Endogenously produced itaconate negatively regulates innate-driven cytokine production and drives global ubiquitination in human macrophages.

A wide variety of electrophilic derivatives of itaconate, the Kreb's cycle-derived metabolite, are immunomodulatory, yet these derivatives have overlapping and sometimes contradictory activities. Therefore, we generated a genetic system to interrogate the immunomodulatory functions of endogenously produced itaconate in human macrophages. Endogenous itaconate is driven by multiple innate signals restraining inflammatory cytokine production.

Automated Insulin Delivery with Remote Real-Time Continuous Glucose Monitoring for Hospitalized Patients with Diabetes: A Multicenter, Single-Arm, Feasibility Trial.

Multiple daily injection insulin therapy frequently fails to meet hospital glycemic goals and is prone to hypoglycemia. Automated insulin delivery (AID) with remote glucose monitoring offers a solution to these shortcomings. In a single-arm multicenter pilot trial, we tested the feasibility, safety, and effectiveness of the Omnipod 5 AID System with real-time continuous glucose monitoring (CGM) for up to 10 days in hospitalized patients with insulin-requiring diabetes on nonintensive care unit medical-surgical units.

Associations of Blood Cardiovascular Biomarkers With Brain Free Water and Its Relationship to Cognitive Decline: A Diffusion-MRI Study.

Background And Objectives: There is an increasing awareness of the "Heart-Brain Connection," whereby cardiovascular function is connected with cognition. Diffusion-MRI studies reported higher brain free water (FW) was associated with cerebrovascular disease (CeVD) and cognitive impairment. In this study, we investigated whether higher brain FW was related to blood cardiovascular biomarkers and whether FW mediated the associations between blood biomarkers and cognition.

Broad immunity to SARS-CoV-2 variants of concern mediated by a SARS-CoV-2 receptor-binding domain protein vaccine.

Background: The SARS-CoV-2 global pandemic has fuelled the generation of vaccines at an unprecedented pace and scale. However, many challenges remain, including: the emergence of vaccine-resistant mutant viruses, vaccine stability during storage and transport, waning vaccine-induced immunity, and concerns about infrequent adverse events associated with existing vaccines.

Methods: We report on a protein subunit vaccine comprising the receptor-binding domain (RBD) of the ancestral SARS-CoV-2 spike protein, dimerised with an immunoglobulin IgG1 Fc domain.

Retrospective analysis of enhancer activity and transcriptome history.

Cell state changes in development and disease are controlled by gene regulatory networks, the dynamics of which are difficult to track in real time. In this study, we used an inducible DCM-RNA polymerase subunit b fusion protein which labels active genes and enhancers with a bacterial methylation mark that does not affect gene transcription and is propagated in S-phase. This DCM-RNA polymerase fusion protein enables transcribed genes and active enhancers to be tagged and then examined at later stages of development or differentiation.

Conglomerate, Racemate, and Achiral Crystals of Polymetallic Europium(III) Compounds of Bis- or Tris-β-diketonate Ligands and Circularly Polarized Luminescence Study.

This work reports (a) conglomerate and racemic crystal structures of [(Δ,Δ,Δ,Δ,Δ,Δ)- or/and (Λ,Λ,Λ,Λ,Λ,Λ)-Eu (TTP)(OH)Na] coordination polymers, (b) racemic crystal structures of (Δ,Δ,Δ,Δ)-/(Λ,Λ,Λ,Λ)-Eu (TTP)(bipy)(MEK)(OH) tetrahedral clusters, and (c) the achiral crystal structure of the [Eu (BTP)(OH)Na] coordination polymer (where BTP = dianionic bis-β-diketonate, TTP = trianionic tris--diketonate, and bipy = 2,2'-bipyridine). The screw coordination arrangement of the TTP ligand has led to the formation of homoconfigurational racemic Eu products. The conglomerate crystallization of [Eu (TTP)(OH)Na] appears to be caused by the presence of the sodium, Na counterions, and interactions between oxygen atoms and the trifluoromethyl unit of the TTP ligand and Na ions.

A pan-cancer organoid platform for precision medicine.

Patient-derived tumor organoids (TOs) are emerging as high-fidelity models to study cancer biology and develop novel precision medicine therapeutics. However, utilizing TOs for systems-biology-based approaches has been limited by a lack of scalable and reproducible methods to develop and profile these models. We describe a robust pan-cancer TO platform with chemically defined media optimized on cultures acquired from over 1,000 patients.

Laser-Activated Corneal Adhesive: Retinal Safety in Rabbit Model.

Purpose: The purpose of this study was to investigate whether laser irradiation, used to activate an adhesive for sealing penetrating corneal incisions, causes any ophthalmoscopically or histologically visible retinal changes.

Methods: Baseline fundus assessment was conducted prior to laser irradiation of eyes of pigmented Dutch Belted rabbits. Treatment group was 18 eyes with the corneal adhesive activated in situ by a near infrared laser (125 mW for 45 seconds).

Structural insight into SARS-CoV-2 neutralizing antibodies and modulation of syncytia.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is initiated by binding of the viral Spike protein to host receptor angiotensin-converting enzyme 2 (ACE2), followed by fusion of viral and host membranes. Although antibodies that block this interaction are in emergency use as early coronavirus disease 2019 (COVID-19) therapies, the precise determinants of neutralization potency remain unknown. We discovered a series of antibodies that potently block ACE2 binding but exhibit divergent neutralization efficacy against the live virus.

Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology.

Impact of the 2003 to 2018 Population Salt Intake Reduction Program in England: A Modeling Study.

[Figure: see text].

Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development.

