A Multi-Feature Fusion Method for Life Prediction of Automotive Proton Exchange Membrane Fuel Cell Based on TCN-GRU.

The Proton Exchange Membrane Fuel Cell (PEMFC) is a fast-developing battery technology, and the key to its reliability and lifespan improvement lies in the accurate assessment of durability. However, the degradation mechanism of the PEMFC is hard to determine and its internal parameters are highly coupled. Thus, the development of a more accurate life prediction model that meets the actual scenarios is to be investigated urgently. To solve this problem, a multi-feature fusion life prediction method based on the Temporal Convolutional Network-Gated Recurrent Unit (TCN-GRU) is proposed. A TCN algorithm is used as the prediction base model, and two GRU modules are included with the model to strengthen the model's expression ability and improve its predictive accuracy. Two widely recognized datasets and two operating conditions are utilized for model training and prediction, respectively. Comparisons are made with single-feature parameter models in terms of Root Mean Square Error (RMSE) and the Determination Coefficient (R2). The results show that the prediction accuracy of the TCN-GRU multi-feature fusion model is higher than that of the single-feature models in terms of stability and anti-interference under both operating conditions. The accuracy of the TCN-GRU (three-feature) model is the most optimal in a steady-state condition at 80% of the training set ratio (RMSE = 3.27 × 10-3, R2 = 0.965). Furthermore, with the increase in the input feature parameter, the TCN-GRU model is closer to the real value, which proves once again that the proposed model can meet the accuracy requirements of the life prediction of the PEMFC.

Risk factor control and adherence to recommended Lifestyle among US hypertension patients.

BACKGROUND: Although hypertension is a significant public health challenge globally, only a few studies have assessed the effectiveness of risk factor control and adherence to recommended lifestyle among United States hypertension patients. METHODS: In this study, a detailed, stratified analysis of the 1999-2018 National Health and Nutrition Examination Survey was conducted to assess the adequacy of risk factor control and conformity to recommended lifestyle among United States patients with hypertension. Logistic regression analysis was used to identify influencing factors associated with not acheving risk factors and lifestyle targets. RESULTS: A total of 21,770 participants (mean age, 62 ± 15 years) were enrolled in this study. About one in five (20%) participants achieved the recommended body mass index goal, 40% achieved the low-density lipoprotein cholesterol goal, and 30% achieved the recommended waist circumference. Most patients (80%) achieved the recommended smoking goal, 58% met the recommended alcohol consumption, and 19% achieved the recommended physical activity goal. Multivariate analysis demonstrated that age, gender, race, education, metabolic syndrome, and diabetes mellitus were independent predictors of not achieving risk factors and lifestyle targets. CONCLUSIONS: Controlling risk factors and adherence to recommended lifestyles are not ideal for hypertension patients. Therefore, further research should assess how to improve the compliance rate and take targeted measures based on influencing factors for long-term prognosis.

Diagnostic Performance of Fractional Flow Reserve Derived From Coronary CT Angiography: The ACCURATE-CT Study.

BACKGROUND: AccuFFRct (ArteryFlow Technology) is a novel noninvasive method for calculating fractional flow reserve (FFR) from coronary computed tomography angiography (CCTA). The accuracy of AccuFFRct has not been adequately assessed. OBJECTIVES: This study sought to evaluate the diagnostic performance of AccuFFRct in detecting lesion-specific ischemia. METHODS: This prospective study enrolled 339 patients with 404 vessels. CCTA-derived FFR was calculated using an on-site computational fluid dynamics-based method and compared with invasive FFR. The performance of AccuFFRct was comprehensively analyzed in all lesions and subgroups, including "gray zone" lesions, various lesion classifications, clinical presentations, stenosis severities, and lesion locations. RESULTS: Using FFR ≤0.80 as a reference standard, the overall diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for AccuFFRct were 90.6% (95% CI: 87.3%-93.3%), 90.9% (95% CI: 85.1%-94.9%), 90.4% (95% CI: 86.1%-93.8%), 85.3% (95% CI: 79.8%-89.5%), and 94.2% (95% CI: 90.8%-96.4%), respectively. Good correlation and agreement were found between the computed AccuFFRct and measured FFR. AccuFFRct showed superior discrimination ability to CCTA (AUC: 0.93 [95% CI: 0.89-0.95] vs 0.77 [95% CI: 0.72-0.81]; P < 0.001) and quantitative coronary angiography (AUC: 0.93 [95% CI: 0.89-0.95] vs 0.89 [95% CI: 0.85-0.92]; P = 0.048) for identifying functionally significant stenosis. Notably, AccuFFRct maintained high diagnostic accuracy across the spectrum of lesion classifications, clinical presentations, stenosis severities, lesion locations, and in the "gray zone". Furthermore, in the cohort with ≥70% stenosis, AccuFFRct could significantly reduce the rate of un-necessary invasive tests (33.1% vs 6.6%; P < 0.001). CONCLUSIONS: The study confirms the potential of AccuFFRct as a noninvasive alternative to invasive FFR for detecting ischemia in coronary artery disease and to risk stratify patients. The results highlight AccuFFRct's robust diagnostic ability across a wide range of lesion classifications, clinical presentations, stenosis severities, lesion locations, and in the "gray zone". (Diagnostic Performance of Fractional Flow Reserve Derived From Coronary CT Angiography [ACCURATE-CT]; NCT04426396).

