Colchicine ameliorates myocardial injury induced by coronary microembolization through suppressing pyroptosis via the AMPK/SIRT1/NLRP3 signaling pathway.

BACKGROUND: Coronary microembolization(CME)is a common complication in acute coronary syndrome and percutaneous coronary intervention, which is closely related to poor prognosis. Pyroptosis, as an inflammatory programmed cell death, has been found to be associated with CME-induced myocardial injury. Colchicine (COL) has potential benefits in coronary artery disease due to its anti-inflammatory effect. However, the role of colchicine in pyroptosis-related CME-induced cardiomyocyte injury is unclear. This study was carried out to explore the effects and mechanisms of colchicine on myocardial pyroptosis induced by CME. METHODS: The CME animal model was constructed by injecting microspheres into the left ventricle with Sprague-Dawley rats, and colchicine (0.3 mg/kg) pretreatment seven days before and on the day of modeling or compound C(CC)co-treatment was given half an hour before modeling. The study was divided into 4 groups: Sham group, CME group, CME + COL group, and CME + COL + CC group (10 rats for each group). Cardiac function, serum myocardial injury markers, myocardial histopathology, and pyroptosis-related indicators were used to evaluate the effects of colchicine. RESULTS: Colchicine pretreatment improved cardiac dysfunction and reduced myocardial injury induced by CME. The main manifestations were the improvement of left ventricular systolic function, the decrease of microinfarction area, and the decrease of mRNA and protein indexes related to pyroptosis. Mechanistically, colchicine increased the phosphorylation level of adenosine monophosphate-activated protein kinase (AMPK), promoted the expression of silent information regulation T1 (SIRT1), and inhibited the expression of NOD-like receptor pyrin containing 3 (NLRP3) to reduce myocardial pyroptosis. However, after CC co-treatment with COL, the effect of colchicine was partially reversed. CONCLUSION: Colchicine improves CME-induced cardiac dysfunction and myocardial injury by inhibiting cardiomyocyte pyroptosis through the AMPK/SIRT1/NLRP3 signaling pathway.

Association of socioeconomic status with hypertension prevalence and control in Nanjing: a cross-sectional study.

BACKGROUND: The role of socioeconomic status (SES) on hypertension prevalence and hypertension control has gotten much attention but with conflicting results. This paper aimed to quantify the association of SES with both hypertension prevalence and hypertension control rate in Nanjing, China. METHODS: A community-based cross-sectional study was conducted using multistage random sampling on 60,283 adults aged more than 18 years between March 2017 and June 2018. Hypertension was defined as systolic blood pressure (BP) ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg or self-reported diagnosis of hypertension or respondent's report of taking antihypertensive medications. The controlled hypertension was defined by systolic BP < 140 mmHg and diastolic BP of < 90 mmHg among the subjects that self-reported exhibiting hypertensive and taking antihypertensive medications. The associations between SES with hypertension prevalence and hypertension control were quantified using generalized mixed model regression analysis and reported as odds ratios (ORs) and 95% confidence interval (CI). RESULTS: There was a high prevalence of subjects with primary educational level (49.6%) or unemployed and retired (49.5%) or lower annual household income level (44.9%) in each SES group, respectively. After adjustments for potential confounding factors, there were higher odds of hypertension among those with primary educational level (OR = 1.56), but lower odds for controlled BP (OR = 0.51). Higher odds of hypertension could be found among unemployed and retired, and higher odds of controlled BP was observed in the mental laborers or students (OR = 1.30), compared with the other categories, respectively. The lower-income group was more likely to be hypertensive (OR = 1.35) and less likely to have controlled hypertension (OR = 0.73). CONCLUSION: Socioeconomic status played an important role in hypertension prevalence and hypertension control among adults in Nanjing, China. Strategies for hypertension prevention and control should especially focus on people in the vulnerable lower SES groups.

'Trend in premature mortality from four major NCDs in Nanjing, China, 2007-2018'.

