Pathobiont-induced suppressive immune imprints thwart T cell vaccine responses.

Pathobionts have evolved many strategies to coexist with the host, but how immune evasion mechanisms contribute to the difficulty of developing vaccines against pathobionts is unclear. Meanwhile, Staphylococcus aureus (SA) has resisted human vaccine development to date. Here we show that prior SA exposure induces non-protective CD4 T cell imprints, leading to the blunting of protective IsdB vaccine responses.

Accurate Intramyocardial Hemorrhage Assessment with Fast, Free-running, Cardiac Quantitative Susceptibility Mapping.

Purpose To evaluate the performance of a high-dynamic-range quantitative susceptibility mapping (HDR-QSM) cardiac MRI technique to detect intramyocardial hemorrhage (IMH) and quantify iron content using phantom and canine models. Materials and Methods A free-running whole-heart HDR-QSM technique for IMH assessment was developed and evaluated in calibrated iron phantoms and 14 IMH female canine models. IMH detection and iron content quantification performance of this technique was compared with the conventional iron imaging approaches, R2*(1/T2*) maps, using measurements from ex vivo imaging as the reference standard.

Mapping fetal brain development of 10 weeks gestational age with 9.4T postmortem MRI and histological sections.

Background And Purpose: The 10th week of gestational age (GA) is a critical period for evaluating brain development, but there is limited knowledge regarding the specific characteristics at this GA. This study is to map the brain structures at 10 weeks GA using 9.4T MRI and histological sections.

Preclinical study and phase II trial of adapting low-dose radiotherapy to immunotherapy in small cell lung cancer.

Background: Immune checkpoint inhibitors (ICIs) provide modest but unsatisfactory benefits for extensive-stage small cell lung cancer (ES-SCLC). Developing strategies for treating ES-SCLC is critical.

Methods: We preliminarily explored the outcomes of salvage low-dose radiotherapy (LDRT) plus ICI on refractory SCLC patients.

Medication-Induced Weight Change Across Common Antidepressant Treatments : A Target Trial Emulation Study.

Background: Antidepressants are among the most commonly prescribed medications, but evidence on comparative weight change for specific first-line treatments is limited.

Objective: To compare weight change across common first-line antidepressant treatments by emulating a target trial.

Design: Observational cohort study over 24 months.

Roles of Al and Mg on the Microstructure and Corrosion Resistance of Zn-Al-Mg Hot-Dipped Coated Steel.

In this work, a novel zinc-aluminum-magnesium (Zn-Al-Mg, ZM) coated steel was prepared using the hot-dip method. The microstructure and corrosion resistance of the ZM-coated steel were investigated. Compared to the conventional galvanized steel (GI), the ZM coating demonstrated a distinctive phase structure, consisting of Zn phase, binary eutectic (Zn/MgZn), and ternary eutectic (Zn/Al/MgZn).

Investigating fungal community characteristics in co-composted cotton stalk and various livestock manure products.

Agricultural wastes, comprising cotton straw and livestock manure, can be effectively managed through aerobic co-composting. Nevertheless, the quality and microbial characteristics of co-composting products from different sources remain unclear. Therefore, this study utilized livestock manure from various sources in Xinjiang, China, including herbivorous sheep manure (G), omnivorous pigeon manure (Y), and pigeon-sheep mixture (GY) alongside cotton stalks, for a 40-day co-composting process.

Hitchhiking of Cas9 with nucleus-localized proteins impairs its controllability and leads to efficient genome editing of NLS-free Cas9.

CRISPR-Cas9 is the most commonly used genome-editing tool in eukaryotic cells. To modulate Cas9 entry into the nucleus to enable control of genome editing, we constructed a light-controlled CRISPR-Cas9 system to control exposure of the Cas9 protein nuclear localization signal (NLS). Although blue-light irradiation was found to effectively control the entry of Cas9 protein into the nucleus with confocal microscopy observation, effective gene editing occurred in controls with next-generation sequencing analysis.

The characteristics of pre-existing humoral imprint determine efficacy of S. aureus vaccines and support alternative vaccine approaches.

