Neutralizing antibody immune correlates in COVAIL trial recipients of an mRNA second COVID-19 vaccine boost.

Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic's evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate's contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.

Lipidic folding pathway of α-Synuclein via a toxic oligomer.

Aggregation intermediates play a pivotal role in the assembly of amyloid fibrils, which are central to the pathogenesis of neurodegenerative diseases. The structures of filamentous intermediates and mature fibrils are now efficiently determined by single-particle cryo-electron microscopy. By contrast, smaller pre-fibrillar α-Synuclein (αS) oligomers, crucial for initiating amyloidogenesis, remain largely uncharacterized.

Liquid-infused nanostructured composite as a high-performance thermal interface material for effective cooling.

Effective heat dissipation remains a grand challenge for energy-dense devices and systems. As heterogeneous integration becomes increasingly inevitable in electronics, thermal resistance at interfaces has emerged as a critical bottleneck for thermal management. However, existing thermal interface solutions are constrained by either high thermal resistance or poor reliability.

Neocortical somatostatin neuron diversity in cognition and learning.

Somatostatin-expressing (SST) neurons are a major class of electrophysiologically and morphologically distinct inhibitory cells in the mammalian neocortex. Transcriptomic data suggest that this class can be divided into multiple subtypes that are correlated with morpho-electric properties. At the same time, availability of transgenic tools to identify and record from SST neurons in awake, behaving mice has stimulated insights about their response properties and computational function.

Complementary Organization of Mouse Driver and Modulator Cortico-Thalamo-Cortical Circuits.

Corticocortical (CC) projections in the visual system facilitate hierarchical processing of sensory information. In addition to direct CC connections, indirect cortico-thalamo-cortical (CTC) pathways through the pulvinar nucleus of the thalamus can relay sensory signals and mediate cortical interactions according to behavioral demands. While the pulvinar connects extensively to the entire visual cortex, it is unknown whether transthalamic pathways link all cortical areas or whether they follow systematic organizational rules.

Pancreatic cancer cell-intrinsic transglutaminase-2 promotes T cell suppression through microtubule-dependent secretion of immunosuppressive cytokines.

Background: Pancreatic ductal adenocarcinoma (PDAC) is mostly refractory to immunotherapy due to immunosuppression in the tumor microenvironment and cancer cell-intrinsic T cell tolerance mechanisms. PDAC is described as a "cold" tumor type with poor infiltration by T cells and factors leading to intratumoral T cell suppression have thus received less attention. Here, we identify a cancer cell-intrinsic mechanism that contributes to a T cell-resistant phenotype and describes potential combinatorial therapy.

PSMC2 promotes resistance against temozolomide in glioblastoma via suppressing JNK-mediated autophagic cell death.

Temozolomide is universally used to treat glioblastoma due to its unique ability to cross the blood-brain barrier and inhibit tumor growth through DNA alkylation. However, over time, the inevitable emergence of resistance to temozolomide impedes successful treatment of this cancer. As a result, there is an urgent need to identify new therapeutic targets to improve treatment outcomes for this malignancy.

MnSOD non-acetylation mimic knock-in mice exhibit dilated cardiomyopathy.

Manganese superoxide dismutase (MnSOD/SOD2) is an essential mitochondrial enzyme that detoxifies superoxide radicals generated during oxidative respiration. MnSOD/SOD2 lysine 68 acetylation (K68-Ac) is an important post-translational modification (PTM) that regulates enzymatic activity, responding to nutrient status or oxidative stress, and elevated levels have been associated with human illness. To determine the in vivo role of MnSOD-K68 in the heart, we used a whole-body non-acetylation mimic mutant (MnSOD) knock-in mouse.

Characterizing Oxidative Stress induced by Aβ Oligomers and the Protective Role of Carnosine in Primary Mixed Glia Cultures.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and memory loss. A critical aspect of AD pathology is represented by oxidative stress, which significantly contributes to neuronal damage and death. Microglia and astrocytes, the primary glial cells in the brain, are crucial for managing oxidative stress and supporting neuronal function.

Role of the International Society of Liquid Biopsy (ISLB) in establishing quality control frameworks for clinical integration.

Liquid biopsy (LB) has revolutionized molecular pathology, offering non-invasive insights into tumor biology. However, widespread adoption is hindered by a lack of standardized protocols, requiring robust quality control and harmonized workflows. Large-scale studies are needed to establish effective standard operating procedures (SOPs), particularly for circulating tumor DNA (ctDNA) assays tailored to different disease stages.

Microplastic migration and transformation pathways and exposure health risks.

Plastics play a crucial role in modern life, but improper use and disposal have resulted in microplastics becoming widespread in the environment, raising significant concerns about both the environment and human health. Extensive research has explored the transformation mechanisms, bioaccumulation, ecological impacts, and health risks associated with microplastics. The present review first analyzes the migration, transformation, and degradation pathways of microplastics on a global scale, and then synthesizes current knowledge on the types, sources, and migration pathways of microplastics in soil, atmosphere, and aquatic environments, emphasizing transformation mechanisms like photo-aging and microbial degradation, and detailing their ecological and human health impacts.

Synaptic protein expression in bipolar disorder patient-derived neurons implicates PSD-95 as a marker of lithium response.

Bipolar disorder (BD) is a severe mental illness characterized by recurrent episodes of depression and mania. Lithium is the gold standard pharmacotherapy for BD, but outcomes are variable, and the relevant therapeutic mechanisms underlying successful treatment response remain uncertain. To identify synaptic markers of BD and lithium response, we measured the effects of lithium on induced pluripotent stem cell-derived neurons from BD patients and controls.

