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 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.

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.

Prediction of the Interface Shear Strength between Ultra-High-Performance Concrete and Normal Concrete Using Artificial Neural Networks.

The bond strength between ultra-high-performance concrete (UHPC) and normal-strength concrete (NC) plays an important role in governing the composite specimens' overall behaviors. Unfortunately, there are still no widely accepted formulas targeting UHPC-NC interfacial strength, either in their specifications or in research papers. To this end, this study constructs an experimental database, consisting of 563 and 338 specimens for splitting and slant shear tests, respectively. Moreover, an additional 35 specimens for "improved" slant shear tests were performed, which could circumvent concrete crushing and trigger interfacial debonding. Additionally, for the first time in our tests, the effect of casting sequence on UHPC-NC bond strength was identified. Based on the database, an artificial neural network (ANN) model is proposed with the following inputs: namely, the normal stress perpendicular to the interface, the interface roughness, and the compressive strengths of the UHPC and NC materials. Based on the ANN analyses, the explicit expression of UHPC-NC bond strength is proposed, which significantly lowers the prediction error. To be fully compatible with the specifications, the conventional shear-friction formula is modified. By splitting the total force into adhesion and friction forces, the modified formula additionally takes the casting sequence into account. Although sacrificing accuracy to some extent compared to the ANN model, the modified formula relies on a solid physical basis and its accuracy is enhanced significantly compared to the existing formulas in specifications or research papers.

Medical Morphology Training Using the Xuexi Tong Platform During the COVID-19 Pandemic: Development and Validation of a Web-Based Teaching Approach.

BACKGROUND: Histology and Embryology and Pathology are two important basic medical morphology courses for studying human histological structures under healthy and pathological conditions, respectively. There is a natural succession between the two courses. At the beginning of 2020, the COVID-19 pandemic suddenly swept the world. During this unusual period, to ensure that medical students would understand and master basic medical knowledge and to lay a solid foundation for future medical bridge courses and professional courses, a web-based medical morphology teaching team, mainly including teachers of courses in Histology and Embryology and Pathology, was established. OBJECTIVE: This study aimed to explore a new teaching mode of Histology and Embryology and Pathology courses during the COVID-19 pandemic and to illustrate its feasibility and acceptability. METHODS: From March to July 2020, our team selected clinical medicine undergraduate students who started their studies in 2018 and 2019 as recipients of web-based teaching. Meanwhile, nursing undergraduate students who started their studies in 2019 and 2020 were selected for traditional offline teaching as the control group. For the web-based teaching, our team used the Xuexi Tong platform as the major platform to realize a new "seven-in-one" teaching method (ie, videos, materials, chapter tests, interactions, homework, live broadcasts, and case analysis/discussion). This new teaching mode involved diverse web-based teaching methods and contents, including flipped classroom, screen-to-screen experimental teaching, a drawing competition, and a writing activity on the theme of "What I Know About COVID-19." When the teaching was about to end, a questionnaire was administered to obtain feedback regarding the teaching performance. In the meantime, the final written pathology examination results of the web-based teaching and traditional offline teaching groups were compared to examine the mastery of knowledge of the students. RESULTS: Using the Xuexi Tong platform as the major platform to conduct "seven-in-one" teaching is feasible and acceptable. With regard to the teaching performance of this new web-based teaching mode, students demonstrated a high degree of satisfaction, and the questionnaire showed that 71.3% or more of the students in different groups reported a greater degree of satisfaction or being very satisfied. In fact, more students achieved high scores (90-100) in the web-based learning group than in the offline learning control group (P=.02). Especially, the number of students with objective scores >60 in the web-based learning group was greater than that in the offline learning control group (P=.045). CONCLUSIONS: This study showed that the web-based teaching mode was not inferior to the traditional offline teaching mode for medical morphology courses, proving the feasibility and acceptability of web-based teaching during the COVID-19 pandemic. Our findings lay a solid theoretical foundation for follow-up studies of medical students.

A leucine-rich repeat receptor-like kinase, OsSTLK, modulates salt tolerance in rice.

Leucine-rich repeat receptor-like kinases (LRR-RLKs) have been widely associated with plant abiotic stress responses. However, the functions of the majority of LRR-RLKs has not been well defined. Here, we identified a novel rice LRR-RLK member involved in salt tolerance and designated as OsSTLK (Oryza sativa L. Salt-Tolerance LRR-RLK). Transcript analysis showed that OsSTLK was significantly induced in response to salt stress in rice shoot and root in a time and dosage-dependent fashion. Phenotypic observations indicated that OsSTLK overexpression exhibited reduced salt sensitivity, and improved salt stress tolerance. Further physiological analysis showed that OsSTLK overexpression remarkably reduced electrolyte leakage, malondialdehyde (MDA) content, reactive oxygen species (ROS) accumulation under salt stress conditions by up-regulating ROS-scavenging activities and modifying stomatal patterning. Moreover, Na+/K+ ratio and MAPK phosphorylation level were also reduced in OsSTLK-overexpression transgenic rice plants compared with WT control. Taken together, our findings suggested that OsSTLK as an important positive regulator of salt stress tolerance perhaps through regulating ROS scavenging system, Na+/K+ ratio and MAPK signal pathway.

Overexpression of an NADP(H)-dependent glutamate dehydrogenase gene, TrGDH, from Trichurus improves nitrogen assimilation, growth status and grain weight per plant in rice.

As glutamate dehydrogenases (GDHs) of microorganisms usually have higher affinity for NH4 + than do those of higher plants, it is expected that ectopic expression of these GDHs can improve nitrogen assimilation in higher plants. Here, a novel NADP(H)-GDH gene (TrGDH) was isolated from the fungus Trichurus and introduced into rice (Oryza sativa L.). Investigation of kinetic properties in vitro showed that, compared with the rice GDH (OsGDH4), TrGDH exhibited higher affinity for NH4 + (K m = 1.48 ± 0.11 mM). Measurements of the NH4 + assimilation rate demonstrated that the NADP(H)-GDH activities of TrGDH transgenic lines were significantly higher than those of the controls. Hydroponic experiments revealed that the fresh weight, dry weight and nitrogen content significantly increased in the TrGDH transgenic lines. Field trials further demonstrated that the number of effective panicles, 1,000-grain weight and grain weight per plant of the transgenic lines were significantly higher than those of the controls, especially under low-nitrogen levels. Moreover, glutelin and prolamine were found to be markedly increased in seeds from the transgenic rice plants. These results sufficiently confirm that overexpression of TrGDH in rice can improve the growth status and grain weight per plant by enhancing nitrogen assimilation. Thus, TrGDH is a promising candidate gene for maintaining yields in crop plants via genetic engineering.