Pharmacological inhibition of macrophage triglyceride biosynthesis pathways does not improve Mycobacterium tuberculosis control in infected mice.

Tuberculosis (TB) necrotic granulomas contain triglyceride-rich macrophages (foam cells) with reduced antimicrobial functions. We assessed the ability of two compounds to reduce triglyceride content and Mycobacterium tuberculosis (Mtb) burden in infected human monocyte-derived macrophages and in the lungs of Mtb-infected C3HeB/FeJ mice: A-922500 (DGATi), an inhibitor of diacylglycerol acyltransferase 1; and LY2584702 (p70S6Ki), an inhibitor of p70 S6 kinase. DGATi and p70S6Ki significantly reduced the lipid content and bacillary burden in Mtb-infected macrophages.

Huang-Lian-Jie-Du decoction alleviates cognitive impairment in high-fat diet-induced obese mice via Trem2/Dap12/Syk pathway.

Background: Cognitive impairment induced by a high-fat diet (HFD) is common, but its mechanism is largely unknown. Huang-Lian-Jie-Du (HLJD) decoction is a classical and powerful prescription in China. It consists of four medicinal plants and is widely used in traditional Chinese medicines (TCM).

Applications of microfluidics in mRNA vaccine development: A review.

The transformative potential of microfluidics in the development of mRNA vaccines is explored in this review, highlighting its pivotal role in enhancing easy-to-use functionality, efficacy, and production efficiency. Moreover, we examine the innovative applications of microfluidics in biomedical research, including its contribution to the rapid and cost-effective synthesis of lipid nanoparticles for mRNA delivery and delve into the advantages of mRNA vaccines, such as targeted delivery and controlled expression. Furthermore, it outlines the future prospects of microfluidic devices, their cutting-edge examples in both research and industry, and the potential to revolutionize vaccine formulation and production.

Use of SMART objectives in an interprofessional training event: screening for fall and osteoporosis risk.

Introduction: SMART objectives are a major component of health coaching and lifestyle medicine, however, there are limited studies describing their use in current health care curriculums. This study incorporated SMART objectives within an Interprofessional Education (IPE) event offered to students who were screening community-dwelling adults within their community for falls and osteoporosis risk. The purpose was to evaluate if students could confidently develop a SMART objective with their client that was relevant to the screening results.

Team science in interdisciplinary health professions education research: a multi-institutional case study.

The interdisciplinary nature of health professions education requires exploration of problems by interdisciplinary research teams. Drawing on the Dynamics of Cross-disciplinary Research Development conceptual framework, this study explores the processes and experiences of an interdisciplinary research team, identifying elements of successful collaboration. Case study data were collected from a team of nine researchers from six universities.

A High-Fidelity Computational Model for Predicting Blood Cell Trafficking and 3D Capillary Hemodynamics in Retinal Microvascular Networks.

Purpose: To present a first principle-based, high-fidelity computational model for predicting full three-dimensional (3D) and time-resolved retinal microvascular hemodynamics taking into consideration the flow and deformation of individual blood cells.

Methods: The computational model is a 3D fluid-structure interaction model based on combined finite volume/finite element/immersed-boundary methods. Three in silico microvascular networks are built from high-resolution in vivo motion contrast images of the superficial capillary plexus in the parafoveal region of the human retina.

Characterizing the role of PP2A B'' family subunits in mechanical stress response and plant development through calcium and ABA signaling in Arabidopsis thaliana.

Protein phosphatase 2AB'' (PP2A B'') family subunits have calcium-binding EF-hand motifs, facilitating interaction with PP2A substrates. In Arabidopsis thaliana, the PP2A B'' family subunits consist of six members, AtB''α-ε and FASS. These subunits can interact with a basic leucine zipper transcription factor, VIP1, and its close homologs.

Oncointerpreter.ai enables interactive, personalized summarization of cancer diagnostics data.

Objectives: Cancer diagnosis comes as a shock to many patients, and many of them feel unprepared to handle the complexity of the life-changing event, understand technicalities of the diagnostic reports, and fully engage with the clinical team regarding the personalized clinical decision-making.

Materials And Methods: We develop Oncointerpreter.ai an interactive resource to offer personalized summarization of clinical cancer genomic and pathological data, and frame questions or address queries about therapeutic opportunities in near-real time via a graphical interface.

Leveraging Implementation Science at the Early-Stage Development of a Novel Telehealth-Delivered Fear of Exercise Program to Understand Intervention Feasibility and Implementation Potential: Feasibility Behavioral Intervention Study.

Background: To increase real-world adoption of effective telehealth-delivered behavioral health interventions among midlife and older adults with cardiovascular disease, incorporating implementation science (IS) methods at earlier stages of intervention development may be needed.

Objective: This study aims to describe how IS can be incorporated into the design and interpretation of a study assessing the feasibility and implementation potential of a technology-delivered behavioral health intervention.

