Apolipoprotein A-I Attenuates Palmitate-Mediated NF-κB Activation by Reducing Toll-Like Receptor-4 Recruitment into Lipid Rafts

While high-density lipoprotein (HDL) is known to protect against a wide range of inflammatory stimuli, its anti-inflammatory mechanisms are not well understood. Furthermore, HDL's protective effects against saturated dietary fats have not been previously described. In this study, we used endothelial cells to demonstrate that while palmitic acid activates NF-κB signaling, apolipoprotein A–I, (apoA-I), the major protein component of HDL, attenuates palmitate-induced NF-κB activation. Further, vascular NF-κB signaling (IL-6, MCP-1, TNF-α) and macrophage markers (CD68, CD11c) induced by 24 weeks of a diabetogenic diet containing cholesterol (DDC) is reduced in human apoA-I overexpressing transgenic C57BL/6 mice compared to age-matched WT controls. Moreover, WT mice on DDC compared to a chow diet display increased gene expression of lipid raft markers such as Caveolin-1 and Flotillin-1, and inflammatory Toll-like receptors (TLRs) (TLR2, TLR4) in the vasculature. However apoA-I transgenic mice on DDC show markedly reduced expression of these genes. Finally, we show that in endothelial cells TLR4 is recruited into lipid rafts in response to palmitate, and that apoA-I prevents palmitate-induced TLR4 trafficking into lipid rafts, thereby blocking NF-κB activation. Thus, apoA-I overexpression might be a useful therapeutic tool against vascular inflammation

Bacillus anthracis and Bacillus cereus PcrA Helicases Can Support DNA Unwinding and In Vitro Rolling-Circle Replication of Plasmid pT181 of Staphylococcus aureus

Replication of rolling-circle replicating (RCR) plasmids in gram-positive bacteria requires the unwinding of initiator protein-nicked plasmid DNA by the PcrA helicase. In this report, we demonstrate that heterologous PcrA helicases from Bacillus anthracis and Bacillus cereus are capable of unwinding Staphylococcus aureus plasmid pT181 from the initiator-generated nick and promoting in vitro replication of the plasmid. These helicases also physically interact with the RepC initiator protein of pT181. The ability of PcrA helicases to unwind noncognate RCR plasmids may contribute to the broad-host-range replication and dissemination of RCR plasmids in gram-positive bacteria

Designed and synthesized de novo ANTPABA-PDI nanomaterial as an acceptor in inverted solar cell at ambient atmosphere

In this work, a novel soluble and air-stable electron acceptor containing perylenediimide moiety named ANTPABA-PDI was designed and synthesized with band gap 1.78eV and that was used as non-fullerene acceptor material. ANTPABA-PDI possess not only good solubility but also much lower LUMO (lowest unoccupied molecular orbital) energy level. Furthermore, its excellent electron acceptor capability also supported by density functional theory calculation which validates the experimental observations. Inverted organic solar cell has been fabricated using ANTPABA-PDI along with P3HT as standard donor material in ambient atmosphere. The device, after characterization in open air, exhibited a power conversion efficiency of 1.70%. This is the first ever PDI based organic solar cell that has been fabricated completely in ambient atmosphere. The characterizations of the device have also been performed in ambient atmosphere. This kind of stable organic material can easily be used in fabricating organic solar cell and therefore it can be used as the best alternative as non-fullerene acceptor materials

HDL or apoA-I attenuates palmitic acid dependent NF- κB signaling in endothelial cells.

<p>HMEC were pretreated with vehicle (labeled as control) or with human HDL (50 µg/ml) or ApoA-1 (50 µg/ml) for 16 hours, washed and then either treated with palmitate complexed with BSA (100 µM) for 3 hours or treated with BSA alone. <b>A–B</b>. ICAM-1 mRNA expression was analyzed using quantitative RT-PCR. IL-6 cytokine levels in supernatants were assessed by ELISA (n = 3). Data represents mean ± SD and *p<0.05,**p<0.01,***p<0.005. <b>C</b>. BAEC lysates were prepared after pretreatment with apoA-I/HDL and phopho-P65 levels were assessed by Western blot.</p

ApoA-I overexpression attenuates the effect of DDC on vascular inflammation and lipid raft markers.

