis. At last, in vivo experiments were performed to explore the impacts of GATA6/miR-193b/ATG7 on neuronal autophagy and ferroptosis in a rat model of middle cerebral artery occlusion (MCAO)-stimulated cerebral I/R injury. It was found that GATA6 and miR-193b were poorly expressed in cerebral I/R injury. GATA6 transcriptionally activated miR-193b to downregulate ATG7. Additionally, GATA6-mediated miR-193b activation suppressed neuronal autophagy and ferroptosis in OGD-treated neurons by inhibiting ATG7. Furthermore, GATA6/miR-193b relieved cerebral I/R injury by restraining neuronal autophagy and ferroptosis via downregulation of ATG7 in vivo. In summary, GATA6 might prevent neuronal autophagy and ferroptosis to alleviate cerebral I/R injury via the miR-193b/ATG7 axis.

Efficacy and Safety of Absorb Everolimus-Eluting Bioresorbable Vascular Scaffold in Peripheral Artery Disease: A Single-Arm Meta-Analysis.

PURPOSE: This study aimed to evaluate the benefits and risks of patients with peripheral artery disease (PAD) treated with Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) by analyzing all the published studies on the clinical characteristics of patients with PAD. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Library were searched for relevant studies. Efficacy, safety, and basic characteristics were analyzed. RESULTS: Four studies were included in meta-analysis, including a total number of 155 patients with PAD. The pooled overall primary patency, freedom from target lesion revascularization (TLR), symptom resolution, and wound healing were 90%, 96%, 94%, and 86%, respectively. The pooled perioperative complication and all-cause mortality were 4% and 9%, respectively. Preoperative total occlusion was detected in 43 of 192 lesions (22%). The mean lesion length was 27.26 mm. In terms of comorbidities, the pooled percentage of hypertension, hyperlipidemia, diabetes mellitus, coronary artery disease, chronic kidney disease history, and smoking were 65%, 74%, 49%, 43%, 20%, and 57%, respectively. CONCLUSION: Among these studies, hypertension, hyperlipidemia, and diabetes mellitus were the most common comorbidities in patients with PAD. The Absorb everolimus-eluting BVS was safe and showed the favorable clinical outcomes in both patency and TLR, especially in infrapopliteal disease with heavy calcification. The conclusions of this meta-analysis still needed to be verified by more relevant studies with more careful design, more rigorous execution, and larger sample size.

Drug-Coated Balloon Angioplasty of Infrapopliteal Lesions in Chronic Limb-Threatening Ischemia: Six-month Outcomes of PRIME-WIFI.

PURPOSE: To evaluate 6-month outcomes of drug-coated balloon (DCB) angioplasty of infrapopliteal lesions in patients with chronic limb-threatening ischemia (CLTI). METHODS: We analyzed 6-month follow-up data from the 10-center PRIME-WIFI prospective registry on 300 consecutive patients (33.000% female) with CLTI who underwent DCB angioplasty for infrapopliteal arterial lesions. The primary outcome was freedom from major adverse event (MAE), a composite of major amputation, all-cause death, and clinically-driven target limb reintervention (CD-TLR). Secondary outcomes included amputation-free survival (AFS), freedom from each primary outcome component, primary sustained clinical improvement, and quality of life (QOL) score. Independent risk factors of MAE were determined using Cox proportional hazards regression analysis. RESULTS: A total of 409 infrapopliteal lesions in 312 limbs were treated with DCB, with 54.167% of the limbs being treated for isolated infrapopliteal lesions. By Kaplan-Meier analysis, at 6 months post- procedure (follow-up rate, 85.000%), freedom from MAE was 86.353%; AFS was 90.318%; and freedom from major amputation, all-cause death, and CD-TLR were 96.429%, 93.480%, and 95.079%, respectively. At 6-month follow-up, 83.590% of patients showed primary sustained clinical improvement, and QOL score (4.902±1.388) improved compared with that before procedure (2.327±1.109; p<0.001). Chronic renal insufficiency, chronic obstructive pulmonary disease, Rutherford grade, and postoperative infrapopliteal runoff score were independent risk factors for MAE within 6 months. CONCLUSION: In CLTI, DCB angioplasty of infrapopliteal lesions yields acceptable early efficacy and safety. CLINICAL IMPACT: This study evaluated the 6-month outcomes of DCB angioplasty in infrapopliteal lesions in CLTI patients by analyzing multicenter prospective data, showing that infrapopliteal DCB angioplasty can be performed with acceptable freedom from MAE rate, amputation-free survival rate, freedom from major amputation rate, survival rate, and freedom from CD-TLR rate. No patient experienced DCB-related intraoperative distal embolism. Chronic renal insufficiency, chronic obstructive pulmonary disease, Rutherford grade and postoperative infrapopliteal runoff score were independent risk factors for MAE within 6 months. Comparative real-world studies are needed.

