The Systemic Effect of Ischemia Training and Its Impact on Bone Marrow-Derived Monocytes.

Objective: Monocytes are innate immune cells that play a central role in inflammation, an essential component during neovascularization. Our recent publication demonstrated that ischemia training by 24 h unilateral occlusion of the femoral artery (FA) can modify bone marrow-derived monocytes (BM-Mono), allowing them to improve collateral remodeling in a mouse model of hindlimb ischemia. Here, we expand on our previous findings, investigating a potential systemic effect of ischemia training and how this training can impact BM-Mono.

Inhibition of post-lanosterol biosynthesis by fentanyl: potential implications for Fetal Fentanyl Syndrome (FFS).

A recent study discovered a novel, complex developmental disability syndrome, most likely caused by maternal fentanyl use disorder. This Fetal Fentanyl Syndrome (FFS) is biochemically characterized by elevated 7-dehydrocholesterol (7-DHC) levels in neonates, raising the question if fentanyl inhibition of the dehydrocholesterol reductase 7 (DHCR7) enzyme is causal for the emergence of the pathophysiology and phenotypic features of FFS. To test this hypothesis, we undertook a series of experiments on Neuro2a cells, primary mouse neuronal and astrocytic cultures, and human dermal fibroblasts (HDFs) with DHCR7 and DHCR7 genotype.

GAPDH inhibition mediated by thiol oxidation in human airway epithelial cells exposed to an environmental peroxide.

Intracellular redox homeostasis in the airway epithelium is closely regulated through adaptive signaling and metabolic pathways. However, inhalational exposure to xenobiotic stressors such as secondary organic aerosols (SOA) can alter intracellular redox homeostasis. Isoprene hydroxy hydroperoxide (ISOPOOH), a ubiquitous volatile organic compound derived from the atmospheric photooxidation of biogenic isoprene, is a major contributor to SOA.

Evaluation of ω-alkynyl-labeled linoleic and arachidonic acids as substrates for recombinant lipoxygenase pathway enzymes.

ω-Alkynyl-fatty acids can be used as probes for covalent binding to intracellular macromolecules. To inform future in vivo studies, we determined the rates of reaction of ω-alkynyl-labeled linoleate with recombinant enzymes of the skin 12R-lipoxygenase (12R-LOX) pathway involved in epidermal barrier formation (12R-LOX, epidermal lipoxygenase-3 (eLOX3), and SDR9C7). We also examined the reactivity of ω-alkynyl-arachidonic acid with representative lipoxygenase enzymes employing either "carboxyl end-first" substrate binding (5S-LOX) or "tail-first" (platelet-type 12S-LOX).

Dose-Response Effects of 7-Dehydrocholesterol Reductase Inhibitors on Sterol Profiles and Vesicular Stomatitis Virus Replication.

Cholesterol is ubiquitous in cells; it plays a critical role in membrane structure and transport as well as in intracellular trafficking processes. There are suggestions that cholesterol metabolism is linked to innate immunity with inhibitors of DHCR7, the last enzyme in the cholesterol pathway, suggested to have potential as viral therapeutics nearly a decade ago. In fact, there are a number of highly prescribed pharmaceuticals that are off-target inhibitors of DHCR7, causing increased cellular levels of 7-dehydrodesmosterol (7-DHD) and 7-dehydrocholesterol (7-DHC).

Impact of Charge Voltage on Factors Influencing Capacity Fade in Layered NMC622: Multimodal X-ray and Electrochemical Characterization.

Ni-rich NMC is an attractive Li-ion battery cathode due to its combination of energy density, thermal stability, and reversibility. While higher delivered energy density can be achieved with a more positive charge voltage limit, this approach compromises sustained reversibility. Improved understanding of the local and bulk structural transformations as a function of charge voltage, and their associated impacts on capacity fade are critically needed.

Characterization of Materials Used as Face Coverings for Respiratory Protection.

Use of masks is a primary tool to prevent the spread of the novel COVID-19 virus resulting from unintentional close contact with infected individuals. However, detailed characterization of the chemical properties and physical structure of common mask materials is lacking in the current literature. In this study, a series of commercial masks and potential mask materials, including 3M Particulate Respirator 8210 N95, a material provided by Oak Ridge National Laboratory Carbon Fiber Technology Facility (ORNL/CFTF), and a Filti Face Mask Material, were characterized by a suite of techniques, including scanning electron microscopy, X-ray diffraction, Raman spectroscopy, and X-ray photoelectron spectroscopy.

Local and Bulk Probe of Vanadium-Substituted α-Manganese Oxide (α-KVMnO) Lithium Electrochemistry.

A series of V-substituted α-MnO (KMnVO·HO, = 0, 0.2, 0.34, 0.

Structural and electrochemical investigation of crystallite size controlled zinc ferrite (ZnFeO).

Zinc ferrite, ZnFeO(ZFO), is a promising electrode material for next generation Li-ion batteries because of its high theoretical capacity and low environmental impact. In this report, synthetic control of crystallite size from the nanometer to submicron scale enabled probing of the relationships between ZFO size and electrochemical behavior. A facile two-step coprecipitation and annealing preparation method was used to prepare ZFO with controlled sizes ranging ∼9 to >200 nm.

Staphylococcus aureus Peptide Methionine Sulfoxide Reductases Protect from Human Whole-Blood Killing.

