Systemic impacts of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) on heart, muscle, and kidney related diseases.

Metabolic dysfunction-associated steatotic liver disease (MASLD), previously known as non-alcoholic fatty liver disease (NAFLD), is the most common liver disorder worldwide, with an estimated global prevalence of more than 31%. Metabolic dysfunction-associated steatohepatitis (MASH), formerly known as non-alcoholic steatohepatitis (NASH), is a progressive form of MASLD characterized by hepatic steatosis, inflammation, and fibrosis. This review aims to provide a comprehensive analysis of the extrahepatic manifestations of MASH, focusing on chronic diseases related to the cardiovascular, muscular, and renal systems.

High-throughput tagging of endogenous loci for rapid characterization of protein function.

To facilitate the interrogation of protein function at scale, we have developed high-throughput insertion of tags across the genome (HITAG). HITAG enables users to rapidly produce libraries of cells, each with a different protein of interest C-terminally tagged. HITAG is based on a modified strategy for performing Cas9-based targeted insertions, coupled with an improved approach for selecting properly tagged lines.

Controlled experimental generation of perturbed high-order Ince-Gaussian laser modes.

We present an experimental approach for generating perturbed high-order Ince-Gaussian laser modes by transforming the low and moderate-intensity lobes of high-order Ince-Gaussian (IG) modes into high-intensity lobes and vice versa. This perturbation reshuffles optical energy among the different lobes and generates new, to the best of our knowledge, modulated Ince-Gaussian (MIG) modes. Computer-generated holograms displayed over spatial light modulators were used to modulate the IGMs.

Inhibition of Ephrin B2 Reverse Signaling Abolishes Multiple Myeloma Pathogenesis.

Unlabelled: Bone marrow vascular endothelial cells (BM EC) regulate multiple myeloma pathogenesis. Identification of the mechanisms underlying this interaction could lead to the development of improved strategies for treating multiple myeloma. Here, we performed a transcriptomic analysis of human ECs with high capacity to promote multiple myeloma growth, revealing overexpression of the receptor tyrosine kinases, EPHB1 and EPHB4, in multiple myeloma-supportive ECs.

Super-oscillatory spots with different inhomogeneous linear polarized states.

We present the formation of super-oscillatory (SO) spots by tightly focusing the inhomogeneous linear polarized beam of different polarization states. At the entrance pupil of the focusing lens, a suitable phase manipulation in the incident beam results in a small super-oscillatory spot. Our numerical study based on the vectorial diffraction theory shows that SO spots of controllable size and various polarization combinations are possible.

Controllable experimental modulation of high-order Laguerre-Gaussian laser modes.

High-order helical and sinusoidal Laguerre-Gaussian (LG) laser modes have uneven energy distribution among their multiple concentric vortex core rings and lobes, respectively. Here, we explore an experimental method to reshuffle the optical energy among their multiple concentric vortex core rings and lobes of high-order LG modes in a controllable manner. We numerically designed a diffractive optical element displayed over a spatial light modulator to rearrange optical energy among multiple concentric vortex core rings.

Recurrent Desmoid Fibromatosis of the Thyroid Gland: A Diagnostic Challenge.

A 31-year-old Indian female with a history of near-total thyroidectomy 2.5 years prior presented with recurrent neck swelling. Magnetic resonance imaging (MRI) of the neck revealed an infiltrating mass involving the thyroid bed.

Nicotinamide riboside rescues dysregulated glycolysis and fatty acid β-oxidation in a human hepatic cell model of citrin deficiency.

Citrin deficiency (CD) is an inborn error of metabolism caused by loss-of-function of the mitochondrial aspartate/glutamate transporter, CITRIN, which is involved in both the urea cycle and malate-aspartate shuttle. Patients with CD develop hepatosteatosis and hyperammonemia but there is no effective therapy for CD. Currently, there are no animal models that faithfully recapitulate the human CD phenotype.

Creation of pure longitudinal super-oscillatory spot.

We present a method that creates a super-oscillatory focal spot of a tightly focused radially polarized beam using the concept of a phase mask. Using vector diffraction theory, we report a super-oscillatory focal spot that is much smaller than the diffraction limit and the super-oscillation criterion. The proposed mask works as a special polarization filter that enhances the longitudinal component and filters out the transverse component of radial polarization at focus, permitting the creation of a pure longitudinal super-oscillatory focal spot.

Metabolic switching of estrogen-related receptor alpha in breast cancer aggression.