Increased Expression of Mevalonate Pathway-Related Enzymes in Angiotensin II-Induced Abdominal Aortic Aneurysms.

Abdominal aortic aneurysm (AAA) is characterized by permanent luminal expansion and a high mortality rate due to aortic rupture. Despite the identification of abnormalities in the mevalonate pathway (MVA) in many diseases, including cardiovascular diseases, the potential impact of this pathway on AAA remains unclear. This study aims to investigate whether the expression of the MVA-related enzyme is altered during the progression of angiotensin II (Ang II) -induced AAA.Ang II 28D and Ang II 5D groups were continuously perfused with Ang II for 28 days and 5 days, respectively, and the Sham group was perfused with saline. The general and remodeling characteristics of AAA were determined by biochemical and histological analysis. Alteration of MVA-related enzyme expressions was revealed by western blot and single-cell RNA sequencing (scRNA-seq).The continuous Ang II infusion for 28 days showed significant aorta expansion and arterial remodeling. Although the arterial diameter slightly increased, the aneurysm formation was not found in Ang II induction for 5 days. MVA-related enzyme expression and activation of small GTP-binding proteins were significantly increased after Ang II-induced. As verified by scRNA-seq, the key enzyme gene expression was also higher in Ang II 28D. Similarly, it was detected that the expression levels of the above enzymes and the activity of small G proteins were elevated in the early stage of AAA as induced by Ang II infusion for 5 days.Continuous Ang II infusion-induced abdominal aortic expansion and arterial remodeling were accompanied by altered expression of key enzymes in the MVA.

The secondary prevention of coronary heart disease in US adults 75 Years and older in daily practice: Results from the National Health and Nutrition Examination Survey 1999-2018 survey.

Background: Pharmacologic therapies, risk factor control, and lifestyle alterations were independently proven to reduce long-term cardiovascular events. However, comprehensive research examining the extent to which individuals aged 75 and above in the United States adhere to national guidelines for the secondary prevention of coronary heart disease is limited. Therefore, the primary objective of this study was to examine the current state of secondary prevention of coronary heart disease in persons 75 years of age and older in the United States and to examine the factors that contribute to inadequate drug utilization and poor control of numerous risk factors. Methods: We identified patients over 75 years of age with coronary heart disease based on the National Health and Nutrition Examination Survey from 1999 to 2018 and analyzed the adequacy of risk factor control and adherence to lifestyle and medication recommendations to assess the effectiveness of coronary heart disease management. Logistic regression analysis was used to identify factors associated with uncontrolled risk factors or noncompliance with recommended medications. Results: We collected information from 1566 known coronary heart disease patients aged ≥75 years of age. The majority were at target goals for blood pressure (58.88%), low-density lipoprotein cholesterol (66.85%), and glycated hemoglobin (76.12%). Only 27.8% and 36.06% were at targets for body mass index and waist circumference, respectively. 91.95% reported smoking cessation, 85.98% followed recommended alcohol consumption, whereas only 10.34% reported sufficient physical activity. For ß blockers, angiotensin -converting enzyme inhibitors/angiotensin receptor blockers, statins, and antiplatelet drugs, the utilization of indicated therapy was 54.41%, 49.36%, 54.79%, and 19.03%, respectively (6.26% for all 4 medications). The results of the logistic regression analysis demonstrated that diabetes mellitus and metabolic syndrome were critical markers of numerous uncontrolled risk variables as well as noncompliance with medication regimens. Conclusions: A vast majority of coronary heart disease patients ≥75 years in the USA exhibited suboptimal overall control of critical coronary heart disease risk factors. For this patient population, more knowledge is necessary to enable patients to receive continuous support, guidance, and counseling.

