Organ-Specific Gene Expression Control Using DNA Origami-Based Nanodevices.

Nanodevices that function in specific organs or cells are one of the ultimate goals of synthetic biology. The recent progress in DNA nanotechnology such as DNA origami has allowed us to construct nanodevices to deliver a payload (e.g., drug) to the tumor. However, delivery to specific organs remains difficult due to the fragility of the DNA nanostructure and the low targeting capability of the DNA nanostructure. Here, we constructed tough DNA origami that allowed us to encapsulate the DNA origami into lipid-based nanoparticles (LNPs) under harsh conditions (low pH), harnessing organ-specific delivery of the gene of interest (GOI). We found that DNA origami-encapsulated LNPs can increase the functionality of payload GOIs (mRNA and siRNA) inside mouse organs through the contribution from different LNP structures revealed by cryogenic electron microscope (Cryo-EM). These data should be the basis for future organ-specific gene expression control using DNA origami nanodevices.

Differential responses to avian pathogenic E. coli and the regulatory role of splenic miRNAs in APEC infection in Silkie chickens.

Avian pathogenic Escherichia coli (APEC) is a bacterial disease that harms the poultry industry worldwide, but its effect on Chinese Silkie has not been reported. Studies on whether there are differences in Silkie individual resistance to APEC and the regulatory role of spleen miRNAs lay the foundation for strategies against APEC. Therefore, 270 Silkie chickens were infected with the median lethal dose of an E. coli O1, O2, and O78 mixture. These chickens were divided into a susceptible group (Group S) and a recovery group (Group R) according to whether they survived 15 days postinfection (dpi). Moreover, 90 uninfected APEC Silkie served as controls (Group C). The splenic miRNA expression profile was examined to evaluate the role of miRNAs in the APEC infection response. Of the 270 Silkies infected with APEC, 144 were alive at 15 dpi. Cluster analysis and principal component analysis (PCA) of splenic miRNAs revealed that the four Group R replicates were clustered with the three Group C replicates and were far from the three Group S replicates. Differentially expressed (DE) miRNAs, especially gga-miR-146b-5p, play essential roles in immune and inflammatory responses to APEC. Functional enrichment analyses of DEmiRNAs suggested that suppression of immune system processes (biological processes) might contribute to susceptibility to APEC and that FoxO signaling pathways might be closely associated with the APEC infection response and postinfection repair. This study paves the way for screening anti-APEC Silkies and provides novel insights into the regulatory role of miRNAs in APEC infection.

Combined analysis of the microbiome, metabolome and transcriptome of silkie chickens in response to avian pathogenic E. coli (APEC).

Avian colibacillosis is a bacterial disease caused by avian pathogenic Escherichia coli (APEC) that results in great losses in the poultry industry every year. Individual Silkie chickens of the same breed that are given the same feed in the same feeding conditions have different levels of resistance or susceptibility to APEC. Differences in gut microbes, gut metabolites, and gene expression in the spleen of APEC-resistant and APEC-susceptible chickens were compared, and multiple omics associations were analyzed to explore the mechanism of resistance to APEC in Silkie chickens. Compared with those in the APEC-susceptible group, the APEC-resistant group showed significantly increased abundances of many gut microorganisms, including Bacillus, Thermoactinomyces, Arthrobacter, and Ureibacillus, which were positively correlated with norvaline, l-arginine, and valyl-glycine levels. Intestinal tryptophan, indole, and indole derivative-related differentially abundant metabolites played an active role in combatting APEC infection. In the spleen, "response to stimulus" was the most significantly enriched GO term, and "cytokine‒cytokine receptor interaction" was the most significantly enriched KEGG pathway. The arginine biosynthesis and PPAR signaling pathways were the KEGG pathways that were significantly enriched with differentially abundant metabolites and differentially expressed genes. This study provides new insight into the prevention and treatment of APEC infection in Silkie chickens and lays a foundation to study the mechanism of APEC infection in poultry.

Thrombus management during direct coronary intervention for acute myocardial infarction.

OBJECTIVE: To study the management of thrombus during direct coronary intervention in patients with acute myocardial infarction (AMI). METHODS: We retrospectively analyzed 332 acute myocardial infarction patients receiving coronary artery intervention in our hospital from May 2017 to May 2019. Among them, 221 patients received thrombus aspiration and 111 patients received thrombus aspiration combined with platelet membrane glycoproteins receptor antagonist. The propensity score matching 1:1 nearest neighbor matching method was adopted to match 50 cases of the two methods as the control group and the experimental group, respectively. The incidence rate of intraoperative and postoperative adverse reactions, the effective rate of treatment, the electrocardiogram (ECG) at 1 h after operation, and the echocardiographic results at 1 week after operation were compared between the two groups. RESULTS: The incidence rate of adverse reactions in the experimental group was significantly lower than that in the control group, (P<0.05). The incidence rate of postoperative adverse reactions in the two groups did not statistically differ (P>0.05). The effective rate was found to be substantially higher in the experimental group when compared with that of the control group (P<0.05). The ECG 1 h after operation was in favor of the experimental group (P<0.05). The echocardiography results 1 week after operation were not statistically different in the two groups (P>0.05). CONCLUSION: Thrombus aspiration combined with receptor antagonist yielded a desirable outcome in direct coronary intervention for AMI, and has a high application value.

