Supercritical water oxidation for the treatment and utilization of organic wastes: Factor effects, reaction enhancement, and novel process.

Supercritical water oxidation (SCWO) has been regarded as a new and efficient technology for the harmless treatment and energy utilization of organic wastes, resulting in the quickly homogeneous oxidation between organics and oxidizers and the former being wholly degraded into small environment-friendly green molecules such as H2O and N2 and inorganic salts. This paper systematically analyzed the influencing behavior and mechanisms of the reaction factors, such as temperature, pressure, residence time, oxidant type, oxidation coefficient, and the concentration and pH values of the raw material, on the treatment effect of organic wastes. For most organic wastes, the SCWO conditions at 550 °C with a residence time of 1min and an oxidation coefficient of 100% can meet the removal rate of more than 99%. To further enhance the degradation rate of organics, the principles, implementation cases, and related equipment components of general enhancement technologies of supercritical water oxidation were discussed, such as fractional oxygen injection, auxiliary fuel co-oxidation, and hydrothermal flame-assisted degradation. This paper proposes a novel supercritical flame-assisted oxidation process in which the reactor performs preheating, corrosion protection, and desalination functions. The use of additive-enhanced oxidation, segmented oxidation, and supercritical hydrothermal flame-assisted oxidation has achieved good results in the complicated treatment process of brutal degradation of organic matter.

The alpha2-adrenergic receptor agonist clonidine protects against cerebral ischemia/reperfusion induced neuronal apoptosis in rats.

Apoptosis is the crucial pathological mechanism following cerebral ischemic injury. Our previous studies demonstrated that clonidine, one agonist of alpha2-adrenergic receptor (α2-AR), could attenuate cerebral ischemic injury in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). However, it's unclear whether clonidine exerts neuroprotective effects by regulating neuronal apoptosis. In this study, we elucidated whether clonidine can exert anti-apoptotic effects in cerebral ischemic injury, and further explored the possible mechanisms. Neurological deficit score was measured to evaluate the neurological function. TTC staining was used for the measurement of brain infarct size. Hematoxylin-Eosin (HE) staining was applied to examine the cell morphology. TUNEL and DAPI fluorescent staining methods were used to analyze the cell apoptosis in brain tissue. Fluorescence quantitative real-time PCR was performed to assess the gene expression of Caspase-3 and P53. Western blotting assay was applied to detect the protein expression of Caspase-3 and P53. The results showed that clonidine improved neurological function, reduced brain infarct size, alleviated neuronal damage, and reduced the ratio of cell apoptosis in the brain with MCAO/R injury. moreover, clonidine down-regulated the gene and protein expression of Caspase-3 and P53 which were over-expressed after MCAO/R injury. Whereas, yohimbine (one selective α2-AR antagonist) mitigated the anti-apoptosis effects of clonidine, accompanied by reversed gene and protein expression changes. The results indicated that clonidine attenuated cerebral MCAO/R injury via suppressing neuronal apoptosis, which may be mediated, at least in part, by activating α2-AR.

Systematically identifying genetic signatures including novel SNP-clusters, nonsense variants, frame-shift INDELs, and long STR expansions that potentially link to unknown phenotypes existing in dog breeds.

