RNase T2 deficiency promotes TLR13-dependent replenishment of tissue-protective Kupffer cells.

Lysosomal stress due to the accumulation of nucleic acids (NAs) activates endosomal TLRs in macrophages. Here, we show that lysosomal RNA stress, caused by the lack of RNase T2, induces macrophage accumulation in multiple organs such as the spleen and liver through TLR13 activation by microbiota-derived ribosomal RNAs. TLR13 triggered emergency myelopoiesis, increasing the number of myeloid progenitors in the bone marrow and spleen.

TNF-α exacerbates SARS-CoV-2 infection by stimulating CXCL1 production from macrophages.

Since most genetically modified mice are C57BL/6 background, a mouse-adapted SARS-CoV-2 that causes lethal infection in young C57BL/6 mice is useful for studying innate immune protection against SARS-CoV-2 infection. Here, we established two mouse-adapted SARS-CoV-2, ancestral and Delta variants, by serial passaging 80 times in C57BL/6 mice. Although young C57BL/6 mice were resistant to infection with the mouse-adapted ancestral SARS-CoV-2, the mouse-adapted SARS-CoV-2 Delta variant caused lethal infection in young C57BL/6 mice.

Accuracy of deep learning-based attenuation correction in Tc-GSA SPECT/CT hepatic imaging.

Introduction: Attenuation correction (AC) is necessary for accurate assessment of radioactive distribution in single photon emission computed tomography (SPECT). The method of computed tomography-based AC (CTAC) is widely used because of its accuracy. However, patients are exposed to radiation during CT examination.

Deep learning-based approach for acquisition time reduction in ventilation SPECT in patients after lung transplantation.

We aimed to evaluate the image quality and diagnostic performance of chronic lung allograft dysfunction (CLAD) with lung ventilation single-photon emission computed tomography (SPECT) images acquired briefly using a convolutional neural network (CNN) in patients after lung transplantation and to explore the feasibility of short acquisition times. We retrospectively identified 93 consecutive lung-transplant recipients who underwent ventilation SPECT/computed tomography (CT). We employed a CNN to distinguish the images acquired in full time from those acquired in a short time.

Airway inflammation in a novel mouse model of asthma-COPD overlap induced by co-exposure to papain and tobacco smoke.

Asthma and chronic obstructive pulmonary disease (COPD) are respiratory diseases associated with airway inflammation, which is the main pathogenesis. Although their causes and characteristics differ, in some cases, asthma and COPD may coexist in the same patient in a condition called asthma-COPD overlap (ACO). The prognosis of ACO is more unfavourable than those of asthma or COPD alone, without any treatment strategies demonstrating efficacy.

Deciphering the Multi-state Conformational Equilibrium of HDM2 in the Regulation of p53 Binding: Perspectives from Molecular Dynamics Simulation and NMR Analysis.

HDM2 negatively regulates the activity of the tumor suppressor p53. Previous NMR studies have shown that apo-HDM2 interconverts between an "open" state in which the N-terminal "lid" is disordered and a "closed" state in which the lid covers the p53-binding site in the core region. Molecular dynamics (MD) simulation studies have been performed to elucidate the conformational dynamics of HDM2, but the direct relevance of the experimental and computational analyses is unclear.

Native myocardial T mapping using inversion recovery T-weighted turbo field echo sequence.

This study proposes the use of the inversion recovery T-weighted turbo field echo (IR-TTFE) sequence for myocardial T mapping and compares the results obtained with those of the modified Look-Locker inversion recovery (MOLLI) method for accuracy, precision, and reproducibility. A phantom containing seven vials with different T values was imaged, thereby comparing the T measurements between the inversion recovery spin-echo (IR-SE) technique, MOLLI, and the IR-TTFE. The accuracy, precision, and reproducibility of the T-mapping sequences were analyzed in a phantom study.

Endosomal Toll-Like Receptors as Therapeutic Targets for Autoimmune Diseases.

Nucleic acid (NA)-sensing Toll-like receptors (TLRs) reside in the endosomal compartment of innate immune cells, such as macrophages and dendritic cells. NAs transported to the endosomal compartment are degraded by DNases and RNases. Degradation products, including single-stranded DNA, oligoRNA, and nucleosides, are recognized by TLR7, TLR8, and TLR9 to drive the defense responses against pathogens.

Aberrant monocytopoiesis drives granuloma development in sarcoidosis.

