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As a self-reactive substance, benzaldehyde oxime (BO) is prone to a highly exothermic runaway reaction and thermal hazard analysis and the reaction kinetics calculation of BO have great significance. In this work, the decomposition products of BO in nitrogen atmosphere were identified by GC–MS and HPLC techniques. The impact of the decomposition products on the decomposition behaviors of BO were analyzed by comparison of the ARC test results of pure BO and mixture of BO and decomposition products. It was found that N-benzylidene benzylamine was the intermediate decomposition product and benzoic acid, benzamide, N-benzyl benzamide, and 2,4,5-triphenylimidazole were the final products of BO. A two-step continuous autocatalytic reaction model was established to depict the decomposition process of BO. The kinetic parameters of the model were calculated by applying the nonlinear optimization method. Finally, thermal behaviors under different process temperature were predicted based on the kinetic model, and the time to maximum rate (TMRad) was predicted as 112.04 °C under 24 h, and 122.19 °C of 8 h, which offer crucial safety information to optimize the safety conditions of BO during usage, storage and transportation, which minimizes the industrial disasters.

Objective: Niacin therapy fails to reduce cardiovascular events in statin-treated subjects even though it increases plasma HDL-C (HDL [high-density lipoprotein] cholesterol) and decreases LDL-C (LDL [low-density lipoprotein] cholesterol) and triglyceride levels. To investigate potential mechanisms for this lack of cardioprotection, we quantified the HDL proteome of subjects in 2 niacin clinical trials: the CPC study (Carotid Plaque Composition) and the HDL Proteomics substudy of the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides). Approach and Results: Using targeted proteomics, we quantified levels of 31 HDL proteins from 124 CPC subjects and 120 AIM-HIGH subjects. The samples were obtained at baseline and after 1 year of statin monotherapy or niacin-statin combination therapy. Compared with statin monotherapy, niacin-statin combination therapy did not reduce HDL-associated apolipoproteins APOC1, APOC2, APOC3, and APOC4, despite significantly lowering triglycerides. In contrast, niacin markedly elevated HDL-associated PLTP (phospholipid transfer protein), CLU (clusterin), and HP/HPR (haptoglobin/haptoglobin-related proteins; P ≤0.0001 for each) in both the CPC and AIM-HIGH cohorts. Conclusions: The addition of niacin to statin therapy resulted in elevated levels of multiple HDL proteins linked to increased atherosclerotic risk, which might have compromised the cardioprotective effects associated with higher HDL-C levels and lower levels of LDL-C and triglycerides. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00715273; NCT00880178; NCT00120289.

Background and aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors reduce cardiovascular events, but their effects on atherosclerotic plaque remain elusive. Using serial magnetic resonance imaging (MRI), we studied changes in carotid plaque lipid content and neovasculature under PCSK9 inhibition with alirocumab. Methods Among patients with low-density lipoprotein cholesterol (LDL-C) ≥70 mg/dl but ineligible for high-dose statin therapy, those with lipid core on carotid MRI were identified to receive alirocumab 150 mg every 2 weeks. Follow-up MRI was performed at 3, 6, and 12 months after treatment. Pre- and post-contrast MRI were acquired to measure percent lipid core volume (% lipid core). Dynamic contrast-enhanced MRI was acquired to measure the extravasation rate of gadolinium contrast (Ktrans), a marker of plaque neovasculature. Results Of 31 patients enrolled, 27 completed the study (mean age: 69 ± 9; male: 67%). From 9.8% at baseline, % lipid core was progressively reduced to 8.4% at 3 months, 7.5% at 6 months, and 7.2% at 12 months (p = 0.014 for trend), which was accompanied by a progressive increase in % fibrous tissue (p = 0.009) but not % calcification (p = 0.35). Ktrans was not reduced until 12 months (from 0.069 ± 0.019 min−1 to 0.058 ± 0.020 min−1; p = 0.029). Lumen and wall areas did not change significantly during the study period. Conclusions Regression in plaque composition and neovasculature were observed under PCSK9 inhibition on carotid MRI, which provides unique insight into the biological process of plaque stabilization with disease-modifying therapies.

N-doped carbon materials as catalyst supports have shown great superiority because of rich porosity, tunable metal-support interaction and electronic promotion effect. Controllable fabrication of carbon materials with specific morphology and different configurations provides wider possibilities for applications in catalysis. Herein, N-doped carbon nanosheets (CNS) were successfully synthesized by using monoclinic ZIF-8 nanosheets as templates. Compared with commercial active carbon and cubic ZIF-8 particles-derived carbon particles, the derived CNS exhibit superior graphitization degree and electronic effect. Consequently, the promoted Fe carburization improved the intrinsic activity for Fe/CNS catalysts in FTS. Further investigation on pyrolysis temperature achieved tunable configuration and content of N dopant. XPS, Raman, Mossbauer spectroscopy, TEM, H2-TPR etc. were combined to elucidate the promotion effect of CNS on dispersion, electronic properties and formation of Fe carbides. By correlating the composition and structure to catalytic performance in FTS, we illustrated the significance of carbon materials in Fe supported catalysts.

Phenylpropanoid metabolism represents a substantial metabolic sink for photosynthetically fixed carbon. The evolutionarily conserved Sucrose Non-Fermenting Related Kinase 1 (SnRK1) is a major metabolic sensor that reprograms metabolism upon carbon deprivation. However, it is not clear if and how the SnRK1-mediated sugar signaling pathway controls phenylpropanoid metabolism. Here, we show that Arabidopsis SnRK1 negatively regulates phenylpropanoid biosynthesis via a group of Kelch domain-containing F-box (KFB) proteins that are responsible for the ubiquitination and degradation of phenylalanine ammonia lyase (PAL). Downregulation of AtSnRK1 significantly promoted the accumulation of soluble phenolics and lignin polymers and drastically increased PAL cellular accumulation but only slightly altered its transcription level. Co-expression of SnRK1α with PAL in Nicotiana benthamiana leaves resulted in the severe attenuation of the latter's protein level, but protein interaction assays suggested PAL is not a direct substrate of SnRK1. Furthermore, up or downregulation of AtSnRK1 positively affected KFBPAL s gene expression, and energy starvation upregulated KFBPAL expression, which partially depends on AtSnRK1. Collectively, our study reveals that SnRK1 negatively regulates phenylpropanoid biosynthesis, and KFBPALs act as regulatory components of the SnRK1 signaling network, transcriptionally regulated by SnRK1 and subsequently mediate proteasomal degradation of PAL in response to the cellular carbon availability.

