Explore the vast range of titles available.

Myocardial delivery of magnetic iron oxide nanoparticles (MNPs) might produce iron overload-induced myocardial injury, and the oxidative stress was regarded as the main mechanism. Therefore, we speculated antioxidant modification might be a reasonable strategy to mitigate the toxicity of MNPs. Antioxidant N-acetylcysteine (NAC) was loaded into magnetic mesoporous silica coated Fe O nanoparticles. Neonatal rat hypoxia/reoxygenation (H/R) cardiomyocytes were incubated with nanoparticles for 24 hrs. NAC can effectively mitigate iron-induced oxidative injury of cardiomyocytes, evidenced by reduced production of MDA, 8-iso-PGF2α, and 8-OHDG and maintained concentrations of SOD, CAT, GSH-Px, and GSH in ELISA and biochemical tests; downregulated expression of CHOP, GRP78, p62, and LC3-II proteins in Western Blot, and less cardiomyocytes apoptosis in flow cytometric analysis. NAC modifying could suppress the toxic effects of Fe O nanoparticles in H/R cardiomyocytes model in vitro, indicating a promising strategy to improve the safety of iron oxide nanoparticles.

This study used the Extreme Gradient Boosting (XGBoost) machine learning model to conduct an in-depth analysis of the potential relationship between pulse index continuous cardiac output (PiCCO) and multiple clinical prognostic indicators, including left ventricular ejection fraction (LVEF), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and 30-day major adverse cardiovascular events (MACE), in patients with cardiogenic shock. The aim of this study was to investigate the predictive ability of PiCCO hemodynamic parameters and the relative contribution features based on the XGBoost model. Multi-class receiver operating characteristic (ROC) curves explored that the XGBoost prediction model performed extremely well about LVEF and NT-proBNP. Further SHapley Additive explanation (SHAP) value analysis revealed the contributions of different PiCCO hemodynamic parameters. Features such as CI (cardiac index), CPI (cardiac power index), and SVRI (systemic vascular resistance index) showed significant positive effects on the prediction of LVEF and NT-proBNP. In terms of MACE, dPmax (index of the left ventricular contractility), CFI (cardiac function index), and GEDVI (global end-diastolic volume index) showed significant predictive value. Overall, XGBoost machine learning model based on PiCCO hemodynamic parameters provide evidence that effectively predict key clinical prognostic indicators in the patients with cardiogenic shock. These results provide important theoretical basis for further individualized clinical decision-making in cardiogenic shock patients.

Aortic regurgitation (AR) is a volume overload disease causing eccentric left ventricular (LV) hypertrophy and eventually heart failure. There is currently no approved drug to treat patients with AR. Endoplasmic reticulum (ER) stress and ER stress-mediated apoptosis is involved in many cardiovascular diseases, but whether they also participate in AR-induced heart failure is still elusive. In this study, we found ER stress activation in myocardial samples from patients with AR. With a unique murine model of AR which induced eccentric cardiac hypertrophy and heart failure, we also found aggravation of cardiac ER stress and apoptosis, as evidenced by a reduction of Bcl-2/Bax ratio and an increase of caspase-3 cleavage. We then examined the signaling effectors involved in ER-initiated apoptosis and found volume overload specifically activated C/EBP homologous protein (CHOP), but not caspase-12 or Jun N-terminal kinase (JNK). Interestingly, tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor, improved cardiac function, and suppressed ER stress, apoptosis, and CHOP. Furthermore, genetic knockdown of CHOP inhibited cardiac Bcl-2/Bax ratio reduction and caspase-3 activation and rescued cardiac dysfunction. In summary, our findings suggest that ER stress-CHOP signaling is involved in the development of volume overload cardiac hypertrophy induced by AR through promoting cardiomyocytes apoptosis and provide a previously unrecognized target in heart failure induced by volume overload.

Angiotensin II (AngII) type 1 receptor (AT1-R) can be activated by mechanical stress (MS) without the involvement of AngII during the development of cardiomyocyte hypertrophy, in which G protein-independent pathways are critically involved. Although β-arrestin2-biased signaling has been speculated, little is known about how AT1-R/β-arrestin2 leads to ERK1/2 activation. Here, we present a novel mechanism by which Src kinase mediates AT1-R/β-arrestin2-dependent ERK1/2 phosphorylation in response to MS. Differing from stimulation by AngII, MS-triggered ERK1/2 phosphorylation is neither suppressed by overexpression of RGS4 (the negative regulator of the G-protein coupling signal) nor by inhibition of Gαq downstream protein kinase C (PKC) with GF109203X. The release of inositol 1,4,5-triphosphate (IP3) is increased by AngII but not by MS. These results collectively suggest that MS-induced ERK1/2 activation through AT1-R might be independent of G-protein coupling. Moreover, either knockdown of β-arrestin2 or overexpression of a dominant negative mutant of β-arrestin2 prevents MS-induced activation of ERK1/2. We further identifies a relationship between Src, a non-receptor tyrosine kinase and β-arrestin2 using analyses of co-immunoprecipitation and immunofluorescence after MS stimulation. Furthermore, MS-, but not AngII-induced ERK1/2 phosphorylation is attenuated by Src inhibition, which also significantly improves pressure overload-induced cardiac hypertrophy and dysfunction in mice lacking AngII. Finally, MS-induced Src activation and hypertrophic response are abolished by candesartan but not by valsartan whereas AngII-induced responses can be abrogated by both blockers. Our results suggest that Src plays a critical role in MS-induced cardiomyocyte hypertrophy through β-arrestin2-associated angiotensin II type 1 receptor signaling.