<p>C57BL/6 (WT) or apoA-I transgenic mice were fed a standard (chow) or a DDC diet for 24 weeks and gene expression from isolated thoracic aortic tissues were assessed by quantitative RT-PCR. <b>A</b>. Fold differences between groups were calculated for MCP-1, IL-6 and TNF-α (NF-κB dependent signaling) CD68, CD11c (monocyte markers) relative to GAPDH. <b>B.</b> Fold differences between groups were calculated for Caveolin-1 and Flotillin-1 (lipid raft markers), TLR2 and TLR4 (Toll-like receptors) relative to GAPDH. *P<0.05, **p<0.001, n = 4–7 for each condition.</p

Disruption of lipid raft integrity by MβCD reduces palmitate-mediated NF- κB signaling and TLR4 migration in endothelial cells.

<p>HMEC cells were pretreated with vehicle or MβCD (5 mM/1 hr) (to disrupt lipid raft integrity) and then stimulated with palmitate/BSA (100 µM) for 3 hr. Cell lysates were assessed by Western blot with an anti-phospho-p65 antibody (n = 3). <b>B</b>. Experiments were repeated in BAEC (n = 3). <b>C</b>. Lipid rafts were isolated and the non-raft and lipid-raft fractions pooled, and assessed for TLR4 and caveolin-1 protein level by Western blot. Representative immunoblots from 3 independent experiments are shown.</p

Machine Learning-Based Classification of Abnormal Liver Tissues Using Relative Permittivity

The search for non-invasive, fast, and low-cost diagnostic tools has gained significant traction among many researchers worldwide. Dielectric properties calculated from microwave signals offer unique insights into biological tissue. Material properties, such as relative permittivity (&epsilon;r) and conductivity (&sigma;), can vary significantly between healthy and unhealthy tissue types at a given frequency. Understanding this difference in properties is key for identifying the disease state. The frequency-dependent nature of the dielectric measurements results in large datasets, which can be postprocessed using artificial intelligence (AI) methods. In this work, the dielectric properties of liver tissues in three mouse models of liver disease are characterized using dielectric spectroscopy. The measurements are grouped into four categories based on the diets or disease state of the mice, i.e., healthy mice, mice with non-alcoholic steatohepatitis (NASH) induced by choline-deficient high-fat diet, mice with NASH induced by western diet, and mice with liver fibrosis. Multi-class classification machine learning (ML) models are then explored to differentiate the liver tissue groups based on dielectric measurements. The results show that the support vector machine (SVM) model was able to differentiate the tissue groups with an accuracy up to 90%. This technology pipeline, thus, shows great potential for developing the next generation non-invasive diagnostic tools

Estimation of Physiologic Pressures: Invasive and Non-Invasive Techniques, AI Models, and Future Perspectives

The measurement of physiologic pressure helps diagnose and prevent associated health complications. From typical conventional methods to more complicated modalities, such as the estimation of intracranial pressures, numerous invasive and noninvasive tools that provide us with insight into daily physiology and aid in understanding pathology are within our grasp. Currently, our standards for estimating vital pressures, including continuous BP measurements, pulmonary capillary wedge pressures, and hepatic portal gradients, involve the use of invasive modalities. As an emerging field in medical technology, artificial intelligence (AI) has been incorporated into analyzing and predicting patterns of physiologic pressures. AI has been used to construct models that have clinical applicability both in hospital settings and at-home settings for ease of use for patients. Studies applying AI to each of these compartmental pressures were searched and shortlisted for thorough assessment and review. There are several AI-based innovations in noninvasive blood pressure estimation based on imaging, auscultation, oscillometry and wearable technology employing biosignals. The purpose of this review is to provide an in-depth assessment of the involved physiologies, prevailing methodologies and emerging technologies incorporating AI in clinical practice for each type of compartmental pressure measurement. We also bring to the forefront AI-based noninvasive estimation techniques for physiologic pressure based on microwave systems that have promising potential for clinical practice