Metabolome and Transcriptome Reveal Chlorophyll, Carotenoid, and Anthocyanin Jointly Regulate the Color Formation of Triadica sebifera.

The Chinese tallow tree (Triadica sebifera) is an economically important plant on account of its ornamental value and oil-producing seeds. Leaf colour is a key characteristic of T. sebifera, with yellow-, red- and purple-leaved varieties providing visually impressive displays during autumn. In this study, we performed metabolomic and transcriptomic analyses to gain a better understanding of the mechanisms underlying leaf colour development in purple-leaved T. sebifera at three stages during the autumnal colour transition, namely, green, hemi-purple, and purple leaves. We accordingly detected 370 flavonoid metabolites and 10 anthocyanins, among the latter of which, cyanidin-3-xyloside and peonidin-3-O-glucoside were identified as the predominant compounds in hemi-purple and purple leaves. Transcriptomic analysis revealed that structural genes associated with the anthocyanin biosynthetic pathway, chlorophyll synthesis pathway and carotenoid synthesis pathway were significantly differential expressed at the three assessed colour stages. Additionally, transcription factors associated with the MYB-bHLH-WD40 complex, including 22 R2R3-MYBs, 79 bHLHs and 44 WD40 genes, were identified as candidate regulators of the anthocyanin biosynthetic pathway. Moreover, on the basis of the identified differentially accumulated anthocyanins and key genes, we generated genetic and metabolic regulatory networks for anthocyanin biosynthesis in T. sebifera. These findings provide comprehensive information on the leaf transcriptome and three pigments of T. sebifera, thereby shedding new light on the mechanisms underlying the autumnal colouring of the leaves of this tree.

A novel single domain bispecific antibody targeting VEGF and TNF-α ameliorates rheumatoid arthritis.

Anti-TNF-α therapy fails in 30% of patients, where TNF-α may not be the key causative factor in these patients. We developed a bispecific single-domain antibody block TNF-α and VEGF (V5-3).The experiments showed that V5-3 effectively activated proliferation and migration of RA-FLS and HUVEC, tube-forming role of HUVEC, and expression of inflammatory factors in vitro. Besides, the experiments indicated that the anti-RA activity of V5-3 was superior to Anbainuo in vivo. Application of V5-3 reduced the expression of inflammatory factors, extent of synovial inflammation and angiogenesis and attenuated the severity of autoimmune arthritis in collagen-induced arthritis (CIA) mice. Mechanistically, V5-3 suppressed p65, AKT and VEGFR2 phosphorylation, as well as production of TNF-α and VEGF in joint tissues. These results demonstrated that V5-3 displayed a superior effect of anti-RA, may be a new therapy to overcome the limitations of anti-TNF-α monoclonal antibody.

Cavity-Enhanced Raman Spectroscopy for Detection of Trace Gaseous Impurities in Hydrogen for Fuel Cells.

Gaseous impurities contained in hydrogen (H2) profoundly affect the performance of hydrogen proton-exchange membrane fuel cells. We demonstrate the utility of cavity-enhanced Raman spectroscopy as a unique approach for detection of gaseous impurities. A dense-pattern multipass cavity which is composed of four spherical mirrors placed in a Z-shaped configuration is used to enhance the Raman signal by extending the laser-gas interaction length. A total of 85 spots are identified on the 2-inch-diameter front (or rear) mirror, which indicates that 510 beams exist in the cavity. Detection limits of the impurity gases, including oxygen (O2), nitrogen (N2), carbon monoxide (CO), carbon dioxide (CO2), methane (CH4), ammonia (NH3), and hydrogen sulfide (H2S), reach sub-ppm- and ppb-levels at a total pressure of 0.1 and 2.5 MPa, respectively. This satisfies the detection requirements according to the maximum allowable concentration for these gases. Our cavity-enhanced Raman spectroscopy (CERS) apparatus can simultaneously measure multiple gases with high sensitivity and selectivity with no sample destruction. It has excellent application prospects in gaseous impurity analysis for the quality assessment of gaseous energy.

