Mechanism of action of microRNA166 on nitric oxide in alfalfa (Medicago sativa L.) under drought stress.

BACKGROUND: Alfalfa is a perennial forage crop of high importance, but its cultivation is often affected by drought stress. Currently, the investigation of drought-related small RNAs is a popular research topic to uncover plant drought resistance mechanisms. Among these small RNAs, microRNA166 (miR166) is associated with drought in numerous plant species. Initial small RNA sequencing studies have shown that miR166 is highly responsive to exogenous nitric oxide (NO) and drought. Therefore, analyzing the expression of Msa-miR166 under nitric oxide and drought treatment is significant. RESULT: Bioinformatics analysis revealed that the miR166 family is widely distributed among plants, ranging from mosses to eudicots, with significant distribution differences between species. The evolutionary degree of Msa-miR166s is highly similar to that of Barrel medic (Medicago truncatula) and Soybean (Glycine max), but significantly different from the model plant Arabidopsis (Arabidopsis thaliana). It is suggested that there are no significant differences in miR166s within the species, and members of Msa-miR166s can form a typical stem-loop. The lowest level of exogenous nitric oxide was observed in Msa-miR166s under drought stress, followed by individual drought, and the highest level was observed after removing endogenous nitric oxide. CONCLUSION: In response to short-term drought, Msa-miR166s down-regulate expression in alfalfa (Medicago sativa L.). Exogenous nitric oxide can reduce the expression of Msa-miR166s in response to short-term drought. These findings suggest that Msa-miR166e-5p is responsive to environmental changes. The expression levels of target genes showed an opposite trend to Msa-miR166s, verifying the accuracy of Degradome sequencing in the early stage. This suggests that alfalfa experiences drought stress when regulated by exogenous nitric oxide, targeting HD ZIP-III, FRI, and CoA ligase genes. Additionally, the expression of Msa-miR166s in response to drought stress varies between leaves and roots, indicating spatiotemporal specificity.

Structure-preserving integrated analysis for risk stratification with application to cancer staging.

To provide appropriate and practical level of health care, it is critical to group patients into relatively few strata that have distinct prognosis. Such grouping or stratification is typically based on well-established risk factors and clinical outcomes. A well-known example is the American Joint Committee on Cancer staging for cancer that uses tumor size, node involvement, and metastasis status. We consider a statistical method for such grouping based on individual patient data from multiple studies. The method encourages a common grouping structure as a basis for borrowing information, but acknowledges data heterogeneity including unbalanced data structures across multiple studies. We build on the "lasso-tree" method that is more versatile than the well-known classification and regression tree method in generating possible grouping patterns. In addition, the parametrization of the lasso-tree method makes it very natural to incorporate the underlying order information in the risk factors. In this article, we also strengthen the lasso-tree method by establishing its theoretical properties for which Lin and others (2013. Lasso tree for cancer staging with survival data. Biostatistics 14, 327-339) did not pursue. We evaluate our method in extensive simulation studies and an analysis of multiple breast cancer data sets.

Thirty-day and 5-year results of percutaneous coronary intervention for in-stent restenotic chronic total occlusion lesions: Data from 2,659 consecutive patients.