To detect whether Danlou Tablet (丹蒌片, DLT) regulates the hypoxia-induced factor (HIF)-1 α-angiopoietin-like 4 (Angptl4) mRNA signaling pathway and explore the role of DLT in treating chronic intermittent hypoxia (CIH)-induced dyslipidemia and arteriosclerosis. The mature adipocytes were obtained from 3T3-L1 cell culturation and allocated into 8 groups including control groups (Groups 1 and 5, 0.1 mL of cell culture grade water); DLT groups (Groups 2 and 6, 0.1 mL of 1,000 µg/mL DLT submicron powder solution); dimethyloxalylglycine (DMOG) groups (Groups 3 and 7, DMOG and 0.1 mL of cell culture grade water); DMOG plus DLT groups (Groups 4 and 8, DMOG and 0.1 mL of 1,000 µg/mL DLT submicron powder solution). Groups 1–4 used mature adipocytes and groups 5–8 used HIF-1 α-siRNA lentivirus-transfected mature adipocytes. After 24-h treatment, real-time polymerase chain reaction and Western blot were employed to determine the mRNA and protein expression levels of HIF-1 α and Angptl4. In animal experiments, the CIH model in ApoE−/− mice was established. Sixteen mice were complete randomly divided into 4 groups including sham group, CIH model group [intermittent hypoxia and normal saline (2 mL/time) gavage once a day]; Angptl4 Ab group [intermittent hypoxia and Angptl4 antibody (30 mg/kg) intraperitoneally injected every week]; DLT group [intermittent hypoxia and DLT (250 mg/kg) once a day], 4 mice in each group. After 4-week treatment, enzyme linked immunosorbent assay was used to detect the expression levels of serum total cholesterol (TC) and triglyceride (TG). Hematoxylin-eosin and CD68 staining were used to observe the morphological properties of arterial plaques. Angptl4 expression was dependent on HIF-1 α, with a reduction in mRNA expression and no response in protein level to DMOG or DLT treatment in relation to siHIF-1 α -transfected cells. DLT inhibited HIF-1 α and Angptl4 mRNA expression (P

The Fischer-Tropsch synthesis (FTS) continues to be an attractive alternative for producing a broad range of fuels and chemicals through the conversion of syngas (H2 and CO), which can be derived from various sources, such as coal, natural gas, and biomass. Among iron carbides, Fe2C, as an active phase, has barely been studied due to its thermodynamic instability. Here, we fabricated a series of Fe2C embedded in hollow carbon sphere (HCS) catalysts. By varying the crystallization time, the shell thickness of the HCS was manipulated, which significantly influenced the catalytic performance in the FTS. To investigate the relationship between the geometric structure of the HCS and the physic-chemical properties of Fe species, transmission electron microscopy, X-ray diffraction, N2 physical adsorption, X-ray photo-electron spectroscopy, hydrogen temperature-programmed reduction, Raman spectroscopy, and Mossbauer spectroscopy techniques were employed to characterize the catalysts before and after the reaction. Evidently, a suitable thickness of the carbon layer was beneficial for enhancing the catalytic activity in the FTS due to its high porosity, appropriate electronic environment, and relatively high Fe2C content.

Repair of segmental bone defects is a challenge in orthopaedics. A bone substitute is a potential solution for this challenge, and angiogenesis and osteogenesis are critical to the performance of scaffold materials. For enhancing angiogenesis and osteogenesis activities of implanted scaffolds, Cu/Zn co-doped calcium phosphate scaffolds carrying GDF-5-release microspheres were prepared and implanted into surgically created critical-sized rabbit radial defects. Radiological examination, histological analysis and biomechanical tests were used to evaluate the bone healing-union. Results showed that, with increasing Cu/Zn concentrations, new bone area, new blood vessel density, and bending failure load all increased significantly. Furthermore, Cu/Zn co-doped scaffolds incorporating GDF-5-release microspheres exhibited further increased angiogenesis and osteogenesis (vs. Cu/Zn co-doped alone), as well as a superior bending failure load. These show that, simultaneous incorporation of trace essential ions and GDF-5 combines pro-angiogenic and pro-osteogenic actions of these bioactive substances, potentially offering an effective approach to assist the healing of critical-sized bone defects.

Dynamic covalent chemistry has reshaped our understanding of chemically crosslinked polymer networks, with broad implications on self-healing, reprocessable, and reconfigurable functional networks. Amongst them, transesterification based polycaprolactone (PCL) networks represent prototypical thermadapt shape memory polymers with unique permanent shape reconfigurability. Despite several studies on this system, structural factors that impact the solid-state plasticity behind the shape reconfigurability are poorly understood. In this work, PCL networks with precisely tunable crosslinking density and hydroxyl content were synthesized using a thiol–ene click reaction. This allows independent evaluation on how these two critical structural parameters determine the network rearrangement kinetics. In particular, we clarify an ambiguity on the role of the hydroxyl groups in such networks. This study leads to PCL based thermadapt shape memory polymers with tunable performance. On a broader basis, it also offers useful guidelines in designing transesterification based dynamic networks.

Lignin is a phenylpropanoid-derived polymer that functions as a major component of cell walls in plant vascular tissues. Biosynthesis of the aromatic amino acid Phe provides precursors for many secondary metabolites, including lignins and flavonoids. Here, we discovered that MYB transcription factors MYB20, MYB42, MYB43, and MYB85 are transcriptional regulators that directly activate lignin biosynthesis genes and Phe biosynthesis genes during secondary wall formation in Arabidopsis (Arabidopsis thaliana). Disruption of MYB20, MYB42, MYB43, and MYB85 resulted in growth development defects and substantial reductions in lignin biosynthesis. In addition, our data showed that these MYB proteins directly activated transcriptional repressors that specifically inhibit flavonoid biosynthesis, which competes with lignin biosynthesis for Phe precursors. Together, our results provide important insights into the molecular framework for the lignin biosynthesis pathway.

Severe haemorrhagic transformation (HT), a common complication of recombinant tissue plasminogen activator (rtPA) treatment, predicts poor clinical outcomes in acute ischaemic stroke. The search for agents to mitigate this effect includes investigating biomolecules involved in neovascularization. This study examines the role of Cathepsin K (Ctsk) in rtPA-induced HT after focal cerebral ischaemia in mice. After knockout of Ctsk, the gene encoding Ctsk, the outcomes of Ctsk+/+ and Ctsk−/− mice were compared 24 h after rtPA-treated cerebral ischaemia with respect to HT severity, neurological deficits, brain oedema, infarct volume, number of apoptotic neurons and activated microglia/macrophage, blood–brain barrier integrity, vascular endothelial growth factor (VEGF) expression and Akt-mTOR pathway activation. We observed that haemoglobin levels, brain oedema and infarct volume were significantly greater and resulted in more severe neurological deficits in Ctsk−/− than in Ctsk+/+ mice. Consistent with our hypothesis, the number of NeuN-positive neurons was lower and the number of TUNEL-positive apoptotic neurons and activated microglia/macrophage was higher in Ctsk−/− than in Ctsk+/+ mice. Ctsk knockout mice exhibited more severe blood–brain barrier (BBB) disruption, with microvascular endothelial cells exhibiting greater VEGF expression and lower ratios of phospo-Akt/Akt and phospo-mTOR/mTOR than in Ctsk+/+ mice. This study is the first to provide molecular insights into Ctsk-regulated HT after cerebral ischaemia, suggesting that Ctsk deficiency may disrupt the BBB via Akt/mTOR/VEGF signalling, resulting in neurological deficits and neuron apoptosis. Ctsk administration has the potential as a novel modality for improving the safety of rtPA treatment following stroke.

