Caffeoylquinic acids protect against alcoholic liver injury and rare C10 acetylenic acids from Erigeron breviscapus.

Three new compounds (1-2, 4) along with ten known ones (3, 5-13), were isolated from the whole plant of Erigeron breviscapus. Compounds 1 and 2, two novel C10 acetylenic acids and compound 4, a jasmone glucoside were elucidated by the detailed analysis of 1D and 2D NMR, HRESIMS spectra, and experimental and calculated electronic circular dichroism (ECD). Compounds 1-3 represent the first example of acetylenic acids incorporating C10 skeleton from E. breviscapus. In addition, the antioxidant effects of all compounds were evaluated by ferric reducing power, 2,2'-Azinobis-(3-ethylbenzthiazoline-6-sulphonate acid) (ABTS) and 2.2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assays. Our results indicated the significant antioxidant activity of caffeoylquinic acids. Additionally, compounds 10-11 and 13 played protective role on alcoholic liver injury cells in a dose-dependent manner.

Macroscale Superlubricity with Ultralow Wear and Ultrashort Running-In Period (∼1 s) through Phytic Acid-Based Complex Green Liquid Lubricants.

Liquid superlubricity has attracted much attention, due to its ability to significantly reduce friction on the macroscale. However, the severe wear caused by the long running-in period is still one of the bottlenecks restricting the practical application of liquid superlubricating materials. In this work, the obtained polyethylene glycol-phytic acid (PEG-PA) composite liquid lubricants showed outstanding superlubricating properties (µ ≈ 0.006) for Si3N4/glass friction pairs with an ultrashort running-in period (∼1 s) under high Hertzian contact pressure of ∼758 MPa. More importantly, even after up to 12 h (∼700 m of travel), only about 100 nm deep wear scars were found on the surface of the glass sheet (wear rate = 2.51× 10-9 mm3 N-1 m-1). From the molecular point of view, the water molecules anchored between the two friction pairs have extremely low shear force during the friction process, and the strong hydrogen bond interaction between PEG and PA greatly improves the bearing capacity of the lubricant. This work addresses the challenge of liquid superlubricant simultaneously exhibiting low shear force and high load-carrying capacity and makes it possible to obtain liquid superlubrication performance with an extremely short running-in time.

Monolayer NbSe2 Favors Ultralow Friction and Super Wear Resistance.

The urgent demand for atomically thin, superlubricating, and super wear-resistant materials in micro/nanoelectromechanical systems has stimulated the research of friction-reducing and antiwear materials. However, the fabrication of subnanometer-thick films with superlubricating and super wear-resistant properties under ambient conditions remains a huge challenge. Herein, high-quality monolayer (ML) NbSe2 (∼0.8 nm) with ultralow friction and super wear resistance in an atmospheric environment was successfully grown by chemical vapor deposition (CVD) for the first time. Moreover, compared with few-layered (FL) NbSe2, ML NbSe2 has a lower friction coefficient and better wear resistance. On the basis of density function theory (DFT) calculations, the adhesion and the degree of charge transfer between ML NbSe2 and the substrate is larger than that of the topmost layer to the underlying layers of NbSe2 with two or more layers, which can be used to explain that the ML NbSe2 favors ultralow friction and super wear resistance.

Prognostic value of myocardial salvage index assessed by cardiovascular magnetic resonance in reperfused ST-segment elevation myocardial infarction.