OBJECTIVES: To investigate the procedure success rate and clinical outcomes of in-stent restenotic chronic total occlusion (ISR-CTO) percutaneous coronary intervention (PCI). BACKGROUND: Few studies have reported the short- and long-term clinical outcomes of ISR-CTO PCI. METHOD: Patients who underwent ISR-CTO (n = 212) or de-novo CTO (n = 2,447) PCI at Fuwai Hospital from 2010 to 2013 were enrolled. Thirty-day and 5-year clinical outcomes were analyzed. The primary outcome was the incidence of all-cause death, myocardial infarction (MI), and heart failure at follow-up. The secondary outcome was the recanalization result (reasonable, suboptimal, or failed recanalization). RESULTS: ISR-CTO PCI had a higher rate of suboptimal recanalization than de-novo CTO PCI (p < .01). The syntax score before PCI (odds ratio (OR): 1.06; 95% confidence interval (CI): 1.02-1.10; p = .002) and occlusion length ≥ 20 mm (OR: 2.70:95% CI: 1.46-4.98; p = .001) were predictors of suboptimal recanalization in ISR-CTO PCI. Cardiac death (p = .03) and 30-day all-cause mortality (p = .05) were higher among patients who underwent ISR-CTO PCI. The ISR-CTO group had a higher rate of MI (p = .07) at 5 years. Suboptimal recanalization (hazard ratio: 2.56; 95% CI: 1.13-5.83; p = .025) was an independent predictor of long-term major adverse events in ISR-CTO. CONCLUSIONS: Suboptimal recanalization, 30-day cardiac death, and long-term MI rates are higher for ISR-CTO PCI than de-novo CTO PCI. Suboptimal recanalization is an independent predictor of long-term major adverse events after ISR-CTO PCI.

New insights into the cultivation of N, N-dimethylformamide-degrading methanogenic consortium: A long-term investigation on the variation of prokaryotic community inoculated with activated sludge.

The cultivation of the N, N-dimethylformamide (DMF)-degrading methanogenic consortium is considered difficult. In this study, an up-flow anaerobic sludge blanket (UASB) was inoculated with activated sludge in order to culture the DMF-degrading anaerobic sludge under a constant DMF concentration of approximately 2000 mg L-1. While the UASB realized a nearly 100% degradation of DMF and a high methane production of 1.03 L d-1 for the first two months, both the removal efficiency and methane production continued to decrease until the end. The characterization of the prokaryotic community reveals that those DMF-hydrolyzing bacteria (DHB) originating from the activated sludge were responsible for the effective degradation of DMF. However, even when fed with a constant concentration of DMF, the DHB kept decreasing all the time while methane-producing archaea were rapidly cultivated. The variation of prokaryotic community suggests that the DHB could not proliferate anaerobically without utilizing the intermediate products from the hydrolysis of DMF, resulting in an unstable DMF-degrading consortium. The cultivation of DHB under the anaerobic condition of the UASB was therefore difficult. The reason it was not possible to culture a DMF-degrading methanogenic consortium in this study is that the DHB are denitrifying bacteria which require nitrate for their cell growth under the anaerobic condition. The solution to maintain the abundance of these DHB is to add doses of nitrate into the system. Nitrate is likely to help these DHB recapture intermediates from methanogens, enabling them to perform a heterotrophic denitrification by using a small proportion of DMF as the carbon source while simultaneously maintaining the cell growth of DHB.

Predictive modeling based on artificial neural networks for membrane fouling in a large pilot-scale anaerobic membrane bioreactor for treating real municipal wastewater.

Membrane fouling is the primary obstacle to applying anaerobic membrane bioreactors (AnMBRs) in municipal wastewater treatment. This issue holds critical significance as efficient wastewater treatment serves as a cornerstone for achieving environmental sustainability. This study uses machine learning to predict membrane fouling, taking advantage of rapid computational and algorithmic advances. Based on the 525-day operation data of a large pilot-scale AnMBR for treating real municipal wastewater, regression prediction was realized using multilayer perceptron (MLP) and long short-term memory (LSTM) artificial neural networks under substantial variations in operating conditions. The models involved employing the organic loading rate, suspended solids concentration, protein concentration in extracellular polymeric substance (EPSp), polysaccharide concentration in EPS (EPSc), reactor temperature, and flux as input features, and transmembrane pressure as the prediction target output. Hyperparameter optimization enhanced the regression prediction accuracies, and the rationality and utility of the MLP model for predicting large-scale AnMBR membrane fouling were confirmed at global and local levels of interpretability analysis. This work not only provides a methodological advance but also underscores the importance of merging environmental engineering with computational advancements to address pressing environmental challenges.

