The progressive loss of cardiomyocytes caused by cell death leads to cardiac dysfunction and heart failure (HF). Rapamycin has been shown to be cardioprotective in pressure-overloaded and ischemic heart diseases by regulating the mechanistic target of rapamycin (mTOR) signaling network. However, the impact of rapamycin on cardiomyocyte death in chronic HF remains undetermined. Therefore, in the current study we addressed this issue using a rat myocardial infarction (MI)-induced chronic HF model induced by ligating the coronary artery. Following surgery, rats were randomly divided into six groups, including the sham-, vehicle- and rapamycin-operated groups, at 8 or 12 weeks post-MI. A period of 4 weeks after MI induction, the rats were treated with rapamycin (1.4 mg-kg-day) or vehicle for 4 weeks. Cardiac function was determined using echocardiography, the rats were subsequently euthanized and myocardial tissues were harvested for histological and biochemical analyses. In the cell culture experiments with H9c2 rat cardiomyocytes, apoptosis was induced using angiotensin II (100 nM; 24 h). Cardiomyocyte apoptosis and autophagy were assessed via measuring apoptosis- and autophagy-associated proteins. The activities of mTOR complex 1 (mTORC1) and mTORC2 were evaluated using the phosphorylation states of ribosomal S6 protein and Akt, respectively. The activity of the endoplasmic reticulum (ER) stress pathway was determined using the levels of GRP78, caspase-12, phospho-JNK and DDIT3. Echocardiographic and histological measurements indicated that rapamycin treatment improved cardiac function and inhibited cardiac remodeling at 8 weeks post-MI. Additionally, rapamycin prevented cardiomyocyte apoptosis and promoted autophagy at 8 weeks post-MI. Rapamycin treatment for 4 weeks inhibited the mTOR and ER stress pathways. Furthermore, rapamycin prevented angiotensin II-induced H9c2 cell apoptosis and promoted autophagy by inhibiting the mTORC1 and ER stress pathways. These results demonstrated that rapamycin reduced cardiomyocyte apoptosis and promoted cardiomyocyte autophagy, by regulating the crosstalk between the mTOR and ER stress pathways in chronic HF.

In order to identify the effects of land-use/ cover types, soil types and soil properties on the soilatmosphere exchange of greenhouse gases (GHG) in semiarid grasslands as well as provide a reliable estimate of the midsummer GHG budget, nitrous oxide (N 2 O), methane (CH 4 ) and carbon dioxide (CO 2 ) fluxes of soil cores from 30 representative sites were determined in the upper Xilin River catchment in Inner Mongolia. The soil N 2 O emissions across all of the investigated sites ranged from 0.18 to 21.8 μg N m -2 h -1 , with a mean of 3.4 μg N m -2 h -1 and a coefficient of variation (CV, which is given as a percentage ratio of one standard deviation to the mean) as large as 130%. CH 4 fluxes ranged from -88.6 to 2,782.8 μg C m -2 h -1 (with a CV of 849%). Net CH 4 emissions were only observed from cores taken from a marshland site, whereas all of the other 29 investigated sites showed net CH 4 uptake (mean: -33.3 μg C m -2 h -1 ). CO 2 emissions from all sites ranged from 3.6 to 109.3 mg C m -2 h -1 , with a mean value of 37.4 mg C m -2 h -1 and a CV of 66%. Soil moisture primarily and positively regulated the spatial variability in N 2 O and CO 2 emissions (R 2 =0.15-0.28, P<0.05). The spatial variation of N 2 O emissions was also influenced by soil inorganic N contents (P< 0.05). By simply up-scaling the site measurements by the various land-use/cover types to the entire catchment area (3,900 km 2 ), the fluxes of N 2 O, CH 4 and CO 2 at the time of sampling (mid-summer 2007) were estimated at 29 t CO 2 -C-eq d -1 , -26 t CO 2 -C-eq d -1 and 3,223 t C d -1 , respectively. This suggests that, in terms of assessing the spatial variability of total GHG fluxes from the soils at a semiarid catchment/region, intensive studies may focus on CO 2 exchange, which is dominating the global warming potential of midsummer soil-atmosphere GHG fluxes. In addition, average GHG fluxes in midsummer, weighted by the areal extent of these land-use/cover types in the region, were approximately -30.0 μg C m -2 h -1 for CH 4 , 2.4 μg N m -2 h -1 for N 2 O and 34.5 mg C m -2 h -1 for CO 2 .