Associations of Physical Activity and Cardiorespiratory Fitness with Incident Chronic Kidney Disease in a Korean Population.

Objective: This large cohort study aimed to examine the overall associations of physical activity (PA) and estimated cardiorespiratory fitness (eCRF) with incident chronic kidney disease (CKD).

Methods: This study included a total of 274,292 participants (mean age, 37.9±8.

The FIRE biosensor illuminates iron regulatory protein activity and cellular iron homeostasis.

On Earth, iron is abundant, bioavailable, and crucial for initiating the first catalytic reactions of life from prokaryotes to plants to mammals. Iron-complexed proteins are critical to biological pathways and essential cellular functions. While it is well known that the regulation of iron is necessary for mammalian development, little is known about the timeline of how specific transcripts network and interact in response to cellular iron regulation to shape cell fate, function, and plasticity in the developing embryo and beyond.

Characterizing substructure via mixture modeling in large-scale genetic summary statistics.

Genetic summary data are broadly accessible and highly useful, including for risk prediction, causal inference, fine mapping, and incorporation of external controls. However, collapsing individual-level data into summary data, such as allele frequencies, masks intra- and inter-sample heterogeneity, leading to confounding, reduced power, and bias. Ultimately, unaccounted-for substructure limits summary data usability, especially for understudied or admixed populations.

Discovery of a DNA methylation profile in individuals with Sifrim-Hitz-Weiss syndrome.

Pathogenic heterozygous variants in CHD4 cause Sifrim-Hitz-Weiss syndrome, a neurodevelopmental disorder associated with brain anomalies, heart defects, macrocephaly, hypogonadism, and additional features with variable expressivity. Most individuals have non-recurrent missense variants, complicating variant interpretation. A few were reported with truncating variants, and their role in disease is unclear.

Metabolic tug-of-war: Microbial metabolism shapes colonization resistance against enteric pathogens.

A widely recognized benefit of gut microbiota is that it provides colonization resistance against enteric pathogens. The gut microbiota and their products can protect the host from invading microbes directly via microbe-pathogen interactions and indirectly by host-microbiota interactions, which regulate immune system function. In contrast, enteric pathogens have evolved mechanisms to utilize microbiota-derived metabolites to overcome colonization resistance and increase their pathogenic potential.

Commensal-derived tryptophan metabolites fortify the skin barrier: Insights from a 50-species gnotobiotic model of human skin microbiome.

The epidermal barrier defends the body against dehydration and harmful substances. The commensal microbiota is essential for proper differentiation and repair of the epidermal barrier, an effect mediated by the aryl hydrocarbon receptor (AHR). However, the microbial mechanisms of AHR activation in skin are less understood.

Research on the PFAS release and migration behavior of multi-layer outdoor jacket fabrics.

Perfluoroalkyl and poly-fluoroalkyl substances (PFAS) release from textiles is a source of human exposure, but the mechanisms behind this release remain insufficiently studied. This research investigates the release and transport mechanisms of PFAS in outdoor jacket fabrics treated with a short side-chain fluorinated polymers (CF-SFPs) for durable water repellency (DWR). PA-based and PET-based fabrics were exposed to outdoor conditions and subjected to accelerated aging, followed by abrasion, washing, and drying experiments to simulate wear and degradation.

"Clinical outcomes and healthcare costs in status epilepticus: A multivariable analysis from a tertiary center in a resource-limited setting".

Background: As a debilitating and severe repercussion, the clinical and economic impact of Status epilepticus (SE) has not been thoroughly explored in various regions around the world, especially those with limited resources. Therefore, we aimed to identify the predictors of mortality and healthcare costs associated with SE in one tertiary care center with limited resources.

Methods: This retrospective single-center cohort study, carried out at Namazi Hospital, Shiraz, Iran, included 130 SE cases from March 21, 2021, to March 20, 2022.

Reduced gray matter volume in limbic and cortical areas is associated with anxiety and depression in alcohol use disorder patients.

Alcohol use disorder (AUD) is a multifactorial disease closely related to neurodevelopment and environmental factors that influence behavior. This study explored the relationships between brain volume and behavior from an Exploratory Structural Equation Modeling (ESEM) based on the Research Domain Criteria. High-resolution magnetic resonance imaging scans were acquired from recent patients with AUD (n = 50) and healthy controls (HC=50).

Fatty acid desaturase 3-mediated α-linolenic acid biosynthesis in plants.

Omega (ω)-3 fatty acids (FAs) are essential components of cell membranes that also serve as precursors of numerous regulatory molecules. α-linolenic acid (ALA), one of the most important ω3 FAs in plants, is synthesized in both the plastid and extraplastidial compartments. FA Desaturase (FAD) 3 is an extraplastidial enzyme that converts linoleic acid (LA) to ALA.

Brain Transcriptome Changes Associated With an Acute Increase of Protein O-GlcNAcylation and Implications for Neurodegenerative Disease.

Enhancing protein O-GlcNAcylation by pharmacological inhibition of the enzyme O-GlcNAcase (OGA) has been considered as a strategy to decrease tau and amyloid-beta phosphorylation, aggregation, and pathology in Alzheimer's disease (AD). There is still more to be learned about the impact of enhancing global protein O-GlcNAcylation, which is important for understanding the potential of using OGA inhibition to treat neurodegenerative diseases. In this study, we investigated the acute effect of pharmacologically increasing O-GlcNAc levels, using the OGA inhibitor Thiamet G (TG), in normal mouse brains.