Morphologically transformable peptide nanocarriers coloaded with doxorubicin and curcumin inhibit the growth and metastasis of hepatocellular carcinoma.

In tumor treatment, the highly disordered vascular system and lack of accumulation of chemotherapeutic drugs in tumors severely limit the therapeutic role of nanocarriers. Smaller drug-containing nanoparticles (NPs) can better penetrate the tumor but are easily removed, which severely limits the tumor-killing properties of the drug. The chemotherapeutic medication doxorubicin (DOX) is highly toxic to the heart, but this toxicity can be effectively mitigated and the combined anticancer effect can be enhanced by clinically incorporating curcumin (CUR) as part of the dual therapy. We designed a small-molecule peptide, Pep1, containing a targeting peptide (CREKA) and a pH-responsive moiety. These NPs can target the blood vessels in tumor microthrombi and undergo a morphological shift in the tumor microenvironment. This process enhances the penetration and accumulation of drugs, ultimately improving the effectiveness of cancer treatment. In vitro and in vivo experiments demonstrated that this morphological transformation allowed rapid and effective drug release into tumors, the effective inhibition of tumor angiogenesis, and the promotion of tumor cell apoptosis, thus effectively killing tumor cells. Our findings provide a novel and simple approach to nhibit the growth and metastasis of hepatocellular carcinoma.

Cardiac remodeling on echocardiogram is related to contrast-associated acute kidney injury after coronary angiography: a cross-section study.

Background: Cardiac dysfunction is a well-established risk factor for contrast-associated acute kidney injury (CA-AKI). Nevertheless, the relationship between cardiac remodeling, as assessed by echocardiography, and CA-AKI remains uncertain. Method: A total of 3,241 patients undergoing coronary angiography (CAG) with/without percutaneous coronary intervention (PCI) were enrolled in this retrospective study. Collected echocardiographic parameters were normalized by body surface area (BSA) and divided according to quartile, including the left ventricular internal end-diastolic diameter index (LVIDDI), left ventricular internal end-systolic diameter index (LVIDSI), and left ventricular mass index (LVMI). Logistic regression analysis was conducted to ascertain the association between structural parameter changes and CA-AKI. Further investigation was performed in different subgroups. Results: The mean age of the participants was 66.6 years, and 16.3% suffered from CA-AKI. LVIDSI [≥22.9 mm/m2: OR = 1.953, 95%CI (1.459 to 2.615), P < 0.001], LVIDDI [≥33.2 mm/m2: OR = 1.443, 95%CI (1.087 to 1.914), P = 0.011], and LVMI [≥141.0 g/m2: OR = 1.530, 95%CI (1.146 to 2.044), P = 0.004] in quartile were positively associated with CA-AKI risk in general (all P for trend <0.05). These associations were consistent when stratified by age, left ventricular ejection fraction, estimated glomerular filtration rate, and N-terminal brain natriuretic peptide (all P for interaction >0.05). The presence of eccentric hypertrophy [OR = 1.400, 95%CI (1.093 to 1.793), P = 0.008] and the coexistence of hypertrophy and dilation [OR = 1.397, 95%CI (1.091 to 1.789), P = 0.008] carried a higher CA-AKI risk. Conclusion: The presence of cardiac remodeling, assessed by echocardiography, is associated with a higher risk of CA-AKI.

Calculation of left ventricular ejection fraction using an 8-layer residual U-Net with deep supervision based on cardiac CT angiography images versus echocardiography: a comparative study.