Multi-Responsive Afterglows from Aqueous Processable Amorphous Polysaccharide Films.

Polymer-based room-temperature phosphorescence (RTP) materials, especially polysaccharide-based RTP materials, earn sustained attention in the fields of anti-counterfeiting, data encryption, and optoelectronics owing to their green regeneration, flexibility, and transparency. However, those with both ultralong phosphorescence lifetime and excitation wavelength-dependent afterglow are rarely reported. Herein, a kind of amorphous RTP material with ultralong lifetime of up to 2.52 s is fabricated by covalently bonding sodium alginate (SA) with arylboronic acid in the aqueous phase. The resulting polymer film exhibits distinguished RTP performance with excitation-dependent emissions from cyan to green. Specifically, by co-doping with other fluorescent dyes, further regulation of the afterglow color from cyan to yellowish-green and near-white can be achieved through triplet-to-singlet Förster resonance energy transfer. In addition, the water-sensitive properties of hydrogen bonds endow the RTP property of SA-based materials with water/heat-responsive characteristics. On account of the color-tunable and stimuli-responsive afterglows, these smart materials are successfully applied in data encryption and anti-counterfeiting.

Regulating Triplet Excitons of Organic Luminophores for Promoted Bioimaging.

Afterglow materials with organic room temperature phosphorescence (RTP) or thermally activated delayed fluorescence (TADF) exhibit significant potential in biological imaging due to their long lifetime. By utilizing time-resolved technology, interference from biological tissue fluorescence can be mitigated, enabling high signal-- to-background ratio imaging. Despite the continued emergence of individual reports on RTP or TADF in recent years, comprehensive reviews addressing these two materials are rare. Therefore, this review aims to provide a comprehensive overview of several typical molecular designs for organic RTP and TADF materials. It also explores the primary methods through which triplet excitons resist quenching by water and oxygen. Furthermore, we analyze the principal challenges faced by afterglow materials and discuss key directions for future research with the hope of inspiring developments in afterglow imaging.

Cardiovascular comorbidities and their prognostic value in small cell lung cancer patients with chemoradiotherapy.

BACKGROUND: Small cell lung cancer (SCLC) is an extremely malignant subtype of lung cancer because of its high potential for metastases. Cardiac invasion of SCLC is a serious concern that may lead to systemic embolism or tract obstruction. It has aroused much concern that cardiovascular comorbidities may significantly affect the survival of SCLC patients and their treatment decisions. METHODS: We consecutively recruited 772 small cell lung cancer (SCLC) patients between January 2011 and December 2018 from 4 cancer specialty hospitals in China. Only newly diagnosed primary cancer inpatients were included. Univariable and multivariable adjusted Cox proportional hazard models were conducted to evaluate the risk factors associated with mortality. Hazard ratios (HRs) for mortality and corresponding 95% confidence intervals (95% CIs) were calculated. RESULTS: The prevalence of cardiovascular diseases (CVDs) was 34.6% in all SCLC patients. Log-rank analysis presented statistically significant differences in median survival time (MST) between patients with CVD and without CVD in all SCLC patients (9.0 months vs. 15.0 months, P = 0.005) and patients with chemotherapy only (12.0 months vs. 18.0 months, P = 0.048). Pericardial effusion (HR 1.671, 95% CI 1.082-2.580, P = 0.021) and heart failure (HR 1.752, 95% CI 1.290-2.379, P < 0.001) were independent risk factors associated with mortality in all SCLC patients. VTE is related to poorer prognosis in patients with chemotherapy only (HR 5.558, 95% CI 1.335-23.135, P = 0.018) and chemoradiotherapy (HR 3.057, 95% CI 1.270-7.539, P = 0.013). CONCLUSIONS: Comprehensive management of CVD comorbidities is of vital importance for the long-term prognosis of SCLC patients.