Midterm Results of Drug-Coated Balloon Alone or Combined with Rotarex Thrombectomy Device for Treatment of Subacute Femoropopliteal Artery Thrombotic Occlusion.

BACKGROUND: This retrospective multicenter study aimed to compare the midterm results of the Rotarex rotational thrombectomy device combined with drug-coated balloon (DCB) and DCB-alone for the treatment of subacute femoropopliteal artery thrombotic occlusion. METHODS: All patients (74, aged 70.1 ± 9.3 years) were nonrandomized and divided into 2 groups based on treatment strategy between 2018 and 2020. Intraoperative technical success (defined as <30% residual stenosis), dissection types and bailout-stenting rates were assessed. Ankle-brachial index (ABI), primary patency (PP, restenosis <50%) and freedom from clinically driven target lesion reintervention (CD-TLR) were documented at follow-up. RESULTS: Among them, 35 patients were treated with the Rotarex catheter combined with DCB while 39 patients underwent DCB-alone. The-overall technical success rate was 100%. Patients in the Rotarex + DCB group showed lower rate of bailout stenting than those in the DCB alone group (22.9% vs. 59.0%; P = 0.01). ABI at discharge was significantly higher in both groups. Mean follow-up time was 18.5 ± 3.4 months; 62 patients completed Doppler ultrasound investigation while 12 patients were censored. According to Kaplan-Meier analysis, the estimated PP was 82.0 ± 6.7% in the Rotarex + DCB group, whereas a significantly lower rate in the DCB alone group (60.9 ± 8.3%, P = 0.04). In addition, the freedom from CD-TLR rate was 82.9 ± 6.4% in the Rotarex + DCB group and 61.5 ± 7.8% in the DCB-alone group (P = 0.04). CONCLUSIONS: These initial data indicate that the Rotarex thrombectomy device combined with DCB is an effective choice for the treatment of subacute femoropopliteal artery thrombotic occlusion compared to DCB-alone. The combined procedure had superior midterm results.

Debris generated by laser and/or balloon cause cerebral infarction with different severity.

The purpose of this study is to determine the effects that debris generated by laser and/or balloon on the brain. Debris generated by laser, balloon, and laser combined with balloon were collected and then injected into rats' left common carotid artery. Rats were divided into five groups: sham, saline, laser (L), balloon (B), and laser combined with balloon (LB). The cognition ability of rats was evaluated by Morris water maze. Cerebral blood flow (CBF) was examined by laser speckle. TTC staining and MRI scan were conducted to detect cerebral ischemic infarction. Intracranial arteries in rats were visualized by MRI angiography via contrast medium injected via tail vein. Immunohistologic staining for NeuN and Iba1 and hematoxylin-eosin staining were performed to assess brain infarction. White matter demyelination was assessed by Luxol fast blue staining. Long-term memory and CBF of rats in different groups exhibited no significant difference. No obstruction sign in intracranial artery tree was noticed in each group. Debris generated by different treatments all caused brain infarction. Infarction lesion caused by debris produced by balloon was much more severe than the one caused by debris generated by laser. While the LB group lay in between. The thickness of white matter decreased in the B group, but not in the L and LB groups. Rat brain has a tolerance for debris as cognition ability and cerebral blood flow are not significantly declined. The severity of cerebral infarction varies by debris generated by different treatments.

Morphological Lesion Types Are Associated with Primary and Secondary Patency Rates after High-Pressure Balloon Angioplasty for Dysfunctional Arteriovenous Fistulas.

