Thermal-stability of the enhanced piezoelectric,energy storage and electrocaloric properties of a lead-free BCZT ceramic

The lead-free Ba_0.85Ca_0.15Zr_0.10Ti_0.90O₃ (BCZT) relaxor ferroelectric ceramic has aroused much attention due to its enhanced piezoelectric, energy storage and electrocaloric properties. In this study, the BCZT ceramic was elaborated by the solid-state reaction route, and the temperature-dependence of the structural, electrical, piezoelectric, energy storage and electrocaloric properties was investigated. X-ray diffraction analysis revealed a pure perovskite phase, and the temperature-dependence of Raman spectroscopy, dielectric and ferroelectric measurements revealed the phase transitions in the BCZT ceramic. At room temperature, the strain and the large-signal piezoelectric coefficient reached a maximum of 0.062% and 234 pm V⁻¹, respectively. Furthermore, enhanced recovered energy density (W_rec = 62 mJ cm⁻³) and high-energy storage efficiency (η) of 72.9% at 130 °C were found. The BCZT ceramic demonstrated excellent thermal stability of the energy storage variation (ESV), less than ±5.5% in the temperature range of 30–100 °C compared to other lead-free ceramics. The electrocaloric response in the BCZT ceramic was explored via the indirect approach by using the Maxwell relation. Significant electrocaloric temperature change (ΔT) of 0.57 K over a broad temperature span (T_span = 70 °C) and enhanced coefficient of performance (COP = 11) were obtained under 25 kV cm⁻¹. The obtained results make the BCZT ceramic a suitable eco-friendly material for energy storage and solid-state electrocaloric cooling devices.

High-thermal stability of the recovered energy density and significant electrocaloric temperature change over a broad temperature span in a lead-free BCZT ceramic.     

Discrete mitochondrial aberrations in the spinal cord of sporadic ALS patients

Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disease characterized by progressive motor neuron degeneration in the brain and spinal cord leading to muscle atrophy, paralysis, and death. Mitochondrial dysfunction is a major contributor to motor neuron degeneration associated with ALS progression. Mitochondrial abnormalities have been determined in spinal cords of animal disease models and ALS patients. However, molecular mechanisms leading to mitochondrial dysfunction in sporadic ALS (sALS) patients remain unclear. Also, segmental or regional variation in mitochondrial activity in the spinal cord has not been extensively examined in ALS. In our study, the activity of mitochondrial electron transport chain complex IV was examined in post‐mortem gray and white matter of the cervical and lumbar spinal cords from male and female sALS patients and controls. Mitochondrial distribution and density in spinal cord motor neurons, lateral funiculus, and capillaries in gray and white matter were analyzed by immunohistochemistry. Results showed that complex IV activity was significantly decreased only in gray matter in both cervical and lumbar spinal cords from ALS patients. In ALS cervical and lumbar spinal cords, significantly increased mitochondrial density and altered distribution were observed in motor neurons, lateral funiculus, and cervical white matter capillaries. Discrete decreased complex IV activity in addition to changes in mitochondria distribution and density determined in the spinal cord in sALS patients are novel findings. These explicit mitochondrial defects in the spinal cord may contribute to ALS pathogenesis and should be considered in development of therapeutic approaches for this disease.     

Vascular effects of glycoprotein130 ligands--part I: pathophysiological role

The vessel wall is no longer considered as only an anatomical barrier for blood cells but is recognized as an active endocrine organ. Dysfunction of the vessel wall occurs in various disease processes including atherosclerosis, hypertension, peripheral artery disease, aneurysms, and transplant and diabetic vasculopathies. Different cytokines were shown to modulate the behavior of the cells, which constitute the vessel wall such as immune cells, endothelial cells and smooth muscle cells. Glycoprotein 130 (gp130) is a common cytokine receptor that controls the activity of a group of cytokines, namely, interleukin (IL)-6, oncostatin M (OSM), IL-11, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine (CLC), IL-27, and neuropoietin (NP). Gp130 and associated cytokines have abundantly diverse functions. Part I of this review focuses on the pathophysiological functions of gp130 ligands. We specifically describe vascular effects of these molecules and discuss the respective underlying molecular and cellular mechanisms.     