[Pyridine degradation characteristics of Rhodococcus sp. LV4 under high salinity conditions].

Biodegradation of pyridine pollutant by microorganisms is one of the economical and effective methods to solve the environmental pollution of pyridine under high salinity conditions. To this end, screening of microorganisms with pyridine degradation capability and high salinity tolerance is an important prerequisite. In this paper, a salt-resistant pyridine degradation bacterium was isolated from the activated sludge of Shanxi coking wastewater treatment plant, and identified as a bacterium belonging to Rhodococcus on the basis of colony morphology and 16S rDNA gene phylogenetic analysis. Salt tolerance experiment showed that strain LV4 could grow and degrade pyridine with the initial concentration of 500 mg/L completely in 0%-6% saline environment. However, when the salinity was higher than 4%, strain LV4 grew slowly and the degradation time of pyridine by strain LV4 was significantly prolonged. Scanning electron microscopy showed that the cell division of strain LV4 became slower, and more granular extracellular polymeric substance (EPS) was induced to secrete in high salinity environment. When the salinity was not higher than 4%, strain LV4 responded to the high salinity environment mainly through increasing the protein content in EPS. The optimum conditions for pyridine degradation by strain LV4 at 4% salinity were 30 ℃, pH 7.0 and 120 r/min (DO 10.30 mg/L). Under these optimal conditions, strain LV4 could completely degrade pyridine with an initial concentration of 500 mg/L at a maximum rate of (29.10±0.18) mg/(L·h) after 12 h adaptation period, and the total organic carbon (TOC) removal efficiency reached 88.36%, indicating that stain LV4 has a good mineralization effect on pyridine. By analyzing the intermediate products in pyridine degradation process, it was speculated that strain LV4 achieved pyridine ring opening and degradation mainly through two metabolic pathways: pyridine-ring hydroxylation and pyridine-ring hydrogenation. The rapid degradation of pyridine by strain LV4 in high salinity environment indicates its application potential in the pollution control of high salinity pyridine environment.

Association of spironolactone treatment and arterial stiffness and cardiovascular disease in hypertensive patients.

Introduction: The aim of the current study was to evaluate the association of spironolactone and arterial stiffness and composite cardiovascular disease (CVD, including coronary heart disease, congestive heart failure and ischemic stroke) in hypertensive patients. Material and methods: Baseline data were collected and arterial stiffness was presented by carotid-femoral pulse wave velocity (cf-PWV) using applanation tonometry. Serum levels of fasting plasma glucose, total cholesterol, C-reactive protein and creatinine were measured using an automatic biochemistry analyzer. Plasma aldosterone concentration and plasma renin activity were determined by radioimmunoassay. The associations of spironolactone and arterial stiffness and composite CVD were evaluated. Results: Compared to patients without spironolactone (n = 274), those with spironolactone (n = 170) were older and more likely to have diabetes and chronic heart failure. No differences in antihypertensive medications used were observed except for spironolactone. Mean number of antihypertensive medications used was significantly higher in the spironolactone group (2.6 ±0.8 vs. 2.2 ±0.6). Compared to patients without spironolactone, those with spironolactone had significantly lower cf-PWV (9.4 ±1.8 vs. 10.1 ±2.2 m/s). After adjustment for covariates, spironolactone was still associated with 10% lower risk of arterial stiffness, with a 95% confidence interval (CI) of 0.85-0.97. In patients without arterial stiffness, after adjustment for covariates, no significant association of spironolactone and composite CVD was observed. However, in patients with increased arterial stiffness, after adjustment for covariates, spironolactone was still independently associated with 11% lower risk of composite CVD (95% CI: 0.83-0.97). Conclusions: Spironolactone treatment is independently associated with lower cf-PWV and lower prevalence of composite CVD in patients with increased arterial stiffness.

Dense-pattern multi-pass cavity based on spherical mirrors in a Z-shaped configuration for Raman gas sensing.