Background: Accurate segmentation of the left ventricle (LV) is an important step in assessing cardiac function. Cardiac CT angiography (CCTA) has become an important means of clinical diagnosis of cardiovascular diseases (CVDs) because of its advantages of non-invasive, short examination time and low cost. In order to obtain the segmentation of LV in CCTA scans, we propose a deep learning method based on 8-layer residual U-Net with deep supervision. In this study we compared the left ventricular ejection fraction (LVEF) calculated by deep learning (DL) method (AccuLV) from CCTA to LVEF by conventional two-dimensional echocardiography (EC). Methods: This was a retrospective cross-sectional study, and consecutive patients who had undergone CCTA and EC in our hospital from February 2021 to May 2021 were recruited. The current study included 180 patients who had undergone CCTA and EC. To obtain LVEF, we used an 8-layer residual U-Net with deep supervision to segment LV contours from CCTA images and compute LVEF (DL-LVEF). The EC and DL-LVEF measurements were compared. A 50% EC-LVEF cut-off value was used as a reference standard to assess the diagnostic performance of AccuLV in assessing LV function. Results: The overall mean EC-LVEF and DL-LVEF values were 64.0% (52.3%, 69.0%) and 73.0% (52.3%, 77.0%), respectively. Three patient groups were studied: (I) hypertensive patients, (II) postmenopausal women, and (III) diabetes. EC-LVEF and DL-LVEF were found to be positively correlated for all of the included patients (r=0.82, P<0.001), with the detailed results for the three groups as follows: hypertensive patients (r=0.77, P<0.001), postmenopausal women (r=0.92, P<0.001) and diabetes (r=0.88, P<0.001). The diagnostic accuracy, sensitivity, and specificity of the DL method in predicting EC-LVEF <50% for all patients were 93.9%, 92.3%, and 94.3%, and for hypertensive patients were 95.4%, 93.8%, and 95.8%, for postmenopausal women were 87.0%, 100%, and 84.2%, for diabetes were 97.4%, 100%, and 96.6%. Conclusions: In comparison to echocardiography, which is commonly used in clinical setting, AccuLV may be a promising, fully automated tool for rapid and accurate quantification of LV function and thus for making reliable clinical decisions.

Erythrocyte parameters, anemia conditions, and sex differences are associated with the incidence of contrast-associated acute kidney injury after coronary angiography.

Objective: Contrast-associated acute kidney injury (CA-AKI) is a critical complication when applying contrast medium, and the risk factors of CA-AKI have not been fully clarified. This study aimed to explore the relationships of CA-AKI with erythrocyte parameters, anemia conditions, and sex differences in patients after coronary angiography (CAG). Methods: In this retrospective study, 4,269 patients who underwent CAG were enrolled. CA-AKI was defined as an increase in plasma creatinine of at least 0.5 mg/dl (44 µmol/L) or 25% within 72 h after exposure to the contrast medium. Three erythrocyte parameters, including hemoglobin, hematocrit, and red blood cell (RBC) count, were collected on admission. Logistic regression analyses were used to examine the associations of sex differences and erythrocyte parameters with CA-AKI in the overall population, restricted cubic splines to visualize these associations flexibly. Moreover, stratified and sensitivity analyses were conducted to assess the robustness of the findings. Results: Overall, the mean (± standard deviations) age of patients was 67.05 ± 10.77 years, and 759 subjects (17.8%) developed CA-AKI. The results showed L-shaped relationships between erythrocyte parameters and CA-AKI incidence in each model (all P < 0.001). The incidence of CA-AKI was positively associated with the severity of anemia, while it showed no significant differences among the types of anemia. Moreover, female patients undergoing CAG had a higher risk of CA-AKI than male patients. Mediation analysis verified that erythrocyte parameters exerted an indirect effect on the sex differences of CA-AKI incidences. Conclusion: In conclusion, females, perioperative anemia conditions, and lower erythrocyte parameters (hemoglobin, hematocrit, and RBC count) were verified as risk factors of CA-AKI in patients undergoing CAG. Furthermore, lower erythrocyte parameters among females exerted indirect effects on the sex differences in CA-AKI incidence.

L-type lectin receptor-like kinase OsCORK1 as an important negative regulator confers copper stress tolerance in rice.

Copper (Cu) is vital for plant growth but becomes toxic in excess, posing potential threats to human health. Although receptor-like kinases (RLKs) have been studied in plant response to abiotic stresses, their roles in Cu stress response remain poorly understood. Therefore, we aimed to evaluate Cu toxicity effects on rice and elucidate its potential molecular mechanisms. Specifically, rice lectin-type RLK OsCORK1 (Copper-response receptor-like kinase 1) function in Cu stress response was investigated. RNA sequencing and expression assays revealed that OsCORK1 is mainly expressed in roots and leaves, and its expression was significantly induced by Cu stress time- and dose-dependently. Kinase activity assays demonstrated OsCORK1 as a Mn2+-preferred functional kinase. Genetically, OsCORK1 gene-edited mutants exhibited increased tolerance to Cu stress and reduced Cu accumulation compared to the wild type (WT). Conversely, OsCORK1 overexpression compromised the Cu stress tolerance observed in OsCORK1 gene-edited mutants. OsCORK1 gene-edited mutants slightly damaged the root tips compared to the WT under Cu stress. Furthermore, OsCORK1 was demonstrated to modulate Cu stress tolerance by mainly altering cell wall components, particularly lignin, in rice. Overall, OsCORK1 is an important negative regulator of Cu stress tolerance, providing a potential gene target to reduce Cu pollution in rice production.