Light is an important environmental factor for plant growth and development. Phytochrome B (phyB), a classical red/far-red light receptor, plays vital role in controlling plant photomorphogenesis and light-induced stomatal opening. Phytohormone abscisic acid (ABA) accumulates rapidly and triggers a series of physiological and molecular events during the responses to multiple abiotic stresses. Recent studies showed that phyB mutant synthesizes more ABA and exhibits improved tolerance to salt and cold stress, suggesting that a crosstalk exists between light and ABA signaling pathway. However, whether ABA signaling components mediate responses to light remains unclear. Here, we showed that SnRK2.6 (Sucrose Nonfermenting 1-Related Protein Kinase 2.6), a key regulator in ABA signaling, interacts with phyB and participates in light-induced stomatal opening. First, we checked the interaction between phyB and SnRK2s, and found that SnRK2.2/2.3/2.6 kinases physically interacted with phyB in yeast and in vitro. We also performed co-IP assay to support that SnRK2.6 interacts with phyB in plant. To investigate the role of SnRK2.6 in red light-induced stomatal opening, we obtained the snrk2.6 mutant and overexpression lines, and found that snrk2.6 mutant exhibited a significantly larger stomatal aperture under red light treatment, while the two independent overexpression lines showed significantly smaller stomatal aperture, indicative of a negative role for SnRK2.6 in red light-induced stomatal opening. The interaction of SnRK2.6 with red light receptor and the negative role of SnRK2.6 in red light-induced stomatal opening provide new evidence for the crosstalk between ABA and red light in guard cell signaling.

AIM To evaluate the prognostic value of triglyceride-glucose (TyG) index in nondiabetic patients with acute coronary syndrome (ACS) with low-density lipoprotein cholesterol (LDL-C) below 1.8 mmol/L. METHODS A total of 1655 nondiabetic patients with ACS with LDL-C below 1.8 mmol/L were included in the analysis. Patients were stratified into two groups. The incidence of acute myocardial infarction (AMI), infarct size in patients with AMI, and major adverse cardiac and cerebral event during a median of 35.6-month follow-up were determined and compared between the two groups. The TyG index was calculated using the following formula: ln [fasting triglycerides (mg/dL)×fasting plasma glucose (mg/dL)/2]. RESULTS Compared with the TyG index ＜8.33 group, the TyG index ≥ 8.33 group had a significantly higher incidence of AMI (21.2% vs. 15.2%, p=0.014) and larger infarct size in patients with AMI [the peak value of troponin I: 10.4 vs. 4.8 ng/ml, p=0.003; the peak value of Creatine kinase MB: 52.8 vs. 22.0 ng/ml, p=0.006; the peak value of myoglobin: 73.7 vs. 46.0 ng/ml, p=0.038]. Although there was no significant difference in mortality between the two groups, the incidence of revascularization of the TyG index ≥ 8.33 group was significantly higher than that of the TyG index ＜8.33 group (8.9% vs. 5.0%, p=0.035). A multivariable Cox regression revealed that the TyG index was positively associated with revascularization [hazard ratio, 1.67; 95% confidence interval, 1.02-2.75; p=0.043]. CONCLUSIONS In nondiabetic patients with ACS with LDL-C below 1.8 mmol/L, a high TyG index level was associated with higher incidence of AMI, larger infarct size, and higher incidence of revascularization. A high TyG index level might be a valid predictor of subsequent revascularization.

Saccharification, the conversion of cellulose to sugar for fermentation-based biofuels, remains problematic for lignocellulosic feedstocks such as wood. Genetic modifications to reduce the amount or change the structure of lignin can improve saccharification efficiency but often result in dwarf plants. Here, we report that overexpression of Pag-MIR408 in hybrid poplar results in a near doubling saccharification efficiency, with no requirement for acid-pretreatment, increased accessibility of secondary cell walls to fungal cellulase and scaffoldin cellulose-binding modules, accompanied by enhanced photosynthesis, and increased number of cambium zone layers, xylem width and vessel diameter. Conversely, Pag-MIR408 loss-of-function plants by CRISPR/Cas9 showed decreased cell wall accessibility. Moreover, miR408 targets LACCASE 19/25, leading to delayed lignification, and modestly reduced lignin content, S/G ratio, as well as the degree of lignin polymerization. This study provides a unique insight into enhanced saccharification efficiency altered wood structure through modulation of the balance between secondary development and lignification.

Ionizing irradiation kills pathogens by destroying nucleic acids without protein structure destruction. However, how pathogens respond to irradiation stress has not yet been fully elucidated. Here, we observed that Pseudomonas aeruginosa PAO1 could release nucleic acids into the extracellular environment under X-ray irradiation. Using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), X-ray irradiation was observed to induce outer membrane vesicle (OMV) formation in P. aeruginosa PAO1. The size distribution of the OMVs of the irradiated PAO1 was similar to that of the OMVs of the non-irradiated PAO1 according to nanoparticle tracking analysis (NTA). The pyocin-related proteins are involved in OMV production in P. aeruginosa PAO1 under X-ray irradiation conditions, and that this is regulated by the key SOS gene recA. The OMV production was significantly impaired in the irradiated PAO1 Δlys mutant, suggesting that Lys endolysin is associated with OMV production in P. aeruginosa PAO1 upon irradiation stress. Meanwhile, no significant difference in OMV production was observed between PAO1 lacking the pqsR, lasR, or rhlR genes and the parent strain, demonstrating that the irradiation-induced OMV biosynthesis of P. aeruginosa was independent of the Pseudomonas quinolone signal (PQS).