BACKGROUND: In light of previous studies that profiled breed-specific traits or used genome-wide association studies to refine loci associated with characteristic morphological features in dogs, the field has gained tremendous genetic insights for known dog traits observed among breeds. Here we aim to address the question from a reserve perspective: whether there are breed-specific genotypes that may underlie currently unknown phenotypes. This study provides a complete set of breed-specific genetic signatures (BSGS). Several novel BSGS with significant protein-altering effects were highlighted and validated. RESULTS: Using the next generation whole-genome sequencing technology coupled with unsupervised machine learning for pattern recognitions, we constructed and analyzed a high-resolution sequence map for 76 breeds of 412 dogs. Genomic structures including novel single nucleotide polymorphisms (SNPs), SNP clusters, insertions, deletions (INDELs) and short tandem repeats (STRs) were uncovered mutually exclusively among breeds. We also partially validated some novel nonsense variants by Sanger sequencing with additional dogs. Four novel nonsense BSGS were found in the Bernese Mountain Dog, Samoyed, Bull Terrier, and Basset Hound, respectively. Four INDELs resulting in either frame-shift or codon disruptions were found in the Norwich Terrier, Airedale Terrier, Chow Chow and Bernese Mountain Dog, respectively. A total of 15 genomic regions containing three types of BSGS (SNP-clusters, INDELs and STRs) were identified in the Akita, Alaskan Malamute, Chow Chow, Field Spaniel, Keeshond, Shetland Sheepdog and Sussex Spaniel, in which Keeshond and Sussex Spaniel each carried one amino-acid changing BSGS in such regions. CONCLUSION: Given the strong relationship between human and dog breed-specific traits, this study might be of considerable interest to researchers and all. Novel genetic signatures that can differentiate dog breeds were uncovered. Several functional genetic signatures might indicate potentially breed-specific unknown phenotypic traits or disease predispositions. These results open the door for further investigations. Importantly, the computational tools we developed can be applied to any dog breeds as well as other species. This study will stimulate new thinking, as the results of breed-specific genetic signatures may offer an overarching relevance of the animal models to human health and disease.

Inhibition of hyperpolarization-activated cyclic nucleotide-gated cation channel attenuates cerebral ischemia reperfusion-induced impairment of learning and memory by regulating apoptotic pathway.

Stroke is the second leading cause of death globally. Cognitive dysfunction is a common complication of stroke, which seriously affects the patient's quality of life. Previous studies have shown that the expression of hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel is closely related to ischemia-reperfusion (IR) injury and subsequent cognitive impairment. We also found that ZD7288, a specific inhibitor of the HCN channel, attenuated IR injury during short-term reperfusion. Since apoptosis can induce cell necrosis and aggravate cognitive impairment after IR, the purpose of this study is to define whether ZD7288 could improve cognitive impairment after prolonged cerebral reperfusion in rats by regulating apoptotic pathways. Our data indicated that ZD7288 can ameliorate spatial cognitive behavior and synaptic plasticity, protect the morphology of hippocampal neurons, and alleviate hippocampal apoptotic cells in IR rats. This effect may be related to down-regulating the expressions of pro-apoptotic proteins such as AIF, p53, Bax, and Caspase-3, and increasing the ratio of Bcl-2/Bax. Taken together, it suggested that inhibition of the HCN channel improves cognitive impairment after IR correlated with its regulation of apoptotic pathways.

Survival outcomes for breast conserving surgery versus mastectomy among elderly women with breast cancer.

PURPOSE: Elderly patients have different physical condition and tumor biology of breast cancer. Surgical choices for older patients are complicated and several studies have reported that breast conserving surgery (BCS) had better survival than mastectomy in different patient population. The major objective of this study was to compare the efficacy of BCS and mastectomy in the whole elderly cohort in SEER database. METHODS: Female patients aged over 70 years old and diagnosed with breast cancer between 2010 and 2015 were included from SEER database. Propensity score matching (PSM) was used to establish a cohort composing of similar characteristics. We compared the overall survival (OS) among patients undergoing BCS and mastectomy. Kaplan-Meier analysis and Cox proportional regression model were used to evaluate the associated factors of survival outcome. RESULTS: Of 44,755 eligible patients, 30,375 (67.9%) patients underwent BCS and 14,380 (32.1%) patients underwent mastectomy. After PSM, 7222 patients in each group were analyzed and there was no significant difference between BCS and mastectomy in terms of the OS rate (85.8% in BCS group and 85.0% in mastectomy group, p = 0.135). Multivariable analysis also indicated that no significant difference between two surgical procedures after adjusting for covariates in matched cohort (HR 1.062, 95% CI 0.997-1.132, p = 0.063). Subgroup analysis demonstrated that postoperative radiotherapy and chemotherapy contributed to the survival benefit of BCS compared to mastectomy (p < 0.05). CONCLUSION: For elderly breast cancer patients, BCS and mastectomy appeared to be comparable in terms of OS after being matched by clinicopathologic features. While our findings suggested that there was statistically survival benefit of BCS in some subsets of patients, including radiotherapy, chemotherapy, and 80-84 year-old subgroups, these results were likely to be related to selection bias and should be interpreted with caution. Thus, for this elderly patient population, BCS should be considered as an equivalent and less aggressive alternative to mastectomy.

