Pro-Oxidant Auranofin and Glutathione-Depleting Combination Unveils Synergistic Lethality in Glioblastoma Cells with Aberrant Epidermal Growth Factor Receptor Expression.

Glioblastoma (GBM) is the most prevalent and advanced malignant primary brain tumor in adults. GBM frequently harbors epidermal growth factor receptor (EGFR) wild-type (EGFRwt) gene amplification and/or EGFRvIII activating mutation. EGFR-driven GBM relies on the thioredoxin (Trx) and/or glutathione (GSH) antioxidant systems to withstand the excessive production of reactive oxygen species (ROS). The impact of EGFRwt or EGFRvIII overexpression on the response to a Trx/GSH co-targeting strategy is unknown. In this study, we investigated Trx/GSH co-targeting in the context of EGFR overexpression in GBM. Auranofin is a thioredoxin reductase (TrxR) inhibitor, FDA-approved for rheumatoid arthritis. L-buthionine-sulfoximine (L-BSO) inhibits GSH synthesis by targeting the glutamate-cysteine ligase catalytic (GCLC) enzyme subunit. We analyzed the mechanisms of cytotoxicity of auranofin and the interaction between auranofin and L-BSO in U87MG, U87/EGFRwt, and U87/EGFRvIII GBM isogenic GBM cell lines. ROS-dependent effects were assessed using the antioxidant N-acetylsteine. We show that auranofin decreased TrxR1 activity and increased ROS. Auranofin decreased cell vitality and colony formation and increased protein polyubiquitination through ROS-dependent mechanisms, suggesting the role of ROS in auranofin-induced cytotoxicity in the three cell lines. ROS-dependent PARP-1 cleavage was associated with EGFRvIII downregulation in U87/EGFRvIII cells. Remarkably, the auranofin and L-BSO combination induced the significant depletion of intracellular GSH and synergistic cytotoxicity regardless of EGFR overexpression. Nevertheless, molecular mechanisms associated with cytotoxicity were modulated to a different extent among the three cell lines. U87/EGFRvIII exhibited the most prominent ROS increase, P-AKT(Ser-473), and AKT decrease along with drastic EGFRvIII downregulation. U87/EGFRwt and U87/EGFRvIII displayed lower basal intracellular GSH levels and synergistic ROS-dependent DNA damage compared to U87MG cells. Our study provides evidence for ROS-dependent synergistic cytotoxicity of auranofin and L-BSO combination in GBM in vitro. Unraveling the sensitivity of EGFR-overexpressing cells to auranofin alone, and synergistic auranofin and L-BSO combination, supports the rationale to repurpose this promising pro-oxidant treatment strategy in GBM.

Solubilities of Ethylene and Carbon Dioxide Gases in Lithium-Ion Battery Electrolyte.

During Li-ion battery operation, (electro)chemical side reactions occur within the cell that can promote or degrade performance. These complex reactions produce byproducts in the solid, liquid, and gas phases. Studying byproducts in these three phases can help optimize battery lifetimes. To relate the measured gas-phase byproducts to species dissolved in the liquid-phase, equilibrium proprieties such as the Henry's law constants are required. The present work implements a pressure decay experiment to determine the thermodynamic equilibrium concentrations between the gas and liquid phases for ethylene (C2H4) and carbon dioxide (CO2), which are two gases commonly produced in Li-ion batteries, with an electrolyte of 1.2 M LiPF6 in 3:7 wt/wt ethylene carbonate/ethyl methyl carbonate and 3 wt % fluoroethylene carbonate (15:25:57:3 wt % total composition). The experimentally measured pressure decay curve is fit to an analytical dissolution model and extrapolated to predict the final pressure at equilibrium. The relationship between the partial pressures and concentration of dissolved gas in electrolyte at equilibrium is then used to determine Henry's law constants of 2.0 × 104 kPa for C2H4 and k CO2 = 1.1 × 104 kPa for CO2. These values are compared to Henry's law constants predicted from density functional theory and show good agreement within a factor of 3.

Revisiting poly(vinyl chloride) reactivity in the context of chemical recycling.

