Multiomic profiling of chronically activated CD4+ T cells identifies drivers of exhaustion and metabolic reprogramming.

Repeated antigen exposure leads to T-cell exhaustion, a transcriptionally and epigenetically distinct cellular state marked by loss of effector functions (e.g., cytotoxicity, cytokine production/release), up-regulation of inhibitory receptors (e.

CD97 maintains tumorigenicity of glioblastoma stem cells via mTORC2 signaling and is targeted by CAR Th9 cells.

Glioblastoma (GBM) stem cells (GSCs) contribute to poor prognosis in patients with GBM. Identifying molecular markers is crucial for developing targeted therapies. Here, we identify cluster of differentiation 97 (CD97) as an optimal GSC surface antigen for potential targeting by chimeric antigen receptor (CAR) T cell therapy through in vitro antibody screening.

PhyloForge: Unifying Micro- and Macroevolution With Comprehensive Genomic Signals.

The dimensions of phylogenetic research have expanded to encompass the study of large-scale populations at the microevolutionary level and comparisons between different species or taxonomic units at the macroevolutionary level. Traditional phylogenetic tools often struggle to handle the diverse and complex data required for these different evolutionary scales. In response to this challenge, we introduce PhyloForge, a robust tool designed to seamlessly integrate the demands of both micro- and macroevolution, comprehensively utilising diverse phylogenomic signals, such as genes, SNPs, and structural variations, as well as mitochondrial and chloroplast genomes.

P4HB maintains Wnt-dependent stemness in glioblastoma stem cells as a precision therapeutic target and serum marker.

Glioblastoma stem cells (GSCs) are pivotal in the recurrence and drug resistance of glioblastoma multiforme (GBM). However, precision therapeutic and diagnostic markers for GSCs have not been fully established. Here, using bioinformatics and experimental analysis, we identified P4HB, a protein disulfide isomerase, as a serum marker that maintains stemness in GSCs through the Wnt/β-catenin signaling pathway.

The influences of ApoE isoforms on endothelial adherens junctions and actin cytoskeleton responding to mCRP.

Apolipoprotein E4 (ApoE4) plays an important role responding to monomeric C-reactive protein (mCRP) via binding to CD31 leading to cerebrovascular damage and Alzheimer's disease (AD). Using phosphor-proteomic profiling, we found altered cytoskeleton proteins in the microvasculature of AD brains, including increased levels of hyperphosphorylated tau (pTau) and the actin-related protein, LIMA1. To address the hypothesis that cytoskeletal changes serve as early pathological signatures linked with CD31 in brain endothelia in ApoE4 carriers, ApoE4 knock-in mice intraperitoneal injected with mCRP revealed that mCRP increased the expressions of phosphorylated CD31 (pCD31) and LIMA1, and facilitate the binding of pCD31 to LIMA1.

Beyond Glycolysis: Aldolase A Is a Novel Effector in Reelin-Mediated Dendritic Development.

Reelin, a secreted glycoprotein, plays a crucial role in guiding neocortical neuronal migration, dendritic outgrowth and arborization, and synaptic plasticity in the adult brain. Reelin primarily operates through the canonical lipoprotein receptors apolipoprotein E receptor 2 (Apoer2) and very low-density lipoprotein receptor (Vldlr). Reelin also engages with noncanonical receptors and unidentified coreceptors; however, the effects of which are less understood.

Pantothenate-encapsulated liposomes combined with exercise for effective inhibition of CRM1-mediated PKM2 translocation in Alzheimer's therapy.

Alzheimer's disease (AD) is a complex neurodegenerative condition characterized by metabolic imbalances and neuroinflammation, posing a formidable challenge in medicine due to the lack of effective treatments. Despite considerable research efforts, a cure for AD remains elusive, with current therapies primarily focused on symptom management rather than addressing the disease's underlying causes. This study initially discerned, through Mendelian randomization analysis that elevating pantothenate levels significantly contributes to the prophylaxis of Alzheimer's disease.

Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment.