The generation of oxidative stress is a host strategy used to control Staphylococcus aureus infections. Sulfur-containing amino acids, cysteine and methionine, are particularly susceptible to oxidation because of the inherent reactivity of sulfur. Due to the constant threat of protein oxidation, many systems evolved to protect S.

Sterol Biosynthesis Inhibition in Pregnant Women Taking Prescription Medications.

Sterol biosynthesis is a critical homeostatic mechanism of the body. Sterol biosynthesis begins during early embryonic life and continues throughout life. Many commonly used medications, prescribed >200 million times in the United States annually, have a sterol biosynthesis inhibition side effect.

Trazodone effects on developing brain.

Trazodone (TRZ) is a commonly prescribed antidepressant with significant off-label use for insomnia. A recent drug screening revealed that TRZ interferes with sterol biosynthesis, causing elevated levels of sterol precursor 7-dehydrocholesterol (7-DHC). Recognizing the well-documented, disruptive effect of 7-DHC on brain development, we designed a study to analyze TRZ effects during pregnancy.

Generation and validation of a conditional knockout mouse model for the study of the Smith-Lemli-Opitz syndrome.

Smith-Lemli-Opitz Syndrome (SLOS) is a developmental disorder (OMIM #270400) caused by autosomal recessive mutations in the Dhcr7 gene, which encodes the enzyme 3β-hydroxysterol-Δ7 reductase. SLOS patients present clinically with dysmorphology and neurological, behavioral, and cognitive defects, with characteristically elevated levels of 7-dehydrocholesterol (7-DHC) in all bodily tissues and fluids. Previous mouse models of SLOS have been hampered by postnatal lethality when Dhcr7 is knocked out globally, while a hypomorphic mouse model showed improvement in the biochemical phenotype with aging and did not manifest most other characteristic features of SLOS.

(De)lithiation of spinel ferrites FeO, MgFeO, and ZnFeO: a combined spectroscopic, diffraction and theory study.

Iron based materials hold promise as next generation battery electrode materials for Li ion batteries due to their earth abundance, low cost, and low environmental impact. The iron oxide, magnetite Fe3O4, adopts the spinel (AB2O4) structure. Other 2+ cation transition metal centers can also occupy both tetrahedral and/or octahedral sites in the spinel structure including MgFe2O4, a partially inverse spinel, and ZnFe2O4, a normal spinel.

Maternal cariprazine exposure inhibits embryonic and postnatal brain cholesterol biosynthesis.

Cariprazine (CAR) is a strong inhibitor of the Dhcr7 enzyme, the last enzyme in the cholesterol biosynthesis pathway. We assessed the effects of CAR on maternally exposed Dhcr7 and wild-type mouse offspring, and tested the biochemical effects of CAR in human serum samples. Dhcr7 and wild-type time-pregnant mice were exposed to vehicle or 0.

Physician Assistant Program Goals: A Thematic Analysis.

Purpose: The purpose of this study was to provide a descriptive analysis of the goals of the accredited physician assistant (PA) programs across the country in order to obtain a baseline understanding of their themes.

Methods: Initial review of the goals resulted in the identification of recurring themes. The goals were evaluated relative to meeting the requirements specified in Standard A3.

Screening ToxCast™ for Chemicals That Affect Cholesterol Biosynthesis: Studies in Cell Culture and Human Induced Pluripotent Stem Cell-Derived Neuroprogenitors.

Background: Changes in cholesterol metabolism are common hallmarks of neurodevelopmental pathologies. A diverse array of genetic disorders of cholesterol metabolism support this claim as do multiple lines of research that demonstrate chemical inhibition of cholesterol biosynthesis compromises neurodevelopment. Recent work has revealed that a number of commonly used pharmaceuticals induce changes in cholesterol metabolism that are similar to changes induced by genetic disorders with devastating neurodevelopmental deficiencies.

Anode Overpotential Control via Interfacial Modification: Inhibition of Lithium Plating on Graphite Anodes.

Lithium-metal deposition on graphite anodes limits the cycle life and negatively impacts safety of the current state of the art Li-ion batteries. Herein, deliberate interfacial modification of graphite electrodes via direct current (DC) magnetron sputtering of nanoscale layers of Cu and Ni is employed to increase the overpotential for Li deposition and suppress Li plating under high rate charge conditions. Due to their nanoscale, the deposited surface films have minimal impact (∼0.

Modified sites and functional consequences of 4-oxo-2-nonenal adducts in HDL that are elevated in familial hypercholesterolemia.

The lipid aldehyde 4-oxo-2-nonenal (ONE) is a highly reactive protein crosslinker derived from peroxidation of n-6 polyunsaturated fatty acids and generated together with 4-hydroxynonenal (HNE). Lipid peroxidation product-mediated crosslinking of proteins in high-density lipoprotein (HDL) causes HDL dysfunction and contributes to atherogenesis. Although HNE is relatively well-studied, the role of ONE in atherosclerosis and in modifying HDL is unknown.

Maternal aripiprazole exposure interacts with 7-dehydrocholesterol reductase mutations and alters embryonic neurodevelopment.

Mutations in both copies in the gene encoding 7-dehydrocholesterol reductase (DHCR7) cause Smith-Lemli-Opitz Syndrome (SLOS), which is characterized by a toxic elevation in 7-dehydrocholesterol (7-DHC). Aripiprazole (ARI) exposure, independent of genetic mutations, also leads to elevation of 7-DHC. We investigated the combined effect of a single-copy Dhcr7 mutation and maternal ARI exposure on the developing offspring brain.