Nonvolatile modulation of luminescence in perovskite oxide thin films by ferroelectric gating.

Nonvolatile and giant modulation of luminescence can be realized by the ferroelectric gating effect in a Ga3+/Pr3+ co-doped BaTiO3 ultra-thin film epitaxially grown on a [Pb(Mg1/3Nb2/3)O3]0.7-[PbTiO3]0.3 single-crystallized substrate. The change behavior of the emission intensity matches that of the ferroelectric polarization hysteresis loop with a giant enhancement of over 13 times with negative polarization orientation. The interaction of O2- at the O2p orbital in the valence band and Pr3+ with injected holes by the ferroelectric gating effect promotes the formation of excited state O-, Pr4+, or Pr3+q. This ferroelectric gating method can promote the development of controllable photo-, electroluminescent, and other optoelectronic devices for display, sensing, communication, and so on.

Organic cation transporter 3 (Oct3) is a distinct catecholamines clearance route in adipocytes mediating the beiging of white adipose tissue.

Beiging of white adipose tissue (WAT) is a particularly appealing target for therapeutics in the treatment of metabolic diseases through norepinephrine (NE)-mediated signaling pathways. Although previous studies report NE clearance mechanisms via SLC6A2 on sympathetic neurons or proinflammatory macrophages in adipose tissues (ATs), the low catecholamine clearance capacity of SLC6A2 may limit the cleaning efficiency. Here, we report that mouse organic cation transporter 3 (Oct3; Slc22a3) is highly expressed in WAT and displays the greatest uptake rate of NE as a selective non-neural route of NE clearance in white adipocytes, which differs from other known routes such as adjacent neurons or macrophages. We further show that adipocytes express high levels of NE degradation enzymes Maoa, Maob, and Comt, providing the molecular basis on NE clearance by adipocytes together with its reuptake transporter Oct3. Under NE administration, ablation of Oct3 induces higher body temperature, thermogenesis, and lipolysis compared with littermate controls. After prolonged cold challenge, inguinal WAT (ingWAT) in adipose-specific Oct3-deficient mice shows much stronger browning characteristics and significantly elevated expression of thermogenic and mitochondrial biogenesis genes than in littermate controls, and this response involves enhanced ß-adrenergic receptor (ß-AR)/protein kinase A (PKA)/cyclic adenosine monophosphate (cAMP)-responsive element binding protein (Creb) pathway activation. Glycolytic genes are reprogrammed to significantly higher levels to compensate for the loss of ATP production in adipose-specific Oct3 knockout (KO) mice, indicating the fundamental role of glucose metabolism during beiging. Inhibition of ß-AR largely abolishes the higher lipolytic and thermogenic activities in Oct3-deficient ingWAT, indicating the NE overload in the vicinity of adipocytes in Oct3 KO adipocytes. Of note, reduced functional alleles in human OCT3 are also identified to be associated with increased basal metabolic rate (BMR). Collectively, our results demonstrate that Oct3 governs ß-AR activity as a NE recycling transporter in white adipocytes, offering potential therapeutic applications for metabolic disorders.

Increased intracellular Cl- concentration mediates neutrophil extracellular traps formation in atherosclerotic cardiovascular diseases.