Methods: We assessed the feasibility and implementation potential of a 2-session, remotely delivered, home-based behavioral intervention composed of psychoeducation, interoceptive exposure through low-to-moderate intensity walking, interoceptive counseling, and homework (Reducing Exercise Sensitivity with Exposure Training; RESET) among patients with recent acute coronary syndrome (ACS) and some fear of exercise.

Electrospun gelatin/hyaluronic acid nanofibers as a platform for uric acid delivery to neural tissue.

Uric acid (UA) is an antioxidant that has been reported to be a neuroprotective compound for injuries and diseases, and specifically, diseases of the central nervous system. However, uric acid is highly insoluble in aqueous solutions, and high levels in the serum lead to gout, which limits its use in humans. Here, we develop a novel drug delivery platform that will release uric acid in a sustained manner for application to neural tissue.

Cyproheptadine inhibits in vitro and in vivo lung metastasis and drives metabolic rewiring.

Background: Non-small cell lung cancer (NSCLC) accounts for 81% of lung cancer cases, among which over 47% presented with distant metastasis at the time of diagnosis. Despite the introduction of targeted therapy and immunotherapy, enhancing the survival rate and overcoming the development of resistance remain a big challenge. Thus, it is crucial to find potential new therapeutics and targets that can mitigate lung metastasis and investigate its effects on biomarkers, such as cellular metabolomics.

Genome Sequencing Identifies 13 Novel Candidate Risk Genes for Autism Spectrum Disorder in a Qatari Cohort.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication, restricted interests, and repetitive behaviors. Despite considerable research efforts, the genetic complexity of ASD remains poorly understood, complicating diagnosis and treatment, especially in the Arab population, with its genetic diversity linked to migration, tribal structures, and high consanguinity. To address the scarcity of ASD genetic data in the Middle East, we conducted genome sequencing (GS) on 50 ASD subjects and their unaffected parents.

Polygenic risk for alcohol use disorder affects cellular responses to ethanol exposure in a human microglial cell model.

Polygenic risk scores (PRSs) assess genetic susceptibility to alcohol use disorder (AUD), yet their molecular implications remain underexplored. Neuroimmune interactions, particularly in microglia, are recognized as notable contributors to AUD pathophysiology. We investigated the interplay between AUD PRS and ethanol in human microglia derived from iPSCs from individuals with AUD high-PRS (diagnosed with AUD) or low-PRS (unaffected).

Which intervention works for whom: Identifying pre-treatment characteristics that predict who will benefit from a specific alcohol text message intervention from a randomized trial.

Introduction: Effective interventions show heterogeneity in treatment response. Addressing this heterogeneity involves identifying which intervention works best for whom. One method to address this heterogeneity identifies treatment-subgroup interactions to determine which of two interventions has greater effect for certain individuals based on their profile of pre-treatment characteristics.

Structure-Based Design of Covalent SARS-CoV-2 Papain-like Protease Inhibitors.

The COVID-19 pandemic is caused by SARS-CoV-2, a highly transmissible and pathogenic RNA betacoronavirus. Like other RNA viruses, SARS-CoV-2 continues to evolve with or without drug selection pressure, and many variants have emerged since the beginning of the pandemic. The papain-like protease, PL, is a cysteine protease that cleaves viral polyproteins as well as ubiquitin and ISG15 modifications from host proteins.

MicroRNA-mediated network redundancy is constrained by purifying selection and contributes to expression robustness in Drosophila melanogaster.

MicroRNAs (miRNAs) are post-transcriptional, non-coding regulatory RNAs that function coordinately with transcription factors (TFs) in gene regulatory networks. TFs and their targets are often co-regulated by miRNAs, forming composite feedforward circuits (cFFCs) with varying degrees of redundancy, primarily mediated by miRNAs. However, the maintenance of miRNA-mediated regulatory redundancy and its impact on gene expression evolution remain elusive.

American Society for Microbiology evidence-based laboratory medicine practice guidelines to reduce blood culture contamination rates: a systematic review and meta-analysis.

SUMMARYBlood cultures (BCs) are one of the critical tests used to detect bloodstream infections. BC results are not 100% specific. Interpretation of BC results is often complicated by detecting microbial contamination rather than true infection.

DNAproDB: an updated database for the automated and interactive analysis of protein-DNA complexes.

DNAproDB (https://dnaprodb.usc.edu/) is a database, visualization tool, and processing pipeline for analyzing structural features of protein-DNA interactions.

Structure-activity relationships and pharmacokinetic evaluation of L-cystine diamides as L-cystine crystallization inhibitors for cystinuria.

Cystinuria is a rare genetic disorder characterized by defective l-cystine reabsorption from the renal proximal tubule, resulting in abnormally high concentrations of L-cystine and subsequent l-cystine crystallization and stone formation in urine. l-Cystine diamides have shown great promise as inhibitors of l-cystine crystallization. The free α-amino groups in l-cystine diamides have previously been shown to be necessary for l-cystine crystallization inhibitory activity.