We report a dense-pattern multi-pass cavity (MPC) based on four spherical mirrors placed in a Z-shaped cavity configuration for improving the Raman signals from gases. The folding structure of the cavity causes dense patterns of spots, and at least 420 beams are reflected in the cavity. Raman spectra of ambient air, methane, and ethylene are recorded to demonstrate the performance of our apparatus. At atmospheric pressure, ppm-level detection limits of the gases are achieved with 10 s of exposure time. The Raman signal intensities of the gases show excellent linearity with the gases' partial pressures, which means that high-accuracy detection is also feasible.

Adsorption desulfurization performance of PdO/SiO2@graphene oxide hybrid aerogel: Influence of graphene oxide.

Preparation of PdO/SiO2@graphene oxide (GO) hybrid aerogels were carried out sol-gel method combined with atmospheric drying technology to study their adsorption performance for thiophenics and compared with PdO/SiO2. Scanning electron microscope (SEM), N2 adsorption-desorption isotherms, X-ray diffraction (XRD) analysis, X-ray photoelectron spectroscopy (XPS), and fourier transformation infrared spectroscopy (FT-IR) for samples were performed. The adsorption performance of PdO/SiO2@GO for thiophene were better than that of PdO/SiO2, attributed to that incorporation of GO increased the specific surface area and the Pd incorporation rate, where Pd2+ ions acted as the π-complexation and sulfur-metal (SM) bond adsorption active centers, as well as GO adsorbed thiophene by the π-π stacking effect. The adsorption capacities of PdO/SiO2@GO-1.0 for thiophene (TH), benzothiophene (BT) and dibenzothiophene (DBT) were 8.89, 9.3 and 12.6 mg-S/gads, respectively. The addition of GO in aerogels could improve the inhibition effect of toluene, cyclohexene and pyridine while decreased the inhibition effect of MTBE and H2O for the adsorption of thiophene, due to the π-π stacking effect and the hydrophobicity of GO, respectively. The adsorption process was spontaneous and exothermic, be well fitted by the apparent second-order kinetic model and dominated by chemical interaction. Pd/SiO2@GO-1.0 had a good solvent elution regeneration performance.

Trimethylamine N-oxide is associated with coronary atherosclerotic burden in non-ST-segment myocardial infarction patients: SZ-NSTEMI prospective cohort study.

Trimethylamine N-oxide (TMAO) is reported to accelerate atherosclerosis and the development of adverse cardiac outcomes. Relationship between coronary atherosclerotic burden and TMAO has been examined in stable coronary artery disease and ST-segment elevation myocardial infarction, but not in non-ST-segment elevation myocardial infarction (NSTEMI). We examined the association between TMAO and coronary atherosclerotic burden in NSTEMI. In this prospective cohort study, two groups including NSTEMI (n = 73) and age-sex matched Healthy (n = 35) individuals were enrolled between 2019 and 2020. Coronary atherosclerotic burden was stratified based on the number of diseased coronary vessels and clinical risk scores including SYNTAX and GENSINI. Fasting plasma TMAO was measured by isotope dilution high-performance liquid chromatography. The median plasma TMAO levels were significantly higher in the NSTEMI group than in the Healthy group, respectively (0.59 µM; interquartile range [IQR]: 0.43-0.78 versus 0.42 µM; IQR: 0.33-0.64; P = 0.006). Within the NSTEMI group, higher TMAO levels were observed in the multivessel disease (MVD) versus single vessel disease (P = 0.002), and intermediate-high risk (score ≥ 23) versus low risk (score < 23) of SYNTAX (P = 0.003) and GENSINI (P = 0.005). TMAO level remained an independent predictor of MVD (odds ratio [OR]: 5.94, P = 0.005), intermediate-high risk SYNTAX (OR: 3.61, P = 0.013) and GENSINI scores (OR: 4.60, P = 0.008) following adjustment for traditional risk factors. Receiver operating characteristic curve (AUC) analysis for TMAO predicted MVD (AUC: 0.73, 95% confidence interval [Cl]: 0.60-0.86, P = 0.002), intermediate-high SYNTAX score (AUC: 0.70, 95% Cl: 0.58-0.82, P = 0.003) and GENSINI score (AUC: 0.70, 95% Cl: 0.57-0.83, P = 0.005). In all, TMAO levels are independently associated with high coronary atherosclerotic burden in NSTEMI.