Aims: Cardiovascular magnetic resonance (CMR) is a powerful tool to quantify the myocardial area at risk (AAR) and infarct size (IS), and evaluate the extent of myocardial salvage in acute ST-segment elevation myocardial infarction (STEMI). This study aimed to assess the prognostic value of myocardial salvage index (MSI) assessed by CMR in reperfused STEMI and investigate whether MSI could improve the predictive efficacy of the Global Registry of Acute Coronary Events (GRACE) risk score. Methods and results: About 104 consecutive patients who were hospitalized with first-time STEMI and received reperfusion therapy were prospectively enrolled. The primary endpoint was the incident of major adverse cardiovascular event (MACE) including all-cause mortality, non-fatal myocardial reinfarction and congestive heart failure within 36 months after the index event. Cox regression analysis was used to evaluate the prognostic association of MSI with MACE risk. About 21 (20.2%) patients developed MACE during the 3-year follow-up period, and patients with MSI < median had a higher incidence of MACE than those with MSI ≥ median [16 (30.8%) vs. 5 (9.6%), P = 0.007]. After adjusting all the parameters associated with MACE in univariate Cox analysis, MSI assessed by CMR remained independently significant as a predictor of MACE in multivariate Cox analysis (hazard ratio 0.963, 95% CI: 0.943-0.983; P < 0.001). Adding MSI to the GRACE risk score significantly increased the prognostic accuracy of the GRACE risk score (area under the curve: 0.833 vs. 0.773; P = 0.044), with a net reclassification improvement of 0.635 (P = 0.009) and an integrated discrimination improvement of 0.101 (P = 0.002). Conclusion: This study confirmed that MSI assessed by CMR had a good long-term prognostic value in reperfused STEMI and improve the prognostic performance of the GRACE risk score.

Comparison of the Effects of High Hydrostatic Pressure and Pasteurization on Quality of Milk during Storage.

High hydrostatic pressure (HHP, 600 MPa/15 min), pasteurization (72 °C/15 s) and pasteurization-HHP (72 °C/15 s + 600 MPa/15 min) processing of milk were comparatively evaluated by examining their effects on microorganisms and quality during 30 days of storage at 4 °C. The counts of total aerobic bacteria in HHP-treated milk were less than 2.22 lgCFU/mL during storage, while they exceeded 5.00 lgCFU/mL in other treated milk. Although HHP changed the color, it had more advantages in maintaining the nutrient (fat, calcium and ß-lactoglobulin) properties of milk during storage. Moreover, the viscosity and particle size of HHP-treated milk were more similar to the untreated milk during storage. However, consumer habits towards heat-treated milk have led to poor acceptance of HHP-treated milk, resulting in a low sensory score. In sum, compared with pasteurization- and pasteurization-HHP-treated milk, HHP-treated milk showed longer shelf life and better nutritional quality, but lower sensory acceptance.

Pressure Control of the Structure and Multiferroicity in a Hydrogen-Bonded Metal-Organic Framework.

Multiferroic materials with the cross-coupling of magnetic and ferroelectric orders provide a new platform for physics study and designing novel electronic devices. However, the weak coupling strength of ferroelectricity and magnetism is the main obstacle for potential applications. The recent research focuses on enhancing the coupling effect via synthesizing novel materials in a chemical route or tuning the multiferroicity in the physical way. Among them, pressure is an effective method to modify multiferroic materials, especially when the chemical doping has reached its tuning limit. In this work, we systemically studied the multiferroic properties in a hydrogen-bonded metal-organic framework (MOF) [(CH3)2NH2]Ni(HCOO)3 under high pressure. X-ray diffraction and Raman scattering reveal that a structural phase transition occurs in a pressure region of 6-9 GPa, and the crystal structure is greatly modified by pressure. With the ac magnetic susceptibility, pyroelectric current, and dielectric constant measurements, we obtain the multiferroic property evolution under high pressure and create a temperature-pressure phase diagram. Our study demonstrates that the pressure can modify the magnetic superexchange interaction and hydrogen bonding simultaneously in these perovskite-like MOFs. The multiferroic phase region has been expanded to higher temperature due to the pressure-enhanced spin-phonon coupling effect.

Incremental Prognostic Value of Pericoronary Adipose Tissue Thickness Measured Using Cardiac Magnetic Resonance Imaging After Revascularization in Patients With ST-Elevation Myocardial Infarction.