Neovascularization and vascular remodeling are functionally important for brain repair after stroke. We show that neutrophils accumulate in the peri-infarct cortex during all stages of ischemic stroke. Neutrophils producing intravascular and intraparenchymal neutrophil extracellular traps (NETs) peak at 3–5 days. Neutrophil depletion reduces blood-brain barrier (BBB) breakdown and enhances neovascularization at 14 days. Peptidylarginine deiminase 4 (PAD4), an enzyme essential for NET formation, is upregulated in peri-ischemic brains. Overexpression of PAD4 induces an increase in NET formation that is accompanied by reduced neovascularization and increased BBB damage. Disruption of NETs by DNase 1 and inhibition of NET formation by genetic ablation or pharmacologic inhibition of PAD increases neovascularization and vascular repair and improves functional recovery. Furthermore, PAD inhibition reduces stroke-induced STING-mediated production of IFN-β, and STING knockdown and IFN receptor-neutralizing antibody treatment reduces BBB breakdown and increases vascular plasticity. Collectively, our results indicate that NET release impairs vascular remodeling during stroke recovery., Following ischemic insult, neovascularization and vascular remodelling play an essential part in the repair of brain damage. Here the authors show that neutrophil extracellular traps serve a detrimental role in the regeneration process, limiting the functional recovery of the brain post injury.

Background Triglyceride glucose (TyG) index is considered a new marker for metabolic disorders. Although recent studies have found an association between TyG index level and vascular disease development, the prognostic value of TyG index in patients with acute myocardial infarction (AMI) remains unclear. Methods A total of 3181 patients with AMI, who underwent coronary angiography, were identified from the Cardiovascular Center of Beijing Friendship Hospital Database Bank and included in the analysis. Patients were stratified into 2 groups according to their baseline TyG index levels: the TyG index 2, smoker, diabetes mellitus, estimated glomerular filtration rate (eGFR) ≥ 60 ml/min/1.73 m2, high-density lipoprotein cholesterol ≥ 1.01 mmol/L and left ventricular ejection fraction (LVEF) ≥ 0.50. The results also revealed that diabetes mellitus, previous AMI, eGFR, LVEF, and multi-vessel/left main coronary artery lesions were independent predictors of MACEs in patients with AMI (all P

Adiabatic calorimetry is one of the main experimental methods to quantitatively study the thermal hazard in chemical process. In this work, a pressure-identification method has been developed to determine the reaction model and evaluate the kinetic parameters in adiabatic process. A theory, named ‘Equivalent adiabatic theory’ was proposed to verify the accuracy of the pressure correction, which states that the calculated generated gas amount is dependable if the equivalent adiabatic initial temperature is constant; otherwise, it is unreliable. Initial conversion calculated by credible generated gas amount can be used as a truth value to determine the kinetic model from models with good fitting by temperature data. Further, this method is applied to two representative substances: 20% DTBP in toluene and 25% CHP in cumene. The validity of this method has been verified by experiment results.

Fully bio-based benzoxazine is classified into sustainable high-performance thermosetting resin and has become current focus in polybenzoxazine field. But lack of bio-based primary diamine restricted the preparation of bis-benzoxazine with high biomass content. In this report, renewable furan-containing diamine (PDFA) derived from furfurylamine was condensed with cardanol/eugenol and formaldehyde under solventless condition to obtain two biomass-based bis-benzoxazine monomers of BBOZ-Ca and BBOZ-Eu. The curing behaviors of two monomers were investigated by non-isothermal DSC method and the results showed that BBOZ-Ca possessed broad processing window comparing with BBOZ-Eu, the characteristic polymerization temperature and activation energy of two monomers were very close to each other, but the total heat releasing (enthalpy of polymerization) of BBOZ-Eu was higher than that of BBOZ-Ca due to its high oxazine content. The TGA results indicated that cured BBOZ-Eu had better thermal resistance than cured BBOZ-Ca, the char yield of cured BBOZ-Eu was 65.4% at 850 °C. Copolymerization with BBOZ-Eu effectively increased the char yield of cured BBOZ-Ca. Isothermal DMA was utilized to further investigate the curing kinetics and the results showed that the storage modulus increased rapidly when polymerization was initiated. The surface properties of cured films were studied using scanning electron microscope (SEM) images and contact angle measurement.

A series of the graphene oxide-ZnAl-layered double hydroxide composites loaded with pesticide chlorpyrifos (CPF/GO-LDH) were fabricated by an exfoliation-restacking method. CPF/GO-LDH composites were characterized by powder X-ray diffraction (XRD), fourier transform infrared spectroscopy (FT-IR), scanning electron microscope (SEM) and transmission electron microscopy (TEM), thermogravimetry analysis and differential scanning calorimetry (TGA-DSC). The interlayer distances of CPF/GO-LDH with various GO/LDH mass ratios were in the range of 0.70–0.87 nm, which were analyzed on the basis of electrostatic interaction between LDH nanosheets and GO substrate. The combustion temperature of CPF in the composites was enhanced 130–170 °C. Release behaviors of CPF/GO-LDH composites in buffer solutions were investigated and analyzed. The sustainable slow releases were observed during the whole stage studied, and the release rates and equilibrium release amounts of CPF were closely dependent on release mediums and GO/LDH mass ratios. The release behaviors of CPF/GO-LDH were fitted with pseudo second-order and parabolic diffusion models. The present study suggested that the CPF/GO-LDH could be potentially applied for controlled-release of the pesticide.

Supplemental Digital Content is available in the text., Background: This study investigated whether the age, creatinine, and ejection fraction (ACEF) score [age (years) /ejection fraction (%) +1 (if creatinine>176μmol/L)] could predict 1-year outcomes following ST-segment elevation myocardial infarction after percutaneous coronary intervention, and whether accuracy could be improved by establishing novel ACEF-derived risk models. Methods: A total of 1146 patients were included. The study endpoint was 1-year major adverse cardio-cerebrovascular events, including all-cause death, nonfatal myocardial infarction, unplanned revascularization, and nonfatal stroke. Accuracy was defined with area under the curve by receiver-operating characteristic curve analysis. Results: The incidence of 1-year major adverse cardio-cerebrovascular event increased with the rising age, creatinine, and ejection fraction score tertiles (4.8%, 8.4%, and 15.2%, P < 0.001 for all). Higher ACEF score was significantly associated with an increased risk of the endpoint in overall (odds ratio = 3.75, 95% confidence interval, 2.44–5.77, P < 0.001) and in subgroups (all P < 0.05). The accuracy of the ACEF score was equivalent to the other complex risk scores. The combination of ACEF, and diabetes (ACEF-diabetes score) yielded a superior discriminatory ability than the original ACEF score (increase in C-statistic from 0.67 to 0.71, P = 0.048; continuous net reclassification improvement = 51.9%, 95% confidence interval, 33.4–70.5%, P < 0.001; integrated discrimination improvement = 0.020, 95% confidence interval, 0.011–0.030, P < 0.001). Conclusions: The simplified ACEF score performed well in predicting 1-year outcomes in ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention. The novel ACEF-diabetes score provided a better predictive value and thus may help stratify high-risk patients and potentially facilitate decision making.