Activation of the CaR-CSE/H2S pathway confers cardioprotection against ischemia-reperfusion injury.

Ischemia-reperfusion (I/R) injury is a multifactorial process triggered when an organ is subjected to transiently reduced blood supply. The result is a cascade of pathological complications and organ damage due to the production of reactive oxygen species following reperfusion. The present study aims to evaluate the role of activated calcium-sensing receptor (CaR)-cystathionine γ-lyase (CSE)/hydrogen sulfide (H2S) pathway in I/R injury. Firstly, an I/R rat model with CSE knockout was constructed. Transthoracic echocardiography, TTC and HE staining were performed to determine the cardiac function of rats following I/R Injury, followed by TUNEL staining observation on apoptosis. Besides, with the attempt to better elucidate how CaR-CSE/H2S affects I/R, in-vitro culture of human coronary artery endothelial cells (HCAECs) was conducted with gadolinium chloride (GdCl3, a CaR agonist), H2O2, siRNA against CSE (siCSE), or W7 (a CaM inhibitor). The interaction between CSE and CaM was subsequently detected. Plasma oxidative stress indexes, H2S and CSE, and apoptosis-related proteins were all analyzed following cell apoptosis. We found that H2S elevation led to the improvement whereas CSE knockdown decreased cardiac function in rats with I/R injury. Moreover, oxidative stress injury in I/R rats with CSE knockout was aggravated, while the increased expression of H2S and CSE in the aortic tissues resulted in alleviated the oxidative stress injury. Moreover, increased H2S and CSE levels were found to inhibit cell apoptotic ability in the aortic tissues after I/R injury, thus attenuating oxidative stress injury, accompanied by inhibited expression of apoptosis-related proteins. In HCAECs following oxidative stress treatment, siCSE and CaM inhibitor were observed to reverse the protection of CaR agonist. Coimmunoprecipitation assay revealed the interaction between CSE and CaM. Taken together, all above-mentioned data provides evidence that activation of the CaR-CSE/H2S pathway may confer a potent protective effect in cardiac I/R injury.

Association of trimethylamine N-oxide with coronary atherosclerotic burden in patients with non-ST-segment elevation myocardial infarction.

BACKGROUND: Recently, trimethylamine N-oxide (TMAO) unexplained gut microbe has been proposed as a promising risk factor for atherosclerotic cardiovascular disease (CVD) pathogenesis and adverse events. The relationship of TMAO with coronary atherosclerotic burden has been evaluated in patients with stable coronary artery disease and ST-segment elevation myocardial infarction, but still needs to be explored in newly diagnosed non-ST-segment elevation myocardial infarction (NSTEMI) patients. MATERIAL AND METHODS: A prospective, single-center, SZ-NSTEMI trial (ChiCTR1900022366) is underway to investigate the relationship of TMAO with the severity and prognosis of coronary atherosclerosis in newly diagnosed NSTEMI patients who will undergo coronary angiography with primary percutaneous coronary intervention (pPCI). The primary endpoint of the study will be assessed the association of TMAO with coronary atherosclerotic severity quantify by the number of diseased coronary arteries and SYNTAX score after the coronary angiography. The secondary endpoints will be identified the TMAO as a prognostic biomarker for the short (1 month) and long-term (12 months) major cardiovascular and cerebrovascular events (MACCEs) rate including myocardial infarction, target vessel revascularization, stroke, heart failure, all-cause rehospitalization, and all-cause mortality after the pPCI. The blood samples will be collected from each patient before the procedure to measure the TMAO by isotope dilution high-performance liquid chromatography. In conclusion, SZ-NSTEMI will be the first cohort that will be investigated the association of TMAO with the severity and prognosis of coronary atherosclerotic burden in NSTEMI patients, aiming to identify TMAO as a predictor and a prognostic biomarker.