BACKGROUND: This study aims to analyze the trends of premature mortality caused from four major non-communicable diseases (NCDs), namely cardiovascular disease (CVD), cancer, chronic respiratory diseases, and diabetes in Nanjing between 2007 and 2018 and project the ability to achieve the "Healthy China 2030" reduction target. METHODS: Mortality data of four major NCDs for the period 2007-2018 were extracted from the Death Information Registration and Management System of Chinese Center for Disease Control and Prevention. Population data for Nanjing were provided by the Nanjing Bureau of Public Security. The premature mortality was calculated using the life table method. Joinpoint regression model was used to estimate the average annual percent changes (AAPC) in mortality trends. RESULTS: From 2007 to 2018, the premature mortality from four major NCDs combined in Nanjing decreased from 15.5 to 9.5%, with the AAPC value at - 4.3% (95% CI [- 5.2% to - 3.4%]). Overall, it can potentially achieve the target, with a relative reduction 28.6%. The premature mortality from cancer, CVD, chronic respiratory diseases and diabetes all decreased, with AAPC values at - 4.2, - 5.0%, - 5.9% and - 1.6% respectively. A relative reduction of 40.6 and 41.2% in females and in rural areas, but only 21.0 and 12.8% in males and in urban areas were projected. CONCLUSION: An integrated approach should be taken focusing on the modifiable risk factors across different sectors and disciplines in Nanjing. The prevention and treatment of cancers, diabetes, male and rural areas NCDs should be enhanced.

Effects of the TLR4/Myd88/NF-κB Signaling Pathway on NLRP3 Inflammasome in Coronary Microembolization-Induced Myocardial Injury.

BACKGROUND/AIMS: Coronary microembolization (CME) is a common complication of acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI); Myocardial inflammation, caused by CME, is the main cause of cardiac injury. TLR4/MyD88/NF-κB signaling plays an important role in the development of myocardial inflammation, but its effects on CME remain unclear. To assess the cardiac protective effects of TAK-242 (TLR4 specific inhibitor) on CME-induced myocardial injury, and explore the underlying mechanism. METHODS: Cardiac function, serum c-troponin I level, microinfarct were examined by cardiac ultrasound, myocardial enzyme assessment, HBFP staining. The levels of TLR4/MyD88/NF-κB signaling and NLRP3 inflammasome pathway were detected by ELISA, qRT-PCR and western blot. RESULTS: The results showed inflammatory responses in the myocardium after CME, with increased expression levels of pro-inflammatory factors TNF-α, IL-1ß and IL-18. Meanwhile, TLR4/MyD88/NF-κB signaling and the NLRP3 inflammasome were involved in the inflammatory process. TAK-242 administration before CME effectively inhibited the inflammatory response in the rat myocardium after CME and reduced myocardial injury, mainly by inhibiting TLR4/ MyD88/NF-κB signaling and reducing NLRP3 inflammasome activation. In addition, in vitro assays with neonatal rat cardiomyocytes further confirmed that TLR4/MyD88/NF-κB signaling was significantly activated in the inflammatory response of LPS-induced cardiomyocytes, via activation of the NLRP3 inflammasome. Inhibition of TLR4/MyD88/NF-κB signaling resulted in increased survival of cardiomyocytes mainly by reducing the release of inflammatory cytokines and decreasing NLRP3 inflammasome activation. CONCLUSIONS: TLR4/MyD88/NF-κB signaling participates in the inflammatory response of the myocardium after CME, activating the NLRP3 inflammasome, promoting the inflammatory cascade, and aggravating myocardial injury. Blocking TLR4/MyD88/NF-κB signaling may help reduce myocardial injury and improve cardiac function after CME.

Pinocembrin protects endothelial cells from oxidized LDL-induced injury.

Oxidized low-density lipoprotein (ox-LDL) is a major risk factor for atherosclerosis and often causes injury to vascular endothelial cells. We found that pinocembrin, a natural antioxidant found in honey and certain herbs, protects human aortic endothelial cells (HAECs) from ox-LDL-induced injury. Pinocembrin suppresses the expression of pro-inflammatory vascular adhesion molecules (VCAM-1, ICAM-1 and E-selectin) and cytokines (TNF-α, IL-1ß, and IL-8), as well as ROS production induced by ox-LDL. Pinocembrin potently inhibits the attachment of monocytes to HAEC cells. Mechanistically, pinocembrin suppresses activation of the MAPK kinase p38 and NF-κB pathways in the context of ox-LDL. Our data indicate that pinocembrin is a promising versatile natural compound that can protect endothelial cells from injury.

An electronic synaptic device based on HfO2TiOx bilayer structure memristor with self-compliance and deep-RESET characteristics.