Aims The purpose of this study was to investigate the therapeutic effect of artemisinin (ART) on atherosclerosis and explore the molecular mechanisms involved by RNA sequencing (RNA-Seq). Main methods Eight-week-old male ApoE−/- mice were treated with ART for eight weeks. Atherosclerotic lesion sizes were determined by Oil Red O staining, and RNA-Seq was used to detect the profile of differentially expressed genes following the administration of ART. The expressions of contractile phenotypic markers were detected by western blot and qRT-PCR, and the ability of the MOVAS cells to migrate and proliferate were assessed using the wound healing and CCK8 assays. Key findings Artemisinin treatment significantly reduced plaque area in the ApoE−/- mice and increased the expression of contractile phenotypic markers. RNA-Seq of aorta tissue revealed a distinct change in gene expression patterns after the mice were treated with ART. Our bioinformatics analysis demonstrated that the most prominently enriched pathway was a set of genes involved in vascular smooth muscle contractile function. Using an in vitro cell model, we demonstrated that ART could effectively reverse PDGF-activated MOVAS migration and proliferation, and elevate the level of proteins involved in the contractile phenotype. Significance We provide in vivo and in vitro evidence supporting a role for ART in the suppression of atherosclerosis, partly through the inhibition of vascular smooth muscle cell phenotype switching to a de-differentiated phenotype. These data further advances our understanding for a potential role for ART and suggests that ART is an excellent candidate for the treatment of atherosclerosis.

Almond domestication is marked by the selection of sweet kernel genotypes. A recent study (Sanchez-Perez et al.) reveals that a nonsynonymous point mutation in a bHLH transcription factor prevents transcription of the two P450 genes in the amygdalin biosynthetic pathway, resulting in the sweet kernel trait.

Background: Exacerbated blood-brain barrier (BBB) damage is related with tissue plasminogen activator (tPA)-induced brain hemorrhage after stroke. Platelets have long been recognized as the cellular orchestrators of primary haemostasis. Recent studies have demonstrated further that platelets are required for supporting intact mature blood vessels and play a crucial role in maintaining vascular integrity during inflammation. Therefore, we sought to investigate whether platelets could reduce tPA-induced deterioration of cerebrovascular integrity and lead to less hemorrhagic transformation. Methods: Mice were subjected to models of collagenase-induced intracerebral hemorrhage (ICH) and transient middle cerebral artery (MCA) occlusion. After 2 hours of MCA occlusion, tPA (10 mg/kg) was administered as an intravenous bolus injection of 1 mg/kg followed by a 9 mg/kg infusion for 30 minutes. Immediately after tPA treatment, mice were transfused with platelets. Hemorrhagic volume, infarct size, neurological deficit, tight junction and basal membrane damages, endothelial cell apoptosis, and extravascular accumulation of circulating dextran and IgG, and Evans blue were quantified at 24 hours. Results: Platelet transfusion resulted in a significant decrease in hematoma volume after ICH. In mice after ischemia, tPA administration increased brain hemorrhage transformation and this was reversed by resting but not activated platelets. Consistent with this, we observed that tPA-induced brain hemorrhage was dramatically exacerbated in thrombocytopenic mice. Transfusion of resting platelets ameliorated tPA-induced loss of cerebrovascular integrity and reduced extravascular accumulation of circulating serum proteins and Evans blue, associated with improved neurological functions after ischemia. No changes were found for infarct volume. Inhibition of platelet receptor glycoprotein VI (GPVI) blunted the ability of platelets to attenuate tPA-induced BBB disruption and hemorrhage after ischemia. Conclusions: Our findings demonstrate the importance of platelets in safeguarding BBB integrity and suggest that transfusion of resting platelets may be useful to improve the safety of tPA thrombolysis in ischemic stroke.

N-Nitrodihydroxyethyl dinitrate (DINA) is a commonly used energetic material. In this work, the effect of diethanolamine (DEA) on the thermal stability of DINA was studied. Firstly, the decomposition kinetics of DINA under the influence of DEA was analyzed by applying dynamic differential scanning calorimeter (DSC) experiments. Then, isothermal DSC tests with the “Interruption and re-scanning” method determined that the decomposition reactions of DINA containing 29% DEA consists of four continuous steps: the first step is a n-order reaction, and the last three steps are autocatalytic reactions. The kinetic parameters of the four-step reaction model were calculated by model-fitting method. Finally, the thermal risk parameter like TMRad was predicted based on the kinetic parameters, which has certain guiding significance for the process production of DINA.

Factors leading to the formation of a hexahydroaporphine-like cyclizing side product were studied systematically for the first time and the ratio of this side product was controlled effectively. To understand better the electronic effect of substrates on the formation of side products, different 1-benzyloctahydroisoquinolines with substituted groups on nitrogen or benzene ring were compared. A plausible mechanism of cyclizing reaction was proposed, and key intermediates as well as transition states were analyzed using DFT calculations.

Main-chain type polybenzoxazine precursors (MCPPs) are a current focus in the polybenzoxazine field for their improved char yield, thermal stability and film-forming ability compared to monomeric benzoxazines resins. To improve sustainability, there is an urgent need to utilize renewable feedstocks instead of fossil-based chemicals in the preparation of MCPPs. Here, renewable furfurylamine and salicylaldehyde were used as staring materials to synthesize high biomass content MCPPs through a three-steps polymerization route. The number-average molecular weight of a bio-based MCPP is 6100 g/mol, and it has a polydispersity index of 1.7. The furan-containing MCPP shows two polymerization stages during heating; the main exothermic stage at approximately 250 °C is attributed to the ring-opening polymerization of benzoxazine units, and the secondary stage at higher temperature is due to a crosslinking reaction between furan rings, forming furfurylamine Mannich bridges, and an oxidization-induced coupling reaction. The average activation energy of an MCPP is approximately 173.8 kJ/mol. The 240 °C-cured film is transparent with a glass transition temperature of over 300 °C. The crosslinked film shows a high thermal stability and a char yield of greater than 66% in a nitrogen atmosphere. Scanning electron microscopy (SEM) images indicated that a defect-free film can be made by controlling the curing parameters.

