Plasmacytoid dendritic cell sensing of African swine fever virus-infected macrophages results in STING-dependent robust interferon-α production.

While several African swine fever virus (ASFV)-encoded proteins potently interfere with the cGAS-STING (cyclic GMP-AMP synthetase-stimulator of interferon genes) pathway at different levels to suppress interferon (IFN) type I production in infected macrophages, systemic IFN-α is induced during the early stages of AFSV infection in pigs. The present study elucidates a mechanism by which such responses can be triggered, at least in vitro. We demonstrate that infection of monocyte-derived macrophages (MDMs) by ASFV genotype 2 strains is highly efficient but immunologically silent with respect to IFN type I, IFN-stimulated gene induction, and tumor necrosis factor production.

Confronting Earth System Model trends with observations.

Anthropogenically forced climate change signals are emerging from the noise of internal variability in observations, and the impacts on society are growing. For decades, Climate or Earth System Models have been predicting how these climate change signals will unfold. While challenges remain, given the growing forced trends and the lengthening observational record, the climate science community is now in a position to confront the signals, as represented by historical trends, in models with observations.

MLX phosphorylation stabilizes the ChREBP-MLX heterotetramer on tandem E-boxes to control carbohydrate and lipid metabolism.

Carbohydrate-responsive element binding protein (ChREBP) and Max-like protein X (MLX) form a heterodimeric transcription factor complex that couples intracellular sugar levels to carbohydrate and lipid metabolism. To promote the expression of target genes, two ChREBP-MLX heterodimers form a heterotetramer to bind a tandem element with two adjacent E-boxes, called carbohydrate-responsive element (ChoRE). How the ChREBP-MLX hetero-tetramerization is achieved and regulated remains poorly understood.

Augmenting rehabilitation robotics with spinal cord neuromodulation: A proof of concept.

Rehabilitation robotics aims to promote activity-dependent reorganization of the nervous system. However, people with paralysis cannot generate sufficient activity during robot-assisted rehabilitation and, consequently, do not benefit from these therapies. Here, we developed an implantable spinal cord neuroprosthesis operating in a closed loop to promote robust activity during walking and cycling assisted by robotic devices.

The role of excitations in supercooled liquids: Density, geometry, and relaxation dynamics.

Low-energy excitations play a key role in all condensed-matter systems, yet there is limited understanding of their nature in glasses, where they correspond to local rearrangements of groups of particles. Here, we introduce an algorithm to systematically uncover these excitations up to the activation energy scale relevant to structural relaxation. We use it in a model system to measure the density of states on a scale never achieved before, confirming that this quantity shifts to higher energy under cooling, precisely as the activation energy does.

In Vitro Activity of Bacteriophages Against Ocular Methicillin-resistant S. aureus Isolates Collected in the US.

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of sight-threatening infections in the US. These strains pose a significant challenge in managing ocular infections, as they frequently exhibit resistance to first-line empirical antibiotics. To assess the potential of bacteriophages as innovative topical therapies for treatment of recalcitrant ocular infections, we evaluated the in vitro antimicrobial activity of a set of anti-S.

Psychometric validation of the Chronic Ocular Pain Questionnaire (COP-Q).

Background: The Chronic Ocular Pain Questionnaire (COP-Q) is a newly developed patient-reported outcome (PRO) measure intended to assess symptoms and impacts associated with Chronic Ocular Surface Pain (COSP). This study assessed the psychometric properties of the COP-Q to determine the adequacy of the COP-Q as a 'fit-for-purpose' instrument to derive trial endpoints for future clinical studies in COSP.

Methods: Patients with COSP completed the COP-Q daily for four weeks on an electronic, touch-screen, tablet device as part of a longitudinal, observational study in the United States (N = 124).

Influence of buccal bone lamella defects on hard and soft tissues with submerged and non-submerged healing in immediate implants - an experimental study in minipigs.

Purpose: This study assessed the impact of the buccal bone on hard and soft tissues in submerged and non-submerged immediate implants using a minipig model.

Methods: Sixty-five titanium implants (Camlog Progressive Line) were placed in four minipigs immediately after tooth extraction. All non-submerged (NSM) implants received a mechanically induced buccal bone defect (NSM-BD), whereas the submerged group (SM) was classified as defective (SM-BD) and intact (SM-BI).

Identification of effect modifiers using a stratified Mendelian randomization algorithmic framework.

Mendelian randomization (MR) is a technique which uses genetic data to uncover causal relationships between variables. With the growing availability of large-scale biobank data, there is increasing interest in elucidating nuances in these relationships using MR. Stratified MR techniques such as doubly-ranked MR (DRMR) and residual stratification MR have been developed to identify nonlinearity in causal relationships.

Minimal changes in patella height after aseptic revision from unicompartmental to total knee arthroplasty.

Introduction: If revision of a unicompartmental knee arthroplasty (UKA) is required, converting it to a total knee arthroplasty (TKA) remains the favored approach. However, worse functional outcomes after revision from UKA to TKA are reported compared to primary TKAs. One potential driver may be a decline in patella height, limiting knee flexion, and increasing patellofemoral stress.