The failure of the Staphylococcus aureus (SA) IsdB vaccine trial can be explained by the recall of non-protective immune imprints from prior SA exposure. Here, we investigate natural human SA humoral imprints to understand their broader impact on SA immunizations. We show that antibody responses against SA cell-wall-associated antigens (CWAs) are non-opsonic, while antibodies against SA toxins are neutralizing.

Defining neutralization and allostery by antibodies against COVID-19 variants.

The changing landscape of SARS-CoV-2 Spike protein is linked to the emergence of variants, immune-escape and reduced efficacy of the existing repertoire of anti-viral antibodies. The functional activity of neutralizing antibodies is linked to their quaternary changes occurring as a result of antibody-Spike trimer interactions. Here, we reveal the conformational dynamics and allosteric perturbations linked to binding of novel human antibodies and the viral Spike protein.

An IgM-like inhalable ACE2 fusion protein broadly neutralizes SARS-CoV-2 variants.

Many of the currently available COVID-19 vaccines and therapeutics are not effective against newly emerged SARS-CoV-2 variants. Here, we developed the metallo-enzyme domain of angiotensin converting enzyme 2 (ACE2)-the cellular receptor of SARS-CoV-2-into an IgM-like inhalable molecule (HH-120). HH-120 binds to the SARS-CoV-2 Spike (S) protein with high avidity and confers potent and broad-spectrum neutralization activity against all known SARS-CoV-2 variants of concern.

Effect of Terahertz Electromagnetic Field on the Permeability of Potassium Channel Kv1.2.

In this paper, the influence of external terahertz electromagnetic fields with different frequencies of 4 THz, 10 THz, 15 THz, and 20 THz on the permeability of the Kv1.2 voltage-gated potassium ion channel on the nerve cell membrane was studied using the combined model of the "Constant Electric Field-Ion Imbalance" method by molecular dynamics. We found that although the applied terahertz electric field does not produce strong resonance with the -C=O groups of the conservative sequence T-V-G-Y-G amino acid residue of the selective filter (SF) of the channel, it would affect the stability of the electrostatic bond between potassium ions and the carbonyl group of T-V-G-Y-G of SF, and it would affect the stability of the hydrogen bond between water molecules and oxygen atoms of the hydroxyl group of the 374THR side chain at the SF entrance, changing the potential and occupied states of ions in the SF and the occurrence probability of the permeation mode of ions and resulting in the change in the permeability of the channel.

Lung adenocarcinoma promotion by air pollutants.

A complete understanding of how exposure to environmental substances promotes cancer formation is lacking. More than 70 years ago, tumorigenesis was proposed to occur in a two-step process: an initiating step that induces mutations in healthy cells, followed by a promoter step that triggers cancer development. Here we propose that environmental particulate matter measuring ≤2.

Comparative Effectiveness of Team-Based Care With and Without a Clinical Decision Support System for Diabetes Management : A Cluster Randomized Trial.

Background: Uncontrolled hyperglycemia, hypercholesterolemia, and hypertension are common in persons with diabetes.

Objective: To compare the effectiveness of team-based care with and without a clinical decision support system (CDSS) in controlling glycemia, lipids, and blood pressure (BP) among patients with type 2 diabetes.

Design: Cluster randomized trial.

Association of Perfusion Lesion Variables With Functional Outcome in Patients With Mild Stroke and Large Vessel Occlusion Managed Medically.

Background And Objectives: The best management of patients with mild stroke and large vessel occlusion (LVO) remains unclear. This study aimed to identify perfusion imaging predictors of poor functional outcome in such patients.

Methods: This cohort study retrospectively selected patients enrolled in the International Stroke Perfusion Imaging Registry between August 2011 and April 2022.

Immunogenicity and safety of BNT162b2 mRNA vaccine in Chinese adults: A phase 2 randomised clinical trial.

Background: BNT162b2, an mRNA vaccine against COVID-19, is being utilised worldwide, but immunogenicity and safety data in Chinese individuals are limited.

Methods: This phase 2, randomised, double-blind, placebo-controlled trial included healthy or medically stable individuals aged 18-85 years enrolled at two clinical sites in China. Participants were stratified by age (≤55 or >55 years) and randomly assigned (3:1) by an independent randomisation professional to receive two doses of intramuscular BNT162b2 30 μg or placebo, administered 21 days apart.

mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits similar B cell expansion, neutralizing responses, and protection from Omicron.

SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-matched vaccines would enhance protection. Here, nonhuman primates that received mRNA-1273 at weeks 0 and 4 were boosted at week 41 with mRNA-1273 or mRNA-Omicron.

Tissue-level alveolar epithelium model for recapitulating SARS-CoV-2 infection and cellular plasticity.

Pulmonary sequelae following COVID-19 pneumonia have been emerging as a challenge; however, suitable cell sources for studying COVID-19 mechanisms and therapeutics are currently lacking. In this paper, we present a standardized primary alveolar cell culture method for establishing a human alveolar epithelium model that can recapitulate viral infection and cellular plasticity. The alveolar model is infected with a SARS-CoV-2 pseudovirus, and the clinically relevant features of the viral entry into the alveolar type-I/II cells, cytokine production activation, and pulmonary surfactant destruction are reproduced.

Body Mass Index and Height in the Friedreich Ataxia Clinical Outcome Measures Study.

Background And Objectives: Body mass index (BMI) and height are important indices of health. We tested the association between these outcomes and clinical characteristics in Friedreich ataxia (FRDA), a progressive neuromuscular disorder.

Methods: Participants (N = 961) were enrolled in a prospective natural history study (Friedreich Ataxia Clinical Outcome Measure Study).

Enhanced clot lysis by a single point mutation in a reteplase variant.

Recombinant tissue-type plasminogen activator (rtPA) is the clot lysis drug approved for clinical use, and is characterised by a short half-life and substantial inactivation by plasminogen activator inhibitor-1 (PAI-1). We previously discovered that a tPA mutation (A419Y) at the protease domain led to enhanced fibrinolysis activity. In the present study, we studied the mechanism of such mutation in enhancing the proteolytic activity, and whether such enhancement persists in reteplase, an United States Food and Drug Administration-approved tPA truncated variant.

Influence of red blood cell indices on HbA1c performance in detecting dysglycaemia in a Singapore preconception cohort study.

Abnormalities of red blood cell (RBC) indices may affect glycated haemoglobin (HbA1c) levels. We assessed the influence of haemoglobin (Hb) and mean corpuscular volume (MCV) on the performance of HbA1c in detecting dysglycaemia among reproductive aged women planning to conceive. Women aged 18-45 years (n = 985) were classified as normal (12 ≤ Hb ≤ 16 g/dL and 80 ≤ MCV ≤ 100 fL) and abnormal (Hb < 12 g/dL and/or MCV < 80 fL).

In-the-Bag Versus Ciliary Sulcus Secondary Intraocular Lens Implantation for Pediatric Aphakia: A Prospective Comparative Study.

Purpose: To compare outcomes of in-the-bag vs ciliary sulcus secondary intraocular lens (IOL) implantation for pediatric aphakia.

Design: Prospective interventional case series.

Methods: This institutional study was conducted in 202 children (355 aphakic eyes) diagnosed as having congenital cataracts and who underwent cataract extraction before age 24 months.

Genomic characterization and outcome evaluation of kinome fusions in lung cancer revealed novel druggable fusions.

Kinase fusions represent an important type of somatic alterations that promote oncogenesis and serve as diagnostic markers in lung cancer. We aimed to identify the landscape of clinically relevant kinase fusions in Chinese lung cancer and to explore rare kinase rearrangements; thus, providing valuable evidence for therapeutic decision making. We performed genomic profiling of 425 cancer-relevant genes from tumor/plasma biopsies from a total of 17,442 Chinese lung cancer patients using next generation sequencing (NGS).

Simultaneous Recognition of Atrophic Gastritis and Intestinal Metaplasia on White Light Endoscopic Images Based on Convolutional Neural Networks: A Multicenter Study.

Introduction: Patients with atrophic gastritis (AG) or gastric intestinal metaplasia (GIM) have elevated risk of gastric adenocarcinoma. Endoscopic screening and surveillance have been implemented in high incidence countries. The study aimed to evaluate the accuracy of a deep convolutional neural network (CNN) for simultaneous recognition of AG and GIM.