Background: Growth differentiation factor 11 (GDF11), a member of transforming growth factor-β (TGF-β) superfamily, was shown to rejuvenate cardiac and skeletal muscle function and to improve cerebral vasculature and neurogenesis in old mice. However, recent experimental data reported that raising GDF11 levels inhibited skeletal muscle regeneration and had no effect on cardiac hypertrophy. Our aim was to investigate the effects of GDF11 on brain repair during the recovery phase after stroke. Methods: Mice were subjected to distal middle cerebral artery occlusion, and recombinant GDF11 (rGDF11) was injected intraperitoneally once a day during days 7–13 after stroke. Neuronal precursor cells (NPCs) proliferation and angiogenesis were assayed at 14 days. Neuronal regeneration was assayed at 42 days. The beam-walking test and CatWalk were used to evaluate behavioral functions. Downstream pathways of GDF11 were also investigated. Results: GDF11 was upregulated in the ipsilateral peri-infarct cortex and subventricular zone (SVZ) at 14 days after stroke. Treatment with rGDF11 enhanced the number of newborn NPCs and endothelial cells, microvascular length and area, and brain capillary perfusion. Western blots showed that rGDF11 upregulated brain-derived neurotrophic factor (BDNF) and increased the levels of proangiogenic factor angiopoietin-2 (Ang-2) and phosphorylation of vascular endothelial growth factor receptor-2 (VEGFR-2). We also found that rGDF11 upregulated the transcription factors Smad2 and Smad3 phosphorylation, but these activations were blocked by a TGF-β receptor inhibitor SB431542. Moreover, rGDF11-induced angiogenic remodeling and NPCs proliferation were reversed by injection of SB431542, suggesting that GDF11 may exert its effect via the TGF-β/Smad2/3 signaling pathway. Finally, treating mice with rGDF11 resulted in a significant increase in neuronal regeneration and functional recovery. Conclusion: GDF11 promoted neurogenesis and angiogenesis and contributed to functional recovery after stroke in mice.

Synthetic scaffolds with multifunctional properties, including angiogenesis and osteogenesis capacities, play an essential role in accelerating bone regeneration. In this study, various concentrations of Cu/Zn ions were incorporated into biphasic calcium phosphate (BCP) scaffolds, and then growth differentiation factor-5 (GDF-5)-loaded poly(lactide-co-glycolide) (PLGA) microspheres were attached onto the ion-doped scaffold. The results demonstrated that with increasing concentration of dopants, the scaffold surface gradually changed from smooth grain crystalline to rough microparticles, and further to a nanoflake film. Additionally, the mass ratio of β-tricalcium phosphate/hydroxyapatite increased with the dopant concentration. Furthermore, GDF-5-loaded PLGA microspheres attached onto the BCP scaffold surface exhibited a sustained release. In vitro co-culture of bone mesenchymal stem cells and vascular endothelial cells showed that the addition of Cu/Zn ions and GDF-5 in the BCP scaffold not only accelerated cell proliferation, but also promoted cell differentiation by enhancing the alkaline phosphatase activity and bone-related gene expression. Moreover, the vascular endothelial growth factor secretion level increased with the dopant concentration, and attained a maximum when GDF-5 was added into the ions-doped scaffold. These findings indicated that BCP scaffold co-doped with Cu/Zn ions exhibited a combined effect of both metal ions, including angiogenic and osteogenic capacities. Moreover, GDF-5 addition further enhanced both the angiogenic and osteogenic capacities of the BCP scaffold. The Cu/Zn co-incorporated BCP scaffold-derived GDF-5 sustained release system produced multifunctional scaffolds with improved angiogenesis and osteogenesis properties.

Lignin biosynthetic enzymes form a complex on the ER. Here we highlight how the recent identification of the membrane steroid binding proteins (MSBPs) as the structural component of the complex have revealed the molecular mechanism underlying the monolignol metabolon formation.

The Pd-catalyzed homodimerization with respect to arylsulfonyl chlorides as an efficient method for the synthesis of biaryls has been developed. This desulfonylative reaction which was performed at reflux in 1,4-dioxane for 4 h under air afforded the desired products in good to excellent yields.

Fluorinated graphene (FG) possess distinctively novel properties different from graphene and is suitable for many biomedical applications. However, the hydrophobic nature and inert properties of FG limit its further application as a biological material. Here we show the preparation of nano-sized FG (ca. 60 nm) that exhibits high NIR absorbance for photothermal therapy. In order to make it stable in physiological solutions, the FG is enriched with oxygen and followed by covalent binding with chitosan as a novel pH-responsive nanocarrier. Furthermore, controlled loading of two anticancer drugs, doxorubicin (DOX) and camptothecin (CPT) has been realized and the functionalized ultrasmall FG shows remarkably high cytotoxicity toward Hela cancer cells compared to that loaded with either CPT or DOX only. This work established nano-sized FG as a novel photothermal agent due to its small size and can be used a stimulus-responsive nanocarrier for mixed drug delivery and combined therapy.

The effects of temperature and relative humidity on the hydrolytic degradation of poly(p-dioxanone) (PPDO) were investigated. The hydrolytic degradation behaviors were monitored by tracing the changes of water absorption, mechanical and crystalline properties, molecular weight and its distribution, surface morphologies, as well as infrared absorption peaks and hydrogen chemical shifts during the degradation. It is found that the water absorption increases whilst the intrinsic viscosity, tensile strength and elongation at break decrease as the temperature or relative humidity increases. With degradation time growing, the molecular weight drops and its distribution broadens. The crystallinity of PPDO has a tendency to increase at first and then to decrease, while the crystalline structure is not significantly changed. At the same time, some cracks are observed on the surface and keep growing and deepening. All results show that temperature plays more significant roles than relative humidity during the degradation. The analyses of Fourier transform infrared spectroscopy and hydrogen nuclear magnetic resonance spectroscopy reveal that the degradation of PPDO is a predominant hydrolysis of ester linkages.

An efficient approach for the synthesis of N-arylated amides was developed via copper(II) triflate-catalyzed direct oxidation of (aryl)methylamines to primary arylamides by air and subsequent N-arylation by diaryliodonium salts. Various substituted benzylamines could be applied in the reaction, providing a series of N-arylated amides in moderate to good yields. This method showed convenient, practical, and environment friendly advantages.

Fish intestine is a byproduct of fish, which is often discarded and causes environmental pollution. In this study, the hydrolysates, with Hydroxyl-Radical-Scavenging Activity (HRSA), were prepared grass carp intestine protein by hydrolysis with complex enzyme. The hydrolytic process was monitored by HRSA and the hydrolysis conditions were optimized as follows: reaction time of 2 h, temperature 50°C, pH 6.5 and 12 mg complex enzyme 50 U/g protein. Under these conditions, maximum HRSA was obtained. The Protein Hydrolysates (PHs) were fractionated into four ranges on the basis of molecular weight using a gel column chromatography. Results indicate that PHs in the PH 3 induced the highest HRSA.

Metabolon-formation governs the biosynthetic efficiency of natural plant products. Identification of membrane-anchored proteins has now led to discovery of the metabolic channelling mechanism of phenylpropanoid biosynthesis.