Accuracy of intravascular ultrasound-derived virtual fractional flow reserve (FFR) and FFR derived from computed tomography for functional assessment of coronary artery disease.

BACKGROUND: Coronary computed tomography-derived fractional flow reserve (CT-FFR) and intravascular ultrasound-derived fractional flow reserve (IVUS-FFR) are two functional assessment methods for coronary stenoses. However, the calculation algorithms for these methods differ significantly. This study aimed to compare the diagnostic performance of CT-FFR and IVUS-FFR using invasive fractional flow reserve (FFR) as the reference standard. METHODS: Six hundred and seventy patients (698 lesions) with known or suspected coronary artery disease were screened for this retrospective analysis between January 2020 and July 2021. A total of 40 patients (41 lesions) underwent intravascular ultrasound (IVUS) and FFR evaluations within six months after completing coronary CT angiography were included. Two novel CFD-based models (AccuFFRct and AccuFFRivus) were used to compute the CT-FFR and IVUS-FFR values, respectively. The invasive FFR ≤ 0.80 was used as the reference standard for evaluating the diagnostic performance of CT-FFR and IVUS-FFR. RESULTS: Both AccuFFRivus and AccuFFRct demonstrated a strong correlation with invasive FFR (R = 0.7913, P < 0.0001; and R = 0.6296, P < 0.0001), and both methods showed good agreement with FFR. The area under the receiver operating characteristic curve was 0.960 (P < 0.001) for AccuFFRivus and 0.897 (P < 0.001) for AccuFFRct in predicting FFR ≤ 0.80. FFR ≤ 0.80 were predicted with high sensitivity (96.6%), specificity (85.7%), and the Youden index (0.823) using the same cutoff value of 0.80 for AccuFFRivus. A good diagnostic performance (sensitivity 89.7%, specificity 85.7%, and Youden index 0.754) was also demonstrated by AccuFFRct. CONCLUSIONS: AccuFFRivus, computed from IVUS images, exhibited a high diagnostic performance for detecting myocardial ischemia. It demonstrated better diagnostic power than AccuFFRct, and could serve as an accurate computational tool for ischemia diagnosis and assist in clinical decision-making.

Diagnostic performance of computational fluid dynamics (CFD)-based fractional flow reserve (FFR) derived from coronary computed tomographic angiography (CCTA) for assessing functional severity of coronary lesions.

Background: Fractional flow reserve (FFR) is the gatekeeper for lesion-specific revascularization decision-making in patients with stable coronary artery disease (CAD). The potential of noninvasive calculation of FFR from coronary computed tomographic angiography (CCTA) to identify ischemia-causing lesions has not been sufficiently assessed. The objective of this study was to evaluate the feasibility and diagnostic accuracy of a novel computational fluid dynamics (CFD)-based technology, termed as AccuFFRct, for the diagnosis of functionally significant lesions from CCTA, using wire-based FFR as a reference standard. Methods: A total of 191 consecutive patients who underwent CCTA and FFR measurement for suspected or known CAD were retrospectively enrolled at 2 medical centers. Three-dimensional anatomic model of coronary tree was extracted from CCTA data, CFD was applied subsequently with a novel strategy for the computation of FFR in a blinded fashion by professionals. Results were compared to invasive FFR, a threshold of ≤0.80 was used to indicate the hemodynamically relevant stenosis. Results: On a per-patient basis, the overall accuracy, sensitivity, specificity of AccuFFRct for detecting ischemia were 91.78% (95% CI: 86.08% to 95.68%), 92.31% (95% CI: 81.46% to 97.86%) and 91.49% (95% CI: 83.92% to 96.25%), respectively; those for per-vessel basis were 91.05% (95% CI: 86.06% to 94.70%), 92.73% (95% CI: 82.41% to 97.98%) and 90.37% (95% CI: 84.10% to 94.77%), respectively. The AccuFFRct and FFR was well correlated on per-patient (r=0.709, P<0.001) and per-vessel basis (r=0.655, P<0.001). The AUC of AccuFFRct determination was 0.935 (95% CI: 0.881 to 0.969) and 0.927 (95% CI: 0.880 to 0.960) on per-patient and per-vessel basis. Conclusions: This novel CFD-based CCTA-derived FFR shows good diagnostic performance for detecting hemodynamic significance of coronary stenoses and may potentially become a new gatekeeper for invasive coronary angiography (ICA).

