Differential roles of human CD4 and CD8 regulatory T cells in controlling self-reactive immune responses.

Here we analyzed the relative contributions of CD4 regulatory T cells expressing Forkhead box protein P3 (FOXP3) and CD8 regulatory T cells expressing killer cell immunoglobulin-like receptors to the control of autoreactive T and B lymphocytes in human tonsil-derived immune organoids. FOXP3 and GZMB respectively encode proteins FOXP3 and granzyme B, which are critical to the suppressive functions of CD4 and CD8 regulatory T cells. Using CRISPR-Cas9 gene editing, we were able to achieve a reduction of ~90-95% in the expression of these genes.

Maternal asthma imprints fetal lung ILC2s via glucocorticoid signaling leading to worsened allergic airway inflammation in murine adult offspring.

The root of asthma can be linked to early life, with prenatal environments influencing risk. We investigate the effects of maternal asthma on the offspring's lungs during fetal and adult life. Adult offspring of asthmatic mothers show an increase in lung group 2 innate lymphoid cell (ILC2) number and function with allergen-induced lung inflammation.

Cell integrity limits ploidy in budding yeast.

Evidence suggests that increases in ploidy have occurred frequently in the evolutionary history of organisms and can serve adaptive functions to specialized somatic cells in multicellular organisms. However, the sudden multiplication of all chromosome content may present physiological challenges to the cells in which it occurs. Experimental studies have associated increases in ploidy with reduced cell survival and proliferation.

Molecular basis for shifted receptor recognition by an encephalitic arbovirus.

After decades of inactivity throughout the Americas, western equine encephalitis virus (WEEV) recently re-emerged in South America, causing a large-scale outbreak in humans and horses. WEEV binds protocadherin 10 (PCDH10) as a receptor; however, nonpathogenic strains no longer bind human or equine PCDH10 but retain the ability to bind avian receptors. Highly virulent WEEV strains can also bind the very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) as alternative receptors.

Gut bacterial sphingolipid production modulates dysregulated skin lipid homeostasis.

Sphingolipids are an essential lipid component of the skin barrier with alterations in skin sphingolipid composition associated with multiple skin disorders including psoriasis, atopic dermatitis, and ichthyosis. Contributions to skin sphingolipid abundance are not well characterized, thus the main method of modulating skin lipid levels is the topical application of creams rich with sphingolipids at the skin surface. Evidence that diet and gut microbiome function can alter skin biology proposes an intriguing potential for the modulation of skin lipid homeostasis through gut microbial metabolism, but potential mechanisms of action are not well understood.

A widespread family of viral sponge proteins reveals specific inhibition of nucleotide signals in anti-phage defense.

Cyclic oligonucleotide-based antiviral signaling systems (CBASS) are bacterial anti-phage defense operons that use nucleotide signals to control immune activation. Here we biochemically screen 57 diverse and phages for the ability to disrupt CBASS immunity and discover anti-CBASS 4 (Acb4) from the phage SPO1 as the founding member of a large family of >1,300 immune evasion proteins. A 2.

Single-base mA epitranscriptomics reveals novel HIV-1 host interaction targets in primary CD4 T cells.

-methyladenosine (mA) is the most prevalent cellular mRNA modification and plays a critical role in regulating RNA stability, localization, and gene expression. mA modification plays a vital role in modulating the expression of viral and cellular genes during HIV-1 infection. HIV-1 infection increases cellular RNA mA levels in many cell types, which facilitates HIV-1 replication and infectivity in target cells.

CEBPA repression by MECOM blocks differentiation to drive aggressive leukemias.

Acute myeloid leukemias (AMLs) have an overall poor prognosis with many high-risk cases co-opting stem cell gene regulatory programs, yet the mechanisms through which this occurs remain poorly understood. Increased expression of the stem cell transcription factor, MECOM, underlies one key driver mechanism in largely incurable AMLs. How MECOM results in such aggressive AML phenotypes remains unknown.

Fluorescence-barcoded cell lines stably expressing membrane-anchored influenza neuraminidases.