Excessive formation of advanced glycation end products (AGEs) impairs voltage-gated potassium (Kv) channels in rat coronary artery smooth muscle cells (CSMCs), resulting in weakened Kv-mediated coronary vasodilation. We hypothesized that induction of the nuclear factor-κB (NF-κB) signaling pathway by AGEs plays a significant role in the regulation of Kv channel-mediated vasodilation in Zucker diabetic fatty (ZDF) rats. Assays of mRNA transcripts, protein expression, and intracellular localization as well as patch-clamp experiments in cultured CSMCs revealed that AGEs significantly induced activation of the NF-κB signaling pathway, reduced Kv1.2/1.5 expression, and inhibited Kv currents. In addition, silencing of the receptor for AGEs (RAGE) or p65 with siRNA and treatment with alagrebrium (ALA) or pyrrolidine dithiocarbamate (PDTC) alleviated the AGE-induced impairment of Kv channels in CSMCs. Compared with Zucker lean (ZL) rats, the amount of AGEs, RAGE protein expression, and NF-κB activity in coronary arteries were higher in ZDF rats; whereas Kv1.2/1.5 expression was significantly lower in ZDF rats. Reduced Kv1.2/1.5 expression in coronary arteries and impaired Kv-mediated coronary relaxation tested by wire myography in ZDF rats were markedly improved by treatment with aminoguanidine (AG), ALA, or PDTC. These effects were accompanied by diminished NF-κB activity, inflammation, and oxidative stress. Taken together, these results indicate that an increased interaction between AGEs and RAGE in diabetic rats leads to impaired Kv channel-mediated coronary vasodilation. Moreover, activation of the NF-κB signaling pathway and a subsequent increase of inflammation and oxidative stress may play an important role in AGE-induced impairment of coronary vasodilation in diabetes.

Different percentage of PdO composited TiO2 photocatalysts (TiO2-PdOX%, X ≥ 1.5) are prepared using the sol-gel way. It can be revealed that the inducted Pd ions play a role of PdO surface species instead of entering into the TiO2 crystal lattice determined by the characterization measurements of X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and High-resolution transmission electron microscopy (HRTEM). The behaviors of photogenerated electron-hole pairs and band structure of the synthesized TiO2-PdOX% (X ≥ 1.5) photocatalysts are investigated by Photoluminescence (PL), PL lifetime decay curves, XPS valence band (VB) spectra, the density-functional theory (DFT) calculation and UV–vis diffuse reflectance spectra. The TiO2-PdOX% (X ≥ 1.5) photocatalysts exhibit higher activity for conversion of CO2 to CH4 than pristine TiO2 due to the presence of PdO. The inactivation mechanism for TiO2-PdOX% photoreduction is also discussed. This work can further explain the influence of surface species on photocatalytic performance.

The evolution of lignin biosynthesis was critical in the transition of plants from an aquatic to an upright terrestrial lifestyle. Lignin is assembled by oxidative polymerization of two major monomers, coniferyl alcohol and sinapyl alcohol. Although two recently discovered laccases, LAC4 and LAC17, have been shown to play a role in lignin polymerization in Arabidopsis thaliana, disruption of both genes only leads to a relatively small change in lignin content and only under continuous illumination. Simultaneous disruption of LAC11 along with LAC4 and LAC17 causes severe plant growth arrest, narrower root diameter, indehiscent anthers, and vascular development arrest with lack of lignification. Genome-wide transcript analysis revealed that all the putative lignin peroxidase genes are expressed at normal levels or even higher in the laccase triple mutant, suggesting that lignin laccase activity is necessary and nonredundant with peroxidase activity for monolignol polymerization during plant vascular development. Interestingly, even though lignin deposition in roots is almost completely abolished in the lac11 lac4 lac17 triple mutant, the Casparian strip, which is lignified through the activity of peroxidase, is still functional. Phylogenetic analysis revealed that lignin laccase genes have no orthologs in lower plant species, suggesting that the monolignol laccase genes diverged after the evolution of seed plants.

There is considerable debate over the capacity of the cell wall polymer lignin to incorporate unnatural monomer units. We have identified Tnt1 retrotransposon insertion mutants of barrel medic ( Medicago truncatula ) that show reduced lignin autofluorescence under UV microscopy and red coloration in interfascicular fibers. The phenotype is caused by insertion of retrotransposons into a gene annotated as encoding cinnamyl alcohol dehydrogenase, here designated M. truncatula CAD1 . NMR analysis indicated that the lignin is derived almost exclusively from coniferaldehyde and sinapaldehyde and is therefore strikingly different from classical lignins, which are derived mainly from coniferyl and sinapyl alcohols. Despite such a major alteration in lignin structure, the plants appear normal under standard conditions in the greenhouse or growth chamber. However, the plants are dwarfed when grown at 30 °C. Glycome profiling revealed an increased extractability of some xylan and pectin epitopes from the cell walls of the cad1-1 mutant but decreased extractability of others, suggesting that aldehyde-dominant lignin significantly alters cell wall structure.

Water sorption and mechanical properties of perfluoro sulfonated acids (PFSAs), Aquivion and Nafion, are compared under environmentally controlled conditions from 25 to 120 degrees C and water activities of 00.95. Under dry conditions Nafion and Aquivion have thermal transitions at 60 degrees C and 95 degrees C, respectively, where the elastic modulus decreases rapidly with increasing temperature. Below their thermal transition temperatures water sorption plasticizes both PFSAs; the elastic moduli decrease with increasing water activity. Above the thermal transition water sorption stiffens both polymers; increasing the water activity from 0 to 0.01 increases the elastic moduli by a factor >10. Plasticization and stiffening are reversible with changing water activity at constant temperature. The thermal transition in PFSAs is suggested to result from reversible clustering of ionic groups. The higher thermal transition temperature for Aquivion is suggested to reduce the risk of membrane thinning and failure due to creep. (c) 2013 Wiley Periodicals, Inc. J. Polym. Sci. Part B: Polym. Phys. 2013, 51, 915925

Angiogenic response is essential for ischemic brain repair. The von Willebrand factor (VWF)-cleaving protease disintegrin and metalloprotease with thrombospondin type I motif, member 13 (ADAMTS13) is required for endothelial tube formation in vitro, but there is currently no in vivo evidence supporting a function of ADAMTS13 in angiogenesis. Here we show that mice deficient in ADAMTS13 exhibited reduced neovascularization, brain capillary perfusion, pericyte and smooth muscle cell coverage on microvessels, expression of the tight junction and basement membrane proteins, and accelerated blood-brain barrier (BBB) breakdown and extravascular deposits of serum proteins in the peri-infarct cortex at 14 days after stroke. Deficiency of VWF or anti-VWF antibody treatment significantly increased microvessels, perfused capillary length, and reversed pericyte loss and BBB changes in Adamts13-/- mice. Furthermore, we observed that ADAMTS13 deficiency decreased angiopoietin-2 and galectin-3 levels in the isolated brain microvessels, whereas VWF deficiency had the opposite effect. Correlating with this, overexpression of angiopoietin-2 by adenoviruses treatment or administration of recombinant galectin-3 normalized microvascular reductions, pericyte loss, and BBB breakdown in Adamts13-/- mice. The vascular changes induced by angiopoietin-2 overexpression and recombinant galectin-3 treatment in Adamts13-/- mice were abolished by the vascular endothelial growth factor receptor-2 antagonist SU1498. Importantly, treating wild-type mice with recombinant ADAMTS13 at 7 days after stroke markedly increased neovascularization and vascular repair and improved functional recovery at 14 days. Our results suggest that ADAMTS13 controls key steps of ischemic vascular remodeling and that recombinant ADAMTS13 is a putative therapeutic avenue for promoting stroke recovery.

