Time-Released Black Phosphorus Hydrogel Accelerates Myocardial Repairing through Antioxidant and Motivates Macrophage Polarization Properties.

The improvement of the myocardial microenvironment largely determines the prognosis of myocardial infarction (MI). After MI, early removal of excessive reactive oxygen species (ROS) in the microenvironment can alleviate oxidative stress injury and promote M2 phenotype polarization of macrophages, which is important for advocating myocardial repair. In this study, we combined traditional natural hydrogel materials chitosan (CS) and gelatin (Gel) to encapsulate polydopamine-modified black phosphorus nanosheets (BP@PDA). We designed an injectable composite gel (CS-Gel-BP@PDA) with a time-released ability to achieve in situ sustained-release BP@PDA in the area of MI. Utilizing the inflammation inhibition ability of CS-Gel itself and the high reactive activity of BP@PDA with ROS, continuous improvement of infarct microenvironment and myocardial repair were achieved. The studies in vivo revealed that, compared with the saline group, CS-Gel-BP@PDA group had alleviated myocardial fibrosis and infarct size and importantly improved cardiac function. Immunofluorescence results showed that the ROS level and inflammatory response in the microenvironment of the CS-Gel-BP@PDA group were decreased. In conclusion, our study demonstrated the time-released ability, antioxidative stress activity and macrophage polarization modulation of the novel composite hydrogel CS-Gel-BP@PDA, which provides inspiration for novel therapeutic modalities for MI.

Development and validation of mortality prediction models for heart transplantation using nutrition-related indicators: a single-center study from China.

Objective: We sought to develop and validate a mortality prediction model for heart transplantation (HT) using nutrition-related indicators, which clinicians could use to identify patients at high risk of death after HT. Method: The model was developed for and validated in adult participants in China who received HT between 1 January 2015 and 31 December 2020. 428 subjects were enrolled in the study and randomly divided into derivation and validation cohorts at a ratio of 7:3. The likelihood-ratio test based on Akaike information was used to select indicators and develop the prediction model. The performance of models was assessed and validated by area under the curve (AUC), C-index, calibration curves, net reclassification index, and integrated discrimination improvement. Result: The mean (SD) age was 48.67 (12.33) years and mean (SD) nutritional risk index (NRI) was 100.47 (11.89) in the derivation cohort. Mortality after HT developed in 66 of 299 patients in the derivation cohort and 28 of 129 in the validation cohort. Age, NRI, serum creatine, and triglyceride were included in the full model. The AUC of this model was 0.76 and the C statistics was 0.72 (95% CI, 0.67-0.78) in the derivation cohort and 0.71 (95% CI, 0.62-0.81) in the validation cohort. The multivariable model improved integrated discrimination compared with the reduced model that included age and NRI (6.9%; 95% CI, 1.8%-15.1%) and the model which only included variable NRI (14.7%; 95% CI, 7.4%-26.2%) in the derivation cohort. Compared with the model that only included variable NRI, the full model improved categorical net reclassification index both in the derivation cohort (41.8%; 95% CI, 9.9%-58.8%) and validation cohort (60.7%; 95% CI, 9.0%-100.5%). Conclusion: The proposed model was able to predict mortality after HT and estimate individualized risk of postoperative death. Clinicians could use this model to identify patients at high risk of postoperative death before HT surgery, which would help with targeted preventative therapy to reduce the mortality risk.

Reducing the Damage of Ox-LDL/LOX-1 Pathway to Vascular Endothelial Barrier Can Inhibit Atherosclerosis.