Association of anti-hyperuricemia treatment and prevalent cardiovascular disease in hypertensive patients.

INTRODUCTION: The current study aimed to evaluate the association of anti-hyperuricemia treatment and prevalent cardiovascular disease (CVD) in hypertensive patients. MATERIAL AND METHODS: Primary hypertensive patients with hyperuricemia were enrolled. All participants were separated into two groups: anti-hyperuricemia and control groups (without anti-hyperuricemia treatment). Comparisons of prevalent CVD including coronary heart disease, ischemic stroke and heart failure were made and the associations of anti-hyperuricemia treatment and prevalent CVD were analyzed. RESULTS: Compared to the anti-hyperuricemia group, patients in the control group had significantly higher serum C-reactive protein (10.6 ±2.8 vs. 7.4 ±1.2 mg/dl) and uric acid (UA) levels (438 ±33 vs. 379 ±64 µmol/l), and were more likely to receive ß-blockers (34.2% vs. 31.1%) and calcium channel blockers (49.2% vs. 43.4%). The prevalence of ischemic stroke was higher in the control group (15.8% vs. 11.3%). Compared to other groups, blood pressure was significantly higher in patients in the 4th quartile serum UA level group. In the unadjusted model, anti-hyperuricemia treatment was significantly associated with a reduced odds ratio (OR) of composite CVD. After adjusting for potential covariates, OR of anti-hyperuricemia treatment for composite CVD was 0.89 with a 95% confidence interval (IC) of 0.82-0.98. Associations of anti-hyperuricemia treatment and ischemic stroke were also significant with OR = 0.93 and 95% CI: 0.88-0.99, while associations of anti-hyperuricemia with coronary heart disease and heart failure attenuated into insignificance after adjusting for covariates. CONCLUSIONS: In hypertensive patients with hyperuricemia, anti-hyperuricemia treatment was associated with lower odds of prevalent CVD.

Improved separated-parameter calibration method for binocular vision measurements with a large field of view.

Large field-of-view (FOV) calibration is indispensable to ensure the accuracy of vision measurement systems for large aviation components. We propose an improved separated-parameter calibration method for large-FOV binocular vision measurements with a high flexibility and accuracy. Firstly, the camera parameters are separately calibrated according to the sub-area features of image. Subsequently, based on the spatial-calibration accuracy, a stereoscopic calibration object is devised. The mean error of the proposed method is experimentally obtained as 0.13 mm for a FOV of 2.0 m × 1.5 m. Its feasibility and effectiveness for the measurement in the field is validated by workshop calibration.

Folate-conjugated nanobubbles selectively target and kill cancer cells via ultrasound-triggered intracellular explosion.

With the rapid development of cancer-targeted nanotechnology, a variety of nanoparticle-based drug delivery systems have clinically been employed in cancer therapy. However, multidrug resistance significantly impacts the therapeutic efficacy. Physical non-drug therapy has emerged as a new and promising strategy. This study aimed to determine whether novel folate-nanobubbles (F-NBs), combined with therapeutic ultrasound (US), could act as a safe and effective physical targeted cancer therapy. Using folate-conjugated N-palmitoyl chitosan (F-PLCS), we developed novel F-NBs and characterised their physicochemical properties, internalization mechanism, targeting ability, therapeutic effects, and killing mechanism. The results showed that the novel F-NBs selectively accumulated in FR-positive endothelial cells and tumour cells via FR coupled with clathrin- and caveolin-mediated endocytosis in vitro and in vivo. In addition, the F-NBs killed target cells by an intracellular explosion under US irradiation. Hoechst/PI staining demonstrated that apoptosis and necrosis accounted for a large proportion of cell death in vivo. F-NBs combined with US therapy significantly inhibited tumour growth and improved the overall survival of tumour-bearing mice. Under US irradiation, the novel F-NBs selectively killed FR-positive tumour cells in vitro and in vivo via intracellular explosion and therefore is a promising alternative for targeted cancer treatment.