Background and Aim: Pericoronary adipose tissue (PCAT) reflects pericoronary inflammation and is associated with coronary artery disease. We aimed to identify the association between local PCTA thickness using cardiac magnetic resonance (CMR) and prognosis of patients with ST-elevation myocardial infarction (STEMI), and to investigate the incremental prognostic value of PCAT thickness in STEMI after reperfusion. Methods: A total of 245 patients with STEMI (mean age, 55.61 ± 10.52 years) who underwent CMR imaging within 1 week of percutaneous coronary intervention therapy and 35 matched controls (mean age, 53.89 ± 9.45 years) were enrolled. PCAT thickness indexed to body surface area at five locations, ventricular volume and function, infarct-related parameters, and global strain indices were evaluated using CMR. Associations between PCAT thickness index and 1-year major adverse cardiovascular events (MACE) after STEMI were calculated. The prognostic value of the standard model based on features of clinical and CMR and updated model including PACT thickness index were further assessed. Results: Patients with MACE had a more significant increase in PCAT thickness index at superior interventricular groove (SIVGi) than patients without MACE. The SIVGi was significantly associated with left ventricular ejection fraction (LVEF), infarct size, and global deformation. SIVGi > 4.98 mm/m2 was an independent predictor of MACE (hazard ratio, 3.2; 95% CI: 1.6-6.38; p < 0.001). The updated model significantly improved the power of prediction and had better discrimination ability than that of the standard model for predicting 1-year MACE (areas under the ROC curve [AUC] = 0.8 [95% CI: 0.74-0.87] vs. AUC = 0.76 [95% CI: 0.68-0.83], p < 0.05; category-free net reclassification index [cfNRI] = 0.38 [95% CI: 0.1-0.53, p = 0.01]; integrated discrimination improvement [IDI] = 0.09 [95% CI: 0.01-0.18, p = 0.02]). Conclusions: This study demonstrated SIVGi as an independent predictor conferred incremental value over standard model based on clinical and CMR factors in 1-year MACE predictions for STEMI.

Fulvivirga marina sp. nov. and Fulvivirga sediminis sp. nov., two novel Bacteroidetes isolated from the marine sediment.

Two novel, designated strains 29W222T and 2943T, were isolated from the marine sediment from Aoshan Bay, Jimo, PR China. Growth was observed at pH 6.0-8.5 (optimum, pH 7.5) for strain 29W222T, and pH 5.5-8.5 (pH 7.0) for strain 2943T. Both strains displayed growth in 0.5-6 % NaCl with an optimum at 1 % for 29W222T; 0.5 % for 2943T. Both strains grew optimally at 33 °C. The results of phylogenetic analyses based on 16S rRNA gene sequences indicated that 29W222T and 2943T represented members of the genus Fulvivirga and strain 29W222T was most closely related to Fulvivirga kasyanovii KMM 6220T (97.9 % sequence similarity) and Fulvivirga imtechensis AK7T (95.0 %), and 2943T to Fulvivirga imtechensis AK7T (95.7 %) and Fulvivirga kasyanovii KMM 6220T (94.8 %). The genomic DNA G+C contents of 29W222T and 2943T were 39.9 and 37.7 mol%, respectively. The results of chemotaxonomic analysis indicated that the sole respiratory quinone was menaquinone 7 (MK-7), and the major fatty acid was iso-C15 : 0 for both strains. Average nucleotide identity and average amino acid identity values between strain 29W222T and Fulvivirga kasyanovii KMM 6220T were 78.9 and 83.6 %, respectively; the corresponding values between 2943T and Fulvivirga imtechensis AK7T were 69.8 and 63.6 %, respectively. Therefore, strains 29W222T and 2943T represent to two novel species of the genus Fulvivirga, for which the names Fulvivirga marina sp. nov. (29W222T=KCTC 62848T=MCCC 1K05194T) and Fulvivirga sediminis sp. nov. (2943T=KCTC 62847T= MCCC 1K05144T) are proposed, respectively.