Poly(vinyl chloride) (PVC) is one of the highest production volume polymers due to its many applications, and it is one of the least recycled due to its chemical structure and frequent formulation with additives. Developing efficient PVC recycling techniques would enable PVC waste to be reused or repurposed in other processes. Within this context, the literature on PVC modification offers considerable insight into versatile reaction pathways, potentially inspiring new approaches for repurposing PVC waste into value-added products. This perspective provides an overview of PVC functionalization through a lens of chemical recycling, discussing various PVC reactivity trends and their applications with a critical assessment and future outlook of their recycling implications.

Pharmacokinetic interaction between rifampicin and clindamycin in staphylococcal osteoarticular infections.

OBJECTIVES: Oral combination of clindamycin and rifampicin is relevant for the treatment of staphylococcal osteoarticular infection (SOAIs). However, rifampicin induces CYP3A4, suggesting a pharmacokinetic interaction with clindamycin with unknown pharmacokinetic/pharmacodynamic (PK/PD) consequences. This study aimed to quantify clindamycin PK/PD markers before and during rifampicin co-administration in SOAI. METHODS: Patients with SOAI were included. After initial intravenous antistaphylococcal treatment, oral therapy was started with clindamycin (600 or 750 mg t.i.d.), followed by addition of rifampicin 36 h later. Population PK analysis was performed using the SAEM algorithm. PK/PD markers were compared with and without rifampicin co-administration, each patient being his own control. RESULTS: In 19 patients, clindamycin median (range) trough concentrations were 2.7 (0.3-8.9) mg/L and <0.05 (<0.05-0.3) mg/L before and during rifampicin administration, respectively. Rifampicin co-administration increased clindamycin clearance by a factor 16 and reduced the AUC0-8h/MIC by a factor 15 (P < 0.005). Clindamycin plasma concentrations were simulated for 1000 individuals, without and with rifampicin. Against a susceptible Staphylococcus aureus strain (clindamycin MIC 0.0625 mg/L), >80% of individuals would reach all proposed PK/PD targets without co-administration of rifampicin, even with low clindamycin dose. For the same strain, when rifampicin was co-administered, the probability to reach clindamycin PK/PD targets dropped to 1% for %fT>MIC = 100% and to 6% for AUC0-24h/MIC > 60, even with high clindamycin dose. CONCLUSION: Rifampicin co-administration with clindamycin has a high impact on clindamycin exposure and PK/PD targets in SOAI, which could result in clinical failure even for fully susceptible strains.

Molecular Analysis of the Superior Efficacy of a Dual Epidermal Growth Factor Receptor (EGFR)-DNA-Targeting Combi-Molecule in Comparison with Its Putative Prodrugs 6-Mono-Alkylamino- and 6,6-Dialkylaminoquinazoline in a Human Osteosarcoma Xenograft Model.

Background: ZR2002 is a dual EGFR-DNA-targeting combi-molecule that carries a chloroethyl group at the six-position of the quinazoline ring designed to alkylate DNA. Despite its good pharmacokinetics, ZR2002 is metabolized in vivo into dechlorinated metabolites, losing the DNA-alkylating function required to damage DNA. To increase the DNA damage activity in tumor cells in vivo, we compared ZR2002 with two of its 6-N,N-disubstituted analogs: "JS61", with a nitrogen mustard function at the six-position of the quinazoline ring, and "JS84", with an N-methyl group. Methods: Tumor xenografts were performed with the human Saos-2 osteosarcoma cell line expressing EGFR. Mice were treated with ZR2002, JS84 or JS61, and the tumor burden was measured with a caliper and CT/PET imaging. Drug metabolism was analyzed with LC-MS. EGFR and ɣ-H2AX phosphorylation were quantified via Western blot analysis and immunohistochemistry. Results: In vivo analysis showed that significant tumor growth inhibition was only achieved when ZR2002 was administered in its naked form. The metabolic dealkylation of JS61 and JS84 did not release sufficient concentrations of ZR2002 for the intratumoral inhibition of P-EGFR or enhanced levels of P-H2AX. Conclusions: The results in toto suggest that intratumoral concentrations of intact ZR2002 are correlated with the highest inhibition of P-EGFR and induction of DNA damage in vivo. ZR2002 may well represent a good drug candidate for the treatment of EGFR-expressing osteosarcoma.