Mulberry leaf extract combined with tryptophan improves sleep and post wake mood in adults with sleep complaints - A randomized cross-over study.

Purpose: In the current study we evaluated a blend of ingredients containing mulberry leaf extract (to lower postprandial glucose of the evening meal), tryptophan (facilitator of the sleep initiation) to benefit sleep initiation and quality in adults with self-reported difficulties with sleep initiation.

Methods: Forty-three adults aged between 25 and 50 years enrolled in a randomized, crossover, double-blind, controlled trial. Participants received standardized meals with a glycemic load of 55 ± 10% and were assigned to receive treatment comprising a combination of mulberry leaf extract (750 mg), whey protein containing 120 mg tryptophan, zinc (1.

IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT): a small animal acute myocardial infarction randomized-controlled multicenter study on the effect of ischemic preconditioning.

Although many cardioprotective interventions have been shown to limit infarct size (IS), in preclinical animal studies of acute myocardial ischemia/reperfusion injury (IRI), their clinical translation to patient benefit has been largely disappointing. A major factor is the lack of rigor and reproducibility in the preclinical studies. To address this, we have established the IMproving Preclinical Assessment of Cardioprotective Therapies (IMPACT) small animal multisite acute myocardial infarction (AMI) network, with centralized randomization and blinded core laboratory IS analysis, and have validated the network using ischemic preconditioning (IPC).

Asymmetry of centrosomes in neural stem cells requires protein phosphatase 4.

Asymmetric cell division is used by stem cells to create diverse cell types while self-renewing the stem cell population. Biased segregation of molecularly distinct centrosomes could provide a mechanism to maintain stem cell fate, induce cell differentiation or both. However, the molecular mechanisms generating molecular and functional asymmetric centrosomes remain incompletely understood.

Beyond-classical computation in quantum simulation.

Quantum computers hold the promise of solving certain problems that lie beyond the reach of conventional computers. Establishing this capability, especially for impactful and meaningful problems, remains a central challenge. Here we show that superconducting quantum annealing processors can rapidly generate samples in close agreement with solutions of the Schrödinger equation.

Selective Azapeptide CD36 Ligand MPE-298 Regulates oxLDL-LOX-1-Mediated Inflammation and Mitochondrial Oxidative Stress in Macrophages.

Macrophage mitochondrial dysfunction, caused by oxidative stress, has been proposed as an essential event in the progression of chronic inflammation diseases, such as atherosclerosis. The cluster of differentiation-36 (CD36) and lectin-like oxLDL receptor-1 (LOX-1) scavenger receptors mediate macrophage uptake of oxidized low-density lipoprotein (oxLDL), which contributes to mitochondrial dysfunction by sustained production of mitochondrial reactive oxygen species (mtROS), as well as membrane depolarization. In the present study, the antioxidant mechanisms of action of the selective synthetic azapeptide CD36 ligand MPE-298 have been revealed.

Spheroids Composed of Reaggregated Neonatal Porcine Islets and Human Endothelial Cells Accelerate Development of Normoglycemia in Diabetic Mice.

The engraftment of transplanted islets depends on the rapid establishment of a novel vascular network. The present study evaluated the effects of cord blood-derived blood outgrowth endothelial cells (BOECs) on the viability of neonatal porcine islets (NPIs) and the post-transplant outcome of grafted NPIs. Dispersed NPIs and human BOECs were reaggregated on microwell cell culture plates and tested for their anti-apoptotic and pro-angiogenic capacity by qRT-PCR and immunohistochemistry.

Germline analysis of an international cohort of pediatric diffuse midline glioma patients.

Background: Factors that drive the development of diffuse midline gliomas (DMG) are unknown. Our study aimed to determine the prevalence of pathogenic/likely pathogenic (P/LP) germline variants in pediatric patients with DMG.

Methods: We assembled an international cohort of 252 pediatric patients with DMG, including diffuse intrinsic pontine glioma (n=153), with germline whole genome or whole exome sequencing.

Dual implication of endothelial adhesion molecules in tumor progression and cancer immunity.

Adhesion molecules are proteins expressed at the surface of various cell types. Their main contribution to immunity is to allow the infiltration of immune cells in an inflamed site. In cancer, adhesion molecules have been shown to promote tumor dissemination favoring the development of metastasis.

Performance of an Automated Insulin Delivery System in People Living With Type 2 Diabetes and Insulin Resistance: First Real-World Evidence in 26 427 Users.

Background: Type 2 diabetes (T2D) is a phenotypically heterogeneous disease. The use of insulin is required in a significant portion of people with T2D, despite recent developments in antidiabetic medications. This study analyzes glycemic outcomes in automated insulin delivery (AID) users with T2D with different insulin requirements.

Ultra-slow self-similar coarsening of physical fibrillar gels formed by semiflexible polymers.

Biopolymers tend to form fibrils that self-assemble into open network structures. While permanently crosslinked flexible polymers are relatively well understood, structure-property relationships of open networks and pseudo-gels formed by bundles of biopolymers are still controversial. Here we employ a generic coarse-grained bead-spring chain model incorporating semiflexibility and cohesive nonbonded interactions, that forms physical instead of chemical crosslinks.