We reported on a Ti/HfO2/TiOx/Pt memristor with self-compliance, deep-RESET characteristics and excellent switching performance, including ultrafast program/erase speed (10 ns), a large memory window (103) and good pulse endurance (107 cycles). The self-compliance and deep-RESET characteristics are beneficial for protecting the device from permanent breakdown in both SET and RESET processes especially under the pulse operation mode. In addition to bistable state switching, we also achieved multiple or even continuous conductance state switching under a DC sweep and a pulse-train operation mode in the Ti/HfO2/TiOx/Pt memristor, which can be seen as a substitution of a biological synapse. The capability of continuous modulation conductance (synaptic weight) in the Ti/HfO2/TiOx/Pt memristor was investigated and the potentiation and depression characteristics of the synaptic weight could be precisely tuned by the number or amplitude of the input pulse-train. Moreover, clear experimental evidence of short-term plasticity (STP) and long-term plasticity (LTP) in a single memristor was also demonstrated. Increasing the pulse amplitude or width, or decreasing the interval of two adjacent pulses of the input pulse-train resulted in the memristor behavior transitioning from STP to LTP. The realization of those important synaptic functions in the Ti/HfO2/TiOx/Pt memristor may be suitable for applications in artificial neural systems.

Presetting conductive pathway induced the switching uniformity evolution of a-SiNx:H resistive switching memory.

Si-based resistive random access memory (RRAM) devices at the nanoscale with high uniformity have great potential applications in the future. We demonstrate that the uniformity evolution of the a-SiNx:H RRAM at the low resistance state (LRS) and the high resistance state (HRS) can be clearly monitored by presetting a Si dangling bond (Si-DB) conductive pathway through thermal energy. It is found that the increased magnitude of uniformity for the LRS and the HRS are determined by the number of preset Si-DBs, which can be controlled by tuning thermal energy. As for LRS, the Si-DBs produced under the electric field along with the preset Si-DB conductive pathways form the main conductive pathway. Theoretical calculation of current-voltage (I-V) curves indicates that the Si-DB conductive pathways obey the trap-assisted tunneling model. In the HRS, the preset Si-DBs induced by thermal energy are the unique source of the conductive pathway. The transmission mechanism involves a trap-to-trap process by the hopping of electrons under a low electric field, Poole-Frenkel emission in the main region under the medium electric field and Fowler-Nordheim tunneling under the high electric field. Our discovery of the uniformity evolution for a-SiNx:H RRAM device through presetting the Si-DB conductive pathway provides new insight into the resistive switching mechanism of next generation Si-based RRAM devices.

Forming-free performance of a-SiN x :H-based resistive switching memory obtained by oxygen plasma treatment.

An a-SiN x -based resistive random access memory (RRAM) device with a forming-free characteristic has significant potentials for the industrialization of the next-generation memories. We demonstrate that a forming-free a-SiN x O y RRAM device can be achieved by an oxygen plasma treatment of ultra-thin a-SiN x :H films. Electron spin resonance spectroscopy reveals that Si dangling bonds with a high density (1019 cm-3) are distributed in the initial state, which exist in the forms of Si2N≡Si·, SiO2≡Si·, O3≡Si·, and N3≡Si·. X-ray photoelectron spectroscopy and temperature-dependent current analyses reveal that the silicon dangling bonds induced by the oxygen plasma treatment and external electric field contribute to the low resistance state (LRS). For the high resistance state (HRS), the rupture of the silicon dangling bond pathway is attributed to the partial passivation of Si dangling bonds by H+ and O2-. Both LRS and HRS transmissions obey the hopping conduction model. The proposed oxygen plasma treatment, introduced to generate a high density of Si dangling bonds in the SiN x O y :H films, provides a new approach to forming-free RRAM devices.

Relationship between circulating miRNA-30e and no-reflow phenomenon in STEMI patients undergoing primary coronary intervention.