Concentration-dependent Cycling of Phenothiazine-based Electrolytes in Nonaqueous Redox Flow Cells.

Increasing redox-active species concentrations can improve viability for organic redox flow batteries by enabling higher energy densities, but the required concentrated solutions can become viscous and less conductive, leading to inefficient electrochemical cycling and low material utilization at higher current densities. To better understand these tradeoffs in a model system, we study a highly soluble and stable redox-active couple, N-(2-(2-methoxyethoxy)ethyl)phenothiazine (MEEPT), and its bis(trifluoromethanesulfonyl)imide radical cation salt (MEEPT-TFSI). We measure the physicochemical properties of electrolytes containing 0.2-1 M active species and connect these to symmetric cell cycling behavior, achieving robust cycling performance. Specifically, for a 1 M electrolyte concentration, we demonstrate 94% materials utilization, 89% capacity retention, and 99.8% average coulombic efficiency over 435 h (100 full cycles). This demonstration helps to establish potential for high-performing, concentrated nonaqueous electrolytes and highlights possible failure modes in such systems.

Association between childhood cognitive skills & adult suicidal behavior: A systematic review and meta-analysis.

BACKGROUND: It is unclear whether cognitive skill deficits during childhood carry risk for suicide attempt or mortality later in adulthood at the population level. We conducted a systematic review and meta-analysis of population-based studies examining the association between childhood cognitive skills and adult suicidal behavior, namely attempt and mortality. METHOD: We systematically searched databases for articles then extracted study characteristics and estimates on the association between childhood cognitive skills (i.e., IQ or school performance at age ≤ 18 years) and later suicide attempt and mortality. Random-effect meta-analysis was used to quantify this association across all studies with available data. RESULTS: Twenty-three studies met the inclusion criteria and suggest an association between lower childhood cognitive skills and increased risk of suicidal behavior. Meta-analysis of the adjusted estimates from 11 studies (N = 2,830,191) found the association to be small but statistically significant. Heterogeneity was significant but moderate, and results were unlikely to be influenced by publication bias. In subgroup analyses, associations were significant only for males. No difference in effect size was found between suicide attempt and suicide mortality. LIMITATIONS: Cognitive skills were measured with different cognitive subtests. Heterogeneity in the age of cognitive skills assessment. Meta-regression and subgroup analyses were based on a relatively low number of studies. CONCLUSIONS: Individuals with lower cognitive skills in childhood have a greater risk of suicidal behavior in adulthood, especially males. Although the association was small, interventions improving cognitive skills may yield large effects on suicide prevention at the population level if the association is causal.

Molecular Profiling of Peanut under Raw, Roasting, and Autoclaving Conditions Using High-Resolution Magic Angle Spinning and Solution 1H NMR Spectroscopy.

Higher rates of peanut allergy have been observed in countries that commonly roast peanuts prior to consumption. Despite the importance of understanding the role of thermal processing in allergy and on peanut composition, studies toward generating signatures that identify molecular contents following processing are scant. Here, we identified spectral signatures to track changes and differences in the molecular composition of peanuts under raw, roasted, and high-pressure and high-temperature autoclaved conditions. We analyzed both the solid flesh of the seed and solutions derived from soaking peanuts using High-Resolution Magic Angle Spinning (HR-MAS) and solution 1H Nuclear Magnetic Resonance (NMR) spectroscopy, respectively. The NMR spectra of intact peanuts revealed triglycerides as the dominant species, assigned on the basis of multiplets at 4.1 and 4.3 ppm, and corresponding defatted flours revealed the presence of sugars. Sucrose assigned based on a doublet at 5.4 ppm (anomeric proton), and triglycerides were the most abundant small molecules observed, with little variation between conditions. Soaked peanut solutions were devoid of lipids, and their resulting spectra matched the profiles of defatted peanuts. Spectral signatures resulting from autoclaving differed strikingly between those from raw and roasted peanuts, with considerable line-broadening in regions corresponding to proteins and amino-acid side chains, from 0.5 to 2.0 ppm and 6.5 to 8.5 ppm. Taken together, by using complementary NMR methods to obtain a fingerprint of the molecular components in peanuts, we demonstrated that autoclaving led to a distinct composition, likely resulting from the hydrolytic cleavage of proteins, the most important molecule of the allergic reaction.