Exosome Derived from Coronary Serum of Patients with Myocardial Infarction Promotes Angiogenesis Through the miRNA-143/IGF-IR Pathway.

PURPOSE: Myocardial ischemia-reperfusion injury primarily causes myocardial infarction (MI), which is manifested by cell death. Angiogenesis is essential for repair and regeneration in cardiac tissue after MI. In this study, we aimed to investigate the effect of exosomes derived from the serum of MI patients in angiogenesis and its related mechanism. PATIENTS AND METHODS: Exosomes, isolated from serum, were collected from MI (MI-exosome) and control (Con-exosome) patients. After coculturing with human umbilical vein endothelial cells, MI-exosome promoted cell proliferation, migration, and tube formation. RESULTS: The results revealed that the production and release of MI-exosome were associated with cardiomyocytes. Moreover, microarray assays demonstrated that miRNA-143 was significantly decreased in MI-exosome. Meanwhile, the overexpression and knockdown of miRNA-143 could inhibit and enhance angiogenesis, respectively. Furthermore, the effect of exosomal miRNA-143 on angiogenesis was mediated by its targeting gene, insulin-like growth factor 1 receptor (IGF-IR), and was associated with the production of nitric oxide (NO). CONCLUSION: Taken together, exosomes derived from the serum of patients with MI promoted angiogenesis through the IGF-IR/NO signaling pathway. The results provide novel understanding of the function of exosomes in MI.

Vitamin D Deficiency Harms Patients with Coronary Heart Disease by Enhancing Inflammation.

BACKGROUND Vitamin D (VD) deficiency and local inflammation of plaque are potential new risk factors and prevention goals for coronary heart disease (CHD). MATERIAL AND METHODS This study included 135 CHD patients and 45 chest tightness or chest pain patients (control group). Basic clinical data and serum 25-OH-VD, TNF-α, IL-6, IL-8, and IL-1ß of the 2 groups were compared by SPSS 25.0. A CHD rat model was used to explore the potential molecular mechanisms. RESULTS The serum 25-OH-VD level in the control group was significantly higher compared to the CHD group, and decreased with the worsening of the CHD condition. Logistic regression found that serum 25-OH-VD was a protective factor in the occurrence of CHD. In CHD patients, the level of serum 25-OH-VD had a negative correlation with serum TNF-α (r=-0.651, P<0.001), IL-6 (r=-0.457, P<0.001), IL-8 (r=-0.755, P<0.001), and IL-1ß (r=-0.628, P<0.001). In animal experiments, VD deficiency enhanced the level of serum TC, TG, and LDL-C. VD deficiency could increase the inflammatory response by upregulating the expression of p65 protein and reducing SIRT1 protein expression in heart tissue, thereby inducing or aggravating the state of CHD. CONCLUSIONS Serum 25-OH-VD was a protective factor in the occurrence of CHD, and VD deficiency could induce or aggravate the state of CHD by enhancing inflammation through the NF-κB pathway.

Study of coronary artery perforation during percutaneous coronary intervention in the Cangzhou Chinese population.

OBJECTIVE: Coronary artery perforation (CAP) is a rare, serious complication of percutaneous coronary intervention (PCI). Many studies have addressed the incidence, risk factors, and management of CAP in different countries except China. The aim of this study is to determine the risk factors and types of treatment for coronary perforation occurring in patients undergoing PCI and living in the Cangzhou Chinese population. METHODS AND RESULTS: A retrospective cohort of 12,113 patients who underwent PCI was used: 64 patients with CAP and 192 case-control patients were evaluated. Clinical data and findings from coronary arteriography and PCI were analysed. Logistic regression was used to evaluate candidate risk factors for CAP. The treatments were also evaluated. The incidence of CAP in patients undergoing PCI was 0.53%, and the mortality was 7.8% (5/64). Risk factors included female gender, hypertension, non-ST-elevation acute coronary syndrome (NSTE-ACS), right coronary artery (RCA) lesion, calcified lesion, and chronic total occlusion (CTO) (all P < 0.05, all OR > 1). CTO had the highest risk (OR = 5.077, P < 0.001). Patients with class I CAP underwent conservative treatment. Patients with class II CAP underwent conservative treatment or low-pressure balloon dilatation (61.1% and 22.2%, respectively). Patients with class III CAP underwent low-pressure balloon dilatation, coated-stent implantation, and emergency surgery (40.9%, 27.3%, and 22.7%, respectively). CONCLUSIONS: CAP risk factors in Cangzhou Chinese patients undergoing PCI included CTO, NSTE-ACS, hypertension, calcified and RCA lesions, and female gender. Different treatment methods should be used according to the different classes of CAP.