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BackgroundPostoperative acute kidney injury (PO-AKI) is a prevalent complication among patients with acute type A aortic dissection (aTAAD) for which unrecognized trajectories of renal function recovery, and their heterogeneity, may underpin poor success in identifying effective therapies.MethodsThis was a retrospective, single-center cohort study in a regional Great Vessel Center including patients undergoing aortic dissection surgery. Estimated glomerular filtration rate (eGFR) recovery trajectories of PO-AKI were defined through the unsupervised latent class mixture modeling (LCMM), with an assessment of patient and procedural characteristics, complications, and early-term survival. Internal validation was performed by resampling.ResultsA total of 1,295 aTAAD patients underwent surgery and 645 (49.8%) developed PO-AKI. Among the PO-AKI cohort, the LCMM identified two distinct eGFR trajectories: early recovery (ER-AKI, 51.8% of patients) and late or no recovery (LNR-AKI, 48.2% of patients). Binary logistic regression identified five critical determinants regarding poor renal recovery, including chronic kidney disease (CKD) history, renal hypoperfusion, circulation arrest time, intraoperative urine, and myoglobin. LNR-AKI was associated with increased mortality, continuous renal replacement therapies, mechanical ventilation, ICU stay, and hospital stay. The assessment of the predictive model was good, with an area under the curve (AUC) of 0.73 (95% CI: 0.69–0.76), sensitivity of 61.74%, and specificity of 75.15%. The internal validation derived a consistent average AUC of 0.73. The nomogram was constructed for clinicians' convenience.ConclusionOur study explored the PO-AKI recovery patterns among surgical aTAAD patients and identified critical determinants that help to predict individuals at risk of poor recovery of renal function.

BackgroundTo establish models for predicting descending thoracic aortic diameters and provide evidence for selecting the size of the stent graft for TBAD patients.MethodsA total of 200 candidates without severe deformation of aorta were included. CTA information was collected and 3D reconstructed. In the reconstructed CTA, a total of 12 cross-sections of peripheral vessels were made perpendicular to the axis of flow of the aorta. Parameters of the cross sections and basic clinical characteristics were used for prediction. The data was randomly split into the training set and the test set in an 8:2 ratio. To fully describe diameters of descending thoracic aorta, three predicted points were set based quadrisection, and a total of 12 models at three predicted points were established using four algorithms included linear regression (LR), support vector machine (SVM), Extra-Tree regression (ETR) and random forest regression (RFR). The performance of models was evaluated by mean square error (MSE) of the prediction value, and the ranking of feature importance was given by Shapley value. After modeling, prognosis of five TEVAR cases and stent oversizing were compared.ResultsWe identified a series of parameters which affect the diameter of descending thoracic aorta, including age, hypertension, the area of proximal edge of superior mesenteric artery, etc. Among four predictive models, all the MSEs of SVM models at three different predicted position were less than 2 mm2, with approximately 90% predicted diameters error less than 2 mm in the test sets. In patients with dSINE, stent oversizing was about 3 mm, while only 1 mm in patients without complications.ConclusionThe predictive models established by machine learning revealed the relationship between basic characteristics and diameters of different segment of descending aorta, which help to provide evidence for selecting the matching distal size of the stent for TBAD patients, thereby reducing the incidence of TEVAR complications.

After high-temperature treatment, both nano-titanium dioxide-modified concrete and ordinary concrete exhibit typical splitting failure. High-temperature heating reduces the mechanical properties and brittleness of concrete and improves the ductility of concrete. The stress–strain relationship of the specimens was obtained through the uniaxial compression test of ordinary concrete and nano-titanium dioxide-modified concrete cube specimens under normal temperature and high-temperature conditions. In addition, the relationship between temperature and damage variables was established, and the unified constitutive model containing damage variables after room temperature and high-temperature treatment of ordinary concrete and nano-titanium dioxide-modified concrete were established. It provides a reference for future research on the mechanical properties of high-performance concrete structures after high temperatures (fire).

S-nitrosylation can influence many pathophysiological processes. Here the authors show that the coupling efficiency of GNAI2 with CXCR5 is enhanced by S-nitrosylation of GNAI2, leading to Hippo-YAP dysfunction in endothelium, and plays a role in diabetes-accelerated atherosclerosis.