Enriched clonal hematopoiesis in seniors with dietary vitamin C inadequacy.

BACKGROUND: The anti-cancer effect of vitamin C (VC) has long been speculated, but studies yielded inconsistency. Recent studies reported that supraphysiological concentration of VC have therapeutic or prevention effects for myeloid malignancies with certain mutation signatures. There was a notable proportion of DAT (i.e., DNMT3A, ASXL1, and TET2) and dozens of other genes that mutate in age-related clonal hematopoiesis (ARCH). METHODS AND RESULTS: Through analyzing the plasma VC concentration and mutations of 21 genes in 215 senior volunteers, we revealed that ARCH is significantly associated with dietary plasma VC concentrations, especially TET2 mutations and non-DAT mutations. CONCLUSION: This study firstly disclosed the significant association between VC inadequacy and ARCH in the senior population. It provides evidence that physiological VC concentration has ARCH prevention effect. It will illuminate future explorations on the oral VC supplement in maintaining sound hematopoiesis, reversal ARCH, adjuvant therapy for myeloid malignancies, and prevention of other ARCH related comorbidities.

CD44-targeted pH-responsive micelles for enhanced cellular internalization and intracellular on-demand release of doxorubicin.

Poor cellular uptake and slow intracellular drug release remain the main barriers for the efficient application of micellar delivery system. Taking advantage of the overexpressed CD44 receptor and mild acidic microenvironment of tumour cells, CD44-targeted pH-responsive micelles based on the self-assembly of histidine-hyaluronic acid-dodecylamine (His-HA-DA) were prepared for the delivery of doxorubicin (DOX). These micelles exhibited pH-responsive behaviour with increased particle size, decreased encapsulation efficiency (EE%) of DOX and rapid release of DOX triggered by low pH. Compared with free DOX, DOX/HHD exhibited relatively high cellular uptake mainly via the CD44-mediated endocytosis. The on-demand intracellular release of DOX from DOX/HHD led to improved cytotoxicity. DOX/HHD also showed great penetration efficiency in 3D tumour spheres in vitro. Moreover, these micelles with suitable particle size gained excellent tumour-targeting effects, as well as improved anti-tumour effects and reduced side effects in vivo. In conclusion, these micelles with CD44 targeted and pH-responsive behaviours provide a promising strategy for the efficient delivery of anti-tumour drugs in vivo.

Radiomics of Non-Contrast-Enhanced T1 Mapping: Diagnostic and Predictive Performance for Myocardial Injury in Acute ST-Segment-Elevation Myocardial Infarction.

OBJECTIVE: To evaluate the feasibility of texture analysis on non-contrast-enhanced T1 maps of cardiac magnetic resonance (CMR) imaging for the diagnosis of myocardial injury in acute myocardial infarction (MI). MATERIALS AND METHODS: This study included 68 patients (57 males and 11 females; mean age, 55.7 ± 10.5 years) with acute ST-segment-elevation MI who had undergone 3T CMR after a percutaneous coronary intervention. Forty patients of them also underwent a 6-month follow-up CMR. The CMR protocol included T2-weighted imaging, T1 mapping, rest first-pass perfusion, and late gadolinium enhancement. Radiomics features were extracted from the T1 maps using open-source software. Radiomics signatures were constructed with the selected strongest features to evaluate the myocardial injury severity and predict the recovery of left ventricular (LV) longitudinal systolic myocardial contractility. RESULTS: A total of 1088 segments of the acute CMR images were analyzed; 103 (9.5%) segments showed microvascular obstruction (MVO), and 557 (51.2%) segments showed MI. A total of 640 segments were included in the 6-month follow-up analysis, of which 160 (25.0%) segments showed favorable recovery of LV longitudinal systolic myocardial contractility. Combined radiomics signature and T1 values resulted in a higher diagnostic performance for MVO compared to T1 values alone (area under the curve [AUC] in the training set; 0.88, 0.72, p = 0.031: AUC in the test set; 0.86, 0.71, p002). Combined radiomics signature and T1 values also provided a higher predictive value for LV longitudinal systolic myocardial contractility recovery compared to T1 values (AUC in the training set; 0.76, 0.55, p < 0.001: AUC in the test set; 0.77, 0.60, p < 0.001). CONCLUSION: The combination of radiomics of non-contrast-enhanced T1 mapping and T1 values could provide higher diagnostic accuracy for MVO. Radiomics also provides incremental value in the prediction of LV longitudinal systolic myocardial contractility at six months.