BACKGROUND: Neointimal hyperplasia (NIH) is believed to be the main reason for arteriovenous fistula (AVF) dysfunction, but other mechanisms are also recognized to be involved in the pathophysiological process. This study investigated whether different morphological types of AVF lesions are associated with the patency rate after percutaneous transluminal angioplasty (PTA). METHODS: This retrospective study included 120 patients who underwent PTA for autogenous AVF dysfunction. All the cases were evaluated under Doppler ultrasound (DU) before intervention and divided into 3 types: Type I (NIH type), Type II (non-NIH type), and Type III (mixed type). Prognostic and clinical data were analyzed by Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS: There was no statistical difference in baseline variables among groups, except for lumen diameter. The primary patency rates in Type I, Type II, and Type III groups were 78.4, 93.2, and 83.2% at 6 months and 59.5, 84.7, and 75.5% at 1 year, respectively. The secondary patency rates in Type I, Type II, and Type III groups were 94.4, 97.1, and 100% at 6 months and 90.5, 97.1, and 94.7% at 1 year, respectively. The Kaplan-Meier curve showed that the primary and secondary patency rates of Type I group were lower than those of Type II group. Multivariable Cox regression analysis demonstrated that postoperative primary patency was correlated with end-to-end anastomosis (hazard ratio [HR] = 2.997, p = 0.008, 95% confidence interval [CI]: 1.328-6.764) and Type I lesion (HR = 5.395, p = 0.004, 95% CI: 1.730-16.824). CONCLUSIONS: NIH-dominant lesions of AVF evaluated by DU preoperatively were a risk factor for poor primary and secondary patency rate after PTA in hemodialysis patients.

A Systematic Review of Total Thoracic Endovascular Aortic Repair in Treatment of Kommerell Diverticulum Combined with Right-Sided Aortic Arch.

Kommerell diverticulum (KD) combined with right-sided aortic arch (RAA) and aberrant left subclavian artery (ALSA) are rare and limited to a few case reports and small series. Thoracic endovascular aortic repair (TEVAR), which is mini-invasive, is widely utilized in complicated aortic disease. We performed a systematic review of the literature to identify all patients who underwent endovascular repair for KD in terms of technical feasibility and procedural outcomes. Published and accepted studies only in English as well as article reference lists were searched and extracted to assess case series reporting solely TEVAR in KD patients. There were 28 patients with KD/RAA identified from 19 studies. All of them underwent endovascular technique for KD exclusion and the median age was 69 years (range 39-83 years). Hypertension (n=17) was the most common comorbidity in this cohort, followed by diabetes mellitus (n=3), hyperlipidemia (n=3), and smoking (n=3). The presenting symptoms were dysphagia (n=8, 29%), intermittent back pain (n=4, 14%), and acute aortic dissection (n=6, 21%), while asymptomatic was found in 9 patients (n=9, 32%). A technical success rate of 100% was reported associated with various managements of ALSA, proximal embolization (n=19, 68%), in-situ revascularization (n=3, 11%), and left carotid-subclavian bypass (n=3, 11%). All patients survived without severe complications and were discharged home within less than 14 days. The mean follow-up time was 9.3 months, patency was found in all patients, thrombosis and distinct shrinkage of KD aneurysm as indicated by CT-scans were noted (n=20, 71%), and type II endoleak was found in only 4 patients (n=4, 14%). TEVAR appears to be safe and offers favorable results, but it still needs substantial evidence to support routine use in KD. TEVAR is an alternative to open repair in selected cases, but it needs further investigation in a large cohort.

A Machine Learning Approach for Predicting Early Phase Postoperative Hypertension in Patients Undergoing Carotid Endarterectomy.