BackgroundAcute Stanford-A aortic dissection (AAAD) is a devastating cardiovascular condition with high mortality, therefore identifying risk prognosis factors is vital for the risk stratification of patients with AAAD. Here, we investigated peripheral blood eosinophil (EOS) counts in patients with AAAD and their possible biological implications.MethodsWe performed a single center retrospective cohort study. From 2011 to 2021, a total of 1,190 patients underwent AAAD surgery. Patients were categorized first by death and then admission EOS counts (0.00 × 109/L or >0.00 × 109/L). Demographics, laboratory data, and outcomes were analyzed using standard statistical analyses. Ascending aorta specimens were used for western blotting and histological assessments.ResultsDeath group patients had lower EOS counts than the non-death group (P = 0.008). When patients were stratified using mean blood EOS counts: 681 patients had low (0.00 × 109/L) and 499 had high (>0.00 × 109/L) counts. Patients with low EOS counts at admission were more likely to have a higher mortality risk (P = 0.017) and longer treatment in the intensive care unit (ICU) days (P = 0.033) than patients with normal EOS counts. Also, the five blood coagulation items between both groups showed significantly different (P

Endothelial dysfunction is the initial process of atherosclerosis. Heat shock protein 90 (Hsp90), as a molecular chaperone, plays a crucial role in various cardiovascular diseases. Hsp90 function is regulated by S-nitrosylation (SNO). However, the precise role of SNO-Hsp90 in endothelial dysfunction during atherosclerosis remains unclear. We here identified Hsp90 as a highly S-nitrosylated target in endothelial cells (ECs) by biotin switch assay combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS). The elevation of SNO-Hsp90 was observed in atherosclerotic human and rodent aortas as well as in oxidized LDL (oxLDL)-treated ECs. Inhibition of inducible nitric oxide synthase (iNOS) or transfection with Hsp90 cysteine 521 (Cys521) mutation plasmid decreased the level of SNO-Hsp90 in oxLDL-cultured ECs. Coimmunoprecipitation and proximity ligation assay demonstrated that SNO-Hsp90 at Cys521 suppressed the interaction between Hsp90 and activator of Hsp90 ATPase activity 1 (AHA1), but promoted the association of Hsp90 and cell division cycle 37 (CDC37). Hsp90 Cys521 mutation increased endothelial nitric oxide synthase (eNOS) activity and inhibited nuclear factor kappa-B (NF-κB) signaling, thereby increasing nitric oxide (NO) bioavailability and alleviating endothelial adhesion, inflammation and oxidative stress in oxLDL-treated ECs. Also, administration of endothelial-specific adeno-associated viruses of Cys521-mutated Hsp90 significantly mitigated vascular oxidative stress, macrophage infiltration and atherosclerosis lesion areas in high fat diet-fed ApoE-/- mice. In conclusion, SNO-Hsp90 at Cys521, that serves as a conformational switch, disrupts Hsp90/AHA1 interaction but promotes recruitment of CDC37 to exacerbate atherosclerosis.

Aortic dissection (AD) is a life-threatening cardiovascular disease with a dismal prognosis. Inflammation plays an important role in AD. Oxylipins are bioactive lipids involved in the modulation of inflammation and may be involved in the pathogenesis and progression of AD. This study aims to identify possible metabolites related to AD. A total of 10 type A Aortic dissection (TAAD) patients, 10 type B Aortic dissection (TBAD) patients and 10 healthy controls were included in this study. Over 100 oxylipin species were identified and quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis. Our investigation demonstrated substantial alterations in 91 oxylipins between AD and healthy individuals. Patients with TAAD had 89 entries accessible compared to healthy controls. According to orthogonal partial least squares discriminant analysis (OPLS-DA), fitness (R2X = 0.362 and R2Y = 0.807, p = 0.03) and predictability (Q2 = 0.517, p = 0.005) are the validation parameters between the two groups. Using multivariate logistic regression, 13-HOTrE and 16(17)-EpDPE were the risk factors in the aortic patients group compared to healthy people (OR = 2.467, 95%CI:1.256–7.245, p = 0.035; OR = 0.015, 95%CI:0.0002–0.3240, p = 0.016, respectively). In KEGG enrichment of differential metabolites, the arachidonic acid metabolism pathway has the most metabolites involved. We established a diagnostic model in distinguishing between AD and healthy people. The AUC was 0.905. Oxylipins were significantly altered in AD patients, suggesting oxylipin profile is expected to exploit a novel, non-invasive, objective diagnosis for AD.