A radiomic nomogram for prediction of major adverse cardiac events in ST-segment elevation myocardial infarction.

OBJECTIVES: This study was conducted to establish and validate a non-contrast T1 map-based radiomic nomogram for predicting major adverse cardiac events (MACEs) in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). METHODS: This retrospective study included 157 consecutive patients (training sets, 109 patients; test sets, 48 patients) with acute STEMI undergoing PCI. An open-source radiomics software was used to segment the myocardium on the non-contrast T1 mapping and extract features. A radiomic signature was constructed to predict MACEs using the least absolute shrinkage and selection operator method. The performance of the radiomic nomogram for predicting MACEs in both the training and test sets was evaluated by its discrimination, calibration, and clinical usefulness. RESULTS: The radiomic signature showed a good prognostic ability in the training sets with an AUC of 0.94 (95% CI, 0.86 to 1.00) and F1 score of 0.71, which was confirmed in the test sets with an AUC of 0.90 (95% CI, 0.74 to 1.00) and F1 score of 0.62. The nomogram consisting of the radiomic scores and cardiac troponin I showed good discrimination ability in the training and test sets with AUCs of 0.96 (95% CI, 0.91 to 1.00; F1 score, 0.71) and 0.94 (95% CI, 0.83 to 1.00; F1 score, 0.70), respectively. CONCLUSIONS: The non-contrast T1 map-based radiomic nomogram is a useful tool for the prediction of MACEs in patients with acute STEMI undergoing PCI that can assist clinicians for optimised risk stratification of individual patients. KEY POINTS: • Radiomic signature improved MACE prediction in acute STEMI patients. • T1 mapping-derived radiomic signature outperformed conventional cardiac MRI parameters in predicting MACEs in acute STEMI patients. • The non-contrast T1 mapping-based radiomic nomogram can be used for prediction of MACEs and improvement of risk stratification in acute STEMI.

Erratum to "Expression Profiles and Ontology Analysis of Circular RNAs in a Mouse Model of Myocardial Ischemia/Reperfusion Injury".

[This corrects the article DOI: 10.1155/2020/2346369.].

Circulating miR-1 as a potential predictor of left ventricular remodeling following acute ST-segment myocardial infarction using cardiac magnetic resonance.