Neutrophil extracellular traps (NETs) play crucial roles in atherosclerotic cardiovascular diseases such as acute coronary syndrome (ACS). Our preliminary study shows that oxidized low-density lipoprotein (oxLDL)-induced NET formation is accompanied by an elevated intracellular Cl- concentration ([Cl-]i) and reduced cystic fibrosis transmembrane conductance regulator (CFTR) expression in freshly isolated human blood neutrophils. Herein we investigated whether and how [Cl-]i regulated NET formation in vitro and in vivo. We showed that neutrophil [Cl-]i and NET levels were increased in global CFTR null (Cftr-/-) mice in the resting state, which was mimicked by intravenous injection of the CFTR inhibitor, CFTRinh-172, in wild-type mice. OxLDL-induced NET formation was aggravated by defective CFTR function. Clamping [Cl-]i at high levels directly triggered NET formation. Furthermore, we demonstrated that increased [Cl-]i by CFTRinh-172 or CFTR knockout increased the phosphorylation of serum- and glucocorticoid-inducible protein kinase 1 (SGK1) and generation of intracellular reactive oxygen species in neutrophils, and promoted oxLDL-induced NET formation and pro-inflammatory cytokine production. Consistently, peripheral blood samples obtained from atherosclerotic ApoE-/- mice or stable angina (SA) and ST-elevation ACS (STE-ACS) patients exhibited increased neutrophil [Cl-]i and SGK1 activity, decreased CFTR expression, and elevated NET levels. VX-661, a CFTR corrector, reduced the NET formation in the peripheral blood sample obtained from oxLDL-injected mice, ApoE-/- atherosclerotic mice or patients with STE-ACS by lowering neutrophil [Cl-]i. These results demonstrate that elevated neutrophil [Cl-]i during the development of atherosclerosis and ACS contributes to increased NET formation via Cl--sensitive SGK1 signaling, suggesting that defective CFTR function might be a novel therapeutic target for atherosclerotic cardiovascular diseases.

Platelet CFTR inhibition enhances arterial thrombosis via increasing intracellular Cl- concentration and activation of SGK1 signaling pathway.

Platelet hyperactivity is essential for thrombus formation in coronary artery diseases (CAD). Dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) in patients with cystic fibrosis elevates intracellular Cl- levels ([Cl-]i) and enhanced platelet hyperactivity. In this study, we explored whether alteration of [Cl-]i has a pathological role in regulating platelet hyperactivity and arterial thrombosis formation. CFTR expression was significantly decreased, while [Cl-]i was increased in platelets from CAD patients. In a FeCl3-induced mouse mesenteric arteriole thrombosis model, platelet-specific Cftr-knockout and/or pre-administration of ion channel inhibitor CFTRinh-172 increased platelet [Cl-]i, which accelerated thrombus formation, enhanced platelet aggregation and ATP release, and increased P2Y12 and PAR4 expression in platelets. Conversely, Cftr-overexpressing platelets resulted in subnormal [Cl-]i, thereby decreasing thrombosis formation. Our results showed that clamping [Cl-]i at high levels or Cftr deficiency-induced [Cl-]i increasement dramatically augmented phosphorylation (Ser422) of serum and glucocorticoid-regulated kinase (SGK1), subsequently upregulated P2Y12 and PAR4 expression via NF-κB signaling. Constitutively active mutant S422D SGK1 markedly increased P2Y12 and PAR4 expression. The specific SGK1 inhibitor GSK-650394 decreased platelet aggregation in wildtype and platelet-specific Cftr knockout mice, and platelet SGK1 phosphorylation was observed in line with increased [Cl-]i and decreased CFTR expression in CAD patients. Co-transfection of S422D SGK1 and adenovirus-induced CFTR overexpression in MEG-01 cells restored platelet activation signaling cascade. Our results suggest that [Cl-]i is a novel positive regulator of platelet activation and arterial thrombus formation via the activation of a [Cl-]i-sensitive SGK1 signaling pathway. Therefore, [Cl-]i in platelets is a novel potential biomarker for platelet hyperactivity, and CFTR may be a potential therapeutic target for platelet activation in CAD.

Clonidine ameliorates cerebral ischemia-reperfusion injury by up-regulating the GluN3 subunits of NMDA receptor.