To investigate the relationship between miRNA-30e level in circulation and no-reflow phenomenon in patients with acute ST-segment elevation myocardial infarction (STEMI) during primary percutaneous coronary intervention (pPCI). A total of 255 consecutive patients with STEMI undergoing pPCI were enrolled in this study. These patients were divided into two groups according to the occurrence of reflow during pPCI, namely normal-reflow group with 214 cases and no-reflow group with 41 cases. The plasma levels of miRNA-30e were quantified using real-time quantitative polymerase chain reaction. The plasma levels of miRNA-30e were significantly lower in the no-reflow group as compared to the normal-reflow group (p < .05). Also, miRNA-30e was positively correlated with left ventricular ejection fraction (LVEF) and negatively correlated with hs-CRP levels (p < .05). Multivariate logistic regression analyses indicated that the plasma level of miRNA-30e (OR = 0.732, 95% CI 0.674-0.851, p = .034), hs-CRP (OR = 1.353, 95% CI 1.129-1.635, p = .012) and Killip class ≥2 at admission (OR = 1.263, 95% CI 1.023-1.532, p = .027), were independent risk factors for no-reflow during pPCI. When plasma miRNA-30e level was used as the test variable, the area under the curve was 0.914 (p < .05) by ROC curve analysis. Lower miRNA-30e levels at admission are associated with no-reflow in STEMI patients undergoing pPCI and may play an important role in the pathogenesis of no-reflow. Plasma miRNA-30e level was an independent predictor of no-reflow during pPCI in patients with STEMI. Therefore, early detection of plasma miRNA-30e level can be a preliminary assessment for risk of no-reflow during pPCI.

MiRNA Expression Profile of the Myocardial Tissue of Pigs with Coronary Microembolization.

BACKGROUND/AIMS: Coronary microembolization (CME) is a serious complication of coronary heart disease and is considered as a strong predictor of poor long-term prognosis and major cardiac adverse events. Here, we identified differentially expressed microRNAs (miRNAs) in the myocardial tissue of CME pigs, and predicted and analyzed the possible functions of their target genes. METHODS: Twelve Bama mini-pigs were randomly assigned to the sham and CME group (n = 6 in each group). The two groups were compared with regard to heart function, area of infarction, cardiomyocyte apoptosis, and myocardial expression of TNF-α, IL-1ß and IL-6. Further, miRNA chip analysis was used to screen for differentially expressed miRNAs, and the results were validated by real-time PCR. Bioinformatics methods were used to predict and analyze the functions of the target genes of the identified miRNAs. RESULTS: The model CME pigs showed significantly increased expression of TNF-α, IL-1ß and IL-6, as well as micro-infarction lesions and cell apoptosis in the myocardial tissue. Thus, the model was established successfully. In the myocardial tissue of the CME pigs, the expression of ssc-miR-92b-5p, ssc-miR-491, ssc-miR-874, ssc-miR-425-3p, ssc-miR-376a-5p, ssc-miR-370, ssc-miR-30c-3p, ssc-miR-493-5p and ssc-miR-323 was significantly increased, whereas the expression of ssc-miR-136 and ssc-miR-142-3p was significantly decreased. GO and KEGG pathway analysis indicated that the target genes of these miRNAs are mainly associated with cell proliferation, apoptosis, necrosis, inflammation, and fibrosis. CONCLUSION: The differentially expressed miRNAs identified in the myocardial tissue of CME pigs could be new biomarkers or potential treatment targets for CME.

Effects of Trimetazidine on PDCD4/NF-κB/TNF-α Pathway in Coronary Microembolization.

BACKGROUND/AIMS: The local inflammatory response caused by coronary microembolization (CME) is the primary cause of progressive cardiac dysfunction. The PDCD4/NF-κB/TNF-α signaling pathway plays a significant role in CME-induced myocardial Inflammation. Trimetazidine (TMZ) reduces myocardial injury, caused by percutaneous coronary intervention, through relieving the CME-induced myocardial systolic dysfunction. Therefore, the present study investigated the role of TMZ pre-treatment in the protection of myocardium after CME and PDCD4/NF-κB/TNF-α in mini pigs. METHODS: 20 Bama mini pigs were randomized into sham operation (sham), microembolization (CME), TMZ, and siRNA-PDCD4 groups (n = 5). The CME model was established by injecting polyethylene microspheres via microcatheter into the left anterior descending coronary artery. The TMZ group was injected 2.5 mg/kg drug via ear vein 30 min before CME; whereas, the siRNA-PDCD4 group was transfected with PDCD4 siRNA at the left anterior descending coronary artery via microcatheter 72h before CME. Cardiac function indexes were measured using cardiac echocardiography. The mRNA expression of PDCD4 and TNF-α in the myocardium was detected by quantitative fluorescence PCR, and the protein expression of PDCD4, NF-κB (p65), and TNF-α by Western blot. RESULTS: Echocardiographic parameters showed lower cardiac function and higher serum cTnI level in the CME group than sham, which was manifested as reduced left ventricular ejection fraction (LVEF), left ventricular fractional shortening (FS), cardiac output (CO), and increased left ventricular diastolic diameter (LVEDd). Compared to the CME group, the CME-induced cardiac function injury was reduced, and the serum cTnI level was decreased in the TMZ and siRNA-PDCD4 groups. The expressions of PDCD4, NF-κB (p65), and TNF-α were significantly increased in the CME than the sham groups (P < 0.05), and significantly decreased in the TMZ and siRNA-PDCD4 groups than the CME group (P < 0.05). CONCLUSION: TMZ pretreatment effectively reduced the myocardial damage caused by CME via inhibiting the PDCD4/NF-κB/ TNF-α pathway in cardiomyocytes.

