Phase and Defect Engineering of MoSe2 Nanosheets for Enhanced NIR-II Photothermal Immunotherapy.

Inducing immunogenic cell death (ICD) during photothermal therapy (PTT) has the potential to effectively trigger photothermal immunotherapy (PTI). However, ICD induced by PTT alone is often limited by inefficient PTT, low immunogenicity of tumor cells, and a dysregulated redox microenvironment. Herein, we develop MoSe2 nanosheets with high-percentage metallic 1T phase and rich exposed active Mo centers through phase and defect engineering of MoSe2 as an effective nanoagent for PTI. The metallic 1T phase in MoSe2 nanosheets endows them with strong PTT performance, and the abundant exposed active Mo centers endow them with high activity for glutathione (GSH) depletion. The MoSe2-mediated high-performance PTT synergizing with efficient GSH depletion facilitates the release of tumor-associated antigens to induce robust ICD, thus significantly enhancing checkpoint blockade immunotherapy and activating systemic immune response in mouse models of colorectal cancer and triple-negative metastatic breast cancer.

[Diagnostic value of copeptin and cancer antigen 125 in acute heart failure patients with atrial fibrillation and their correlations with short-term cardiovascular events].

OBJECTIVE: To evaluate the diagnostic value of copeptin and cancer antigen 125 (Ca-125) in acute heart failure (AHF) patients with atrial fibrillation, and to explore the relationship between copeptin, Ca-125 and short-term cardiovascular events. METHODS: A total of 376 patients with acute left heart failure or permanent atrial fibrillation admitted to the Department of Cardiology of First Affiliated Hospital of Nanjing Medical University from January 2016 to January 2018 were enrolled as the study group. According to whether having atrial fibrillation or not, 376 patients were divided into atrial fibrillation group (n = 108), AHF group (n = 134) and AHF with atrial fibrillation group (n = 134). 102 healthy persons in the same period were enrolled as healthy control group. Copeptin, Ca-125, N-terminal pro-brain natriuretic peptide (NT-proBNP) within 24 hours after admission or on the day of physical examination were determined, and cardiac function indexes including left atrial diameter (LAD), left ventricular diameter (LVD) and left ventricular ejection fraction (LVEF) at 1 week after admission or on the day of physical examination were determined. Correlation analysis among above indexes was conducted by Pearson correlation analysis. Receiver operating characteristic (ROC) curve was plotted to evaluate the diagnostic value of copeptin and Ca-125 in AHF with atrial fibrillation. RESULTS: Compared with the healthy control group, copeptin, Ca-125, NT-proBNP, LAD, and LVD in atrial fibrillation group, AHF group and AHF with atrial fibrillation group showed a tendency of gradual increase [copeptin (pmol/L): 12.43±4.36, 18.77±5.29, 32.82±7.07 vs. 6.68±1.94; Ca-125 (kU/L): 18.82±7.39, 27.97±11.47, 61.37±25.49 vs. 4.43±1.74; NT-proBNP (ng/L): 1 070.87±428.84, 1 734.13±725.09, 2 745.92±709.91 vs. 570.40±213.87; LAD (mm): 37.24±6.35, 41.31±7.94, 46.24±10.96 vs. 33.29±4.53; LVD (mm): 49.46±5.19, 52.51±8.09, 55.96±6.49 vs. 45.99±6.26, all P < 0.05], and LVEF showed a tendency of gradual decrease (0.52±0.11, 0.46±0.10, 0.41±0.09 vs. 0.57±0.08, all P < 0.05), indicating that the deterioration of all indexes in AHF patients with atrial fibrillation was more obvious. Correlation analysis showed that copeptin was positively correlated with LAD (r = 0.479, P = 0.012) and LVD (r = 0.513, P = 0.005), and it was negatively correlated with LVEF (r = -0.626, P < 0.001). Ca-125 was positively correlated with LAD (r = 0.479, P = 0.011) and LVD (r = 0.513, P = 0.028), and it was negatively correlated with LVEF (r = -0.645, P = 0.019). ROC curve analysis showed that the area under ROC curve (AUC) of copeptin, Ca-125, NT-proBNP and copeptin combined with Ca-125 in the diagnosis of AHF with atrial fibrillation was 0.750, 0.623, 0.647 and 0.842, respectively, with diagnostic value on AHF with atrial fibrillation. The diagnostic value of copeptin combined with Ca-125 was the largest, with a sensitivity of 72.64% and a specificity of 92.47%. Compared with the healthy control group, the incidence of cardiovascular events after 3 months of follow-up in the atrial fibrillation group, AHF group and AHF with atrial fibrillation group was significantly increased [6.5% (7/108), 9.0% (12/134), 30.6% (41/134) vs. 1.0% (1/102), χ2 = 56.574, P = 0.000], indicating that patients with AHF and atrial fibrillation were more likely to have cardiovascular events. Copeptin combined with Ca-125 showed a significant positive correlation with short-term cardiovascular events (r = 0.641, P = 0.004). CONCLUSIONS: The combination of copeptin and Ca-125 has a higher diagnostic accuracy for AHF patients with atrial fibrillation. Copeptin and Ca-125 were positively correlated with short-term cardiovascular events. It may be used to assess the prognosis of AHF patients with atrial fibrillation.

A genetic variant near adaptor-related protein complex 2 alpha 2 subunit gene is associated with coronary artery disease in a Chinese population.

BACKGROUND: Adaptor-related protein complex 2 alpha 2 subunit (AP2A2) gene encodes a protein-a subunit of the AP-2 adaptor protein complex. Evidence has revealed that benzodiazepine receptor-associated protein 1 (BZRAP1) is abundant in the hippocampus with potential effects on brain diseases. Recently, an epidemiological study reported that two variants (rs7396366 and rs2526378) closest to the AP2A2 and BZRAP1 genes are associated with higher plasma lipids and Alzheimer's disease. Whether the two single nucleotide polymorphisms (SNPs) are actually relevant to coronary artery disease (CAD) and CAD severity remains elusive. Our aim was to assess whether these two SNPs are relevant to CAD and its severity in a Chinese population. METHODS: Three hundred and thirty-five patients with documented CAD (282 stable CAD, 28 non-ST-segment elevation myocardial infarction, 25 ST-segment elevation myocardial infarction), and 372 non-CAD controls were included in the study. The participants were divided into two groups according to coronary angiography results. CAD patients were further demarcated into subgroups with one-, two-, or three-vessel stenosis. Genotypes at rs7396366 and rs2526378 were examined using polymerase chain reaction-ligase detection reaction. The association between these two SNPs with CAD and its severity were analyzed. RESULTS: The frequency of the rs7396366 TT genotype was significantly higher in CAD patients than in controls (13.7% vs. 7.8%, 95% CI: 1.15-3.07, P = 0.014). Subjects with a variant genotype T allele had an increased risk of CAD compared with G allele carriers (additive model: 95% CI: 1.21-3.35, P = 0.008). After adjustment for traditional cardiovascular risk factors, analysis of the dominant models involving rs7396366 also showed that T allele carriers had a significantly higher risk for CAD than G allele carriers had (dominant model: OR 1.48, 95% CI: 1.03-2.14, P = 0.035). Age, sex, type 2 diabetes mellitus, fasting plasma glucose, and the TT genotype in rs7396366 were significantly associated with three-vessel lesions. Despite these significant outcomes of rs7396366, information on rs2526378 showed no significant difference between CAD patients and non-CAD controls. CONCLUSION: Our results show that the T allele and TT genotype in rs7396366, closest to the AP2A2 gene, are linked to an increased risk of CAD and its severity in a Chinese population.