JOURNAL/nrgr/04.03/01300535-202504000-00029/figure1/v/2024-07-06T104127Z/r/image-tiff Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients, with evidence suggesting exercise may reduce mortality risks and aid neural regeneration. The role of the small ubiquitin-like modifier (SUMO) protein, especially post-exercise, in cancer progression, is gaining attention, as are the potential anti-cancer effects of SUMOylation.

PANAMA-enabled high-sensitivity dual nanoflow LC-MS metabolomics and proteomics analysis.

High-sensitivity nanoflow liquid chromatography (nLC) is seldom employed in untargeted metabolomics because current sample preparation techniques are inefficient at preventing nanocapillary column performance degradation. Here, we describe an nLC-based tandem mass spectrometry workflow that enables seamless joint analysis and integration of metabolomics (including lipidomics) and proteomics from the same samples without instrument duplication. This workflow is based on a robust solid-phase micro-extraction step for routine sample cleanup and bioactive molecule enrichment.

High-Resolution Spatiotemporal Modeling for PM Major Components in the Pearl River Delta and Its Implications for Epidemiological Studies.

Distinguishing the effects of different fine particulate matter components (PMCs) is crucial for mitigating their effects on human health. However, the sparse distribution of locations where PM is collected for component analysis makes it challenging to investigate the relevant health effects. This study aimed to investigate the agreement between data-fusion-enhanced exposure assessment and site monitoring data in estimating the effects of PMCs on gestational diabetes mellitus (GDM).

Vancomycin trough concentration in adult patients with periprosthetic joint infection: A machine learning-based covariate model.

Aims: Although there are various model-based approaches to individualized vancomycin (VCM) administration, few have been reported for adult patients with periprosthetic joint infection (PJI). This work attempted to develop a machine learning (ML)-based model for predicting VCM trough concentration in adult PJI patients.

Methods: The dataset of 287 VCM trough concentrations from 130 adult PJI patients was split into a training set (229) and a testing set (58) at a ratio of 8:2, and an independent external 32 concentrations were collected as a validation set.

A Preoperative Prediction Model for Lymph Node Metastasis in Patients with Gastric Cancer Using a Machine Learning-based Ultrasomics Approach.

Objective: This study aimed to develop an ultrasomics model for predicting lymph node metastasis preoperative in patients with gastric cancer (GC).

Methods: This study enrolled GC patients who underwent preoperative ultrasound examination. Manual segmentation of the region of interest (ROI) was performed by an experienced radiologist to extract radiomics features using the Pyradiomics software.

Physiologically-based pharmacokinetic modeling to predict the exposure and provide dosage regimens of Ustekinumab in pediatric patients with inflammatory bowel disease.

Ustekinumab (UST), a fully human immunoglobulin G1 κ monoclonal antibody, exhibiting high affinity for the p40 subunit shared by IL-12 and IL-23, which play key roles in the pathogenesis of inflammatory bowel disease (IBD). By scaling the physiologically-based pharmacokinetic modeling (PBPK) model of UST in adult patients with IBD, we aim to predict effective dosages for UST in pediatric patients, thereby offering a more practical dosing regimen for real-world applications. In this work, a PBPK model for UST in adult patients with IBD has been developed using PK-Sim and Mobi.

Modeling an evaluation of the efficacy of the novel neuroanalgesic drug mirogabalin for diabetic peripheral neuropathic pain and postherpetic neuralgia therapy.

Diabetic peripheral neuropathic pain (DPNP) and postherpetic neuralgia (PHN) are challenging and often intractable complex medical conditions, with a substantial impact on the quality of life. Mirogabalin, a novel voltage-gated Ca channel α2δ ligand, was approved for the indication of DPNP and PHN. However, the time course of effects has not yet been clarified.

The association between PM components and blood pressure changes in late pregnancy: A combined analysis of traditional and machine learning models.

Background: PM is a harmful mixture of various chemical components that pose a challenge in determining their individual and combined health effects due to multicollinearity issues with traditional linear regression models. This study aimed to develop an analytical methodology combining traditional and novel machine learning models to evaluate PM's combined effects on blood pressure (BP) and identify the most toxic components.

Methods: We measured late-pregnancy BP of 1138 women from the Heshan cohort while simultaneously analyzing 31 PM components.