In sarcoidosis, granulomas develop in multiple organs including the liver and lungs. Although mechanistic target of rapamycin complex 1 (mTORC1) activation in macrophages drives granuloma development in sarcoidosis by enhancing macrophage proliferation, little is known about the macrophage subsets that proliferate and mature into granuloma macrophages. Here, we show that aberrantly increased monocytopoiesis gives rise to granulomas in a sarcoidosis model, in which Tsc2, a negative regulator of mTORC1, is conditionally deleted in CSF1R-expressing macrophages (Tsc2csf1rΔ mice).

Deep learning-based attenuation correction method in Tc-GSA SPECT/CT hepatic imaging: a phantom study.

This study aimed to evaluate a deep learning-based attenuation correction (AC) method to generate pseudo-computed tomography (CT) images from non-AC single-photon emission computed tomography images (SPECT) for AC in Tc-galactosyl human albumin diethylenetriamine pentaacetic acid (GSA) scintigraphy and to reduce patient dosage. A cycle-consistent generative network (CycleGAN) model was used to generate pseudo-CT images. The training datasets comprised approximately 850 liver phantom images obtained from SPECT and real CT images.

TLR7 promotes smoke-induced experimental lung damage through the activity of mast cell tryptase.

Toll-like receptor 7 (TLR7) is known for eliciting immunity against single-stranded RNA viruses, and is increased in both human and cigarette smoke (CS)-induced, experimental chronic obstructive pulmonary disease (COPD). Here we show that the severity of CS-induced emphysema and COPD is reduced in TLR7-deficient mice, while inhalation of imiquimod, a TLR7-agonist, induces emphysema without CS exposure. This imiquimod-induced emphysema is reduced in mice deficient in mast cell protease-6, or when wild-type mice are treated with the mast cell stabilizer, cromolyn.

Task-based assessment of resolution properties of CT images with a new index using deep convolutional neural network.

In this study, we propose a method for obtaining a new index to evaluate the resolution properties of computed tomography (CT) images in a task-based manner. This method applies a deep convolutional neural network (DCNN) machine learning system trained on CT images with known modulation transfer function (MTF) values to output an index representing the resolution properties of the input CT image [i.e.

[Characteristics of the Z-resolution Measurement in the Digital Breast Tomosynthesis].

Purpose: Digital breast tomosynthesis (DBT) offers a choice of image acquisition conditions. The object of observation is the entire detector in the full depth (Z-axis) direction. In this study, we investigated the effect of each acquisition condition on Z-resolution with a micro-metallic sphere (bead) as an imaged object in DBT images.

Energy simulation and CFD coupled analysis for the optimal operation of combined convection and radiant air conditioning considering dehumidification.

The use of radiant panels in homes has increased recently because they do not cause a drafty feeling, unlike air conditioners. However, air conditioners are more power-efficient than radiant panels and have a higher coefficient of performance (COP). Therefore, combining radiant panels and air conditioning can provide an optimal solution for thermal control in residences.

TLR7/8 stress response drives histiocytosis in SLC29A3 disorders.

Loss-of-function mutations in the lysosomal nucleoside transporter SLC29A3 cause lysosomal nucleoside storage and histiocytosis: phagocyte accumulation in multiple organs. However, little is known about the mechanism by which lysosomal nucleoside storage drives histiocytosis. Herein, histiocytosis in Slc29a3-/- mice was shown to depend on Toll-like receptor 7 (TLR7), which senses a combination of nucleosides and oligoribonucleotides (ORNs).

Performance of Generative Large Language Models on Ophthalmology Board-Style Questions.

Purpose: To investigate the ability of generative artificial intelligence models to answer ophthalmology board-style questions.

Design: Experimental study.

Methods: This study evaluated 3 large language models (LLMs) with chat interfaces, Bing Chat (Microsoft) and ChatGPT 3.

An increase in tumor-infiltrating lymphocytes after treatment is significantly associated with a poor response to neoadjuvant endocrine therapy for estrogen receptor-positive/HER2-negative breast cancers.

Background: The reason for the poor prognosis of estrogen receptor (ER) + /human epidermal growth factor receptor 2 (HER2)- breast cancer patients with high levels of tumor-infiltrating lymphocytes (TILs) is poorly understood. The association between TILs and response to neoadjuvant endocrine therapy (NET) was examined.

Methods: We recruited 170 patients with ER + /HER2- breast cancer who were treated with preoperative endocrine monotherapy.