Serum Human Epidermal Growth Factor 2 is a Novel Biomarker for Recurrence and Metastasis in Triple Negative Breast Cancer.

BACKGROUND: The aim of this study was to evaluate the predictive value of serum human epidermal growth factor 2 (HER2) for recurrence and metastasis in triple negative breast cancer (TNBC). METHODS: A total of 200 patients with benign breast tumors and 300 patients with breast cancer treated in the Department of Breast Surgery, Women and Children's Hospital of Ningbo City (China) between December 2006 and December 2013 were enrolled. Another 500 age- and gender-matched healthy individuals served as controls. The serum level of HER2 was determined using suspension array technology. Patients with breast cancer were further divided into ER-/PR-/HER2- and ER-/PR-/HER2+ groups and followed up for 5 years to analyze the serum concentration of HER2. RESULTS: The serum HER2 concentration was significantly higher in patients with breast cancer than in healthy controls or patients with benign tumors (both p < 0.01). The serum HER2 concentration also was significantly higher in patients with TNBC than in healthy controls (p < 0.01). The serum concentration of HER2 was significantly higher in TNBC patients who experienced recurrence and metastasis than in TNBC patients who did not experience recurrence and metastasis (both p < 0.01). Notably, the serum HER2 concentration in TNBC patients who experienced recurrence and metastasis was increased to a level statistically similar to that in patients with HER2+ breast cancer (p > 0.05). CONCLUSIONS: Patients with TNBC still have an increased serum HER2 concentration, and serum HER2 may be a valuable, novel biomarker for recurrence and metastasis in TNBC.

Reproducibility and validity of dietary patterns identified using factor analysis among Chinese populations.

In the present study, we evaluated the reproducibility and validity of dietary patterns among Chinese adult populations. A random subsample of 203 participants (aged 31-80 years) from a community-based nutrition and health survey was enrolled. An eighty-seven-item FFQ was administered twice (FFQ1 and FFQ2) 1 year apart; four 3 consecutive day, 24-h dietary recalls (24-HDR, as a reference method) were performed between the administrations of the two FFQ every 3 months. Dietary patterns from three separate dietary sources were derived using factor analysis based on twenty-eight predefined food groups. Comparisons between dietary pattern scores were made by using Pearson's or intraclass correlation coefficients (ICC), cross-classification analysis, weighted κ statistic and Bland-Altman plots; the four major dietary patterns identified from FFQ1, FFQ2 and 24-HDR were similar. Regarding reproducibility, ICC for z-scores between FFQ1 and FFQ2 were all >0·6 for dietary patterns. The 'animal and plant protein' pattern had the highest ICC of 0·870. For validity, the adjusted Pearson's correlation coefficients for dietary pattern z-scores between two FFQ and the mean of four 3 consecutive day 24-HDR ranged from 0·387 for the 'Chinese traditional' pattern to 0·838 for the 'animal and plant protein' pattern. More than 75 % of the participants were classified into the same or adjacent quartile, and <5 % were misclassified into opposite quartiles. The weighted κ ranged from 0·259 to 0·680. Bland-Altman plots indicated that no significant deviation was found between two dietary assessment methods. Our findings indicate a good reasonable reproducibility and a reasonable validity of dietary patterns derived by factor analysis in China.

Reproducibility and validity of an FFQ developed for adults in Nanjing, China.