Circular RNAs (circRNA) are involved in a variety of human heart diseases, however, circRNA expression profiles and circRNA-miRNA-mRNA regulatory network in human atrial fibrillation (AF) especially with valvular heart diseases (VHD) remain poorly understood. A high-throughput RNA sequencing was used to investigate the differentially expressed circRNAs in left atrial appendage from VHD patients with or without persistent AF. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to predict the potential functions of the host genes of differentially expressed circRNA and their downstream targets. CircRNA–miRNA-mRNA regulatory network was constructed to identify mechanisms underlying circRNAs. qRT-PCR and sanger sequencing were further performed to validate the results. Compared with sinus rhythm (SR) patients, there were 3094 upregulated and 4472 downregulated circRNAs in AF patients respectively. The expression of 10 most differentially expressed circRNAs (circ 255-ITGA7, circ 418-KCNN2, circ 13913-MIB1, circ 44670-BARD1, circ 44782-LAMA2, circ 81906-RYR2, circ 35880-ANO5, circ 22249-TNNI3K, circ 3136-TNNI3K, circ 56186-TNNI3K) between SR and persistent AF patients were verified by qRT-PCR. In addition, specific back-splicing sites of these circRNAs was confirmed by sanger sequencing. GO and KEGG pathway analysis indicated that cAMP signal pathway and Wnt signal pathway might play important role in the development of AF in VHD patients, which might be affected by circRNAs. This study provided a preliminary landscape of circRNAs expression profiles which are involved in persistent AF due to VHD, and established the possibility for future related researches in this field.

The black soil of Northeast China has a strong adhesion ability because of its unique physical properties, and the soil often adheres to the surface of the grouser shoes of tracked vehicles during the operation. The adhesion performance depends largely on structure parameters of the grouser shoes. The grouser height, the grouser thickness, and the grouser splayed angle were selected as structure parameters. The adhesion force and adhesive soil mass were selected as indicators of adhesion performance. Therefore, the mathematical model between structure parameters and response indicators was established by the response surface method (RSM). The optimal parameters combination was that the grouser height was 20 mm, grouser thickness was 6.34 mm, and grouser splayed angle was 40.45°. The average data of verification experiments occurred when the adhesion force reached 1.11 kPa and adhesive soil mass reached 22.68 g. Compared with the average value of un-optimized experiment results, the adhesion force and adhesive soil mass reduced by 12.84% and 4.63%, respectively. The relative error of the predicted values and measured values was less than 5%, proving the reliability of the regression models. This study could provide a reference method for parameters optimization, and a new structure of the grouser shoes of tracked vehicles will be designed to reduce adhesion.

CircRNAs are involved in a variety of human diseases, however, the expression profiles and the potential diagnostic value of circRNAs in human acute Stanford type A aortic dissection (AAAD) remains largely unknown. In this study, high-throughput RNA sequencing (RNA-Seq) was used to investigate the differentially expressed circRNAs, microRNAs (miRs) and mRNAs in human AAAD tissues (n = 10) compared with normal aortic tissues (n = 10). The results of RNA-Seq revealed that 506 circRNAs were significantly dysregulated (P2). The subsequent weighted gene correlation network analysis and the following co-expression network analysis revealed that tyrosine-protein kinase Fgr might play important roles in the occurrence and development of AAAD. According to the circRNA-miRNA-mRNA network, we found that the upstream regulatory molecule of Fgr is circMARK3. Finally, a receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of the serum circMARK3 as biomarkers for AAAD (cutoff value = 1.497, area under the curve = 0.9344, P < 0.0001, sensitivity = 90.0%, specificity = 86.7%). These results provided a preliminary landscape of circRNAs expression profiles and indicated that circMARK3 was a potential biomarker for AAAD diagnosis.

Jittering sieve is a significant component of corn harvester, and it is used to separate kernels from impurities. The sieves may be blocked by kernels during the separating process, leading to the reduction of working performance. Unfortunately, the automatic recognition of blockage has not been studied yet. To address this issue, in this study we develop machine-vision-based algorithms to divide the jittering sieve into sub-sieves and to recognize kernel blockages. Additionally, we propose the metric to evaluate blocking level of each sub-sieve, aiming to provide the basis for automatic blockage clearing. The performance of the proposed algorithm is verified through simulation experiments on real images. The success ratio of edge determination reaches 100%. The mean cross-correlation coefficient of the blockage levels and the actual numbers of blocked kernels for all test scenes is 0.932. The results demonstrate the proposed algorithm can be used for accurate blockage recognition, and the proposed metric is appropriate for evaluating the blockage level.