BACKGROUND: This study aimed to establish and validate a machine learning-based model for the prediction of early phase postoperative hypertension (EPOH) requiring the administration of intravenous vasodilators after carotid endarterectomy (CEA). METHODS: Perioperative data from consecutive CEA procedures performed from January 2013 to August 2019 were retrospectively collected. EPOH was defined in post-CEA patients as hypertension involving a systolic blood pressure above 160 mm Hg and requiring the administration of any intravenous vasodilator medications in the first 24 hr after a return to the vascular ward. Gradient boosted regression trees were used to construct the predictive model, and the featured importance scores were generated by using each feature's contribution to each tree in the model. To evaluate the model performance, the area under the receiver operating characteristic curve was used as the main metric. Four-fold stratified cross-validation was performed on the data set, and the average performance of the 4 folds was reported as the final model performance. RESULTS: A total of 406 CEA operations were performed under general anesthesia. Fifty-three patients (13.1%) met the definition of EPOH. There was no significant difference in the percentage of postoperative stroke/death between patients with and without EPOH during the hospital stay. Patients with EPOH exhibited a higher incidence of postoperative cerebral hyperperfusion syndrome (7.5% vs. 0, P < 0.001), as well as a higher incidence of cerebral hemorrhage (3.8% vs. 0, P < 0.001). The gradient boosted regression trees prediction model achieved an average AUC of 0.77 (95% CI 0.62 to 0.92). When the sensitivity was fixed near 0.90, the model achieved an average specificity of 0.52 (95% CI 0.28 to 0.75). CONCLUSIONS: We have built the first-ever machine learning-based prediction model for EPOH after CEA. The validation result from our single-center database was very promising. This novel prediction model has the potential to help vascular surgeons identify high-risk patients and reduce related complications more efficiently.

Design and Analysis of Two Piezoelectric Cymbal Transducers with Metal Ring and Add Mass.

Based on traditional sandwich structure, two piezoelectric transducers were designed to meet the strict underwater application backgrounds such as high pressure, corrosion resistance, and high strength. Both transducers integrated most of previous researches while one transducer has a multilayer cavity structure which is different from the other structure and previous transducer structures. After a detailed simulation analysis of every structural parameter, key parameters were pointed out to have an obvious influence on its performance. Then, two models were constructed and compared with chosen sets of geometry parameters and manufacturing process, which can also provide a reference for low-frequency transducer design. The simulation results and experimental results of our transducers show a good consistency which indicates the cavity structure can reduce the resonance frequency.

Long noncoding RNA HIF1A-AS1A reduces apoptosis of vascular smooth muscle cells: implications for the pathogenesis of thoracoabdominal aorta aneurysm.

Long non-coding RNAs (IncRNAs) play important roles in various biological processes, such as transcriptional regulation, cell growth and tumorigenesis. However, little is known about the role of IncRNA HIF 1 alpha-antisense RNA 1 (HIF1a-AS1) in regulating the proliferation and apoptosis of vascular smooth muscle cells (VSMCs) and the expression of HIF1a-AS1 in serum of thoracoabdominal aortic aneurysm (TAAA) patients. The cell viability was detected by the CCK8 assay. The cell apoptosis was assessed by annexin V-PI double-labeling staining. Expression of genes and proteins were analyzed by real-time PCR and western blotting, respectively. Cells were transfected with siRNAs as a gene silencing method. In serum of TAAA patients, the expression of HIF1a-AS1 was significantly increased (superior to 6-fold) compared to the normal control. Moreover, Palmitic acid (PA) induced cell apoptosis in VSMCs in a time- and dose-dependent manner, and the proportion of the apoptotic cells had gained as compared to untreatment group. PA also induced up-regulation expression of HIF1a-AS1. We also found that transfection of cells with HIF1a-AS1 siRNA decreased the expression of caspase-3 and caspase-8 and increased the expression of Bcl2, and protected PA-induced cell apoptosis in VSMCs. HIF1a-AS1 was overexpressed in the TAAA and the interaction between HIF1a-AS1 and apoptotic proteins plays a key role in the proliferation and apoptosis of VSMCs in vitro, which may contribute to the pathogenesis of TAAA.

Combined antegrade femoral artery and retrograde popliteal artery recanalization for chronic occlusions of the superficial femoral artery.

PURPOSE: To evaluate the efficacy and safety of a dual femoral-popliteal approach in the supine position after failed antegrade recanalization attempts in chronic total occlusion (CTO) of the superficial femoral artery (SFA). MATERIALS AND METHODS: From May 2011 to October 2012, 21 patients underwent dual femoral-popliteal recanalization for CTO of the SFA, with a mean lesion length of 87.4 mm ± 5.8. When contralateral antegrade recanalization of SFA occlusions via the common femoral artery could not be achieved, the occlusions were intrainterventionally accessed by retrograde approach via the popliteal artery, which was punctured anteriorly with gently flexed knee and crus extorsion. When the SFA had been recanalized, further angioplasty and stent placement procedures were completed via the femoral artery. RESULTS: A technical success rate of 100% (entailing puncture of the popliteal artery and SFA recanalization) was achieved, and no hemorrhage, hematoma, pseudoaneurysm, arteriovenous fistula, or other complications developed. During a mean follow-up of 9.8 months ± 1.5, claudication severity, rest pain, and toe ulcers improved significantly. The pulse of the distal arteries, as well as the filling of the veins, could be distinctly felt. Ankle-brachial index changed from 0.48 ± 0.17 to 0.84 ± 0.11 at 1 year after intervention (P < .001), and patency rates at 1, 6, and 12 months after interventions were 100%, 80%, and 42%, respectively. CONCLUSIONS: A dual femoral-popliteal approach in the supine position is an alternative backup option after failed attempts at the antegrade approach for patients with proximal barriers in CTO or lesions with major extending collateral vessels.