This study aimed to investigate the protective effects of the alpha-2 adrenergic receptor (α2-AR) agonist, clonidine, on the cerebral ischemia-reperfusion (I/R) injury and elaborate the underlying mechanisms. Cerebral I/R model was established by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 4 h in adult male SD rats. Saline, clonidine and yohimbine (an α2-AR antagonist) were intraperitoneally administered each day for one week before surgery. Neurological deficit was evaluated just before decapitation. TTC staining was applied for correlation of cerebral infarction volume. HE staining was performed to observe the neuron morphology. Immunohistochemical staining was performed to detect the localization and expression of GluN3 proteins. Western blot analysis also was used to detect the expression levels of GluN3 proteins. Our data showed that clonidine ameliorated neurological deficit and reduced the cerebral infarction volume of the rats with cerebral I/R. It is worth noting that treatment with clonidine up-regulated the protein expression of GluN3 in the rats with the cerebral I/R, especially in the cell membrane. Moreover, clonidine also up-regulated the transposition from cytoplasm to cell membrane of GluN3 after cerebral I/R. In addition, yohimbine abolished the neuroprotective effects of clonidine. The results indicated that clonidine played a protective role in cerebral I/R injury through regulation of the protein expression of GluN3 subunits of N-methyl-D-aspartate (NMDA) receptor.

Antiplatelet and Antithrombotic Effects of Isaridin E Isolated from the Marine-Derived Fungus via Downregulating the PI3K/Akt Signaling Pathway.

Isaridin E, a cyclodepsipeptide isolated from the marine-derived fungus Amphichorda felina (syn. Beauveria felina) SYSU-MS7908, has been demonstrated to possess anti-inflammatory and insecticidal activities. Here, we first found that isaridin E concentration-dependently inhibited ADP-induced platelet aggregation, activation, and secretion in vitro, but did not affect collagen- or thrombin-induced platelet aggregation. Furthermore, isaridin E dose-dependently reduced thrombosis formation in an FeCl3-induced mouse carotid model without increasing the bleeding time. Mechanistically, isaridin E significantly decreased the ADP-mediated phosphorylation of PI3K and Akt. In conclusion, these results suggest that isaridin E exerts potent antithrombotic effects in vivo without increasing the risk of bleeding, which may be due to its important role in inhibiting ADP-induced platelet activation, secretion and aggregation via the PI3K/Akt pathways.

Polysaccharides derived from Balanophora polyandra significantly suppressed the proliferation of ovarian cancer cells through P53-mediated pathway.

Ovarian cancer (OC) is ranked the first among the cancers threatening women's health. It attracts tremendous attention of cancer researchers because of its extremely high mortality rate. Recent studies have indicated that traditional herbal medicines (THMs) can play a pivotal role in cancer prevention and treatment. THMs are gaining popularity as a source of anti-cancer agents. The plant of Balanophora polyandra, which has been used as a traditional herbal medicine, has been known for exhibiting potential haemostatic, analgesic, anti-inflammatory and anti-cancer properties. However, few studies on inhibitory effect of B. polyandra on OC have been performed. In the present study, we found that B. polyandra polysaccharides (BPP) induced cell cycle arrest at S phase, triggered apoptosis and inhibited migration and invasion of OC cells. Furthermore, we also found that there was a potential and close relationship between BPP and P53-mediated pathway. Overall, these findings suggest that BPP can be a potential therapeutic agent for the treatment of OC.

Raman spectroscopic imaging of pH values in cancerous tissue by using polyaniline@gold nanoparticles.

A core-shell nanocomposite consisting of polyaniline and gold nanoparticles (PANI@AuNPs) is shown to enable intracellular monitoring of pH values by surface-enhanced Raman scattering (SERS) spectroscopy. The method exploits the pH-responsive property of PANI and the SERS-enhancing effect of AuNPs. The intensity of the PANI Raman peak at 1164 cm-1 decreases on increasing the pH value from 4.6 to 7.4. This is the pH range encountered in normal cells and in cancer cells. The PANI@AuNPs were incorporated into HeLa cancer cells and 5 other kinds of cells for Raman based imaging of pH values. The results show that this pH nanoprobe can be applied for imaging of both normal cells and cancer cells. The core-shell composite was also applied to tissue imaging. In our perception, this core-shell nanoprobe is a valuable tool for imaging pH values of cancerous tissue. Graphical abstract Schematic presentation of a core-shell nanocomposite, polyaniline@gold nanoparticle, which was synthesized via a rapid method. With the pH of solution changing from alkaline to acidic, the polyaniline can change from emeraldine base (EB, blue shell) transition to emeraldine salt (ES, green shell) transition. Due to the pH-responsive property of polyaniline combined with the surface-enhanced Raman scattering spectroscopy effect of AuNPs. The polyaniline@gold nanoparticles were successfully applied as an intracellular pH probe.