BACKGROUND: The identification of patients with a high likelihood of left ventricular (LV) remodeling with a high-risk prognosis has critical implications for risk stratification after acute ST-segment elevation myocardial infarction (STEMI). This study aimed to evaluate the relationship between circulating miR-1 and 6-month post-infarct LV remodeling based on cardiac magnetic resonance (CMR) imaging. METHODS: A total of 80 patients with a first STEMI treated with primary percutaneous coronary intervention (PCI) who underwent CMR imaging 1 week and 6 months after STEMI were evaluated. The percentage changes of LV ejection fraction (LVEF), LV end-diastolic volume (LVEDV), LV end-systolic volume index (LVESV) at 1 week and 6 months after PCI (%ΔLVEF, %ΔLVEDV and %ΔLVESV) were calculated. miR-1 was measured using polymerase chain reaction (PCR)-based technologies in plasma samples that were collected at admission. The study group was divided into two groups based on a 10% cutoff value for the percentage of change in the LV end-diastolic volume (%ΔLVEDV): remodeling at high risk of major adverse cardiac events (MACEs) (%ΔLVEDV ≥10%, termed the LV remodeling group) and remodeling at lower risk of MACEs (%ΔLVEDV <10%, termed the non-LV remodeling group). The associations of miR-1 expression with the %ΔLVEDV, percentage change in the LV end-systolic volume (%ΔLVESV), and percentage change in the LV ejection fraction at follow-up were estimated. RESULTS: Twenty-two patients (27.5%) showed adverse LV remodeling, and 58 patients (72.5%) did not show adverse LV remodeling at the 6-month follow-up of CMR. The mean LVEF, LVEDV index, and LVESV index values at 1 week were 50.6%±8.2%, 74.6±12.8 mL/m2, and 37.2±10.2 mL/m2, respectively. Mean LVEF at follow-up (53.5%±10.6%) was increased compared with baseline (P<0.001). There were significant decreases in LVEDV index and LVESV index values at follow-up (72.0±14.9 mL/m2 and 33.7±11.0 mL/m2, respectively; P=0.009 and P<0.001, respectively). The expression of miR-1 at admission was positively correlated with the %ΔLVEDV (r=0.611, P<0.001) and %ΔLVESV (r=0.268, P=0.016). Receiver operating characteristic (ROC) analysis showed that miR-1 expression predicted LV remodeling with an area under the curve (AUC) value of 0.68 (95% CI: 0.56-0.78). Compared with the clinical factors of peak creatine kinase-myocardial band (CK-MB) and peak troponin T level, peak logNT-proBNP showed the highest predictive power, with an AUC value of 0.75 (95% CI: 0.64-0.84). A model including the clinical, CMR, and miR-1 factors showed greater predictive power (P=0.034) than a model including only clinical and CMR factors, with AUCs of 0.89 (95% CI: 0.80-0.95) and 0.81 (95% CI: 0.71-0.89), respectively. CONCLUSIONS: Circulating miR-1 at admission is an independent predictor of LV remodeling 6 months after STEMI. miR-1 showed incremental value in predicting LV remodeling compared with the clinical and CMR measurements.

Expression Profiles and Ontology Analysis of Circular RNAs in a Mouse Model of Myocardial Ischemia/Reperfusion Injury.

Circular RNAs (circRNAs) play important roles in cellular physiology. The association between circRNAs and myocardial ischemia/reperfusion (I/R) injury remains largely unknown. The aim of this study was to test the effects of myocardial I/R circRNA expression and explore the potential roles of these circRNAs. CircRNAs were screened by high-throughput sequencing, and the expression of dysregulated circRNAs was further validated using quantitative real-time polymerase chain reaction. Nineteen upregulated and 20 downregulated circRNAs were identified. Gene Ontology analysis indicated that the dysregulated transcripts were associated with fundamental pathophysiologic processes. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed significant changes in adherens junction, the HIF-1 signaling pathway, the cell cycle, and the FoxO signaling pathway which have a close relationship with myocardial I/R injury. The circRNA-miRNA analysis demonstrated the broad potential of the differentially expressed circRNAs to regulate target genes by acting on the miRNAs. This study provides a foundation for understanding the roles and mechanisms of circRNAs in myocardial I/R injury.

Influence of Different Inactivation Methods on Severe Acute Respiratory Syndrome Coronavirus 2 RNA Copy Number.