Antiferroptosis therapy alleviated the development of atherosclerosis.

Ferroptosis has been confirmed to be associated with various diseases, but the relationship between ferroptosis and atherosclerosis (AS) remains unclear. Our research detailly clarified the roles of ferroptosis in three continuous and main pathological stages of AS respectively (injury of endothelial cells [ECs], adhesion of monocytes, and formation of foam cells). We confirmed that oxidized low-density lipoprotein (ox-LDL), the key factor in the pathogenesis of AS, strongly induced ferroptosis in ECs. Inhibition of ferroptosis repressed the adhesion of monocytes to ECs by inhibiting inflammation of ECs. Ferroptosis also participated in the formation of foam cells and lipids by regulating the cholesterol efflux of macrophages. Further research confirmed that ox-LDL repressedthe activity of glutathione peroxidase 4 (GPX4), the classic lipid peroxide scavenger. Treatment of a high-fat diet significantly induced ferroptosis in murine aortas and aortic sinuses, which was accompanied by AS lesions and hyperlipidemia. Treatment with ferroptosis inhibitors significantly reduced ferroptosis, hyperlipidemia, and AS lesion development. In conclusion, our research determined that ox-LDL induced ferroptosis by repressing the activity of GPX4. Antiferroptosis treatment showed promising treatment effects in vivo. Ferroptosis-associated indexes also showed promising diagnostic potential in AS patients.

Copious Dislocations Defect in Amorphous/Crystalline/Amorphous Sandwiched Structure P-NiMoO4 Electrocatalyst toward Enhanced Hydrogen Evolution Reaction.

The design and synthesis of efficient, inexpensive, and long-term stable heterostructured electrocatalysts with high-density dislocations for hydrogen evolution reaction in alkaline media and seawater are still a great challenge. An amorphous/crystalline/amorphous sandwiched structure with abundant dislocations were synthesized through thermal phosphidation strategies. The dislocations play an important role in the hydrogen evolution reactions. Copious dislocation defects, combined with cracks, and the synergistic interfacial effect between crystalline phase and amorphous phase regulate the electronic structure of electrocatalyst, provide more active sites, and thus endow the electrocatalysts with excellent catalytic activity under alkaline water and seawater. The overpotentials of P-NiMoO4 at 10 mA/cm2 in 1 M KOH aqueous solution and seawater are 45 and 75 mV, respectively. Additionally, the P-NiMoO4 electrocatalyst exhibits long-term stability over 100 h. This study provides a simple approach for synthesizing amorphous/crystalline/amorphous sandwiched non-noble-metal electrocatalysts with abundant dislocations for hydrogen evolution reaction.

Analysis of Pollution Characteristics and Emissions Reduction Measures in the Main Cotton Area of Xinjiang.