Development and validation of a risk score nomogram model to predict the risk of 5-year all-cause mortality in diabetic patients with hypertension: A study based on NHANES data.

Background: The present study aimed to develop and validate a prediction nomogram model for 5-year all-cause mortality in diabetic patients with hypertension. Methods: Data were extracted from the National Health and Nutrition Examination Survey (NHANES). A total of 3291 diabetic patients with hypertension in the NHANES cycles for 1999-2014 were selected and randomly assigned at a ratio of 8:2 to the training cohort (n = 2633) and validation cohort (n = 658). Multivariable Cox regression was conducted to establish a visual nomogram model for predicting the risk of 5-year all-cause mortality. Receiver operating characteristic curves and C-indexes were used to evaluate the discriminant ability of the prediction nomogram model for all-cause mortality. Survival curves were created using the Kaplan-Meier method and compared by the log-rank test. Results: The nomogram model included eight independent predictors: age, sex, education status, marital status, smoking, serum albumin, blood urea nitrogen, and previous cardiovascular disease. The C-indexes for the model in the training and validation cohorts were 0.76 (95% confidence interval: 0.73-0.79, p < 0.001) and 0.75 (95% confidence interval: 0.69-0.81, p < 0.001), respectively. The calibration curves indicated that the model had satisfactory consistency in the two cohorts. The risk of all-cause mortality gradually increased as the tertiles of the nomogram model score increased (log-rank test, p < 0.001). Conclusion: The newly developed nomogram model, a readily useable and efficient tool to predict the risk of 5-year all-cause mortality in diabetic patients with hypertension, provides a novel risk stratification method for individualized intervention.

SpatialDM for rapid identification of spatially co-expressed ligand-receptor and revealing cell-cell communication patterns.

Cell-cell communication is a key aspect of dissecting the complex cellular microenvironment. Existing single-cell and spatial transcriptomics-based methods primarily focus on identifying cell-type pairs for a specific interaction, while less attention has been paid to the prioritisation of interaction features or the identification of interaction spots in the spatial context. Here, we introduce SpatialDM, a statistical model and toolbox leveraging a bivariant Moran's statistic to detect spatially co-expressed ligand and receptor pairs, their local interacting spots (single-spot resolution), and communication patterns. By deriving an analytical null distribution, this method is scalable to millions of spots and shows accurate and robust performance in various simulations. On multiple datasets including melanoma, Ventricular-Subventricular Zone, and intestine, SpatialDM reveals promising communication patterns and identifies differential interactions between conditions, hence enabling the discovery of context-specific cell cooperation and signalling.

Serum total bilirubin and one-year prognosis of patients with coronary artery disease and psoriasis.

To evaluate the potential predictive value of total bilirubin (TBIL) for one-year prognosis in patients with coronary artery disease (CAD) and psoriasis. 278 psoriasis patients who underwent coronary angiography and were diagnosed as CAD were recruited. Baseline TBIL was measured at admission. Patients were divided into three groups according to the third tertiles of TBIL. The coronary angiography showed that lower TBIL was associated with the severity of lesion calcification. After a mean follow-up of 315 days, major adverse cardiac and cerebrovascular events (MACCEs) were reported in 61 patients. Compared with patients with higher TBIL tertiles, the incidence of MACCEs increased significantly in patients with middle and lower TBIL tertiles. The incidence of MACCEs in one-year follow-up was significantly different between higher and lower tertiles. The findings indicate that decreased TBIL is a potential predictor of poor prognosis in patients with psoriasis and CAD.

The phosphorus harvest from low-temperature mainstream wastewater through iron phosphate crystallization in a pilot-scale partial nitritation/anammox reactor.