Convolutional neural network-based magnetic resonance image differentiation of filum terminale ependymomas from schwannomas.

Purpose: Preoperative diagnosis of filum terminale ependymomas (FTEs) versus schwannomas is difficult but essential for surgical planning and prognostic assessment. With the advancement of deep-learning approaches based on convolutional neural networks (CNNs), the aim of this study was to determine whether CNN-based interpretation of magnetic resonance (MR) images of these two tumours could be achieved.

Methods: Contrast-enhanced MRI data from 50 patients with primary FTE and 50 schwannomas in the lumbosacral spinal canal were retrospectively collected and used as training and internal validation datasets.

Corrigendum: Integrated metabolomics and proteomics reveal biomarkers associated with hemodialysis in end-stage kidney disease.

[This corrects the article DOI: 10.3389/fphar.2023.

Electric Field Switching of Magnon Spin Current in a Compensated Ferrimagnet.

Manipulation of directional magnon propagation, known as magnon spin current, is essential for developing magnonic devices featuring nonvolatile functionalities and ultralow power consumption. Magnon spin current can usually be modulated by magnetic field or current-induced spin torques. However, these approaches may lead to energy dissipation due to Joule heating.

DataColor: unveiling biological data relationships through distinctive color mapping.

In the era of rapid advancements in high-throughput omics technologies, the visualization of diverse data types with varying orders of magnitude presents a pressing challenge. To bridge this gap, we introduce DataColor, an all-encompassing software solution meticulously crafted to address this challenge. Our aim is to empower users with the ability to handle a wide array of data types through an assortment of tools, while simultaneously streamlining parameter selection for rapid insights and detailed enhancements.

Beyond Glycolysis: Aldolase A is a Novel Effector in Reelin Mediated Dendritic Development.

Unlabelled: Reelin, a secreted glycoprotein, plays a crucial role in guiding neocortical neuronal migration, dendritic outgrowth and arborization, and synaptic plasticity in the adult brain. Reelin primarily operates through the canonical lipoprotein receptors apolipoprotein E receptor 2 (Apoer2) and very low-density lipoprotein receptor (Vldlr). Reelin also engages with non-canonical receptors and unidentified co-receptors; however, the effects of which are less understood.

Integrated metabolomics and proteomics reveal biomarkers associated with hemodialysis in end-stage kidney disease.

We hypothesize that the poor survival outcomes of end-stage kidney disease (ESKD) patients undergoing hemodialysis are associated with a low filtering efficiency and selectivity. The current gold standard criteria using single or several markers show an inability to predict or disclose the treatment effect and disease progression accurately. We performed an integrated mass spectrometry-based metabolomic and proteomic workflow capable of detecting and quantifying circulating small molecules and proteins in the serum of ESKD patients.

Physiological Properties of Perennial Rice Regenerating Cultivation in Two Years with Four Harvests.

Crop perennialization has garnered global attention recently due to its role in sustainable agriculture. However, there is still a lack of detailed information regarding perennial rice's regenerative characteristics and physiological mechanisms in crop ratooning systems with different rice stubble heights. In addition, the response of phytohormones to varying stubble heights and how this response influences the regenerative characteristics of ratoon rice remains poorly documented.

Loss of ADAR1 in macrophages in combination with interferon gamma suppresses tumor growth by remodeling the tumor microenvironment.

Background: ADAR1, the major enzyme for RNA editing, has emerged as a tumor-intrinsic key determinant for cancer immunotherapy efficacy through modulating interferon-mediated innate immunity. However, the role of ADAR1 in innate immune cells such as macrophages remains unknown.

Methods: We first analyzed publicly accessible patient-derived single-cell RNA-sequencing and perturbed RNA sequencing data to elucidate the ADAR1 expression and function in macrophages.

Gestational age modifies the association between exposure to fine particles and fetal death: findings from a nationwide epidemiological study in the contiguous United States.

Backgrounds: The vulnerability of fetuses differs at different developmental stages, in response to environmental stressors such as fine particulate matter (PM), a ubiquitous air pollutant. Whether gestational age (GA) modifies the association between prenatal fine particulate matter (PM) exposure and fetal death remains unclear.

Methods: We selected approximately 47.