Orphan nuclear receptor estrogen-related receptor alpha (ERRα) is an important regulator of energy metabolism, whereas its hyperactivation in breast cancer has been shown to regulate cell migration, proliferation, and tumour development. These findings suggest a fine balance in the status of ERRα in regulating metabolic homeostasis or promoting cancer progression. In this issue, Brindisi et al.

Experimental realization of modulated Hermite-Gaussian laser modes: a maximum number of highly intense lobes.

Here, we present an experimental method that redistributes the optical energy among the lobes of high-order standard Hermite-Gaussian (SHG) laser modes in a controlled manner. We numerically designed diffractive optical elements, displayed over a spatial light modulator for redistribution of optical energy that converts low and moderate intense lobes into all highly intense lobes and vice versa at the Fourier plane. Such precise generation of modulated HG (MHG) laser modes offers a maximum number of highly intense lobes compared to SHG modes.

Spermidine-mediated hypusination of translation factor EIF5A improves mitochondrial fatty acid oxidation and prevents non-alcoholic steatohepatitis progression.

Spermidine is a natural polyamine that has health benefits and extends life span in several species. Deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH) are key enzymes that utilize spermidine to catalyze the post-translational hypusination of the translation factor EIF5A (EIF5A). Here, we have found that hepatic DOHH mRNA expression is decreased in patients and mice with non-alcoholic steatohepatitis (NASH), and hepatic cells treated with fatty acids.

Vitamin B and folate decrease inflammation and fibrosis in NASH by preventing syntaxin 17 homocysteinylation.

Background & Aims: Several recent clinical studies have shown that serum homocysteine (Hcy) levels are positively correlated, while vitamin B (B) and folate levels are negative correlated, with non-alcoholic steatohepatitis (NASH) severity. However, it is not known whether hyperhomocysteinemia (HHcy) plays a pathogenic role in NASH.

Methods: We examined the effects of HHcy on NASH progression, metabolism, and autophagy in dietary and genetic mouse models, patients, and primates.

Gastric Outlet Obstruction Following Recurrent Pancreatitis Uncovers a Giant Parathyroid Adenoma: A Case Report.

A 35-year-old female presented with abdominal pain, fever, projectile vomiting, and a diffuse tender epigastric mass. She was diagnosed to have acute persistent pancreatitis with a pancreatic pseudocyst. Elevated serum calcium levels provided an etiologic link between hypercalcemia and pancreatitis.

Thyroid Hormone Decreases Hepatic Steatosis, Inflammation, and Fibrosis in a Dietary Mouse Model of Nonalcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is characterized by hepatic steatosis, lobular inflammation, and fibrosis. Thyroid hormone (TH) reduces steatosis; however, the therapeutic effect of TH on NASH-associated inflammation and fibrosis is not known. This study examined the therapeutic effect of TH on hepatic inflammation and fibrosis during NASH and investigated THs molecular actions on autophagy and mitochondrial biogenesis.

Caffeine prevents restenosis and inhibits vascular smooth muscle cell proliferation through the induction of autophagy.

Caffeine is among the most highly consumed substances worldwide, and it has been associated with decreased cardiovascular risk. Although caffeine has been shown to inhibit the proliferation of vascular smooth muscle cells (VSMCs), the mechanism underlying this effect is unknown. Here, we demonstrated that caffeine decreased VSMC proliferation and induced macroautophagy/autophagy in an vascular injury model of restenosis.

A nexus of miR-1271, PAX4 and ALK/RYK influences the cytoskeletal architectures in Alzheimer's Disease and Type 2 Diabetes.

Alzheimer's Disease (AD) and Type 2 Diabetes (T2D) share a common hallmark of insulin resistance. Reportedly, two non-canonical Receptor Tyrosine Kinases (RTKs), ALK and RYK, both targets of the same micro RNA miR-1271, exhibit significant and consistent functional down-regulation in post-mortem AD and T2D tissues. Incidentally, both have Grb2 as a common downstream adapter and NOX4 as a common ROS producing factor.

Pleomorphic liposarcoma of the male breast: lessons from a rare malignancy during COVID-19 pandemic.

A 52-year-old man presented with a recurrent right side breast lump. He had undergone excision of a lump on the right breast followed by adjuvant chemoradiotherapy 1 year ago for a diagnosis of pleomorphic liposarcoma. Imaging revealed a 47×36 mm lesion on the right side of the chest wall involving the pectoralis muscle.