Toward a Mechanically Rechargeable Solid Fuel Flow Battery Based on Earth-Abundant Materials.

Metal-air batteries are a promising energy storage solution, but material limitations (e.g., metal passivation and low active material utilization) have stymied their adoption. We investigate a solid fuel flow battery (SFFB) architecture that combines the energy density of metal-air batteries with the modularity of redox flow batteries. Specifically, a metallic solid electrochemical fuel (SEF) is spatially separated from the anodic current collector, a dissolved redox mediator (RM) shuttles charges between the two, and an oxygen reduction cathode completes the circuit. This modification decouples power and energy system components while enabling mechanical recharging and mitigating the effects of nonuniform metal oxidation. We conduct an exploratory study showing that metallic SEFs can chemically reduce organic RMs repeatedly. We subsequently operate a proof-of-concept SFFB cell for ca. 25 days as an initial demonstration of technical feasibility. Overall, this work illustrates the potential of this storage concept and highlights scientific and engineering pathways to improvement.

Development of 3D-QSAR and pharmacophoric models to design new anti-Trypanosoma cruzi agents based on 2-aryloxynaphthoquinone scaffold.

In this work we have collected a set of 30 trypanosomicidal naphthoquinones and developed pharmacophoric and 3D-QSAR models as tools for the design of new potential anti-Chagasic compounds. Firstly, qualitative information was obtained from SAR and pharmacophoric models identifying some fragments around the 2-aryloxynaphthoquinone scaffold important for the antiparasitic activity. Then, 3D-QSAR CoMFA and CoMSIA models were developed. The models showed adequate statistical parameters where the steric, electrostatic, and hydrophobic features explain the trypanosomicidal effect. Therefore, to validate our models, we carried out the design, synthesis, and biological evaluation on T. cruzi epimastigotes of five new compounds (33a-e). According to CoMFA model, three out of five compounds showed pIC50 values within one logarithmic unit of deviation. The two compounds that did not fit the predictions were those with high lipophilicity, which agreed with the SAR and pharmacophore models. Docking and molecular dynamic studies were performed on T. cruzi trypanothione reductase, in a proposed binding site for this type of naphthoquinone. Interestingly, 33a-e showed the same interaction pattern as a naphthoquinone inhibitor (2). Finally, predicted drug-likeness properties indicated that 33a-e have optimal oral bioavailability. Thus, this study provides new in silico models for obtaining novel trypanosomicidal compounds.

Synthesis and Characterization of Lithium-Conducting Composite Polymer-Ceramic Membranes for Use in Nonaqueous Redox Flow Batteries.

Redox flow batteries (RFBs) are a burgeoning electrochemical platform for long-duration energy storage, but present embodiments are too expensive for broad adoption. Nonaqueous redox flow batteries (NAqRFBs) seek to reduce system costs by leveraging the large electrochemical stability window of organic solvents (>3 V) to operate at high cell voltages and to facilitate the use of redox couples that are incompatible with aqueous electrolytes. However, a key challenge for emerging nonaqueous chemistries is the lack of membranes/separators with suitable combinations of selectivity, conductivity, and stability. Single-ion conducting ceramics, integrated into a flexible polymer matrix, may offer a pathway to attain performance attributes needed for enabling competitive nonaqueous systems. Here, we explore composite polymer-inorganic binder-filler membranes for lithium-based NAqRFBs, investigating two different ceramic compounds with NASICON-type (NASICON: sodium (Na) superionic conductor) crystal structure, Li1.3Al0.3Ti1.7(PO4)3 (LATP) and Li1.4Al0.4Ge0.2Ti1.4(PO4)3 (LAGTP), each blended with a polyvinylidene fluoride (PVDF) polymeric matrix. We characterize the physicochemical and electrochemical properties of the synthesized membranes as a function of processing conditions and formulation using a range of microscopic and electrochemical techniques. Importantly, the electrochemical stability window of the as-prepared membranes lies between 2.2-4.5 V vs Li/Li+. We then integrate select composite membranes into a single electrolyte flow cell configuration and perform polarization measurements with different redox electrolyte compositions. We find that mechanically robust, chemically stable LATP/PVDF composites can support >40 mA cm-2 at 400 mV cell overpotential, but further improvements are needed in selectivity. Overall, the insights gained through this work begin to establish the foundational knowledge needed to advance composite polymer-inorganic membranes/separators for NAqRFBs.