Aim: The destruction of the vascular endothelial barrier mediated by Ox-LDL is the initial link to atherosclerosis. Here, we aimed to determine whether the immunological intervention with Ox-ApoB polypeptide fragment (Ox-ApoB-PF) can block the deposition of Ox-LDL in vascular endothelial cells through LOX-1 receptors, thereby protecting the barrier function and survival status of vascular endothelial cells and inhibiting the progression of atherosclerosis. Methods and Results: In order to determine the harm of Ox-LDL to vascular endothelial cells and the protective effect of immune intervention with Ox-ApoB-PF, we conducted a series of corresponding experiments in vitro and in vivo. The in vitro results showed that Ox-LDL can activate endothelial cell apoptosis pathway; reduce the expression of endothelial junction proteins; affect the migration, deformation, and forming ability; and ultimately destroy the vascular endothelial barrier function. The increased permeability of endothelial cells led to a sharp increase in the phagocytosis of Ox-LDL by macrophages under the endothelial layer. Meanwhile, Ox-LDL stimulation induced a significant upregulation of LOX-1 in endothelial cells and increased the expression of endothelial cell chemokines and adhesion factors. Ox-ApoB-PF antibodies can significantly reduce the abovementioned harmful effects. The in vivo results showed that active immune intervention through Ox-ApoB-PF can protect the endothelial barrier function; reduce macrophage deposition and the inflammatory response in plaques; alleviate lipid deposition in the plaques, as well as apoptosis and necrosis; and increase the ability of liver macrophages to clear Ox-LDL. Eventually, the progression of plaque and the formation of necrotic cores in plaques can be inhibited. Conclusions: An Ox-ApoB-PF antibody may protect the endothelial cell physiological function and survival status by blocking the combination of Ox-LDL/LOX-1 in vascular endothelial cells. Immune intervention with Ox-ApoB-PF inhibits the occurrence and development of atherosclerotic lesions by protecting the vascular endothelial barrier function.

Investigating the Effect of School Bus Stopping Process on Driver Behavior of Surrounding Vehicles Based on a Driving Simulator Experiment.

School bus safety has attracted widespread attention with economic development and the improvement of overall quality of the population. However, violations of school bus regulations and school bus-related crashes often occur. Limited research has been conducted on the impact of the school bus stopping process on surrounding drivers' behavior. This study provides a driving simulator experiment to explore drivers' behaviors during the school bus stopping process under different traffic law awareness status, traffic volume status, and initial location status. Eight variables about behavior decision and kinetic parameters were assessed for analysis by a logistic regression model and multivariate analysis of variance (MANOVA). Results show that the mean speed decreases and the number of people complying with the regulations increases after publicizing the regulations. The proportion of surrounding vehicles in the acceleration state increases, especially under the scenario that the traffic volume is large and the initial distance is far. This indicates that the enforcement of the regulations may stimulate unsafe driving behavior. The findings of this study could help policy makers to better understand the prevalence and compliance of current school bus stopping regulations among drivers and support improvements in the practical application of the regulations.

Apolipoprotein B-100 peptide 210 antibody inhibits atherosclerosis by regulation of macrophages that phagocytize oxidized lipid.

Immunization with peptides derived from apolipoprotein B-100 (ApoB-100) has been shown to ameliorate atherosclerosis in apolipoprotein E knockout (ApoE-/-) mice. However, the exact mechanism underlying the therapeutic effects remains elusive. To shed light on this mechanism, we immunized ApoE-/- mice that were fed a Western diet with either malondialdehyde-modified ApoB-100 peptide 210 (P210) emulsified in Freund's adjuvant or anti-malondialdehyde-modified P210 antibody (P210-Ab). Mice immunized with Freund's adjuvant or bovine serum albumin served as controls. Macrophages were incubated in vitro with oxidized low-density lipoprotein (ox-LDL) or ox-LDL plus P210-Ab. Our results show that P210-Ab promoted cholesterol efflux, inhibited lipid accumulation in vitro, and reduced plasma levels of high-sensitivity C-reactive protein (hsCRP), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). Furthermore, dramatically increased the expression of Fc receptors (FcR) on peripheral blood mononuclear macrophages, suggesting that the mechanism of phagocytosis of ox-LDL by mononuclear macrophages may rely more on FcR than the cluster of differentiation 36 (CD36) scavenger receptor with P210-Ab. Both in vitro and in vivo, P210-Ab triggered the promoter of ATP-binding cassette transporter A1 (ABCA1) to increase peroxisome proliferator-activated receptor alpha (α) activity and inhibit the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. In addition, P210-Ab significantly attenuated macrophage infiltration and markedly improved the stability of atheromatous plaque. In conclusion, the anti-atherosclerotic effect of P210-Ab is related to its preferential inhibition of inflammation and reversion of cholesterol transportation by altering the pathway by which macrophages phagocytize ox-LDL.