Simultaneous Quantitative Analysis of Six Isothiazolinones in Water-Based Adhesive Used for Food Contact Materials by High-Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS).

In this study, a target analytical approach using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed to simultaneously determine six isothiazolinones containing 2-Methylisothiazol-3(2H)-one (MI), 5-Chloro-2-methyl-4-isothiazolin-3-one (CMI), 1,2-benzisothiazolin-3-one (BIT), 2-Octyl-3(2H)-isothiazolinone (OIT), Dichlorooctylisothiazolinone (DCOIT), and 2-methyl-1,2-benzisothiazolin-3-one (MBIT) in water-based adhesive used for food contact materials. The main factors affecting extraction efficiency such as extraction method, extraction time, extraction solvent, and solid-liquid ratio have been evaluated by using real adhesive samples. Multiple-reaction monitoring (MRM) was used for the qualitative and quantitative analyses of targeted isothiazolinones. This method was demonstrated as an effective and reliable technique for detecting multiple isothiazolinones with satisfactory recoveries (81.5~107.3%), and the limits of detection (LOD) and quantification (LOQ) were obtained at a low level. This method was validated and applied to the determination of six isothiazolinones in commercial water-based adhesives. The present results revealed that these adhesives contained a combination of isothiazolinones (BIT, MI, CMI, and MBIT) with the concentration ranging from 2.27 to 123.5 mg/kg. To our knowledge, it is the first time it has been reported that MBIT was detected in water-based adhesives used for food contact materials, which requires a further investigation for its migration to food and the risk to human health.

Synthesis, Spectra, and Theoretical Investigations of 1,3,5-Triazines Compounds as Ultraviolet Rays Absorber Based on Time-Dependent Density Functional Calculations and three-Dimensional Quantitative Structure-Property Relationship.

A series of 1,3,5-triazines were synthesized and their UV absorption properties were tested. The computational chemistry methods were used to construct quantitative structure-property relationship (QSPR), which was used to computer aided design of new 1,3,5-triazines ultraviolet rays absorber compounds. The experimental UV absorption data are in good agreement with those predicted data using the Time-dependent density functional theory (TD-DFT) [B3LYP/6-311 + G(d,p)]. A suitable forecasting model (R > 0.8, P < 0.0001) was revealed. Predictive three-dimensional quantitative structure-property relationship (3D-QSPR) model was established using multifit molecular alignment rule of Sybyl program, which conclusion is consistent with the TD-DFT calculation. The exceptional photostability mechanism of such ultraviolet rays absorber compounds was studied and confirmed as principally banked upon their ability to undergo excited-state deactivation via an ultrafast excited-state proton transfer (ESIPT). The intramolecular hydrogen bond (IMHB) of 1,3,5-triazines compounds is the basis for the excited state proton transfer, which was explored by IR spectroscopy, UV spectra, structural and energetic aspects of different conformers and frontier molecular orbitals analysis.

Total Mortality, Major Adverse Cardiac Events, and Echocardiographic-Derived Cardiac Parameters with Fragmented QRS Complex.