We evaluated the reproducibility and validity of an FFQ used in a Chinese community-based nutrition and health survey. A total of ninety-nine males and 104 females aged 31-80 years completed four three consecutive 24-h dietary recalls (24-HDR, served as a reference method, one three consecutive 24-HDR for each season) and two FFQ (FFQ1 and FFQ2) over a 1-year interval. The reproducibility of the FFQ was estimated with correlation coefficients, misclassification and weighted κ statistic. The validity was evaluated by comparing the data obtained from FFQ2 with the mean 24-HDR (m24-HDR). Compared with the m24-HDR, the FFQ tended to underestimate intake of most nutrients and food groups. For all nutrients and food groups, the Spearman's and intra-class correlation coefficients between FFQ1 and FFQ2 ranged from 0·66 to 0·88 and from 0·65 to 0·87, respectively. Most correlation coefficients decreased after adjusting for energy. More than 90% of the subjects were classified into the same or adjacent categories by both FFQ. For all nutrients and food groups, the crude, energy-adjusted and de-attenuated Spearman's correlation coefficients between FFQ2 and the m24-HDR ranged from 0·21 to 0·69, 0·19 to 0·58 and 0·25 to 0·71, respectively. More than 70% of the subjects were classified into the same and adjacent categories by both instruments. Both weighted κ statistic and the Bland-Altman plots showed reasonably acceptable agreement between the FFQ2 and the m24-HDR. The FFQ developed for adults in the Nanjing area can be used to reliably and validly measure usual intake of major nutrients and food groups.

A supramolecular strategy to leverage the liquid-phase exfoliation of graphene in the presence of surfactants: unraveling the role of the length of fatty acids.

Achieving the full control over the production as well as processability of high-quality graphene represents a major challenge with potential interest in the field of fabrication of multifunctional devices. The outstanding effort dedicated to tackle this challenge in the last decade revealed that certain organic molecules are capable of leveraging the exfoliation of graphite with different efficiencies. Here, a fundamental understanding on a straightforward supramolecular approach for producing homogenous dispersions of unfunctionalized and non-oxidized graphene nanosheets in four different solvents is attained, namely N-methyl-2-pyrrolidinone, N,N-dimethylformamide, ortho-dichlorobenzene, and 1,2,4-trichlorobenzene. In particular, a comparative study on the liquid-phase exfoliation of graphene in the presence of linear alkanes of different lengths terminated by a carboxylic-acid head group is performed. These molecules act as graphene dispersion-stabilizing agents during the exfoliation process. The efficiency of the exfoliation in terms of concentration of exfoliated graphene is found to be proportional to the length of the employed fatty acid. Importantly, a high percentage of single-layer graphene flakes is revealed by high-resolution transmission electron microscopy and Raman spectroscopy analyses. A simple yet effective thermodynamic model is developed to interpret the chain-length dependence of the exfoliation yield. This approach relying on the synergistic effect of a ad-hoc solvent and molecules to promote the exfoliation of graphene in liquid media represents a promising and modular strategy towards the rational design of improved dispersion-stabilizing agents.

Ultrasound-Targeted Microbubble Destruction Enhances Gene Expression of microRNA-21 in Swine Heart via Intracoronary Delivery.

BACKGROUND: Ultrasound-targeted microbubble destruction (UTMD) has proved to be a promising method for gene delivery. However, the feasibility and efficacy of UTMD-mediated gene delivery to the heart of large animals remain unclear. The present study was to explore the probability of increasing the transfection of microRNA-21 (miR-21) in swine heart by UTMD, and to search for the most suitable transfection conditions. METHODS: We first optimized ultrasound intensity for successful miR-21 delivery. After intravenous injection of miR-21/microbubble mixture (miR-21/MB), transthoracic ultrasound irradiation (US) was applied from the left anterior chest using different intensities (1, 2, and 3 W/cm(2)). Then the efficacy of UTMD-mediated miR-21 delivery into myocardium via intracoronary injection was explored. Solution of miR-21/MB was infused intravenously or intracoronarily with US over the heart. Swine undergoing phosphate-buffered saline (PBS) injection, miR-21/MB injection via ear vein or coronary artery without US served as the control. The dynamic changes of left ventricular ejection fraction (LVEF) and serum troponin I (cTnI) after UTMD were detected, then the left ventricular myocardium was harvested for hematoxylin and eosin (H&E) staining 4 days later; the expression levels of miR-21 and programmed cell death 4 (PDCD4) were detected by quantitative real time polymerase chain reaction (qRT-PCR) and Western blot, respectively. RESULTS: Results showed that pulse ultrasound at an intensity of 2 W/cm(2) and a 50% duty ratio for 20 minutes, there was no increase in serum cTnI, no histological sign of myocardial damage, and no noted cardiac dysfunction with relatively higher miR-21 expression (P < 0.05). Compared to miR-21/MB alone, UTMD significantly increased gene expression in myocardium regardless of the delivery routes (P < 0.05). Interestingly, the transfection efficiency was found to be a little bit higher with intracoronary injection than that with intravenous injection, though the dose for intracoronary injection was half of the intravenous injection (P < 0.05). CONCLUSION: Under suitable conditions, UTMD can efficiently enhance gene expression in swine heart regardless of the delivery routes. The intravenous injection might be superior to intracoronary injection with less invasiveness and lower requirement of the technique. And for those undergoing percutaneous coronary intervention, intracoronary injection seems to be another alternative.

miR-135a inhibition protects A549 cells from LPS-induced apoptosis by targeting Bcl-2.

