Trophectoderm-like cells from EPS cells enable generating EPS cell-derived post-implantation embryoids that complete gastrulation.

Mouse extended pluripotent stem (EPS) cells have demonstrated significant potential for generating embryo models in vitro. However, their limited capacity for extraembryonic trophoblast development has hindered their use in constructing whole embryo models, particularly post-implantation embryoids. Here, we establish a stepwise induction protocol to generate trophectoderm-like cells from mouse EPS cells.

LILRB4 exacerbates myocardial ischemia-reperfusion injury by promoting inflammation and pyroptosis.

Inflammation and pyroptosis are pivotal in myocardial ischemia-reperfusion injury. Although leukocyte immunoglobulin-like receptor subfamily B4 (LILRB4) modulates inflammation in conditions such as myocardial hypertrophy, its involvement in myocardial ischemia-reperfusion injury (MIRI) remains ambiguous. Recombinant adenoviral vectors were designed to induce the overexpression or knockdown of LILRB4 in H9C2 cardiomyocytes or rat myocardial tissue.

Impact of ionizable lipid type on the pharmacokinetics and biodistribution of mRNA-lipid nanoparticles after intravenous and subcutaneous injection.

Ionizable lipids play a crucial role in mRNA-lipid nanoparticle (LNP) formulations by facilitating mRNA encapsulation, promoting cell uptake, and enhancing endosomal escape of mRNA-LNPs. Despite their importance in mRNA delivery, the specific effects of ionizable lipids on mRNA-LNP in vivo pharmacokinetics (PK) and biodistribution remain underexplored. This study examines the effect of SM-102, ALC-0315, DLin-MC3-DMA (MC3), and 113-O12B ionizable lipids in mRNA-LNP formulations on plasma PK of lipid and mRNA, and biodistribution of expressed protein following subcutaneous (SC) and intravenous (IV) administration in mice.

Efficient mRNA delivery to resting T cells to reverse HIV latency.

A major hurdle to curing HIV is the persistence of integrated proviruses in resting CD4 T cells that remain in a transcriptionally silent, latent state. One strategy to eradicate latent HIV is to activate viral transcription, followed by elimination of infected cells through virus-mediated cytotoxicity or immune-mediated clearance. We hypothesised that mRNA-lipid nanoparticle (LNP) technology would provide an opportunity to deliver mRNA encoding proteins able to reverse HIV latency in resting CD4 T cells.

Effects of different physical exercise types on health outcomes of individuals with hypertensive disorders of pregnancy: a prospective randomized controlled clinical study.

Objective: To explore the impacts of different types of physical exercise on health outcomes of individuals with hypertensive disorders of pregnancy (HDPs).

Methods: Forty individuals with HDPs admitted to a tertiary hospital providing maternal and pediatric care between July 2023 and March 2024 were enrolled in this prospective randomized controlled clinical study and completed a ≥4-week intervention. Data were collected before the intervention and before delivery.

RP105 Attenuates Ischemia/Reperfusion-Induced Oxidative Stress in the Myocardium via Activation of the Lyn/Syk/STAT3 Signaling Pathway.

Although our previous studies have established the crucial role of RP105 in myocardial ischemia/reperfusion injury (MI/RI), its involvement in regulating oxidative stress induced by MI/RI remains unclear. To investigate this, we conducted experiments using a rat model of ischemia/reperfusion (I/R) injury. Adenovirus carrying RP105 was injected apically at multiple points, and after 72 h, the left anterior descending coronary artery was ligated for 30 min followed by 2 h of reperfusion.

The mechanism of the NFAT transcription factor family involved in oxidative stress response.

As a transcriptional activator widely expressed in various tissues, nuclear factor of activated T cells (NFAT) is involved in the regulation of the immune system, the development of the heart and brain systems, and classically mediating pathological processes such as cardiac hypertrophy. Oxidative stress is an imbalance of intracellular redox status, characterized by excessive generation of reactive oxygen species, accompanied by mitochondrial dysfunction, calcium overload, and subsequent lipid peroxidation, inflammation, and apoptosis. Oxidative stress occurs during various pathological processes, such as chronic hypoxia, vascular smooth muscle cell phenotype switching, ischemia-reperfusion, and cardiac remodeling.

Research progress of B subfamily of leucocyte immunoglobulin-like receptors in inflammation.

Leucocyte immunoglobulin-like receptors subfamily B (LILRB) belongs to the type I transmembrane glycoproteins, which is the immunosuppressive receptor. LILRBs are widely expressed in bone marrow cells, hematopoietic stem cells, nerve cells and other body cells. Studies have found that LILRBs receptor can bind to a variety of ligands and has a variety of biological functions such as regulating inflammatory response, immune tolerance and cell differentiation.

Physiological substrates and ontogeny-specific expression of the ubiquitin ligases MARCH1 and MARCH8.