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Circulating microRNAs (miRNAs) have been proposed as potential biomarkers for left ventricular remodeling in postinfarction heart failure (HF). However, the diagnostic reproducibility of the use of circulating miRNAs may be affected by the temporal expression of miRNAs following myocardial infarction (MI). In the current study, using a MI-induced HF rat cohort (4-, 8-, and 12-week post-MI groups), we investigated the temporal expression of plasma miRNAs during the development of left ventricular remodeling. The plasma miRNA expression profile was obtained using miRNA sequencing. The expression of candidate miRNAs in plasma and tissues was examined with real-time PCR. Target genes of candidate miRNAs were predicted using a parallel miRNA-messenger RNA expression profiling approach. The value of plasma miRNAs as biomarkers for left ventricular remodeling was evaluated in patients with postinfarction HF (n = 32) and control patients with stable angina and without significant coronary lesions and HF (n = 16) with real-time PCR. Although the expression levels of miR-20a-5p, miR-340-5p, and let-7i-5p were temporally regulated in plasma, myocardium, and peripheral blood mononuclear cells, the expression levels of plasma miRNAs, especially miR-20a-5p, were associated with the development of left ventricular remodeling in the postinfarction HF rat cohort. The target genes of these 3 miRNAs were associated with the mechanistic target of rapamycin, nuclear factor-κB, tumour necrosis factor, apoptosis, and p53 signaling pathways. Additionally, the plasma levels of miR-20a-5p, miR-340-5p, and let-7i-5p were significantly increased in patients with postinfarction HF. However, only the expression levels of miR-20a-5p presented significant positive correlations with left ventricular internal end diastolic dimension and left ventricular end diastolic volume. In conclusion, the expression levels of plasma miR-20a-5p were significantly associated with the degree of left ventricular dilatation, and plasma miR-20a-5p may be a potential biomarker for postinfarction left ventricular remodeling.

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Trans-radial access for percutaneous coronary intervention or angiography has gained popularity amongst interventional cardiologists. Radial access is also thought to reduce the incidence of acute kidney injury (AKI) in the immediate post-operative period. The purpose of the present study was to perform a comprehensive updated systematic review and meta-analysis comparing the incidence of AKI following the radial vs. femoral route of coronary catheterization. An electronic literature search of the PubMed, BioMed Central, Scopus, Cochrane Central Register of Controlled Trials and Google Scholar databases up to 1st January 2020 was performed. A total of 14 studies were included, 2 of which were randomized controlled trials (RCTs), and 6 studies utilized propensity score matching. Comparison of the data of 21,479 patients in the radial group and 25,337 patients in the femoral group indicated a reduced incidence of AKI with the radial route [odds ratio (OR):0.66, 95% CI: 0.54-0.81, P<0.0001, I 2 =74%]. Similar results were obtained with subgroup analyses for RCTs (OR: 0.87, 95% CI: 0.77-0.98, P=0.02, I 2 =0%), retrospective studies (OR: 0.57, 95% CI: 0.36-0.90, P=0.02, I 2 =86%) and propensity score-matched studies (OR: 0.63, 95% CI: 0.48-0.83, P=0.0009, I 2 =45%). Multivariable-adjusted ORs of AKI for the radial vs. femoral route were extracted from non-RCTs and pooled for a meta-analysis, which also demonstrated similar results (OR: 0.70, 95% CI: 0.57-0.88, P=0.002, I 2 =70%). Within the limitations of the study, the present results indicate that, as compared to femoral access, the use of trans-radial access for coronary catheterization is associated with a significantly reduced incidence of AKI. A reduction of AKI by ~34% may be expected with the use of radial access.