Accelerated senescence is triggered by key mediators of arrhythmogenic substrates and contributes to atrial fibrillation (AF). We sought to understand senescence in AF and the extent to which it aggravates the AF process. Twenty-six AF patients undergoing open-heart surgery were included, and 12 patients with sinus rhythm served as controls. Another cohort included 120 consecutive persistent AF patients with valvular heart diseases. HL-1 atrial myocytes were tachypaced (TP) to simulate experimental AF. Compared with sinus rhythm, left atrial appendages (LAAs) with AF presented a significantly increased positive area of cellular senescence, with upregulated expression of p16, p21 and p53. Next, p21 mRNA was increased in patients with AF recurrence compared with that in patients without recurrence. In multivariate analysis, p21 (OR: 2.97; 95% CI: 1.65-5.34; P<0.001) was a significant independent predictor of AF early recurrence. Interestingly, TP induced HL-1 atrial myocyte senescence in vitro, accompanied by a marked increase in the senescence-associated secretory phenotype (SASP) and altered the expression of sarcoplasmic reticulum (SR)-related proteins. Suppression of p21 by siRNA reduced TP induced cell senescence and IL-1ß, IL-6 elevation, and partly changed SR-related proteins expression. Moreover, we show that the level of H2AX, a marker of DNA damage, was higher in AF patients than in sinus rhythm controls. Similarly, an increase in H2AX levels was observed following TP. AF underlies cardiomyocyte senescence and contributes to deleterious atrial remodeling during disease progression. This finding may help facilitate the search for new therapeutic approaches for antiaging therapy for AF. [ABSTRACT FROM AUTHOR]

Background: Aortic aneurysm and aortic dissection (AAD) are life-threatening vascular diseases, with endothelium being the primary target for AAD treatment. Protein S-sulfhydration is a newly discovered posttranslational modification whose role in AAD has not yet been defined. This study aims to investigate whether protein S-sulfhydration in the endothelium regulates AAD and its underlying mechanism., Methods: Protein S-sulfhydration in endothelial cells (ECs) during AAD was detected and hub genes regulating homeostasis of the endothelium were identified. Clinical data of patients with AAD and healthy controls were collected, and the level of the cystathionine γ lyase (CSE)/hydrogen sulfide (H 2 S) system in plasma and aortic tissue were determined. Mice with EC-specific CSE deletion or overexpression were generated, and the progression of AAD was determined. Unbiased proteomics and coimmunoprecipitation combined with mass spectrometry analysis were conducted to determine the upstream regulators of the CSE/H 2 S system and the findings were confirmed in transgenic mice., Results: Higher plasma H 2 S levels were associated with a lower risk of AAD, after adjustment for common risk factors. CSE was reduced in the endothelium of AAD mouse and aorta of patients with AAD. Protein S-sulfhydration was reduced in the endothelium during AAD and protein disulfide isomerase (PDI) was the main target. S-sulfhydration of PDI at Cys343 and Cys400 enhanced PDI activity and mitigated endoplasmic reticulum stress. EC-specific CSE deletion was exacerbated, and EC-specific overexpression of CSE alleviated the progression of AAD through regulating the S-sulfhydration of PDI. ZEB2 (zinc finger E-box binding homeobox 2) recruited the HDAC1-NuRD complex (histone deacetylase 1-nucleosome remodeling and deacetylase) to repress the transcription of CTH , the gene encoding CSE, and inhibited PDI S-sulfhydration. EC-specific HDAC1 deletion increased PDI S-sulfhydration and alleviated AAD. Increasing PDI S-sulfhydration with the H 2 S donor GYY4137 or pharmacologically inhibiting HDAC1 activity with entinostat alleviated the progression of AAD., Conclusions: Decreased plasma H 2 S levels are associated with an increased risk of aortic dissection. The endothelial ZEB2-HDAC1-NuRD complex transcriptionally represses CTH , impairs PDI S-sulfhydration, and drives AAD. The regulation of this pathway effectively prevents AAD progression.