With cotton production in Xinjiang increasing annually, the impact on the environment of agricultural waste produced to improve production has been reflected. This study selected Bozhou of Xinjiang, the main cotton producing region in northern Xinjiang, as the research object, and collected hourly concentration data of six pollutants from 2017 to 2021, and analyzed the spatial and temporal distribution characteristics of each pollutant. At the same time, Morlet wavelet analysis was used to further analyze the variation period of PM2.5 (PM particles with aerodynamic diameters less than 2.5 µm) concentration. The Weather Research and Forecasting model coupled with the Community Multiscale Air Quality (WRF-CMAQ) model was used to evaluate the emissions reduction measures for the most polluted month. The results showed that the concentration of particulate matter (PM particles with aerodynamic diameters less than 2.5 µm and 10 µm) decreased from the southern mountains to the north; moreover, the concentrations of CO (carbon monoxide), NO2 (nitrogen dioxide), and SO2 (sulfur dioxide) in the suburbs were higher than those in the urban center. The concentration of O3 (Ozone) was the highest in summer, while the concentrations of other pollutants were high in autumn and winter. Under the time scale of a = 13, 24, PM2.5 had significant periodic fluctuation. The health risk values of PM2.5 and PM10 in this study were within the scope of the United States Environmental Protection Agency (USEPA) criteria, but it is still necessary to keep a close watch on them. In the context of emissions reduction measures, agricultural sources reduced by 20%, residential sources by 40%, industrial sources by 20%, and transportation sources by 20%; no change in the power source remains. Under these conditions, the daily average value of each pollutant met the first level of the national ambient air quality standard. The research results provide a reference for the local government to formulate heavy pollution emissions reduction policies.

RGD1564534 represses NLRP3 inflammasome activity in cerebral injury following ischemia-reperfusion by impairing miR-101a-3p-mediated Dusp1 inhibition.

BACKGROUND: Mitochondrial autophagy, the elimination of damaged mitochondria through autophagy, contributes to neuron survival in cerebral ischemia. Long non-coding RNAs (lncRNAs)/microRNAs (miRNAs)/mRNAs are important regulatory networks implicated in various biological processes, including cerebral ischemia-reperfusion (I/R) injury. Therefore, this work clarifies a novel RGD1564534-mediated regulatory network on mitochondrial autophagy in cerebral I/R injury. METHODS: Differentially expressed lncRNAs in cerebral I/R injury were predicted by bioinformatics analysis. Expression of RGD1564534 was examined in the established middle cerebral artery occlusion (MCAO) rats and oxygen glucose deprivation/reoxygenation (OGD/R)-exposed neurons. We conducted luciferase activity, RNA pull-down and RIP assays to illustrate the interaction among RGD1564534, miR-101a-3p and Dusp1. Gain- or loss-of-function approaches were used to manipulate RGD1564534 and Dusp1 expression. The mechanism of RGD1564534 in cerebral I/R injury was evaluated both in vivo and in vitro. RESULTS: RGD1564534 was poorly expressed in the MCAO rats and OGD/R-treated cells, while its high expression attenuated nerve damage, cognitive dysfunction, brain white matter and small vessel damage in MCAO rats. In addition, RGD1564534 promoted mitochondrial autophagy and inhibited NLRP3 inflammasome activity. RGD1564534 competitively bound to miR-101a-3p and attenuated its binding to Dusp1, increasing the expression of Dusp1 in neurons. By this mechanism, RGD1564534 enhanced mitochondrial autophagy, reduced NLRP3 inflammasome activity and suppressed the neuron apoptosis induced by OGD/R. CONCLUSION: Altogether, RGD1564534 elevates the expression of Dusp1 by competitively binding to miR-101a-3p, which facilitates mitochondrial autophagy-mediated inactivation of NLRP3 inflammasome and thus retards cerebral I/R injury.

Porous N-Doped Carbon Decorated with Atomically Dispersed Independent Dual Metal Sites from Energetic Zeolite Imidazolate Frameworks as Bidirectional Catalysts for Lithium-Sulfur Batteries.

Lithium-sulfur (Li-S) batteries have ultrahigh theoretical specific capacity and energy density, which are considered to be very promising energy storage devices. However, the slow redox kinetics of polysulfides are the main reason for the rapid capacity decay of Li-S batteries. A reasonable electrocatalyst for the Li-S battery should reduce the reaction barrier and accelerate the reaction kinetics of the bidirectional catalytic conversion of lithium polysulfides (LiPSs), thereby reducing the cumulative concentration of LiPSs in the electrolyte. In this report, porous N-doped carbon nanofibers decorated with independent dual metal sites as catalysts for Li-S batteries were fabricated in one step using a fusion-foaming method. Experimental and theoretical analyses demonstrate that the synergistic effect of independent dual metal sites provides strong LiPS affinity, improved electronic conductivity, and enhanced redox kinetics of polysulfides. Therefore, the assembled Li-S battery exhibits high rate performance (discharge specific capacity of 771 mA h g-1 at 2C) and excellent cycle stability (capacity decay rate of 0.51% after 1000 cycles at 1C).