Acute lung injury (ALI) is a severe clinical condition with high morbidity and mortality. Apoptosis is a key pathologic feature of ALI, and Bcl-2 plays an important role during the pathogenesis of ALI via the regulation of apoptosis. However, the regulation of Bcl-2 during ALI, particularly through microRNAs, remains unclear. We hypothesize that certain miRNAs may play deleterious or protective roles in ALI via the regulation of Bcl-2. The LPS stimulation of A549 cells was used to mimic ALI in vitro. First, we confirmed that Bcl-2 is involved in LPS-induced apoptosis in A549 cells. Then, bioinformatic analyses and quantitative real-time polymerase chain reaction assays were performed to screen for miRNAs targeting Bcl-2. We observed that miR-135a was markedly increased in LPS-challenged A549 cells. miR-135a inhibition markedly restored Bcl-2 expression and protected A549 cells from LPS-induced apoptosis. Furthermore, bioinformatic analysis and luciferase activity assays were conducted to confirm that miR-135a binds directly to the 3'-untranslated region of Bcl-2 and suppresses its expression. Interestingly, the inhibition of miR-135a did not attenuate apoptosis under LPS-treated conditions when Bcl-2 was knocked down. Therefore, we suggest that miR-135a regulation of LPS-induced apoptosis in A549 cells may depend in part on the regulation of Bcl-2. The miR-135a/Bcl-2 signaling pathway may be a novel therapeutic target for the prevention of ALI.

Hexagonal Ag nanoarrays induced enhancement of blue light emission from amorphous oxidized silicon nitride via localized surface plasmon coupling.

A significant enhancement of blue light emission from amorphous oxidized silicon nitride (a-SiNx:O) films is achieved by introduction of ordered and size-controllable arrays of Ag nanoparticles between the silicon substrate and a-SiNx:O films. Using hexagonal arrays of Ag nanoparticles fabricated by nanosphere lithography, the localized surface plasmons (LSPs) resonance can effectively increase the internal quantum efficiency from 3.9% to 13.3%. Theoretical calculation confirms that the electromagnetic field-intensity enhancement is through the dipole surface plasma coupling with the excitons of a-SiNx:O films, which demonstrates a-SiNx:O films with enhanced blue emission are promising for silicon-based light-emitting applications by patterned Ag arrays.

Raman fingerprint of aligned graphene/h-BN superlattices.

Graphene placed on hexagonal-boron nitride (h-BN) experiences a superlattice (Moiré) potential, which leads to a strong reconstruction of graphene's electronic spectrum with new Dirac points emerging at sub-eV energies. Here we study the effect of such superlattices on graphene's Raman spectrum. In particular, the 2D Raman peak is found to be exquisitely sensitive to the misalignment between graphene and h-BN lattices, probably due to the presence of a strain distribution with the same periodicity of the Moiré potential. This feature can be used to identify graphene superlattices with a misalignment angle smaller than 2°.

Harnessing the liquid-phase exfoliation of graphene using aliphatic compounds: a supramolecular approach.

The technological exploitation of the extraordinary properties of graphene relies on the ability to achieve full control over the production of a high-quality material and its processing by up-scalable approaches in order to fabricate large-area films with single-layer or a few atomic-layer thickness, which might be integrated in working devices. A simple method is reported for producing homogenous dispersions of unfunctionalized and non-oxidized graphene nanosheets in N-methyl-2-pyrrolidone (NMP) by using simple molecular modules, which act as dispersion-stabilizing compounds during the liquid-phase exfoliation (LPE) process, leading to an increase in the concentration of graphene in dispersions. The LPE-processed graphene dispersion was shown to be a conductive ink. This approach opens up new avenues for the technological applications of this graphene ink as low-cost electrodes and conducting nanocomposite for electronics.