The phosphorus harvest along nitrogen removal in the partial nitritation/anammox (PNA) reactor is promising for saving space and simplifying the management of mainstream wastewater treatment facilities. In this study, the phosphorus recovery from the low-temperature mainstream wastewater was explored through iron phosphate crystallization in a pilot-scale PNA reactor. With the COD-alleviated municipal wastewater as the influent, the ammonium concentration of about 50 mg/L and the phosphorus concentration ranged from 5.4 to 7.1 mg/L, under the temperature of 15 °C and the addition of external ferrous iron of 14 mg/L, the achieved nitrogen removal efficiency and the phosphorus removal efficiency were 37.6 % and 62.7 %, respectively. The good settleability of sludge indicated that the formed iron phosphate was well combined with the biomass. The quantitative analysis confirmed that the main iron phosphate in dry sludge was graftonite, and qualitative analysis confirmed that the equivalent of P2O5 content in the sludge was 5.8 %, which was suitable as fertilizer on agricultural land to realize the direct recycle of discharged phosphorus. In all, this study proposed a pioneering scheme to realize the nitrogen removal and phosphorus cycle in human society and given a meaningful reference for further research and application.

Effects of Metabolic Syndrome on Cardiovascular Outcomes of Psoriatic Patients with Coronary Artery Disease: A Single Center Retrospective Cohort Study.

Background: Psoriasis is associated with an increased prevalence of cardiovascular risk factors, including metabolic syndrome (MetS). To date, it is unclear whether MetS causes differences in cardiovascular outcomes in psoriatic patients with coronary artery disease. Methods: We conducted a retrospective cohort study to determine the effects of MetS in psoriatic patients with coronary artery disease. Comparisons were made between patients with and without MetS. Cox regression analysis and Kaplan-Meier survival analysis were used to evaluate the association between variables. Results: Of the 307 psoriatic patients with coronary artery disease, 94 met criteria (30.6%) for MetS. Individuals with MetS were more likely to be female (p <0.001). Levels of platelet counts and high-sensitivity C-reactive protein were higher in the MetS group (p = 0.038 and 0.005, respectively). After a mean follow-up of 35.32 months, major adverse cardiovascular events (MACEs) and non-fatal myocardial infarction were more likely in the MetS than the non-MetS group (33.3% vs 20.6%, p = 0.02; 26.4% vs 15.7%, p = 0.032, respectively). Kaplan-Meier estimates showed the same trend. Cox regression analysis showed that MetS (hazard ratio 1.738; 95% confidence interval 1.045-2.891; p = 0.033) and left ventricular ejection fraction (hazard ratio 0.968; 95% confidence interval 0.945-0.991; p = 0.006) were associated with an increased risk of MACEs. Conclusion: In psoriatic patients with coronary artery disease, MetS independently predicted MACEs. In addition, left ventricular ejection fraction was negatively associated with an increased risk of MACEs. To reduce the cardiovascular disease risk, it is necessary to increase awareness of MetS in psoriatic patients with coronary artery disease.

Drug-eluting stent and drug-coated balloon for the treatment of de novo diffuse coronary artery disease lesions: A retrospective case series study.

BACKGROUND: The hybrid strategy of a combination of drug-eluting stent (DES) and drug-coated balloon (DCB) is promising for the treatment of de novo diffuse coronary artery disease (CAD). HYPOTHESIS: To investigate the efficacy and functional results of hybrid strategy. METHODS: This case series study included patients treated with a hybrid approach for de novo diffuse CAD between February 2017 and November 2021. Postprocedural quantitative flow ratio (QFR) was used to evaluate the functional results. The primary endpoint was procedural success rate. The secondary endpoints were major adverse cardiovascular events (MACE) including cardiac death, myocardial infarction (MI) (including peri-procedural MI), and target vessel revascularization. RESULTS: A total of 109 patients with 114 lesions were treated. DES and DCB were commonly used in larger proximal segments and smaller distal segments, respectively. The mean QFR value was 0.9 ± 0.1 and 105 patients (96.3%) had values >0.8 in all the treated vessels. Procedural success was achieved in 106 (97.2%) patients. No cases of cardiac death were reported at a median follow-up of 19 months. Spontaneous MI occurred in three (2.8%) patients and target vessel revascularization in six (5.5%) patients. Estimated 2-year rate of MACE excluding peri-procedural MI was higher in the group with lower QFR value (12.1 ± 5.7% vs. 5.6 ± 4.4%, log-rank p = .035) (cut-off value 0.9). CONCLUSION: Hybrid strategy is a promising approach for the treatment of de novo diffuse CAD. Postprocedural QFR has some implications for prognosis and may be helpful in guiding this approach.

