Association of Glymphatic Function With Clinical Characteristics in Patients With Clinical and Asymptomatic Creutzfeldt-Jakob Disease.

Background And Objectives: Abnormal glymphatic system-related proteins have been identified in a small-scale pathologic study of patients with Creutzfeldt-Jakob disease (CJD). However, it remains unclear whether glymphatic dysfunction occurs in vivo in patients with CJD and whether this decline begins during the preclinical stage. This study aimed to investigate the relationship between glymphatic dysfunction and clinical characteristics in patients with CJD, as well as potential glymphatic impairment in preclinical CJD.

The Value of Necrotic Area Features in Contrast-Enhanced Ultrasound for Distinguishing Between Benign and Malignant Subpleural Pulmonary Lesions.

Objective: To analyze Necrotic Area Features of subpleural pulmonary lesions (SPLs) demonstrated by contrast-enhanced ultrasound (CEUS) and investigate their value in differentiating between malignant and benign SPLs.

Methods: Patients with SPLs who underwent CEUS at our hospital from January to May 2021. The following patient information was recorded: (i) age, (ii) sex, (iii) lesion size, (iv) lesion location, (v) size of necrotic areas and (vi) necrotic area morphology, including sieve-like necrosis, necrotic area with septal enhancement, necrotic area with annular enhancement margins, and necrotic area with burr-like enhancement margins.

Individually addressed entangling gates in a two-dimensional ion crystal.

Two-dimensional (2D) ion crystals may represent a promising path to scale up qubit numbers for ion trap quantum information processing. However, to realize universal quantum computing in this system, individually addressed high-fidelity two-qubit entangling gates still remain challenging due to the inevitable micromotion of ions in a 2D crystal as well as the technical difficulty in 2D addressing. Here we demonstrate two-qubit entangling gates between any ion pairs in a 2D crystal of four ions.

Variation in the metagenomic analysis of fecal microbiome composition calls for a standardized operating approach.

The reproducibility in microbiome studies is limited due to the lack of one gold-standard operating procedure. The aim of this study was to examine the impact of protocol variations on microbiome composition using metagenomic data sets from a single center. We assessed the variation in a data set consisted of 2,722 subjects, including 9 subcohorts harboring healthy subjects and patients with various disorders, such as inflammatory bowel disease, colorectal cancer, and type 2 diabetes.

Functional characterization of chlorophyll b reductase NON-YELLOW COLORING 1 in Medicago truncatula.

Chlorophyll degradation is a characteristic process of leaf senescence. Two mutant lines, which showed green leaves and seeds during senescence, were identified by screening a Tnt-1 retrotransposon-tagged population of Medicago truncatula. Genetic and molecular analyses indicated that the mutated gene is NON-YELLOW COLORING 1 (MtNYC1) in M.

Structural basis of μ-opioid receptor targeting by a nanobody antagonist.

The μ-opioid receptor (μOR), a prototypical G protein-coupled receptor (GPCR), is the target of opioid analgesics such as morphine and fentanyl. Due to the severe side effects of current opioid drugs, there is considerable interest in developing novel modulators of μOR function. Most GPCR ligands today are small molecules, however biologics, including antibodies and nanobodies, represent alternative therapeutics with clear advantages such as affinity and target selectivity.

Reconstruction of single-cell lineage trajectories and identification of diversity in fates during the epithelial-to-mesenchymal transition.

Exploring the complexity of the epithelial-to-mesenchymal transition (EMT) unveils a diversity of potential cell fates; however, the exact timing and mechanisms by which early cell states diverge into distinct EMT trajectories remain unclear. Studying these EMT trajectories through single-cell RNA sequencing is challenging due to the necessity of sacrificing cells for each measurement. In this study, we employed optimal-transport analysis to reconstruct the past trajectories of different cell fates during TGF-beta-induced EMT in the MCF10A cell line.

FOXP4 Is a Direct YAP1 Target That Promotes Gastric Cancer Stemness and Drives Metastasis.

The Hippo-YAP1 pathway is an evolutionally conserved signaling cascade that controls organ size and tissue regeneration. Dysregulation of Hippo-YAP1 signaling promotes initiation and progression of several types of cancer, including gastric cancer. As the Hippo-YAP1 pathway regulates expression of thousands of genes, it is important to establish which target genes contribute to the oncogenic program driven by YAP1 to identify strategies to circumvent it.

Immune mechanisms in fibrotic interstitial lung disease.