Tissue plasminogen activator (tPA) is an effective treatment for ischemic stroke, but its neurotoxicity is a significant problem. Here we tested the hypothesis that recombinant ADAMTS 13 (rADAMTS 13) would reduce tPA neurotoxicity in a mouse model of stroke. We show that treatment with rADAMTS 13 in combination with tPA significantly reduced infarct volume compared with mice treated with tPA alone 48 hours after stroke. The combination treatment significantly improved neurological deficits compared with mice treated with tPA or vehicle alone. These neuroprotective effects were associated with significant reductions in fibrin deposits in ischemic vessels and less severe cell death in ischemic brain. The effect of rADAMTS13 on tPA neurotoxicity was mimicked by the N-methyl-D-aspartate (NMDA) receptor antagonist M-801 and was abolished by injection of NMDA. Moreover, rADAMTS 13 prevents the neurotoxicity effect of tPA, by blocking its interaction with the NMDA receptor NR2B and the attendant phosphorylation of NR2B and activation of ERK1/2. Finally, the NR2B-specific NMDA receptor antagonist ifenprodil abolished tPA neurotoxicity and rADAMTS 13 treatment had no further beneficial effect. Our data suggest that the combination of rADAMTS 13 and tPA may provide a novel treatment of ischemic stroke by diminishing the neurotoxic effects of exogenous tPA.

Objective— We investigated relationships between statin and niacin/statin combination therapy and the concentration of high-density lipoprotein particles (HDL-P) and cholesterol efflux capacity, 2 HDL metrics that might better assess cardiovascular disease risk than HDL-cholesterol (HDL-C) levels. Approach— In the Carotid Plaque Composition Study, 126 subjects with a history of cardiovascular disease were randomized to atorvastatin or combination therapy (atorvastatin/niacin). At baseline and after 1 year of treatment, the concentration of HDL and its 3 subclasses (small, medium, and large) were quantified by calibrated ion mobility analysis (HDL-P IMA ). We also measured total cholesterol efflux from macrophages and ATP-binding cassette transporter A1 (ABCA1)–specific cholesterol efflux capacity. Results— Atorvastatin decreased low-density lipoprotein cholesterol by 39% and raised HDL-C by 11% ( P =0.0001) but did not increase HDL-P IMA or macrophage cholesterol efflux. Combination therapy raised HDL-C by 39% ( P IMA by only 14%. Triglyceride levels did not correlate with HDL-P IMA ( P =0.39), in contrast to their strongly negative correlation with HDL-C ( P P P =0.013) in statin-treated subjects, with or without niacin therapy. Conclusions— Statin therapy increased HDL-C levels but failed to increase HDL-P IMA . It also reduced ABCA1-specific cholesterol efflux capacity. Adding niacin to statin therapy increased HDL-C and macrophage efflux, but had much less effect on HDL-P IMA . It also failed to improve ABCA1-specific efflux, a key cholesterol exporter in macrophages. Our observations raise the possibility that niacin might not target the relevant atheroprotective population of HDL.

Objective Tissue plasminogen activator (tPA) is approved for treatment of acute ischemic stroke, but it increases the risk of cerebral hemorrhage. Accumulating evidence suggests that von Willebrand factor (VWF) plays a pivotal role in thrombus formation and microcirculatory disturbances after ischemic stroke. By cleaving VWF, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) protects mice from stroke. Therefore, we hypothesized that recombinant ADAMTS13 (rADAMTS13) could increase the safety of tPA thrombolysis in stroke. Methods We examined blood–brain barrier (BBB) permeability after intraventricular injection of tPA, VWF, and rADAMTS13 in nonischemic mice. We investigated the role of rADAMTS13 on reducing tPA-induced BBB dysfunction and cerebral hemorrhage in a mouse stroke model. Results Intraventricular injection of tPA or VWF under nonischemic conditions resulted in a significant increase in BBB permeability. In contrast, rADAMTS13 blocked both tPA- and VWF-induced BBB opening. BBB disruption following stroke was exacerbated by intravenous administration of tPA, but this was attenuated by injection of rADAMTS13. Correspondingly, tPA-associated hemorrhage after stroke was significantly reduced by rADAMTS13. The antihemorrhagic effect of rADAMTS13 was reversed by injection of recombinant VWF. We also showed that rADAMTS13 inhibited tPA-mediated upregulation of vascular endothelial growth factor (VEGF) in vascular endothelium after stroke. The upregulation of VEGF was suppressed by either an Akt inhibitor wortmannin or a Rho kinase inhibitor fasudil. Furthermore, rADAMTS13 downregulated tPA-induced phosphorylation of Akt and activation of RhoA. Interpretation These findings demonstrate that the VWF-cleaving protease rADAMTS13 reduced tPA-induced hemorrhage by regulating BBB integrity, and suggest that this effect may occur through the Akt/RhoA-mediated VEGF pathways. ANN NEUROL 2013;73:189–198

Novel high near-infrared reflecting inorganic pigments Y6-xSmxMoO12+σ (03+ in yttrium molybdate through a simple solid-state reaction method. The composites were characterized using scanning electron microscope, X-ray diffraction, UV-vis-NIR spectrophotometer and CIE 1976 L*a*b* color scales. The substitution of Sm3+ for Y3+ in Y6MoO12 changed the color from bright yellow to dark yellow and most importantly increased near-infrared reflectance in the wavelength range of 700-2500 nm. The chemical stability of the pigments was also evaluated.

Methanol and ethanol sorption and transport in 1100 equivalent weight H+Nafion were compared to water sorption and transport. Sorption isotherms for methanol and ethanol were fit to a solvation shell model, with four molecules in the first solvation shell. The larger molar volume of alcohols resulted in greater swelling from sorption. Proton conductivity is five times greater for water saturated Nafion than alcohol saturated Nafion. Alcohol pervaporation and alcohol vapor permeation is slower than water pervaporation and water vapor permeation. The Nafion/vapor interfacial transport coefficients for alcohols and water scale with vapor pressure. The diffusivity of water is 3–4 times greater than the diffusivity of methanol and ethanol. The results indicate that alcohols sorb by solvating the sulfonic acid groups, similar to the interaction of water with Nafion. Larger alcohol molecules diffuse slower in the hydrophilic channels of Nafion than the smaller water molecules.