Recent studies have unveiled that myocardial hypertrophic preconditioning (HP), which is produced by de-banding (De-TAC) of short-term transverse aortic constriction (TAC), protects the heart against hypertrophic responses caused by subsequent re-constriction (Re-TAC) in mice. Although cardiac substrate metabolism is impaired in heart failure, it remains unclear about the role of HP-driven energetics in the development of cardiac hypertrophy. Here, we investigated energy metabolism, cardiac hypertrophy, and function following variational loading conditions, as well as their relationships in HP. Male C57BL/6J mice (10–12 weeks old) were randomly subjected to Sham, HP [TAC for 3days (TAC 3d), de-banding the aorta for 4 days (De-TAC 4d), and then re-banding the aorta for 4 weeks (Re-TAC 4W)], and TAC (TAC for 4 weeks without de-banding). Cardiac echocardiography, hemodynamics, and histology were utilized to evaluate cardiac remodeling and function. The mRNA expression levels of fetal genes ( ANP and BNP ), glucose metabolism-related genes ( glut4, pdk4 ), and fatty acid oxidation-related genes ( mcad, pgc1 α, mcd, ppar α) were quantitated by real-time quantitative PCR. Activation of hypertrophy regulators ERK1/2, a metabolic stress kinase AMP-activated protein kinase (AMPK), and its downstream target acetyl-coA carboxylase (ACC) were explored by western blot. Compared with TAC 4W mice, Re-TAC 4W mice showed less impairment in glucose and fatty acid metabolism, as well as less cardiac hypertrophy and dysfunction. Moreover, no significant difference was found in myocardial hypertrophy, fibrosis, and cardiac function in TAC 3d and De-TAC 4d groups compared with Sham group. However, glut4, pdk4, mcad, pgc1 α, mcd , and ppar α were all decreased, while AMPK and ACC were activated in TAC 3d and returned to Sham level in De-TAC 4d, suggesting that the change in myocardial energy metabolism in HP mice was earlier than that in cardiac structure and function. Collectively, HP improves energy metabolism and delays cardiac remodeling, highlighting that early metabolic improvements drive a potential beneficial effect on structural and functional restoration in cardiac hypertrophy.

Background: Cardiac troponin T (cTNT) has been widely used in detecting cardiac damage. Elevated cTNT level has been reported to be associated with increased mortality in multiple cardiac conditions. It is not uncommon to observe an increased level of cTNT in patients after left atrial appendage occlusion (LAAO). The objective of the study is to study the incidence, significance, and factors associated with cTNT elevation after LAAO. Methods: We prospectively included patients who underwent LAAO from January 2019 to July 2020 in Fudan Zhongshan Hospital. Patients were divided into those with elevated cTNT after procedure and those with normal postprocedure cTNT. All individuals were followed up for 1 year. The primary outcome is major adverse cardiovascular events, which include myocardial infarction, heart failure, cardiac death, and stroke. The second outcome is periprocedure complication, including chest pain, tachycardia, cardiac tamponade, change of electrocardiograph, and atrial thrombus. Results: A total of 190 patients were enrolled. Of the patients, 85.3% had elevated cTNT after LAAO, while 14.7% of them did not. Exposure time, dosage of contrast, types of devices, shapes, and sizes of LAA could contribute to elevated postprocedure cTNT. We found that patients with a Watchman device were more likely to have elevated postprocedure cTNT than those with a Lambre device (89.2 vs. 76.7%, p = 0.029). LAAO shapes were associated with cTNT levels in patients with a Watchman device, while the diameter of the outer disc and LAA depth mattered for the Lambre device. There was no significant difference in the primary and second outcome between the two groups ( p -value: 0.619, 0.674). Conclusion: LAAO was found to be commonly accompanied with cTNT elevation, which might not to be related to the complications and adverse cardiac outcomes within 1 year of follow-up. Moreover, eGFR at baseline, exposure time, dosage of contrast, types of LAAO device, and LAA morphology could contribute to cTNT elevation.