Comparison of Recurrent With First-Time In-Stent Restenosis.

Recurrent in-stent restenosis (Re-ISR) remains a therapeutic challenge. We aimed to investigate the clinical characteristics, treatment, and long-term outcomes in patients with Re-ISR compared with those with first-time ISR (First-ISR). This retrospective study consecutively enrolled patients who underwent percutaneous coronary intervention (PCI) for ISR in Fuwai Hospital between January 2017 and December 2018. Re-ISR was defined as a second event of ISR after a previous successful treatment of the ISR lesion. The primary outcome was defined as a composite of all-cause death, spontaneous myocardial infarction, and repeat revascularization. A total of 2,006 patients (2,154 lesions) with ISR underwent successful PCI were enrolled and categorized into 2 groups: the Re-ISR group (246 patients/259 lesions) and the First-ISR group (1,760 patients/1,895 lesions). During a mean follow-up of 36 months, the primary outcomes occurred in 80 patients (32.5%) in the Re-ISR group and 349 patients (19.3%) in the First-ISR group (p <0.001 by log-rank test), major driven by spontaneous myocardial infarction (4.9% vs 2.7%, p = 0.049) and repeat revascularization (30.1% vs 16.5%, p <0.001). The multivariable Cox regression analysis revealed that Re-ISR was independently associated with a higher rate of major adverse cardiovascular events (adjusted hazard ratio 1.88, 95% confidence interval 1.39 to 2.53, p <0.001) and repeated revascularization (adjusted hazard ratio 2.09, 95% confidence interval 1.53 to 2.84, p <0.001). The relation remained consistent after the propensity score analysis. In conclusion, in the present cohort of patients who underwent PCI for ISR, Re-ISR was significantly associated with a higher risk of long-term outcomes than First-ISR.

Association between lipoprotein(a) and long-term outcomes after percutaneous coronary intervention for lesions with in-stent restenosis.

OBJECTIVES: This study aimed to evaluate the association between increased lipoprotein (a) [Lp(a)] and long-term outcomes in patients undergoing percutaneous coronary intervention (PCI) for in-stent restenosis (ISR). BACKGROUND: Elevated Lp(a) is demonstrated to be associated with recurrent ischemic events after PCI. However, the impact of Lp(a) in patients with ISR remains undetermined. METHODS: Between January 2017 and December 2018, a total of 2086 patients who underwent PCI for ISR were consecutively enrolled. Patients were categorized as elevated group (> 30 mg/dL, n=834) and non-elevated group (≤ 30 mg/dL, n=1252) according to baseline Lp(a) levels. The primary outcome was the rate of major adverse cardiac events (MACE), defined as a composite endpoint of all-cause death, spontaneous myocardial infarction (MI), or repeat revascularization. RESULTS: During a median follow-up of 36 months, the primary outcome occurred in 202 of 1252 patients (26.7%) in the elevated Lp(a) group and 237 of 834 patients (21.8%) in the non-elevated Lp(a) group (adjusted hazard ratio: 1.31; 95% confidence interval: 1.08-1.58; P = 0.007), driven by higher rate of all-cause death (4.1% vs. 2.5%, P = 0.002 by Log-rank test; aHR: 1.77; 95% CI: 1.07-2.94; P = 0.03) and repeat revascularization (22.3% vs. 19.5%, P = 0.04 by Log-rank test; aHR: 1.18; 95% CI: 0.94-1.49; P = 0.16). Adding continuous or categorical Lp(a) to the Cox model led to a significant improvement in C-statistic, net reclassification, and integrated discrimination. The results were consistent across subgroups. CONCLUSIONS: In the current cohort of patients who underwent PCI for ISR, elevated Lp(a) at baseline is associated with higher risk of long-term MACE.