The outbreak of coronavirus disease 2019 (COVID-19) has spread across the world and was characterized as a pandemic. To protect medical laboratory personnel from infection, most laboratories inactivate the virus causing COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in clinical samples before testing. However, the effect of inactivation on the detection results remains unknown. Here, we used a digital PCR assay to determine the absolute SARS-CoV-2 RNA copy number in 63 nasopharyngeal swab samples and assess the effect of inactivation methods on viral RNA copy number. Viral inactivation was performed by three different methods: (i) incubation with the TRIzol LS reagent for 10 min at room temperature, (ii) heating in a water bath at 56°C for 30 min, and (iii) high-temperature treatment, including autoclaving at 121°C for 20 min, boiling at 100°C for 20 min, and heating at 80°C for 20 min. Compared to the amount of RNA in the original sample, TRIzol treatment destroyed 47.54% of the nucleocapsid protein (N) gene and 39.85% of open reading frame (ORF) 1ab. For samples treated at 56°C for 30 min, the copy number of the N gene and ORF 1ab was reduced by 48.55% and 56.40%, respectively. The viral RNA copy number dropped by 50 to 66% after heating at 80°C for 20 min. Nearly no viral RNA was detected after autoclaving at 121°C or boiling at 100°C for 20 min. These results indicate that inactivation reduced the quantity of detectable viral RNA and may cause false-negative results, especially in weakly positive cases. Thus, use of the TRIzol reagent rather than heat inactivation is recommended for sample inactivation, as the TRIzol reagent had the least effect on the RNA copy number among the tested methods.

Depression and myocardial injury in ST-segment elevation myocardial infarction: A cardiac magnetic resonance imaging study.

BACKGROUND: Depression is common in patients with myocardial infarction and has been independently associated with adverse outcomes. However, the association between depression and myocardial injury on cardiac magnetic resonance (CMR) in patients with ST-segment elevation myocardial infarction (STEMI) has still not been assessed. AIM: To assess the association between depression and myocardial injury on CMR in patients with STEMI. METHODS: A total of 107 STEMI patients undergoing primary percutaneous coronary intervention (P-PCI) were analyzed in this prospectivecohort study. Each subject completed the Patient Health Questionnaire-9 (PHQ-9) to assess the presence and severity of depressive symptoms. CMR was performed at a median of 3 d after P-PCI for quantifying post-MI myocardial injury. Correlations between depression identified by the PHQ-9 and myocardial injury measured on CMR were assessed. RESULTS: In this study, 19 patients (17.8%) were diagnosed with major depression identified by the PHQ-9 ≥ 10. PHQ-9 was analyzed both as a continuous variable and dichotomous variable. After multivariable adjustment, the proportion of patients with large infarction size was significantly higher in the major depression group (PHQ-9 ≥ 10) (OR: 4.840, 95%CI: 1.122-20.868, P =0.034). When the PHQ-9 was evaluated as a continuous variable, after multivariable adjustment, an increased PHQ-9 score was associated with an increased risk of large infarction size (OR: 1.226, 95%CI: 1.073-1.401, P =0.003). CONCLUSION: In patients with STEMI undergoing PCI, depression was independently associated with a large infarction size.

Intracoronary compared with intravenous bolus tirofiban on the microvascular obstruction in patients with STEMI undergoing PCI: a cardiac MR study.

To investigate the potential effect of intracoronary administration of the glycoprotein IIb/IIIa inhibitor tirofiban on the microvascular obstruction (MVO) assessed by cardiac magnetic resonance (CMR) imaging compared to the intravenous route in patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention (PCI). Two hundred eight patients were randomized into two groups (tirofiban i.v. and tirofiban i.c.). CMR was completed within 3-7 days after ST-segment-elevation myocardial infarction. One hundred thirty-two patients had a follow-up CMR at 6 months after discharge. The primary end point was the CMR measurements including myocardium strain, myocardial perfusion index, final infarct size, prevalence and extent of MVO, and the change of left ventricular end-diastolic volume (LVEDV) at six months follow-up. The second endpoint was major adverse cardiovascular events (composite of all-cause death, nonfatal reinfarction and congestive heart failure) in one year. The MVO prevalence and extent [56% versus 36%, p = 0.004; 2.08 (IQR: 1.18-5.07) g versus 1.68 (IQR: 0.30-3.28) g, p = 0.041] showed a significant difference between the intravenous and intracoronary groups. Global left ventricular peak longitudinal strain was significantly different in intracoronary groups compared to intravenous groups, - 12.5 [IQR: - 13.4 to - 10.9] versus - 12.3 [IQR: - 13.4 to - 10.4], respectively (P = 0.042). Infarcted myocardial perfusion index was significantly different in intracoronary groups compared to intravenous groups, 0.11 [IQR: 0.08 to 0.15] versus 0.09 [IQR: 0.07 to 0.14], respectively (P = 0.026). Intracoronary tirofiban was associated with a higher change in LVEDV compared with intravenous group (- 10.2% [IQR: - 13.7% to - 2.6%] versus 1.3% [IQR: - 5.6% to 6.1%], p < 0.001). Intracoronary tirofiban application showed no benefit on the occurrence of major adverse cardiovascular events during follow-up compared to intravenous administration. This CMR study in ST-segment-elevation myocardial infarction patients showed a benefit in MVO and left ventricular remodeling for intracoronary tirofiban administration compared to intravenous administration in patients undergoing PCI.