A lack of standardization in heart team implementation potentially leads to suboptimal decision-making quality, and we previously established a modified heart team protocol to improve the decision-making quality. The present trial was to validate the effect of the modified heart team implementation protocol on improving the decision-making quality versus the conventional protocol in complex coronary artery disease (CAD). Eligible interventional cardiologists, cardiac surgeons and non-interventional cardiologists were randomly allocated to the intervention or control arm and established 12 heart teams in each arm. The 12 heart teams in each arm were randomly divided into 6 pairs, and 480 historic cases with complex CAD into 6 sets of 80 cases. In each arm, each set of 80 cases was discussed independently by one pair of heart teams, with each case finally receiving two heart team decisions ('pairwise decisions'). The intervention arm conducted heart team decision-making according to the previously established protocol and the control arm based on guideline recommendations. The primary outcome was the overall percent agreement of the inter-team pairwise decisions. Decision-making appropriateness was further analysed. A total of 36 cardiac surgeons, 36 interventional cardiologists and 12 non-interventional cardiologists from 26 centres were enrolled. The overall percent agreement was significantly higher in the intervention arm than the control arm (72.1% vs 65.8%, P = 0.04; kappa 0.51 vs 0.37). Both team-level (19.4% vs 33.0%; P < 0.001) and specialist-level (interventional cardiologists, 19.8% vs 37.7%, P < 0.001; cardiac surgeons, 19.8% vs 28.7%, P < 0.001) inappropriateness rate of decision-making was significantly lower in the intervention arm than the control arm. The modified heart team implementation protocol improved the decision-making quality and appropriateness compared with the guideline-based protocol.

Objectives Elevation of left ventricular end-systolic pressure (LVESP) and hypertrophic response in mice varies after transverse aorta constriction (TAC). Micromanometric catheterization, conventionally used to select the mice with successful TAC, is invasive and nonreusable. We aimed to establish noninvasive imaging protocols for early estimation of successful TAC by ultrasound biomicroscopy (UBM). Methods Out of 55 C57BL/6J mice, we randomly selected 45 as TAC group and 10 as controls. UMB was performed before TAC, and at day3 and day14 after TAC. In all mice, LVESP was measured with a Millar conductance catheter at day14. Results With LVESP≥150 mm Hg set as indicator of successful TAC (TAC+) and LVESP<150 mm Hg as unsuccessful (TAC-), receiver operating characteristic curve analysis demonstrated that postoperative inner diameter at aortic banding site (IDb), peak flow velocity at aortic banding site (PVb), and peak flow velocity of right/left common carotid artery (PVr/l) at day 3 served as most effective predictors for LVESP at day14 (area under curve=0.9016, 0.9143, 0.8254, respectively. p<0.01 for all). Among all UBM parameters at day3, IDb, PVb, right common carotid artery peak flow velocity (PR), and PVr/l correlated best with LVESP at day14 (R2=0.5740, 0.6549, 0.5208, 0.2274, respectively. p<0.01 for all). Furthermore, IDb, PVb, and PVr/l at day3 most effectively predict long-term cardiac hypertrophy, using the cut-off values of 0.45 mm, 2698.00 mm/s, 3.08, respectively. Conclusions UBM can be a noninvasive and effective option for early estimation of LVESP and prediction of successful TAC.

This study proposes an integrated constrained static optimization framework for optimizing crop-planting strategies in rural regions under uncertainty. Unlike conventional deterministic or dynamic programming approaches, the proposed model formalizes the decision process as a static multi-objective optimization problem that simultaneously maximizes economic profit and minimizes production risk. The framework integrates three complementary algorithms–Particle Swarm Optimization (PSO) for global exploration, Simulated Annealing (SA) for local refinement, and Monte Carlo Simulation (MCS) for stochastic robustness evaluation. A real-world case study based on empirical agricultural data from northern Anhui Province (2022–2024) provides empirical evidence of the framework’s potential effectiveness, showing that the hybrid PSO–SA–MCS model increases the expected profit by 12.6% and reduces yield variance by 11.0% compared with the baseline PSO. Convergence and sensitivity analyses confirm stable performance across parameter variations within ±10%. The proposed framework enhances the transparency, reproducibility, and robustness of agricultural decision-making, providing a practical tool for data-driven, sustainable crop planning and resource allocation in rural development. Moreover, the proposed PSO–SA–MCS framework is not limited to the specific study region or crop categories considered in this paper. By adjusting land-use data, yield coefficients, and market parameters, the model can be readily extended to other regions, cropping systems, and agricultural planning scenarios, indicating potential generalizability and scalability, subject to further validation under different regional and agricultural settings.