Diagnostic Ultrasound and Microbubbles Treatment Improves Outcomes of Coronary No-Reflow in Canine Models by Sonothrombolysis.

OBJECTIVES: Effective treatment for microvascular thrombosis-induced coronary no-reflow remains an unmet clinical need. This study sought to evaluate whether diagnostic ultrasound and microbubbles treatment could improve outcomes of coronary no-reflow by dissolving platelet- and erythrocyte-rich microthrombi. DESIGN: Randomized controlled laboratory investigation. SETTING: Research laboratory. SUBJECTS: Mongrel dogs. INTERVENTIONS: Coronary no-reflow models induced by platelet- or erythrocyte-rich microthrombi were established and randomly assigned to control, ultrasound, recombinant tissue-type plasminogen activator, ultrasound + microbubbles, or ultrasound + microbubbles + recombinant tissue-type plasminogen activator group. All treatments lasted for 30 minutes. MEASUREMENTS AND MAIN RESULTS: Percentage of microemboli-obstructed coronary arterioles was lower in ultrasound + microbubbles group than that in control group for platelet- (> 50% obstruction: 10.20% ± 3.56% vs 31.80% ± 3.96%; < 50% obstruction: 14.80% ± 4.15% vs 28.20% ± 3.56%) and erythrocyte-rich microthrombi (> 50% obstruction: 8.20% ± 3.11% vs 30.60% ± 4.83%; < 50% obstruction: 12.80% ± 4.15% vs 25.80% ± 3.70%) (p < 0.001). Percentage change of myocardial blood flow in left anterior descending artery-dominated region, left ventricular ejection fraction, fractional shortening, and ST-segment resolution were higher, whereas infarcted area, troponin I, and creatine kinase MB isoenzyme were lower in ultrasound + microbubbles group than that in control group for both types of microthrombi (p < 0.001). Percentage change of myocardial blood flow, ejection fraction, fractional shortening, and ST-segment resolution were higher, whereas infarcted area, troponin I, and creatine kinase MB isoenzyme were lower in ultrasound + microbubbles and ultrasound + microbubbles + recombinant tissue-type plasminogen activator groups than that in recombinant tissue-type plasminogen activator group for platelet-rich microthrombi (p < 0.05). CONCLUSIONS: Ultrasound + microbubbles treatment could dissolve platelet- and erythrocyte-rich microthrombi, thereby improving outcomes of coronary no-reflow, making it a promising supplement to current reperfusion therapy for acute ST-segment elevation myocardial infarction.

Microbubble-Mediated Sonothrombolysis Improves Outcome After Thrombotic Microembolism-Induced Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Microthrombi originating from disintegrated clots or formed in situ may account for the poor clinical improvement of acute ischemic stroke after recanalization therapy. We attempted to determine whether microbubble-mediated sonothrombolysis could dissolve platelet-rich and erythrocyte-rich microthrombi, thereby reducing their brain injury-causing potential. METHODS: Platelet- and erythrocyte-rich microthrombosis were induced by periadventitial application of 5% ferric chloride or thrombin to mesenteric microvessels in 75 Sprague-Dawley rats. Acute ischemic stroke was induced by intracarotid injection of platelet- or erythrocyte-rich microthrombi in another 50 rats. Rats were randomly divided into control (CON), ultrasound (US), ultrasound and microbubble (US+MB), recombinant tissue-type plasminogen activator (r-tPA), and US+MB+r-tPA groups. The post-treatment mesenteric microvessel recanalization rates, cerebral infarct volumes, and neurological scores were determined. RESULTS: The recanalization rates of platelet- and erythrocyte-rich microthrombi in mesenteric microvessels were higher (P<0.05), and the cerebral infarct volumes and neurological scores of rats with either microthrombi were lower in the US+MB group than in the CON group (P<0.01). The infarct volumes and neurological scores were greater in the r-tPA group than in the US+MB and US+MB+r-tPA groups after treatment of rats with platelet-rich microthrombi (P<0.05). In contrast, after treatment of rats with erythrocyte-rich microthrombi, the infarct volumes and neurological scores were similar in the r-tPA and US+MB groups, but smaller in the US+MB+r-tPA group (P<0.05). CONCLUSIONS: Microbubble-mediated sonothrombolysis improved the outcomes of microthrombi-induced acute ischemic stroke. Thus, this method may serve as an attractive adjunct to recanalization therapy for acute ischemic stroke.