BACKGROUND: Fragmented QRS complex (fQRS), an easily evaluated noninvasive electrocardiographic parameter, is associated with worse outcomes in patients with several cardiovascular conditions. The presence of fQRS on ECG may be an indicator of myocardial damage in patients with coronary artery disease (CAD). In this article, we performed a meta-analysis in order to characterize the presence of fQRS on ECG in patients with CAD. METHODS: We searched English-language randomized controlled trials involving fQRS on ECG in patients with CAD (n = 3279 patients, 12 trials). Two reviewers independently extracted data. Data on LVEF, LVESD, LVEDD, LVESV, LVEDV, total mortality, stroke, and MACE were collected. fQRS was performed a comparison with non-fQRS, calculating pooled relatives risk (RRs) and weighted mean difference (WMD), and associated 95% confidence intervals (CIs). RESULTS: fQRS was associated with significant increased WMD of LVEDD (WMD, 2.26; 95%CI, 0.92 to 0.36, P = 0.0009), LVESD (WMD, 2.71; 95%CI, 1.23 to 4.19, P = 0.0003), LVEDV (WMD, 31.37; 95%CI, 24.82 to 37.92, P < 0.00001), and LVESV (WMD, 28.45; 95%CI, 22.92 to 33.98, P < 0.00001). As compared to non-fQRS, fQRS increased risk of total mortality (RR, 3.09; 95%CI, 1.76 to 5.44, P < 0.0001) and MACE (RR, 2.85; 95%CI, 1.98 to 4.09, P < 0.00001) in patients with CAD. However, a decreased trend was observed for LVEF (WMD, -3.59; 95%CI, -7.05 to -0.12, P = 0.04). For the incidence of stoke, there was no difference between fQRS and non-fQRS group. CONCLUSIONS: Our findings indicate that fQRS is a valuable factor to predict total mortality and MACE in patients with CAD.

Characterization of metal kinetics and bioavailability using diffusive gradients in thin films technique in sediments of Taihu Lake, China.

For an improved understanding of the metal behavior between the sediment and overlaying water of Taihu Lake, the technique of diffusive gradients in thin films (DGT) was used to characterize the DGT measured concentration in sediments and release kinetics of Cr, Ni, Cu, Zn, Cd and Pb in representative lake parts. Spatially, the DGT-measured concentration of heavy metals showed that Zn, Cu, Ni, Cr, and Pb had higher concentrations in the northern lake than in the eastern Lake Taihu. The order of the release flux for the studied metals from sediments to overlaying water was Zn>Cu>Ni, Cr>Pb>Cd (p<0.05). DGT devices were deployed over a series of time (0.5, 1, 2, 4, 8, 12, 24 and 48 h) in sediment cores from the two typical lake parts (northwest algae dominant area and southeast macrophyte dominant area) to explore the dynamics in the sediment/DGT system, and the best fitted regression model was selected to characterize the release of metals in the two lake parts. The fitted results showed that the equilibration time of the metal release was approximately 24h and Zn had a higher release capacity than other metals. Further analyses indicated that significant correlation existed between the DGT-measured metal concentrations in sediments and metal concentrations in lake organisms (r=0.943 and 0.996 for zoobenthos and coilia ectenes, p<0.05), suggesting that DGT technique is more effective to predict the metal bioavailability in lake sediments.

Levosimendan Treatment for Heart Failure: A Systematic Review and Meta-Analysis.

OBJECTIVE: Emerging studies suggest that administration of levosimendan therapy may be better than dobutamine or placebo in decompensated heart failure. The authors performed an updated meta-analysis of trials to obtain the best estimates of the efficacy and safety of levosimendan for the initial treatment of decompensated heart failure. DESIGN: A meta-analysis. SETTING: Hospitals. PARTICIPANTS: A total of 5,349 patients from 25 randomized controlled studies were included in the analysis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The authors performed a meta-analysis of trials comparing levosimendan therapy with dobutamine or placebo in patients with decompensated heart failure. Twenty-five trials, involving 5,349 patients, were included. Two reviewers performed independent article review and study quality assessment. Data on overall mortality, early-term mortality, midterm mortality, long-term mortality, efficacy outcomes, and adverse events were collected. Mortality outcomes were according to follow-up duration: early term (≤30-day), midterm (30-day to≤6-month), and long term (>6-month). Levosimendan was compared with dobutamine or placebo, calculating pooled relatives risk (RRs) and associated 95% confidence intervals (CIs). A random-effects model was selected for meta-analysis if there was significant heterogeneity. Levosimendan significantly reduced total mortality (17.1% versus 20.8%; RR, 0.84; 95% CI, 0.75-0.94). Compared with dobutamine, levosimendan was associated with significant reduction in mortality at final follow-up (RR, 0.86; 95% CI, 0.76-0.97; I(2) = 7%; p = 0.02).Compared with placebo, levosimendan was associated with a nonsignificant trend in favor of placebo in mortality at final follow-up (11.6% versus 16.2%, RR, 0.75; 95% CI, 0.56-1.01; p = 0.06), but it was associated with a significant reduction in long-term mortality (RR, 0.34; 95%CI, 0.15-0.76; p = 0.009). Compared with dobutamine or placebo, levosimendan therapy was associated with improvements in hemodynamically- and echocardiographically-derived cardiac parameters. Levosimendan therapy increased the risks of extrasystoles (RR, 1.88; 95% CI, 1.26-2.81), hypotension (RR, 1.33; 95% CI, 1.15-1.53), and headache or migraine (RR, 1.94; 95% CI, 1.54-2.43) when compared with control therapy. CONCLUSIONS: As compared to placebo or dobutamine, levosimendan in patients with heart failure seemed to have hemodynamic and cardiac benefits. It reduced total mortality and was associated with an increased risk of cardiovascular adverse events.