Atorvastatin accelerates both neointimal coverage and re-endothelialization after sirolimus-eluting stent implantation in a porcine model: new findings from optical coherence tomography and pathology.

BACKGROUND: Delayed vessel healing after drug-eluting stent implantation is thought to be the underlying mechanisms of late stent thrombosis (LST). METHODS AND RESULTS: In the animal model of stenting, 45 minipigs were divided into 3 groups (n=15 each): bare metal stent (BMS), sirolimus-eluting stent (SES), and SES plus atorvastatin treatment (SES+ator). Neointimal coverage and endothelium coverage were evaluated separately by optical coherence tomography (OCT), pathology, and scanning electron microscopy (SEM) at days 7, 14 and 28. OCT showed that SES significantly delayed neointimal coverage compared with BMS and the percentage of uncovered struts in the SES+ator group was significantly decreased on days 7 (42.7±1.3% vs. 56.8±5.7%, P<0.01) and 14 (24.8±4.3% vs. 45.3±2.8%, P<0.01) compared with the SES group. However, re-endothelialization was even more seriously delayed than neointima formation after SES deployment (P<0.05). Pathology and SEM revealed improved re-endothelialization of the neointima with atorvastatin therapy in terms of more struts covered by endothelium, less platelet adhesion, and higher endothelial nitric oxide synthase expression of the endothelial cells in the SES+ator group. Flow cytometry illustrated that the SES+ator group had more mobilized endothelial progenitor cells (EPCs) compared with the SES group at day 7 (0.21±0.02% vs. 0.11±0.03%, P=0.022). CONCLUSIONS: Atorvastatin pretreatment can accelerate both neointimal coverage and re-endothelialization after SES implantation, which may be mediated by the mobilization of EPC and enhancement of the endothelial function of the neointima.

[Ischemic preconditioning attenuates myocardial no-reflow and reperfusion injury after revascularization of acute myocardial infarction by reducing myocardial edema via the protein kinase A pathway].

OBJECTIVE: Myocardial edema plays an important role in the development of myocardial no-reflow and reperfusion injury after the revascularization of acute myocardial infarction (AMI). The present study investigated whether the effect of ischemic preconditioning (IPC) against myocardial no-reflow and reperfusion injury was related to the reduction of myocardial edema through the protein kinase A (PKA) pathway. METHODS: Twenty-four minipigs were randomized into sham, AMI, IPC, and IPC + H-89 (PKA inhibitor, 1.0 µg · kg(-1) · min(-1)) groups. The area of no-reflow (ANR), area of necrosis (AN), and water content in left ventricle and ischemic-myocardium and non-ischemic area were determined by pathological studies. Microvascular permeability was determined by FITC-labeled dextran staining. Cardiomyocyte cross-sectional area (CSA) and mitochondria cross-sectional area (MSA) were evaluated by histological analysis. Myocardial expression of aquaporins (AQPs) was detected by Western blot. RESULTS: Compared with the MI group, the sizes of no-reflow and infarct were reduced by 31.9% and 46.6% in the IPC group (all P < 0.01), water content was decreased by 5.7% and 4.6% in the reflow and no-reflow myocardium of the IPC group (all P < 0.05), microvascular permeability and cardiomyocytes swelling in the reflow area were inhibited by 29.8% and 21.3% in the IPC group (all P < 0.01), mitochondrial water accumulation in the reflow and no-reflow areas of the IPC group were suppressed by 45.5% and 34.8% respectively (all P < 0.01), and the expression of aquaporin-4, -8, and -9 in the reflow and no-reflow myocardium were blocked in the IPC group. However, these beneficial effects of IPC were partially abolished in the IPC + H-89 group. CONCLUSIONS: The cardioprotective effects of IPC against no-reflow and reperfusion injury is partly related to the reduction of myocardial edema by inhibition of microvascular permeability and aquaporins up-regulation via PKA pathway.