Inhibition of farnesyl pyrophosphate synthase alleviates cardiomyopathy in diabetic rat.

This study investigated the effects of ibandronate (IBN) on cardiomyopathy remodeling in diabetic rats. A rat model of diabetic cardiomyopathy (DCM) was established by supplementing them with a high-calorie diet combined with a low dose of streptozotocin (STZ). The diabetic rats received IBN (5 µg/kg per day) or normal saline subcutaneously for 16 weeks. The hematoxylin and eosin (H&E) and Masson's trichrome staining were performed for evaluating the myocardial morphologies of the rats. Echocardiography and cardiac catheter were performed to assess their cardiac functional parameters. The protein levels of connective tissue growth factor (CTGF), farnesyl pyrophosphate synthase (FPPS), and mitogen-activated protein kinase (MAPK) were determined using Western blot analysis. RhoA activation was detected using a small GTP protease-linked immunosorbent assay (GLISA). The diabetic rats showed the development of moderate hyperglycemia, insulin resistance, hyperlipidemia, myocardial fibrosis, FPPS overexpression, cardiac systolic, and diastolic dysfunction. Inhibiting the FPPS could ameliorate myocardial hypertrophy and fibrosis. These anatomical findings were accompanied by a significant improvement in heart function. Furthermore, the inhibition of FPPS, the increased activation of RhoA, and phosphorylation of p38 and extracellular signal-regulated kinase (ERK)1/2 in DCM decreased significantly with the treatment of IBN. This study for the first time demonstrated that the upregulation of FPPS expression might be involved in diabetic myocardial remodeling in diabetes mellitus (DM). In addition, IBN might exert its inhibitory effects on myocardial tissue remodeling by suppressing the RhoA/ERK1/2 and RhoA/p38 MAPK pathways in DCM.

Sex differences in the association between visceral adipose tissue and atherosclerosis in type 2 diabetes patients with normal bodyweight: A study in a Chinese population.

AIMS/INTRODUCTION: To investigate the impact of visceral adipose tissue (VAT) on atherosclerosis in type 2 diabetes patients with normal bodyweight (OB[-]) in the Chinese population, and to further assess the sex-age differences between them. MATERIALS AND METHODS: A total of 8,839 type 2 diabetes patients from two of the National Metabolic Management Centers in China were included in this study. Participants were classified into four groups by visceral fat area (VFA; cm2 ) and body mass index (BMI; kg/m2 ): VFA < 100 and BMI < 23.9 (VA[-]OB[-]), VFA < 100 and BMI ≥ 23.9 (VA[-]OB[+]), VFA ≥ 100 and BMI < 23.9 (VA[+]OB[-]), VFA ≥ 100 and BMI ≥ 23.9 (VA[+]OB[+]). Atherosclerosis was defined by brachial-ankle pulse wave velocity (baPWV; cm/s), and we analyzed the association between VFA, BMI and the tertiles of baPWV values. RESULTS: The VA(+)OB(-) prevalence was 3.7% among these participants. Patients with VA(+)OB(-) had the highest baPWV value (P < 0.001) and the highest proportion of the tertile 3 of baPWV (P < 0.001) among four groups, and were significantly associated with baPWV (standardized ß = 0.026, P = 0.008). VFA was significantly related to tertile 2 to tertile 3 of baPWV in (OB[-]) type 2 diabetes patients, when compared with tertile 1 of baPWV, respectively. In sex-age stratified analysis, the association of VFA and the tertiles of baPWV showed sex differences. For the 55 years age stratification analysis, there was no age difference in the relationship between VFA and baPWV in (OB[-]) patients. CONCLUSION: Increased VAT was an independent risk factor for atherosclerosis in female type 2 diabetes patients with normal weight.

E3 ubiquitin ligase OsPIE3 destabilises the B-lectin receptor-like kinase PID2 to control blast disease resistance in rice.