Quantitative Analysis of the Potency of Equimolar Two-Drug Combinations and Combi-Molecules Involving Kinase Inhibitors In Vitro: The Concept of Balanced Targeting.

The median-effect principle proposed by Chou and Talalay is the most effective approach to parameterize interactions between several agents in combination. However, this method cannot be used to evaluate the effectiveness of equimolar drug combinations, which are comparative references for dual-targeting molecular design. Here, using data acquired through the development of "combi-molecules" blocking two kinases (e.g., EGFR-c-Src and EGFR-c-Met), we established potency indices for equimolar and dual-targeted inhibitors. If the fold difference (κ) between the IC50 of the two individual kinase inhibitors was >6, the IC50 of their equimolar combination resembled that of the more potent inhibitor. Hence, the "combi-targeting" of the two kinases was considered "imbalanced" and the combination ineffective. However, if κ ≤ 6, the IC50 of the combination fell below that of each individual drug and the combi-targeting was considered "balanced" and the combination effective. We also showed that combi-molecules should be compared with equimolar combinations only under balanced conditions and propose a new parameter Ω for validating their effectiveness. A multi-targeted drug is effective if Ω < 1, where Ω is defined as the IC50 of the drug divided by that of the corresponding equimolar combination. Our study provides a methodology to determine the in vitro potency of equimolar two-drug combinations as well as combi-/hybrid molecules inhibiting two different kinase targets.

Low MoCA performances correlate with suicidal ideation in late-life depression.

Late-life depression remains an underdiagnosed clinical entity, mainly because the presence of cognitive impairment in the elderly leads clinicians to suspect dementia rather than depression. Our objective was to analyze the cognitive abilities of elderly depressed patients using the Montreal Cognitive Assessment (MoCA) in relation to the presence or absence of suicidal ideation. The MoCA, Beck Scale of Suicidal Ideation, Hamilton Anxiety Scale, and Hamilton Depression Scale were administered to 72 patients with a recent history of late life depression: 43 with suicidal ideation and 29 non-suicidal controls. The results show that suicidal patients demonstrated significantly worse performance on the MoCA total score and the delayed recall subtest in comparison to non-suicidal controls. In addition, after adjusting for age and depression, poorer performance on the MoCA total score correlated to the presence of suicidal ideation. We found that the MoCA total score is able to predict the presence of suicidal ideation in depressed elderly patients in a fair-to-good manner. As late-life depression is already established as a potential prodrome of dementia, longitudinal follow-up may determine whether depressed individuals with suicidal ideation are at higher risk of converting to dementia.

Aspect ratio of nano/microstructures determines Staphylococcus aureus adhesion on PET and titanium surfaces.

AIMS: Joint infections cause premature implant failure. The avoidance of bacterial colonization of implant materials by modification of the material surface is therefore the focus of current research. In this in vitro study the complex interaction of periodic structures on PET and titanium surfaces on the adhesion of Staphylococcus aureus is analysed. METHODS AND RESULTS: Using direct laser interference patterning as well as roll-to-roll hot embossing methods, structured periodic textures of different spatial distance were produced on surfaces and S. aureus were cultured for 24 h on these. The amount of adhering bacteria was quantified using fluorescence microscopy and the local adhesion behaviour was investigated using scanning electron microscopy. For PET structures, minimal bacterial adhesion was identified for an aspect ratio of about 0·02. On titanium structures, S. aureus adhesion was significantly decreased for profile heights of < 200 nm. Our results show a significantly decreased bacterial adhesion for structures with an aspect ratio range of 0·02 to 0·05. CONCLUSIONS: We show that structuring on surfaces can decrease the amount of S. aureus on titanium and PET as common implant materials. SIGNIFICANCE AND IMPACT OF THE STUDY: The study highlights the immense potential of applying specific structures to implant materials to prevent implant colonization with pathogen bacteria.

