Liver-gut axis signaling regulates circadian energy metabolism in shift workers.

Circadian rhythm is critical to maintaining the whole-body metabolic homeostasis of an organism. Chronic disruption of circadian rhythm by shift work is an important risk factor for metabolic diseases. Fibroblast growth factor 15/19 (FGF15/19), a key component in the liver-gut axis, potently suppresses bile acid (BA) synthesis and improves insulin sensitivity.

High-throughput capture of transcription factor-driven epigenome dynamics using PHILO ChIP-seq.

Assessing the dynamics of chromatin features and transcription factor (TF) binding at scale remains a significant challenge in plants. Here, we present PHILO (Plant HIgh-throughput LOw input) ChIP-seq, a high-throughput ChIP-seq platform that enables the cost-effective and extensive capture of TF binding and genome-wide distributions of histone modifications. The PHILO ChIP-seq pipeline is adaptable to many plant species, requires very little starting material (1mg), and provides the option to use MNase (micrococcal nuclease) for chromatin fragmentation.

Protein data bank: From two epidemics to the global pandemic to mRNA vaccines and Paxlovid.

Structural biologists and the open-access Protein Data Bank (PDB) played decisive roles in combating the COVID-19 pandemic. Global biostructure data were turned into global knowledge, allowing scientists and engineers to understand the inner workings of coronaviruses and develop effective countermeasures. Two mRNA vaccines, initially designed with guidance from PDB structures of the SARS-CoV-1 and MERS-CoV spike proteins, prevented infections entirely or reduced the likelihood of morbidity and mortality for more than five billion individual recipients worldwide.

Mathematical modeling suggests heterogeneous replication of Mycobacterium tuberculosis in rabbits.

Tuberculosis (TB), the disease caused by Mycobacterium tuberculosis (Mtb), remains a major health problem with 10.6 million cases of the disease and 1.6 million deaths in 2021.

Discovery of A-967079 as an Enterovirus D68 Antiviral by Targeting the Viral 2C Protein.

Enterovirus D68 (EV-D68) has had several outbreaks worldwide, yet no FDA-approved antiviral is available for treating this viral infection. EV-D68 infection typically leads to respiratory illnesses and, in severe cases, can cause neurological complications and even death, particularly in children. This study identified a small molecule, A-967079, as an EV-D68 antiviral through phenotypical screening.

Search for Soft Unclustered Energy Patterns in Proton-Proton Collisions at 13 TeV.

The first search for soft unclustered energy patterns (SUEPs) is performed using an integrated luminosity of 138  fb^{-1} of proton-proton collision data at sqrt[s]=13  TeV, collected in 2016-2018 by the CMS detector at the LHC. Such SUEPs are predicted by hidden valley models with a new, confining force with a large 't Hooft coupling. In events with boosted topologies, selected by high-threshold hadronic triggers, the multiplicity and sphericity of clustered tracks are used to reject the background from standard model quantum chromodynamics.

Imaging the large-scale and cellular response to focal traumatic brain injury in mouse neocortex.

Traumatic brain injury (TBI) affects neural function at the local injury site and also at distant, connected brain areas. However, the real-time neural dynamics in response to injury and subsequent effects on sensory processing and behaviour are not fully resolved, especially across a range of spatial scales. We used in vivo calcium imaging in awake, head-restrained male and female mice to measure large-scale and cellular resolution neuronal activation, respectively, in response to a mild/moderate TBI induced by focal controlled cortical impact (CCI) injury of the motor cortex (M1).

BindingDB in 2024: a FAIR knowledgebase of protein-small molecule binding data.

BindingDB (bindingdb.org) is a public, web-accessible database of experimentally measured binding affinities between small molecules and proteins, which supports diverse applications including medicinal chemistry, biochemical pathway annotation, training of artificial intelligence models and computational chemistry methods development. This update reports significant growth and enhancements since our last review in 2016.

plasmid-encoded protein Pgp2 is a replication initiator with a unique β-hairpin necessary for iteron-binding and plasmid replication.

The virulence plasmid of the obligate intracellular bacterium encodes eight proteins. Among these, Pgp3 is crucial for pathogenicity, and Pgp4 functions as a transcriptional regulator of both plasmid and chromosomal genes. The remaining proteins, Pgp1, Pgp5, Pgp6, Pgp7, and Pgp8, are predicted to play various roles in plasmid replication or maintenance based on their amino acid sequences.

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.