The discovery of broadly protective antibodies to the influenza virus neuraminidase (NA) has raised interest in NA as a vaccine target. However, recombinant, solubilized tetrameric NA ectodomains are often challenging to express and isolate, hindering the study of anti-NA humoral responses. To address this obstacle, we established a panel of 22 non-adherent cell lines stably expressing native, historical N1, N2, N3, N9, and NB NAs anchored on the cell surface.

Cross-reactive sarbecovirus antibodies induced by mosaic RBD-nanoparticles.

Therapeutic monoclonal antibodies (mAbs) against SARS-CoV-2 become obsolete as spike substitutions reduce antibody binding. To induce antibodies against conserved receptor-binding domain (RBD) regions for protection against SARS-CoV-2 variants of concern and zoonotic sarbecoviruses, we developed mosaic-8b RBD-nanoparticles presenting eight sarbecovirus RBDs arranged randomly on a 60-mer nanoparticle. Mosaic-8b immunizations protected animals from challenges from viruses whose RBDs were matched or mismatched to those on nanoparticles.

Analysis of risk factors of infection in patients with inflammatory bowel disease.

Introduction: infection (CDI) is one of the most important challenges in contemporary gastroenterology. However, data from CDI studies are sometimes contradictory.

Aim: To analyse the risk factors for CDI in patients with inflammatory bowel disease (IBD).

Quantitative investigation of a 3D bubble trapper in a high shear stress microfluidic chip using computational fluid dynamics and L*A*B* color space.

Microfluidic chips often face challenges related to the formation and accumulation of air bubbles, which can hinder their performance. This study investigated a bubble trapping mechanism integrated into microfluidic chip to address this issue. Microfluidic chip design includes a high shear stress section of fluid flow that can generate up to 2.

Efficacy of Subcutaneous, Sublingual and Oral Immunotherapy for Allergens: A Comparative Study.

The purpose of this study was to compare the efficacy and safety of subcutaneous, sublingual, oral specific immunotherapy in patients who suffer from allergic conditions to pollen from trees, grasses and weeds, house dust mites and Alternaria alternata spores. A literature search was performed separately for each type of allergen and each administration route of the drug. As a result, it was found that all administration routes were quite effective.

Erwinia phage Asesino is a nucleus-forming phage that lacks PhuZ.

As nucleus-forming phages become better characterized, understanding their unifying similarities and unique differences will help us understand how they occupy varied niches and infect diverse hosts. All identified nucleus-forming phages fall within the Chimalliviridae family and share a core genome of 68 unique genes including chimallin, the major nuclear shell protein. A well-studied but non-essential protein encoded by many nucleus-forming phages is PhuZ, a tubulin homolog which aids in capsid migration, nucleus rotation, and nucleus positioning.

Comparative efficacy and safety of tissue plasminogen activators (tPA) in acute ischemic stroke: A systematic review and network meta-analysis of randomized controlled trials.

Background: Intravenous alteplase (ALT) is the standard treatment for acute ischemic stroke (AIS). However, recent trials comparing other tissue plasminogen activators (tPAs) like tenecteplase (TNK) and reteplase with ALT have yielded conflicting results. This necessitated a network meta-analysis to compare the efficacy and safety of various tPAs in AIS patients.

Effects of dioscin from Dioscorea nipponica on TL1A/DR3 and Th9 cells in a collagen-induced arthritis mouse model.

Rheumatoid arthritis (RA) is a systemic autoimmune disease, and TL1A and its receptor DR3 play important roles in its pathogenesis. Th9 cells are involved in RA development. Dioscin from Dioscorea nipponica (DDN) has a therapeutic effect on RA, but its effect on TL1A/DR3 and Th9 cells remains unclear.

Fraxin inhibits ovariectomized-induced bone loss and osteoclastogenesis by suppressing ROS activity.

Osteoporosis is characterized by increased osteoclast activity, which is strongly associated with increased levels of reactive oxygen species (ROS). Fraxin, a natural coumarin glycoside, has shown anti-inflammatory and antioxidant properties, but its effects on bone homeostasis are obscure. The effects of fraxin on osteoclast formation and activation were measured via an in vitro osteoclastogenesis assay.

A pH/GSH Dual-Responsive Triple Synergistic Bimetallic Nanocatalyst for Enhanced Tumor Chemodynamic Therapy.