Selective depletion of tumor neovasculature by microbubble destruction with appropriate ultrasound pressure.

Low-intensity ultrasound-microbubble (LIUS-MB) treatment is a promising antivascular therapy for tumors. We sought to determine whether LIUS-MB treatment with an appropriate ultrasound pressure could achieve substantial and persistent cessation of tumor perfusion without having significant effects on normal tissue. Further, we investigated the mechanisms underlying this treatment. Murine S-180 sarcomas, thigh muscles, and skin tissue from 60 tumor-bearing mice were subjected to sham therapy, an ultrasound application combined with microbubbles in four different ultrasound pressures (0.5, 1.5, 3.0, 5.0 MPa), or ultrasound at 5.0 MPa alone. Subsequently, contrast-enhanced ultrasonic imaging and histological studies were performed. Tumor microvessels, tumor cell necrosis, apoptosis, tumor growth, and survival were evaluated in 85 mice after treatment with the selected ultrasound pressure. We found that twenty-four hours after LIUS-MB treatment at 3.0 MPa, blood perfusion and microvessel density of the tumor had substantially decreased by 84 ± 8% and 84%, respectively (p < 0.01). Similar reductions were not observed in the muscle or skin. Additionally, an extreme reduction in the number of immature vessels was observed in the tumor (reduced by 90%, p < 0.01), while the decrease in mature vessels was not significant. Further, LIUS-MB treatment at 3.0 MPa promoted tumor cell necrosis and apoptosis, delayed tumor growth, and increased the survival rate of tumor-bearing mice (p < 0.01). These findings indicate that LIUS-MB treatment with an appropriate ultrasound pressure could selectively and persistently reduce tumor perfusion by depleting the neovasculature. Therefore, LIUS-MB treatment offers great promise for clinical applications in antivascular therapy for solid tumors.

Pharmacological modulation of autophagy to protect cardiomyocytes according to the time windows of ischaemia/reperfusion.

BACKGROUND AND PURPOSE: Targeted modulation of autophagy induced by myocardial ischaemia/reperfusion has been the subject of intensive investigation, but it is debatable whether autophagy is beneficial or harmful. Hence, we evaluated the effects of pharmacological manipulation of autophagy on the survival of cardiomyocytes in different time windows of ischaemia/reperfusion. EXPERIMENTAL APPROACH: We examined the autophagy and apoptosis in cardiomyocytes subjected to different durations of anoxia/re-oxygenation or ischaemia/reperfusion, and evaluated the effects of the autophagic enhancer rapamycin and inhibitor wortmannin on cell survival. KEY RESULTS: In neonatal rat cardiomyocytes (NRCs) or murine hearts, autophagy was increased in response to anoxia/reoxygenation or ischaemia/reperfusion in a time-dependent manner. Rapamycin-enhanced autophagy in NRCs led to higher cell viability and less apoptosis when anoxia was sustained for ≦ 6 h. When anoxia was prolonged to 12 h, rapamycin did not increase cell viability, induced less apoptosis and more autophagic cell death. When anoxia was prolonged to 24 h, rapamycin increased autophagic cell death, while wortmannin reduced autophagic cell death and apoptosis. Similar results were obtained in mice subjected to ischaemia/reperfusion. Rapamycin inhibited the opening of mitochondrial transition pore in NRCs exposed to 6 h anoxia/4 h re-oxygenation but did not exert any effect when anoxia was extended to 24 h. Similarly, rapamycin reduced the myocardial expression of Bax in mice subjected to short-time ischaemia, but this effect disappeared when ischaemia was extended to 24 h. CONCLUSIONS AND IMPLICATIONS: The cardioprotection of autophagy is context-dependent and therapies involving the modification of autophagy should be determined according to the duration of ischaemia/reperfusion.