Vascular effects of glycoprotein130 ligands--part II: biomarkers and therapeutic targets

Glycoprotein130 (gp130) ligands are defined by the use of the common receptor subunit gp130 and comprise interleukin (IL)-6, oncostatin M (OSM), IL-11, leukemia inhibitory factor (LIF), cardiotrophin-1 (CT-1), cardiotrophin-like cytokine (CLC), ciliary neurotrophic factor (CNTF), IL-27 and neuropoietin (NP). In part I of this review we addressed the pathophysiological functions of gp130 ligands with respect to the vascular wall. In part II of this review on the vascular effects of gp130 ligands we will discuss data about possible use of these molecules as biomarkers to predict development or progression of cardiovascular diseases. Furthermore, the possibility to modulate circulating levels of gp130 ligands or their tissue expression by specific antibodies, soluble gp130 protein, renin-angiotensin-aldosterone system (RASS) inhibitors, statins, agonists of peroxisome proliferator-activated receptors (PPAR), hormone replacement therapy, nonsteroidal anti-inflammatory drugs (NSAID) or lifestyle modulating strategies are presented. Recent knowledge about the application of recombinant cytokines from the gp130 cytokine family as therapeutic agents in obesity or atherosclerosis is also summarized. Thus the purpose of this review is to cover a possible usefulness of gp130 ligands as biomarkers and targets for therapy in cardiovascular pathologies.     

The therapeutic role of endothelial progenitor cells in Type 1 diabetes mellitus

Pancreatic β-cells sense and adjust the blood glucose level by secretion of insulin. In Type 1 diabetes mellitus, these insulin-producing cells are destroyed, leaving the patients incapable of regulating blood glucose homeostasis. At the time of diagnosis, most patients still have 20-30% of their original β-cell mass remaining. These residual β-cells are targets for intervention therapies aimed at preventing further autoimmune destruction, in addition to increasing the number of existing β-cells. Such a therapeutic option is highly desirable since it may lead to a full recovery of newly diagnosed patients, with no need for further treatment with immunosuppressant drugs or exogenous insulin administration. In this article, we propose that endothelial progenitor cells, a cell type known to promote and support neovascularization following endothelial injury, may be used as part of a combinational stem cell therapy aimed to improve the vascularization, survival and proliferation of β-cells.     

Sleep deprivation and daily torpor impair object recognition in Djungarian hamsters

Sleep has been shown to play a facilitating role in memory consolidation, whereas sleep deprivation leads to performance impairment both in humans and rodents. The effects of 4-h sleep deprivation on recognition memory were investigated in the Djungarian hamster (Phodopus sungorus). Because sleep during the first hours after daily torpor has many similarities to recovery from sleep deprivation, the effects of spontaneous torpor on object recognition were also assessed. A 4-h sleep deprivation, starting immediately after an object learning task, diminished the ability of the hamsters to: (1) discriminate between an already encountered object (target) and a novel object presented in a novel context, (2) retrieve a target within a complex spatial scene, and (3) detect a spatial rearrangement of familiar objects in a familiar context. Plasma stress hormone levels were similar in sleep-deprived and control hamsters. The occurrence of a daily torpor episode during retention was associated with impaired old-new object discrimination performance in the more effortful complex spatial scene task only, and in a two-object choice situation in a novel context no torpor-induced deficit was found. Our results show that post learning sleep deprivation and daily torpor induce a deficit in familiar object retrieval performance in a complex spatial scene, while sparing familiarity-based recognition and novelty processing. Sleep deprivation during the first 4 h of memory consolidation hampered also recency memory for discrete objects. Stress was not a factor contributing to the sleep deprivation-induced impairment.     

Myo‐inositol trispyrophosphate‐mediated hypoxia reversion controls pancreatic cancer in rodents and enhances gemcitabine efficacy

Hypoxia and dysfunctional tumor vessels represent a prominent feature of pancreatic cancer, being, at least in part, responsible for chemotherapy resistance and immune suppression in these tumors. We tested whether the increase of oxygen delivery induced in vivo by myo‐inositol trispyrophosphate (ITPP) can reverse hypoxia, control tumor growth and improve chemotherapy response. Tumor size, metastatic development (microcomputed tomography scan follow‐up) and the survival of rats and nude or NOD.SCID mice, (bearing syngenic rat and MiaPaCa2‐ or patient‐derived pancreatic tumors), were determined on ITPP and/or gemcitabine treatment. Partial oxygen pressure, expression of angiogenic factors and tumor histology were evaluated. Infiltration and oxidative status of immune cells, as well as chemotherapy penetration in tumors, were determined by fluorescence‐activated cell sorting, fluorometry, nitric oxide release assays, Western blot and confocal microscopy. Weekly intravenous ITPP application resulted in the inhibition of metastasis development and restricted primary tumor growth, showing a superior effect on the rats' survival compared with gemcitabine. ITPP treatment restored tumor normoxia and caused a reduction in hypoxia inducible factor‐1α levels, with subsequent VEGF and Lox downregulation, resulting in improved vessel structure and decreased desmoplasia. The latter effects translated into elevated immune cells influx and improved susceptibility to gemcitabine treatment. Growth of human pancreatic tumor xenografts was strongly inhibited by administration of ITPP. ITPP exploits a two‐stage mechanism causing rapid, early and sustainable late stage normoxia. This is due to the angiogenic factor modulation and vascular normalization, leading to enhanced chemotherapy delivery and synergistic life prolongation, on combination with low doses of gemcitabine.