Targeted protein degradation (TPD) refers to the use of small molecules to induce ubiquitin-dependent degradation of proteins. TPD is of interest in drug development, as it can address previously inaccessible targets. However, degrader discovery and optimization remains an inefficient process due to a lack of understanding of the relative importance of the key molecular events required to induce target degradation.

Twenty-Four-Hour Urinary Sodium and Potassium Excretion and Their Associations With Blood Pressure Among Adults in China: Baseline Survey of Action on Salt China.

This study aimed to assess current level of sodium and potassium intake and their associations with blood pressure (BP) using the 24-hour urinary data in a large sample of China. Data from participants aged 18 to 75 years were collected as the baseline survey of Action on Salt China in 2018. Of 5454 adults, 5353 completed 24-hour urine collection.

Visible Circularly Polarized Luminescence of Octanuclear Circular Eu(III) Helicate.

This work reports on the structural and photophysical characterization of -symmetrical octanuclear circular Ln helicates, [()- or ()-Pr-Pybox](Ln)(THP) (where Ln = Eu and Tb, THP = trianionic tris-β-diketonate, and Pr-Pybox = chiral bis(4-isopropyl-2-oxazolinyl)pyridine). X-ray crystallographic analysis revealed that the octanuclear circular helicate possesses square antiprism architecture and consists of four [()- or ()-Pr-Pybox]Ln(THP) asymmetric units arranged in a closed ring form. Ligand-to-ligand interactions between the THP and the Pr-Pybox ligands have successfully directed formation of enantiopure, homoconfigurational (Δ,Δ,Δ,Δ,Δ,Δ,Δ,Δ)- and (Λ,Λ,Λ,Λ,Λ,Λ,Λ,Λ)- isomers.

Bivalent binding of a fully human IgG to the SARS-CoV-2 spike proteins reveals mechanisms of potent neutralization.

antibody selection against pathogens from naïve combinatorial libraries can yield various classes of antigen-specific binders that are distinct from those evolved from natural infection. Also, rapid neutralizing antibody discovery can be made possible by a strategy that selects for those interfering with pathogen and host interaction. Here we report the discovery of antibodies that neutralize SARS-CoV-2, the virus responsible for the COVID-19 pandemic, from a highly diverse naïve human Fab library.

Nutrition Profile of Products with Cartoon Animations on the Packaging: A UK Cross-Sectional Survey of Foods and Drinks.

Background: Marketing, including the use of cartoon animations on packaging, has been shown to influence the food children choose to eat. This paper aims to determine the nutritional quality of UK food and drink products featuring child-friendly characters on pack.

Methods: A comprehensive cross-sectional survey of food and drink with packaging appealing to children available in the UK.

The yield of long-term electrocardiographic recordings in refractory focal epilepsy.

Objective: To determine the incidence of clinically relevant arrhythmias in refractory focal epilepsy and to assess the potential of postictal arrhythmias as risk markers for sudden unexpected death in epilepsy (SUDEP).

Methods: We recruited people with refractory focal epilepsy without signs of ictal asystole and who had at least one focal seizure per month and implanted a loop recorder with 2-year follow-up. The devices automatically record arrhythmias.

Sensing Plant Physiology and Environmental Stress by Automatically Tracking F and F Features in PSII Chlorophyll Fluorescence Induction.

Following a step excitation, chlorophyll fluorescence (ChlF) from photosystem II (PSII) of a dark-adapted photosynthetic organism exhibits the well-known OJIP pattern. The OJIP induction has been widely used in plant science and agriculture engineering. While the J and I phases are related to transitions of photochemical reaction redox states, characteristic fluorescence intensities at the two phases (F and F ) are often treated at fixed time points in routine measurement and thus do not account for variations in plant and experimental conditions, this (1) neglects the differences in the time of appearance of these phases, which is potentially useful information for characterizing plant status and environmental factors, and (2) leads to errors in measured F and F values in the many publications.

Reformulation and Priorities for Reducing Energy Density; Results from a Cross-Sectional Survey on Fat Content in Pre-Packed Cakes and Biscuits Sold in British Supermarkets.

Cakes and biscuits contribute to energy, total and saturated fat and sugar in British diets. So far, the UK government has prompted manufacturers to reduce energy density in these products through a reduction of their sugar content. We conducted a cross-sectional survey of the fat content of cakes and biscuits available in nine UK supermarket chains.

Patient Preferences for Coronary CT Angiography with Stress Perfusion, SPECT, or Invasive Coronary Angiography.

Background Patient preference is pivotal for widespread adoption of tests in clinical practice. Patient preferences for invasive versus other noninvasive tests for coronary artery disease are not known. Purpose To compare patient acceptance and preferences for noninvasive and invasive cardiac imaging in North and South America, Asia, and Europe.

Prognostic Value of Combined CT Angiography and Myocardial Perfusion Imaging versus Invasive Coronary Angiography and Nuclear Stress Perfusion Imaging in the Prediction of Major Adverse Cardiovascular Events: The CORE320 Multicenter Study.

Purpose To compare the prognostic importance (time to major adverse cardiovascular event [MACE]) of combined computed tomography (CT) angiography and CT myocardial stress perfusion imaging with that of combined invasive coronary angiography (ICA) and stress single photon emission CT myocardial perfusion imaging. Materials and Methods This study was approved by all institutional review boards, and written informed consent was obtained. Between November 2009 and July 2011, 381 participants clinically referred for ICA and aged 45-85 years were enrolled in the Combined Noninvasive Coronary Angiography and Myocardial Perfusion Imaging Using 320-Detector Row Computed Tomography (CORE320) prospective multicenter diagnostic study.