Extracellular electron transfer across bio-nano interfaces for CO2 electroreduction.

Acetogenic bacteria represent a class of organisms capable of converting reducing equivalents and carbon dioxide into products with carbon-carbon bonds. Materials-based bio-electrochemical approaches are attractive for supplying biological organisms directly with grid-supplied electrons to convert carbon dioxide to value-added chemicals. Carbon nanotube-modified biocathodes have emerged as promising candidates for microbial electrosynthesis with high yields of carbon product formation, but a fundamental understanding of extracellular charge transfer at this electrode-biofilm interface is still lacking. Here, we utilize solid-state interfaces between semiconducting single-walled carbon nanotubes (s-SWCNT) and a model acetogenic bacterium for mechanistic studies of electro-catalytic CO2 conversion to acetate. Studies of bacteria/s-SWCNT interactions in a transistor-based device suggest direct extracellular electron transfer (EET) at the bio-nano interface. Deuterium isotope labeling experiments confirmed that the availability of electrochemically produced H2 as a redox mediator does not limit the efficiency of EET and CO2 electro-reduction for C. ljungdahlii biofilms, suggesting the primary reducing equivalents are the electrons delivered across the electrode/bacterium interface or involvement of biological redox mediators. Additional isotope labeling studies demonstrate high Faradaic efficiency for CO2 electro-reduction at the SWCNT/bacterium interface. These results provide important information about EET across the bacterium/material interface in a model biocathode.

MMP-9 mediated Syndecan-4 shedding correlates with osteoarthritis severity.

OBJECTIVE: Osteoarthritis (OA) is a degenerative joint disease inducing the degradation of the articular cartilage. Syndecan-4 (Sdc4) is a heparan sulfate proteoglycan, expressed under inflammatory conditions and by chondrocytes during OA. Little is known about Sdc4 shedding and its regulation in OA. Therefore, we investigated the regulation of Sdc4 shedding and underlying shedding mechanisms under OA conditions. DESIGN: Articular cartilage, serum, synovial fluid and synovial membrane from OA patients with different radiological severity were analyzed. ELISA, RT-qPCR and IHC for Sdc4, MMP-2 and -9 were performed. MMP inhibitors and siRNA were evaluated for their effect on Sdc4 shedding by ELISA and on IL-1 signaling by western blot (pERK/ERK). RESULTS: Shed Sdc4 was increased in synovial fluid of OA patients, but not in the serum and is a good predictor (AUC = 0.72) for OA severity with a sensitivity of 67.5% and specificity 65.2%. MMP-9, but not MMP-2, was increased in cartilage and synovial membrane at mRNA levels and in the synovial fluid at protein levels. Shed Sdc4 correlated with the amount of MMP-9 in synovial fluid. Further, the inhibition and knock-down of MMP-9 decreased the amount of shed Sdc4 in vitro. Increased Sdc4 shedding resulted in less phosphorylation of ERK upon IL-1ß stimulation. CONCLUSION: Shed Sdc4 might be a good prognostic biomarker for OA mediated cartilage degradation. MMP-9 seems to be the relevant sheddase for Sdc4 under OA conditions, desensitizing chondrocytes towards IL-1 signaling.

Subcellular distribution and mechanism of action of AL906, a novel and potent EGFR inhibitor rationally designed to be green fluorescent.

To enhance the potency of EGFR inhibitors, we developed a novel strategy that seeks to conjugate EGFR to a bioactive moiety leading to a molecule termed "combi-molecule". In order to mimic the penetration of this type of molecules, based upon previously reported structure activity relationship studies, we designed a new molecule containing a quinazoline moiety tethered to a p-nitrobenzoxadiazole (NBD) moiety [molecular weight (MW) 700]. Despite its size, AL906 growth inhibitory activity was superior to that of the clinical drug gefitinib. Furthermore, AL906 retained significant EGFR inhibitory activity and good cellular penetration with abundant distribution in the perinuclear region of the cells. In an isogenic NIH3T3 transfected cell panel, it selectively inhibited the growth  of the NIH3T3-EGFR and HER2 transfectants. Confocal microscopy analysis revealed that it was capable of penetrating multilayer aggregates although to a lesser extent than FD105, a small inhibitor of EGFR inhibitor of the same class (MW 300). Its ability to inhibit EGFR auto-phosphorylation in monolayer culture was stronger than in the aggregates. The results suggest that our strategy did not negatively affect EGFR inhibitory potency, EGFR selectivity and growth inhibition. However, its molecular size may account for its decreased aggregate penetration when compared with a smaller EGFR inhibitor of the quinazoline class.