Effects of mineralocorticoid receptor antagonists in patients with preserved ejection fraction: a meta-analysis of randomized clinical trials.

BACKGROUND: Mineralocorticoid receptor antagonists (MRAs) have been shown to be effective in patients with heart failure or myocardial infarction complicated by a reduced ejection fraction. However, the role of MRAs in patients with preserved ejection fraction (PEF) remains to be clarified. We aimed to summarize the evidence for the efficacy of MRAs in patients with either heart failure with PEF (HF-PEF) or myocardial infarction with PEF (MI-PEF). METHODS: We searched PubMed, EMBASE, Cochrane Library, and clinical trials databases for randomized controlled trials, through June 2014, assessing MRA treatment in HF-PEF or MI-PEF patients. Fourteen randomized controlled trials (MI-PEF, 5; HF-PEF, 9; n = 6,428 patients) were included. RESULTS: MRA treatment reduced the risk of hospitalization for heart failure (relative risk, 0.83; 95% confidence interval [CI], 0.70 to 0.98), improved quality of life (weighted mean difference [WMD], -5.16; 95% CI, -8.03 to -2.30), left ventricular end-diastolic diameter (standardized mean difference, -0.21; 95% CI, 0.32 to -0.11), and serum amino-terminal peptide of procollagen type-III level (WMD, -1.50, 95% CI, -1.72 to -1.29) in patients with PEF. In addition, MRAs reduced E/e'(an echocardiographic estimate of filling pressure for assessment of diastolic function; WMD, -1.82; 95% CI, -2.23 to -1.42) in HF-PEF patients and E/A ratio (the ratio of early to late diastolic transmitral flow; WMD, 0.12; 95% CI, 0.10 to 0.14) in MI-PEF patients. However, all-cause mortality was not improved by MRAs in either HF-PEF (P = 0.90) or MI-PEF (P = 0.27) patients. CONCLUSIONS: MRA treatment in PEF patients led to reduced hospitalization for heart failure, quantifiable improvements in quality of life and diastolic function, and reversal of cardiac remodeling, but did not provide any all-cause mortality benefit.

[Effect of acupoint sticking of "Hua yutie" on VEGF expression in rats of focal cerebral ischemia].

OBJECTIVE: To explore the mechanism of acupoint sticking of "Hua yutie" in improving ischemic stroke. METHODS: Eighty rats were randomly divided into 5 groups, a model group, an acupoint sticking group, an acupuncture group, a Nimodipine group and a normal group. Middle cerebral artery occlusion (MCAO) was used for preparation of focal cerebral ischemic rat model. After modeling, any treatment was not given to the model group; for the acupoint sticking group, "Hua yutie" was applied at "Dazhui" (GV 14) ,"Qihai" (CV 6) and "Mingmen" (GV 4); for the acupuncture group, acupuncture was given at the same acupoints as those in the acupoint sticking group; the Nimodipine group received intragastric administration of Nimodipine. And the normal group did not receive any treatment. Their infarction volume, the cerebral water content, expression of vascular endothelial growth factor (VEGF) and the protein level were observed. RESULTS: The infarction volume coincided with the dominative scope of the middle cerebral artery of the electric coagulation. There were significant differences in the cerebral water content as the various treatment groups compared with that of the model group (all P<0.05). The VEGF positive cell number and the protein level around the infarction area in the acupoint sticking group were increased as compared with those in the model group (P<0.01), with no significant difference as compared with the Nimodipine group and the acupuncture group (all P>0.05). CONCLUSION: Acupoint sticking of "Hua yutie" alleviates the cerebral damage after ischemia possibly through enhancing the expression and protein level of VEGF.