Chemodynamic therapy (CDT) has garnered significant attention in the field of tumor therapy due to its ability to convert overexpressed hydrogen peroxide (HO) in tumors into highly toxic hydroxyl radicals (•OH) through metal ion-mediated catalysis. However, the effectiveness of CDT is hindered by low catalyst efficiency, insufficient intra-tumor HO level, and excessive glutathione (GSH). In this study, a pH/GSH dual responsive bimetallic nanocatalytic system (CuFeMOF@GOx@Mem) is developed by modifying red blood cell membranes onto glucose oxidase (GOx)-loaded Fe-Cu bimetallic MOFs, enhancing the efficacy of CDT through a triple-enhanced way by HO self-supply, catalysts self-cycling, and GSH self-elimination.

Visualizing lipid nanoparticle trafficking for mRNA vaccine delivery in non-human primates.

mRNA delivered using lipid nanoparticles (LNPs) has become an important subunit vaccine modality, but mechanisms of action for mRNA vaccines remain incompletely understood. Here, we synthesized a metal chelator-lipid conjugate enabling positron emission tomography (PET) tracer labeling of LNP/mRNA vaccines for quantitative visualization of vaccine trafficking in live mice and non-human primates (NHPs). Following intramuscular injection, we observed LNPs distributing through injected muscle tissue, simultaneous with rapid trafficking to draining lymph nodes (dLNs).

Retinal Displacement Following Vitrectomy for Rhegmatogenous Retinal Detachment: A Systematic Review of Surgical Techniques, Tamponade Agents, and Outcomes.

Rhegmatogenous retinal detachment (RRD) is a severe condition that may lead to permanent vision loss if untreated. Pars plana vitrectomy (PPV) has become a preferred surgical intervention, particularly in complex cases. Objective: Retinal displacement (RD) following PPV for RRD can lead to visual distortions and can negatively impact patient quality of life.

A Comparative Study of Intense Pulsed Light with Two Different Filters in Meibomian Gland Dysfunction: A Prospective Randomized Study.

To compare the long-term efficacy and safety of intense pulsed light (IPL) treatments using a 590-nm and an acne filter. In this prospective, randomized, paired-eye trial study, 30 patients with moderate and severe meibomian gland dysfunction (MGD) were followed up for at least one month after their last treatment. Group A received IPL treatment with an acne filter, a type of notch filter that blocks wavelengths between 600 and 800 nm, allowing IPL to emit wavelengths between 400-600 nm and 800-1200 nm.

Maximal Intensity Exercise Induces Adipokine Secretion and Disrupts Prooxidant-Antioxidant Balance in Young Men with Different Body Composition.

Maximal physical effort induces a disturbance in the body's energy homeostasis and causes oxidative stress. The aim of the study was to determine whether prooxidant-antioxidant balance disturbances and the secretion of adipokines regulating metabolism, induced by maximal intensity exercise, are dependent on body composition in young, healthy, non-obese individuals. We determined changes in the concentration of advanced protein oxidation products (AOPP), markers of oxidative damage to nucleic acids (DNA/RNA/ox), and lipid peroxidation (LPO); catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activity, as well as concentrations of visfatin, leptin, resistin, adiponectin, asprosin, and irisin in the blood before and after maximal intensity exercise in men with above-average muscle mass (NFAT-HLBM), above-average fat mass (HFAT-NLBM), and with average body composition (NFAT-NLBM).

Defining Mechanistic Links Between the Non-Coding Variant rs17673553 in and Lupus Susceptibility.

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by widespread inflammation and autoantibody production. Its development and progression involve genetic, epigenetic, and environmental factors. Although genome-wide association studies (GWAS) have repeatedly identified a susceptibility signal at 16p13, its fine-scale source and its functional and mechanistic role in SLE remain unclear.

Harnessing Mesenchymal Stromal Cells for Advanced Wound Healing: A Comprehensive Review of Mechanisms and Applications.

Chronic wounds and injuries remain a substantial healthcare challenge, with significant burdens on patient quality of life and healthcare resources. Mesenchymal stromal cells (MSCs) present an innovative approach to enhance tissue repair and regeneration in the context of wound healing. The intrinsic presence of MSCs in skin tissue, combined with their roles in wound repair, ease of isolation, broad secretory profile, and low immunogenicity, makes them especially promising for treating chronic wounds.