[Evaluation of very early neointimal coverage post drug-eluting stent implantation using optical coherence tomography].

OBJECTIVE: To investigate the neointimal coverage at the very early phase after drug-eluting stent (DES) implantation using optical coherence tomography (OCT). METHODS: OCT examination was performed immediately after stent deployment and about one week post stenting in 12 patients with coronary artery disease to detect neointimal coverage and stent thrombus. Sirolimus eluting stent implantation was also performed in 5 healthy Chinese minipigs, OCT and histopathology examination were made one week later in these minipigs. RESULTS: (1) Twenty-nine DES were implanted in 12 patients. There was no major cardiovascular event post stenting. The mean time of follow-up was (7.7 ± 2.6) d, the mean percentage of stent coverage was (21.8 ± 17.7)%, and neointimal hyperplasia thickness was (42.9 ± 32.2) µm and the percentage of malapposition struts was (1.5 ± 3.0)%, respectively. Mural stent thrombus was found in 2 of the 12 patients (the percentage is 16.7%). (2) In the minipigs model, OCT evidenced that (43.2 ± 11.5)% struts were covered by neointima with a mean neointimal hyperplasia thickness of (24.0 ± 8.5) µm at one week. Histopathology examination illustrated that the neointima was mainly consisted of proteoglycan, inflammation cells, fibrin and organized thrombus at the very early phase after DES implantation, while endothelial cells were barely found on the neointima. CONCLUSIONS: Neointimal coverage is found as early as one week after DES implantation by OCT. The covered struts rate is very low and the main components of neointima are proteoglycan, inflammation cells, fibrin and organized thrombus. Re-endothelialization is rather poor at the very early phase post DES implantation.

Improvement of aquaculture water quality by mixed Bacillus and its effects on microbial community structure.

Microbial remediation, especially the application of probiotics, has recently gained popularity in improving water quality and maintaining aquatic animal health. The efficacy and mechanism of mixed Bacillus for improvement of water quality and its effects on aquatic microbial community structure remain unknown. To elucidate these issues, we applied two groups of mixed Bacillus (Bacillus megaterium and Bacillus subtilis (A0 + BS) and Bacillus megaterium and Bacillus coagulans (A0 + BC)) to the aquaculture system of Crucian carp. Our results showed that the improvement effect of mixed Bacillus A0 + BS on water quality was better than that of A0 + BC, and the NH4+-N, NO2--N, NO3--N, and total phosphorus (TP) concentrations were reduced by 46.3%, 76.3%, 35.6%, and 80.3%, respectively. In addition, both groups of mixed Bacillus increased the diversity of the bacterial community and decreased the diversity of the fungal community. Microbial community analysis showed that mixed Bacillus A0 + BS increased the relative abundance of bacteria related with nitrogen and phosphorus removal, such as Proteobacteria, Actinobacteria, Comamonas, and Stenotrophomonas, but decreased the relative abundance of pathogenic bacteria (Acinetobacter and Pseudomonas) and fungi (Epicoccum and Fusarium). Redundancy analysis showed that NH4+-N, NO2--N, and TP were the primary environmental factors affecting the microbial community in aquaculture water. PICRUST analysis indicated that all functional pathways in the A0 + BS group were richer than those in other groups. These results indicated that mixed Bacillus A0 + BS addition produced good results in reducing nitrogenous and phosphorus compounds and shaped a favorable microbial community structure to further improve water quality.