Feeding Tall Fescue Seed Reduces Ewe Milk Production, Lamb Birth Weight and Pre-Weaning Growth Rate.

Endophyte-infected tall fescue (E+) produces ergovaline and ergovalinine, which are mycotoxins that act as dopamine agonists to suppress prolactin and induce vasoconstriction. The experiment was designed as a 3 × 2 × 2 factorial with DRD2 genotype (AA, AG, GG), fescue seed (endophyte-free, E- or endophyte-infected, E+), stage of gestation (MID, d (day) 35-85; LATE, d 86-parturition) and all interactions in the model. Pregnant Suffolk ewes (n = 60) were stratified by genotype and fed E+ or E- seed in a total mixed ration according to treatment assignment. Serum prolactin concentrations were lower (p < 0.05) in ewes fed E+ seed but did not differ by maternal DRD2 genotype or two-way interaction. Lamb birth weight was lower (p < 0.05) in ewes fed E+ seed in last trimester. Pre-weaning growth rate, milk production and total weaning weight was reduced (p < 0.05) in ewes fed E+ fescue seed during MID and LATE gestation. Ingestion of ergovaline/ergovalinine in last trimester reduces lamb birth weight; however, lamb growth rate, milk production and total weaning weight are reduced in all ewes fed E+ during mid and last trimester.

[Coronary aneurysm, it exists !] / L'anévrisme coronarien, ça existe !

Coronary aneurysm has an incidence of 1,1 to 4,9 % in patients undergoing a coronary angiography. Many etiologies may be accused, atherosclerosis is associated in up to 50 % of cases. We report the case of a 76-year-old patient with a large coronary aneurysm.

L'anévrisme coronarien a une incidence de 1,1 à 4,9 % chez les patients bénéficiant d'une coronarographie. De nombreuses étiologies peuvent être incriminées, l'athérosclérose y est associée dans 50 % des cas. Nous rapportons ici le cas d'un patient de 76 ans présentant un volumineux anévrisme coronarien.

Effect of Water Concentration in LiPF6-Based Electrolytes on the Formation, Evolution, and Properties of the Solid Electrolyte Interphase on Si Anodes.

A trace amount of water in an electrolyte is one of the factors detrimental to the electrochemical performance of silicon (Si)-based lithium-ion batteries that adversely affect the formation and evolution of the solid electrolyte interphase (SEI) on Si-based anodes and change its properties. Thus far, a lack of fundamental and mechanistic understanding of SEI formation, evolution, and properties in the presence of water has inhibited efforts to stabilize the SEI for improved electrochemical performance. Thus, we investigated the SEI formed in a Gen2 electrolyte (1.2 M LiPF6 in ethylene carbonate/ethyl methyl carbonate, 3:7 wt %, water content: <10 ppm) with and without additional water (50 ppm) at varying potentials (1.0, 0.5, 0.2, and 0.01 V vs Li/Li+). The impact of additional water on the morphological, (electro)chemical, and structural properties of SEI was studied using microscopic (atomic force microscopy and scanning spreading resistance microscopy) and spectroscopic (X-ray photoelectron spectroscopy, attenuated total reflection Fourier-transform infrared spectroscopy, and time-of-flight secondary ion mass spectrometry) techniques. The SEI exhibits both potential- and water concentration-dependent trends in its morphology and chemical composition. The presence of additional water in the electrolyte causes parasitic reactions, which onset at ∼1.0 V, resulting in a reduction of electrolyte components and result in the formation of an insulating, fluorophosphate-rich SEI. In addition, hydrolysis of LiPF6 creates hydrofluoric acid, which reacts with the surface oxide layer on the Si electrode, leading to a pitted and inhomogeneous SEI structure.