The incorporation of MALDI mass spectrometry imaging in studies to identify markers of toxicity following opioid exposures in mouse fetuses.

Introduction: In 2015, the FDA released a Drug Safety Communication regarding a possible link between opioid exposure during early pregnancy and an increased risk of fetal neural tube defects (NTDs). At the time, the indications for opioid use during pregnancy were not changed due to incomplete maternal toxicity data and limitations in human and animal studies. To assess these knowledge gaps, largescale animal studies are ongoing; however, state-of-the-art technologies have emerged as promising tools to assess otherwise non-standard endpoints.

Type I IFN induces long-chain acyl-CoA synthetase 1 to generate a phosphatidic acid reservoir for lipotoxic saturated fatty acids.

Long-chain acyl-CoA synthetase 1 (ACSL1) catalyzes the conversion of long-chain fatty acids to acyl-CoAs. ACSL1 is required for β-oxidation in tissues that rely on fatty acids as fuel, but no consensus exists on why ACSL1 is induced by inflammatory mediators in immune cells. We used a comprehensive and unbiased approach to investigate the role of ACSL1 induction by interferon type I (IFN-I) in myeloid cells in vitro and in a mouse model of IFN-I overproduction.

Chronic inflammation and vascular cell plasticity in atherosclerosis.

Vascular smooth muscle cells, endothelial cells and macrophages undergo phenotypic conversions throughout atherosclerosis progression, both as a consequence of chronic inflammation and as subsequent drivers of it. The inflammatory hypothesis of atherosclerosis has been catapulted to the forefront of cardiovascular research as clinical trials have shown that anti-inflammatory therapy reduces adverse cardiovascular events. However, no current therapies have been specifically designed to target the phenotype of plaque cells.

Hyperchylomicronemia causes endothelial cell inflammation and increases atherosclerosis.

The effect of increased triglycerides (TGs) as an independent factor in atherosclerosis development has been contentious, in part, because severe hypertriglyceridemia associates with low levels of low-density lipoprotein cholesterol (LDL-C). To test whether hyperchylomicronemia, in the absence of markedly reduced LDL-C levels, contributes to atherosclerosis, we created mice with induced whole-body lipoprotein lipase (LpL) deficiency combined with LDL receptor (LDLR) deficiency. On an atherogenic Western-type diet (WD), male and female mice with induced global LpL deficiency (i ) and LDLR knockdown ( ) developed hypertriglyceridemia and elevated cholesterol levels; all the increased cholesterol was in chylomicrons or large VLDL.

Targeting Unc5b in macrophages drives atherosclerosis regression and pro-resolving immune cell function.

Atherosclerosis results from lipid-driven inflammation of the arterial wall that fails to resolve. Imbalances in macrophage accumulation and function, including diminished migratory capacity and defective efferocytosis, fuel maladaptive inflammation and plaque progression. The neuroimmune guidance cue netrin-1 has dichotomous roles in inflammation partly due to its multiple receptors; in atherosclerosis, netrin-1 promotes macrophage survival and retention via its receptor Unc5b.

FITM2 deficiency results in ER lipid accumulation, ER stress, and reduced apolipoprotein B lipidation and VLDL triglyceride secretion in vitro and in mouse liver.

Objective: Triglycerides (TGs) associate with apolipoprotein B100 (apoB100) to form very low density lipoproteins (VLDLs) in the liver. The repertoire of factors that facilitate this association is incompletely understood. FITM2, an integral endoplasmic reticulum (ER) protein, was originally discovered as a factor participating in cytosolic lipid droplet (LD) biogenesis in tissues that do not form VLDL.

Total outward leakage of face-worn products used by the general public for source control.

Background: During Coronavirus disease 2019 pandemic, the general public used any face-worn products they could get to overcome the shortage of N95 respirators and surgical masks. These products, often not meeting any standards, raised concerns about their effectiveness in reducing the spread of respiratory viruses.

Methods: This study quantified total outward leakage (TOL) of units from 9 face-worn product categories used by members of the general public.

Collagen-targeted protein nanomicelles for the imaging of non-alcoholic steatohepatitis.

In vivo molecular imaging tools hold immense potential to drive transformative breakthroughs by enabling researchers to visualize cellular and molecular interactions in real-time and/or at high resolution. These advancements will facilitate a deeper understanding of fundamental biological processes and their dysregulation in disease states. Here, we develop and characterize a self-assembling protein nanomicelle called collagen type I binding - thermoresponsive assembled protein (Col1-TRAP) that binds tightly to type I collagen in vitro with nanomolar affinity.

The emerging role of fat-inducing transcript 2 in endoplasmic reticulum proteostasis and lipoprotein biogenesis.

Purpose Of Review: This review examines the evolving role of the fat-inducing transcript 2 (FIT2) protein in lipid droplet (LD) biology and its broader implications in cellular physiology and disease. With recent advancements in understanding FIT2 function across various model systems, this review provides a timely synthesis of its mechanisms and physiological significance.

Recent Findings: FIT2, an endoplasmic reticulum (ER)-resident protein, has been established as a critical regulator of LD formation in diverse organisms, from yeast to mammals.

Development of an experimental technique to determine the barrier performance of medical gloves when stretched.

Protective clothing standards, such as test methods published by ASTM International, play an integral role in ensuring the performance of personal protective equipment. The standard tests are not without limitations and are periodically reviewed and often updated. Some tests may not be reflective of in-use conditions.

Assessment of glove stretch and storage temperature on fentanyl permeation: Implications for standard test methods and PPE recommendations.

The National Institute for Occupational Safety and Health recommends the use of nitrile gloves with a minimum thickness of 5.0 ± 2.0 mil [0.

Imbalance of APOB Lipoproteins and Large HDL in Type 1 Diabetes Drives Atherosclerosis.

Background: Individuals with type 1 diabetes (T1D) generally have normal or even higher HDL (high-density lipoprotein)-cholesterol levels than people without diabetes yet are at increased risk for atherosclerotic cardiovascular disease (CVD). Human HDL is a complex mixture of particles that can vary in cholesterol content by >2-fold. To investigate if specific HDL subspecies contribute to the increased atherosclerosis associated with T1D, we created mouse models of T1D that exhibit human-like HDL subspecies.

The IRG1-itaconate axis protects from cholesterol-induced inflammation and atherosclerosis.

Atherosclerosis is fueled by a failure to resolve lipid-driven inflammation within the vasculature that drives plaque formation. Therapeutic approaches to reverse atherosclerotic inflammation are needed to address the rising global burden of cardiovascular disease (CVD). Recently, metabolites have gained attention for their immunomodulatory properties, including itaconate, which is generated from the tricarboxylic acid-intermediate cis-aconitate by the enzyme Immune Responsive Gene 1 (IRG1/ACOD1).

Clonal Expansion in Cardiovascular Pathology.

Clonal expansion refers to the proliferation and selection of advantageous "clones" that are better suited for survival in a Darwinian manner. In recent years, we have greatly enhanced our understanding of cell clonality in the cardiovascular context. However, our knowledge of the underlying mechanisms behind this clonal selection is still severely limited.

β-Carotene accelerates the resolution of atherosclerosis in mice.

β-Carotene oxygenase 1 (BCO1) catalyzes the cleavage of β-carotene to form vitamin A. Besides its role in vision, vitamin A regulates the expression of genes involved in lipid metabolism and immune cell differentiation. BCO1 activity is associated with the reduction of plasma cholesterol in humans and mice, while dietary β-carotene reduces hepatic lipid secretion and delays atherosclerosis progression in various experimental models.