Previous studies have reported that PID2, which encodes a B-lectin receptor-like kinase, is a key gene in the resistance of rice to Magnaporthe oryzae strain ZB15. However, the PID2-mediated downstream signalling events remain largely unknown. The U-box E3 ubiquitin ligase OsPIE3 (PID2-interacting E3) was isolated and confirmed to play key roles in PID2-mediated rice blast resistance. Yeast two-hybrid analysis showed that the armadillo repeat region of OsPIE3 is required for its interaction with PID2. Further investigation demonstrated that OsPIE3 can modify the subcellular localisation of PID2, thus promoting its nuclear recruitment from the plasma membrane for protein degradation in the ubiquitin-proteasome system. Site-directed mutagenesis of a conserved cysteine site (C230S) within the U-box domain of OsPIE3 reduces PID2 translocation and ubiquitination. Genetic analysis suggested that OsPIE3 loss-of-function mutants exhibited enhanced resistance to M. oryzae isolate ZB15, whereas mutants with overexpressed OsPIE3 exhibited reduced resistance. Furthermore, the OsPIE3/PID2-double mutant displayed a similar blast phenotype to that of the PID2 single mutant, suggesting that OsPIE3 is a negative regulator and functions along with PID2 in blast disease resistance. Our findings confirm that the E3 ubiquitin ligase OsPIE3 is necessary for PID2-mediated rice blast disease resistance regulation.

Closing gaps in medication taking for secondary prevention of coronary heart disease patients among US adults.

Background: The secondary preventive medical remedies used in the U.S. general population, particularly those with numerous co-morbidities, are poorly understood. We aimed to assess health outcomes and the extent of their adherence to guideline-based secondary prevention medications among U.S. coronary heart disease (CHD) patients. Methods: We analysed information from the U.S. National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 on people in the United States aged 18 to 85 who had a personal history of coronary heart disease (CHD). Logistic regression analyses were used to identify characteristics related to healthcare access that were linked with not taking any indicated drugs among CHD and other co-morbidity patients in the U.S. Results: We gathered 4256 CHD patients aged 18 and above. Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs), statins, and antiplatelet medications were taken by 50.94%, 48.26%, 53.41 %, and 19.78% of the population, respectively. Surprising, not received recommended drugs was reached up to 21.12%, and taking all four drugs was only 7.64%. In conclusion, the logistic regression analysis revealed that the chance of not taking prescribed drugs increased with age (18-39), race (Hispanic and Non-Hispanic Black), low income, lack of insurance, and the absence of co-morbidities (hypertension, heart failure, and diabetes mellitus). Conclusions: The gap between the proposed secondary preventative measures and their actual execution remains sizable. In order to achieve 'Healthy Aging', a systematic approach for prevention of CHD is urgently needed.

Platelet TGF-ß1 inhibits the migration and proliferation of smooth muscle cells in aneurysms.

BACKGROUND: The study explored the role of platelet TGF-ß1 from the perspective of inhibiting the excessive proliferation, migration and invasion of murine aortic vascular smooth muscle cells (MASMCs). METHOD: The platelets were first extracted from C57BL/6 mice, and the TGF-ß1 protein was obtained after the purification of protein. In vitro, the concentrations of angiotensin Ⅱ (Ang Ⅱ) and TGF-ß1 for intervention were screened by testing the viability of MASMCs, followed by the analysis concerning the effects of platelets, Ang Ⅱ and TGF-ß1 on the proliferation, migration, invasion, and the expressions of pathway-related proteins in MASMCs. In vivo, an Ang Ⅱ-induced mouse model was established. TGF-ß1 was injected into the tail of mice as a therapeutic agent, and its action mechanism was further verified by the treatment of inhibitor SB505124. The results of the cell experiment were validated by evaluating the maximum diameter of abdominal aorta, the proportion of total weight, the changes of both pathology and the expressions of pathway-related proteins in the mice. RESULT: 0.5 ng/mL Ang Ⅱ and 15 ng/mL TGF-ß1 were chosen for treatment. The following results of cell functional experiments and Western blot assay demonstrated that Ang Ⅱ promoted the proliferation, migration and invasion of MASMCs via regulating related pathways, the effects of which were evidently reversed by TGF-ß1 and platelets. Consistent results were also observed in the animal experiments, where TGF-ß1 effectively alleviated Ang Ⅱ-induced abdominal aortic injury in mice. CONCLUSION: TGF-ß1 in platelets inhibits Ang Ⅱ-induced proliferation, migration and invasion of MASMCs.

Single-Cell RNA Sequencing Technology Revealed the Pivotal Role of Fibroblast Heterogeneity in Angiotensin II-Induced Abdominal Aortic Aneurysms.