Fibrotic interstitial lung diseases (fILDs) have poor survival rates and lack effective therapies. Despite evidence for immune mechanisms in lung fibrosis, immunotherapies have been unsuccessful for major types of fILD. Here, we review immunological mechanisms in lung fibrosis that have the potential to impact clinical practice.

Vaccine Therapy for Heart Failure Targeting the Inflammatory Cytokine Igfbp7.

Background: The heart comprises many types of cells such as cardiomyocytes, endothelial cells (ECs), fibroblasts, smooth muscle cells, pericytes, and blood cells. Every cell type responds to various stressors (eg, hemodynamic overload and ischemia) and changes its properties and interrelationships among cells. To date, heart failure research has focused mainly on cardiomyocytes; however, other types of cells and their cell-to-cell interactions might also be important in the pathogenesis of heart failure.

Serum Anion Gap at Admission Predicts All-Cause Mortality in Critically Ill Patients With Cirrhosis: A Retrospective Cohort Study.

Introduction: The primary objective of this study was to evaluate admission serum anion gap (AG) as a predictor of all-cause mortality in critically ill patients with cirrhosis.

Methods: A total of 3,084 cirrhotic patients were included and randomly divided into training and validation cohorts (n = 2,159 and 925, respectively). Patients were categorized into high and normal AG groups based on their AG values.

Enzyme-Instructed Photoactivatable Supramolecular Antigens on Cancer Cell Membranes for Precision-Controlled T-Cell-Based Cancer Immunotherapy.

Cancer immunotherapies based on cytotoxic CD8 T lymphocytes (CTLs) are highly promising for cancer treatment. The specific interaction between T-cell receptors and peptide-MHC-I complexes (pMHC-I) on cancer cell membranes critically determines their therapeutic outcomes. However, the lack of appropriate endogenous antigens for MHC-I presentation disables tumor recognition by CTLs.

β-Aminopropionitrile Induces Distinct Pathologies in the Ascending and Descending Thoracic Aortic Regions of Mice.

Background: β-aminopropionitrile (BAPN) is a pharmacological inhibitor of LOX (lysyl oxidase) and LOXLs (LOX-like proteins). Administration of BAPN promotes aortopathies, although there is a paucity of data on experimental conditions to generate pathology. The objective of this study was to define experimental parameters and determine whether equivalent or variable aortopathies were generated throughout the aortic tree during BAPN administration in mice.

Development of a chimeric cytokine receptor that captures IL-6 and enhances the antitumor response of CAR-T cells.

The efficacy of chimeric antigen receptor (CAR)-engineered T cell therapy is suboptimal in most cancers, necessitating further improvement in their therapeutic actions. However, enhancing antitumor T cell response inevitably confers an increased risk of cytokine release syndrome associated with monocyte-derived interleukin-6 (IL-6). Thus, an approach to simultaneously enhance therapeutic efficacy and safety is warranted.

Circular RNA vaccines against monkeypox virus provide potent protection against vaccinia virus infection in mice.

Since the outbreak of monkeypox (mpox) in 2022, widespread concern has been placed on imposing an urgent demand for specific vaccines that offer safer and more effective protection. Using an efficient and scalable circular RNA (circRNA) platform, we constructed four circRNA vaccines that could induce robust neutralizing antibodies as well as T cell responses by expressing different surface proteins of mpox virus (MPXV), resulting in potent protection against vaccinia virus (VACV) in mice. Strikingly, the combination of the four circular RNA vaccines demonstrated the best protection against VACV challenge among all the tested vaccines.

Associations of evening-type and insomnia symptoms with depressive symptoms among youths.

Background: Evening-type and insomnia symptoms are significantly related to each other and independently associated with depressive symptoms, yet few studies have examined the potential interaction between these two conditions. Therefore, we aimed to examine the associations of evening-type and insomnia symptoms with depressive symptoms among Chinese youths, with a specific focus on the joint effects of the two conditions on depressive symptoms.

Methods: Participants aged between 12 and 25 were invited to participate in an online survey from December 15, 2022, to May 26, 2023.

VISTA checkpoint inhibition by pH-selective antibody SNS-101 with optimized safety and pharmacokinetic profiles enhances PD-1 response.

VISTA, an inhibitory myeloid-T-cell checkpoint, holds promise as a target for cancer immunotherapy. However, its effective targeting has been impeded by issues such as rapid clearance and cytokine release syndrome observed with previous VISTA antibodies. Here we demonstrate that SNS-101, a newly developed pH-selective VISTA antibody, addresses these challenges.