Homeobox D3, A Novel Link Between Bone Morphogenetic Protein 9 and Transforming Growth Factor Beta 1 Signaling.

AIMS: Several signaling pathways contribute to endothelial-mesenchymal transitions and vascular calcification, including bone morphogenetic protein (BMP) and transforming growth factor (TGF) ß signaling. The transcription factor homeobox D3 (Hoxd3) is known to regulate an invasive endothelial phenotype, and the aim of the study is to determine if HOXD3 modulates BMP and TGFß signaling in the endothelium. METHODS AND RESEARCH: We report that the endothelium with high BMP activity due to the loss of BMP inhibitor matrix Gla protein (MGP) shows induction of Hoxd3. HOXD3 is part of a BMP-triggered cascade. When activated by BMP9, activin receptor-like kinase (ALK) 1 induces HOXD3 expression. Hoxd3 promoter is a direct target of phosphorylated (p) SMAD1, a mediator of BMP signaling. High BMP activity further results in enhanced TGFß signaling due to induction of TGFß1 and its receptor, ALK5. This is mediated by HOXD3, which directly targets the Tgfb1 promoter. Finally, TGFß1 and BMP9 stimulate the expression of MGP, which limits the enhanced ALK1 induction by counteracting BMP4. The cascade of BMP9-HOXD3-TGFß also affects Notch signaling and angiogenesis through induction of Notch ligand Jagged 2 and suppression of Notch ligand delta-like 4 (Dll4). CONCLUSION: The results suggest that HOXD3 is a novel link between BMP9/ALK1 and TGFß1/ALK5 signaling. TRANSLATIONAL PERSPECTIVE: BMP and TGFß signaling are instrumental in vascular disease such as vascular calcification and atherosclerosis. This study demonstrated a novel type of cross talk between endothelial BMP and TGFß signaling as mediated by HOXD3. The results provide a possible therapeutic approach to control dysfunctional BMP and TGFß signaling by regulating HOXD3.

Skip is essential for Notch signaling to induce Sox2 in cerebral arteriovenous malformations.

Notch signaling and Sry-box (Sox) family transcriptional factors both play critical roles in endothelial cell (EC) differentiation in vascularization. Recent studies have shown that excessive Notch signaling induces Sox2 to cause cerebral arteriovenous malformations (AVMs). Here, we examine human pulmonary AVMs and find no induction of Sox2. Results of epigenetic studies also show less alteration of Sox2-DNA binding in pulmonary AVMs than in cerebral AVMs. We identify high expression of ski-interacting protein (Skip) in brain ECs, a Notch-associated chromatin-modifying protein that is lacking in lung ECs. Knockdown of Skip abolished Notch-induction of Sox2 in brain ECs, while restoration of Skip in lung ECs enabled Notch-mediated Sox2 induction. The results suggest that Skip is a key factor for induction of Sox2 in cerebral AVMs.