The mechanism of abdominal aortic aneurysm (AAA) has not been fully elucidated. In this study, we aimed to map the cellular heterogeneity, molecular alteration, and functional transformation of angiotensin (Ang) II-induced AAA in mice based on single-cell RNA sequencing (sc-RNA seq) technology. sc-RNA seq was performed on suprarenal abdominal aorta tissue from male Apoe-/- C57BL/6 mice of Ang II-induced AAA and shame models to determine the heterogeneity and phenotypic transformation of all cells. Immunohistochemistry was used to determine the pathophysiological characteristics of AAA. The single-cell trajectory was performed to predict the differentiation of fibroblasts. Finally ligand-receptor analysis was used to evaluate intercellular communication between fibroblasts and smooth muscle cells (SMCs). More than 27,000 cells were isolated and 25 clusters representing 8 types of cells were identified, including fibroblasts, macrophages, endothelial cells, SMCs, T lymphocytes, B lymphocytes, granulocytes, and natural killer cells. During AAA progression, the function and phenotype of different type cells altered separately, including activation of inflammatory cells, alternations of macrophage polarization, phenotypic transformation of vascular smooth muscle cells, and endothelial to mesenchymal transformation. The alterations of fibroblasts were the most conspicuous. Single-cell trajectory revealed the critical reprogramming genes of fibroblasts mainly enriched in regulation of immune system. Finally, the ligand-receptor analysis confirmed that disorder of collagen metabolism led by fibroblasts was one of the most prominent characteristics of Ang II-induced AAA. Our study revealed the cellular heterogeneity of Ang II-induced AAA. Fibroblasts may play a critical role in Ang II-induced AAA progression according to multiple biological functions, including immune regulation and extracellular matrix metabolic balance. Our study may provide us with a different perspective on the etiology and pathogenesis of AAA.

Diagnostic performance of AccuFFRangio in the functional assessment of coronary stenosis compared with pressure wire-derived fractional flow reserve.

BACKGROUND: Non-invasive fractional flow reserve (FFR) has been increasingly used in the clinical workflow to assist clinical decision-making for percutaneous coronary intervention (PCI). This clinical study evaluates the diagnostic accuracy of coronary stenosis assessed by a non-invasive FFR analysis method (termed AccuFFRangio) based on invasive coronary angiography (ICA). It is a blinded, self-controlled, retrospective, and dual-center clinical investigation study. METHODS: Coronary angiography data and the related information of 320 patients with 320 vessels were collected, and AccuFFRangio was used to assess the FFR for these patients. Compared with the wire-measured FFR values, we evaluated AccuFFRangio performance by its accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: The diagnostic accuracy, sensitivity, specificity, PPV, and NPV for AccuFFRangio in identifying hemodynamically significant coronary stenosis were 93.3%, 92.6%, 93.5%, 84.3%, and 97.1%, respectively. The direct correlation between computed AccuFFRangio and measured FFR was 0.812 (P<0.001), and the area under the receiver operating characteristic curve (AUC) value of AccuFFRangio was 0.96. CONCLUSIONS: This clinical study demonstrates the efficiency and accuracy of AccuFFRangio for clinical implementation when using invasive wire-measured FFR as a reference. Further validation is required in a large prospective multicenter study.

Diagnostic performance of deep learning and computational fluid dynamics-based instantaneous wave-free ratio derived from computed tomography angiography.

BACKGROUND AND OBJECTIVES: Both fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are widely used to evaluate ischemia-causing coronary lesions. A new method of CT-iFR, namely AccuiFRct, for calculating iFR based on deep learning and computational fluid dynamics (CFD) using coronary computed tomography angiography (CCTA) has been proposed. In this study, the diagnostic performance of AccuiFRct was thoroughly assessed using iFR as the reference standard. METHODS: Data of a total of 36 consecutive patients with 36 vessels from a single-center who underwent CCTA, invasive FFR, and iFR were retrospectively analyzed. The CT-derived iFR values were computed using a novel deep learning and CFD-based model. RESULTS: Mean values of FFR and iFR were 0.80 ± 0.10 and 0.91 ± 0.06, respectively. AccuiFRct was well correlated with FFR and iFR (correlation coefficients, 0.67 and 0.68, respectively). The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of AccuiFRct ≤ 0.89 for predicting FFR ≤ 0.80 were 78%, 73%, 81%, 73%, and 81%, respectively. Those of AccuiFRct ≤ 0.89 for predicting iFR ≤ 0.89 were 81%, 73%, 86%, 79%, and 82%, respectively. AccuiFRct showed a similar discriminant function when FFR or iFR were used as reference standards. CONCLUSION: AccuiFRct could be a promising noninvasive tool for detection of ischemia-causing coronary stenosis, as well as facilitating in making reliable clinical decisions.