Piracetam ameliorated oxygen and glucose deprivation-induced injury in rat cortical neurons via inhibition of oxidative stress, excitatory amino acids release and P53/Bax.

Our previous work has demonstrated that piracetam inhibited the decrease in amino acid content induced by chronic hypoperfusion, ameliorated the dysfunction of learning and memory in a hypoperfusion rat model, down-regulated P53, and BAX protein, facilitated the synaptic plasticity, and may be helpful in the treatment of vascular dementia. To explore the precise mechanism, the present study further evaluated effects of piracetam on Oxygen and glucose deprivation (OGD)-induced neuronal damage in rat primary cortical cells. The addition of piracetam to the cultured cells 12 h before OGD for 4 h significantly reduced neuronal damage as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and lactate dehydrogenase release experiments. Piracetam also lowered the levels of malondialdehyde, nitrogen monoxidum, and xanthine oxidase which was increased in the OGD cells, and enhanced the activities of superoxide dismutase and glutathione peroxidase, which were decreased in the OGD cells. We also demonstrated that piracetam could decrease glutamate and aspartate release when cortical cells were subjected to OGD. Furthermore, Western blot study demonstrated that piracetam attenuated the increased expression of P53 and BAX protein in OGD cells. These observations demonstrated that piracetam reduced OGD-induced neuronal damage by inhibiting the oxidative stress and decreasing excitatory amino acids release and lowering P53/Bax protein expression in OGD cells.

Dopamine inhibits excitatory neurotransmission in basolateral amygdala during development via pre-synaptic mechanism.

OBJECTIVES: Dopaminergic signaling in the basolateral amygdala (BLA) is important for emotion-related activity. However, little is known about the influence of dopamine (DA) on excitatory synaptic transmission of pyramidal neurons in BLA at early developmental stage. Here in this study, we observed the effect of DA on excitatory neurotransmission in the pyramidal cells of BLA in acute slices. METHODS: Acute slices from amygdala of rats at the age of 14-16 days were prepared and maintained in vitro using standard method. Whole-cell patch clamp recordings were performed to examine the evoked excitatory postsynaptic current (eEPSC), spontaneous excitatory postsynaptic current (sEPSC) and miniature excitatory postsynaptic current (mEPSC). Drugs including DA and synaptic blockers were added in recording solution due to different experimental designs. RESULTS: We found that bath application of DA at a concentration of 100 µM significantly inhibited the amplitude of evoked EPSC. However, the amplitude and frequency of mEPSC were not affected. We also found increased pair pulse facilitation after DA application, indicating DA inhibited excitatory neurotransmission through suppression of release probability at the pre-synaptic terminals. Importantly, DA was also effective in decreasing activity induced upregulation in sEPSCs. Moreover, the DA effects were not affected by either antagonist of dopamine 1 or dopamine 2-like receptors. CONCLUSION: We studied the effects of DA on excitatory neurotransmission and found that DA inhibited glutamatergic synaptic transmission via modulation of pre-synaptic release probability.