MARCH1 and MARCH8 are ubiquitin ligases that control the expression and trafficking of critical immunoreceptors. Understanding of their function is hampered by three major knowledge gaps: (i) it is unclear which cell types utilize these ligases; (ii) their level of redundancy is unknown; and (iii) most of their putative substrates have been described in cell lines, often overexpressing MARCH1 or MARCH8, and it is unclear which substrates are regulated by either ligase . Here we address these questions by systematically analyzing the immune cell repertoire of MARCH1- or MARCH8-deficient mice, and applying unbiased proteomic profiling of the plasma membrane of primary cells to identify MARCH1 and MARCH8 substrates.

Ubiquitin-like protein 3 (UBL3) is required for MARCH ubiquitination of major histocompatibility complex class II and CD86.

The MARCH E3 ubiquitin (Ub) ligase MARCH1 regulates trafficking of major histocompatibility complex class II (MHC II) and CD86, molecules of critical importance to immunity. Here we show, using a genome-wide CRISPR knockout screen, that ubiquitin-like protein 3 (UBL3) is a necessary component of ubiquitination-mediated trafficking of these molecules in mice and in humans. Ubl3-deficient mice have elevated MHC II and CD86 expression on the surface of professional and atypical antigen presenting cells.

MHC Class II Ubiquitination Regulates Dendritic Cell Function and Immunity.

MHC class II (MHC II) Ag presentation by dendritic cells (DCs) is critical for CD4 T cell immunity. Cell surface levels of MHC II loaded with peptide is controlled by ubiquitination. In this study, we have examined how MHC II ubiquitination impacts immunity using mice expressing mutant MHC II molecules that are unable to be ubiquitinated.

The Effect of Reduced Access to Chiropractic Care on Medical Service Use for Spine Conditions Among Older Adults.

Objective: The purpose of this study was to examine the extent to which access to chiropractic care affects medical service use among older adults with spine conditions.

Methods: We used Medicare claims data to identify a cohort of 39,278 older adult chiropractic care users who relocated during 2010-2014 and thus experienced a change in geographic access to chiropractic care. National Plan and Provider Enumeration System data were used to determine chiropractor per population ratios across the United States.

Downregulated MicroRNA-327 Attenuates Oxidative Stress-Mediated Myocardial Ischemia Reperfusion Injury Through Regulating the FGF10/Akt/Nrf2 Signaling Pathway.

Although miR-327 had a protective effect on cardiomyocytes as described previously, the potential mechanism still needs further exploration. The aim of this study was to investigate the role and mechanism of miR-327 on oxidative stress in myocardial ischemia/reperfusion injury (MI/RI) process. Oxidative stress and cardiomyocytes injury were detected in rat model of MI/RI, hypoxia/reoxygenation (H/R), and tert-butyl hydroperoxide (TBHP) model of H9c2 cells.

Endoplasmic reticulum chaperones stabilize ligand-receptive MR1 molecules for efficient presentation of metabolite antigens.

The antigen-presenting molecule MR1 (MHC class I-related protein 1) presents metabolite antigens derived from microbial vitamin B synthesis to activate mucosal-associated invariant T (MAIT) cells. Key aspects of this evolutionarily conserved pathway remain uncharacterized, including where MR1 acquires ligands and what accessory proteins assist ligand binding. We answer these questions by using a fluorophore-labeled stable MR1 antigen analog, a conformation-specific MR1 mAb, proteomic analysis, and a genome-wide CRISPR/Cas9 library screen.

The Effect of Healthcare Provider Availability on Spine Spending.

Background: Spine conditions are costly and a major cause of disability. A growing body of evidence suggests that healthcare utilization and spending are driven by provider availability, which varies geographically and is a topic of healthcare policy debate.

Objective: To estimate the effect of provider availability on spine spending.

Ubiquitination of MHC Class II Is Required for Development of Regulatory but Not Conventional CD4 T Cells.

MHC class II (MHC II) displays peptides at the cell surface, a process critical for CD4 T cell development and priming. Ubiquitination is a mechanism that dictates surface MHC II with the attachment of a polyubiquitin chain to peptide-loaded MHC II, promoting its traffic away from the plasma membrane. In this study, we have examined how MHC II ubiquitination impacts the composition and function of both conventional CD4 T cell and regulatory T cell (T) compartments.

Maternity waiting homes in Liberia: Results of a countrywide multi-sector scale-up.

Objective: Descriptions of maternity waiting homes (MWHs) as an intervention to increase facility delivery for women living in remote geographic areas dates back to the 1950s, yet there is limited information on the scale-up and sustainability of MWHs. The objective of this study was to describe the evolutionary scale-up of MWHs as a component of health system strengthening efforts and document the successes, challenges, and barriers to sustainability in Liberia.

Methods: Data were collected from a national sample of 119 MWHs in Liberia established between 2010-2018.