BCR, not TCR, repertoire diversity is associated with favorable COVID-19 prognosis.

Introduction: The SARS-CoV-2 pandemic has had a widespread and severe impact on society, yet there have also been instances of remarkable recovery, even in critically ill patients.

Materials And Methods: In this study, we used single-cell RNA sequencing to analyze the immune responses in recovered and deceased COVID-19 patients during moderate and critical stages.

Results: Expanded T cell receptor (TCR) clones were predominantly SARS-CoV-2-specific, but represented only a small fraction of the total repertoire in all patients.

Clonal landscape of autoantibody-secreting plasmablasts in COVID-19 patients.

Whereas severe COVID-19 is often associated with elevated autoantibody titers, the underlying mechanism behind their generation has remained unclear. Here we report clonal composition and diversity of autoantibodies in humoral response to SARS-CoV-2. Immunoglobulin repertoire analysis and characterization of plasmablast-derived monoclonal antibodies uncovered clonal expansion of plasmablasts producing cardiolipin (CL)-reactive autoantibodies.

Identification of risk loci for postpartum depression in a genome-wide association study.

Aim: Genome-wide association studies (GWAS) of postpartum depression (PPD) based on accumulated cohorts with multiple ethnic backgrounds have failed to identify significantly associated loci. Herein, we conducted a GWAS of Japanese perinatal women along with detailed confounding information to uncover PPD-associated loci.

Methods: The first and second cohorts (n = 9260 and n = 8582 perinatal women enrolled in the Tohoku Medical Megabank Project) and the third cohort (n = 997), recruited at Nagoya University, underwent genotyping.

Natural antagonistic flavones for AhR inhibit indoxyl sulfate-induced inflammatory gene expression and renal pathological damages .

Background: Uremic toxin indoxyl sulfate (IS) induces vascular inflammation, a crucial event in renal failure, and vascular complications in patients with chronic kidney disease (CKD). In endothelial cells, IS increases the production of inflammatory cytokines partially via the activation of the aryl hydrocarbon receptor (AhR), and several food flavonoids have been reported to act as antagonists of AhR.

Objective: This study aimed to investigate whether antagonistic flavonoids can attenuate IS-induced inflammatory responses in vascular endothelial cells and renal failure .

Enterovirus 3A protein disrupts endoplasmic reticulum homeostasis through interaction with GBF1.

Enteroviruses are single-stranded, positive-sense RNA viruses causing endoplasmic reticulum (ER) stress to induce or modulate downstream signaling pathways known as the unfolded protein responses (UPR). However, viral and host factors involved in the UPR related to viral pathogenesis remain unclear. In the present study, we aimed to identify the major regulator of enterovirus-induced UPR and elucidate the underlying molecular mechanisms.

A descriptive analysis of real-world oncology biosimilar use in Japan.

To describe patient and treatment characteristics associated with bevacizumab BS-Pfizer, rituximab BS-Pfizer and trastuzumab BS-Pfizer and their reference products in Japan. This retrospective observational study used an administrative claims database to identify patients with ≥1 biosimilar or reference product prescription from 2019 to 2022 for approved indications. Descriptive statistics were calculated.

Humoral responses are enhanced by facilitating B cell viability by Fcrl5 overexpression in B cells.

B cell initial activity is regulated through a balance of activation and suppression mediated by regulatory molecules expressed in B cells; however, the molecular mechanisms underlying this process remain incompletely understood. In this study, we investigated the function of the Fc receptor-like (Fcrl) family molecule Fcrl5, which is constitutively expressed in naive B cells, in humoral immune responses. Our study demonstrated that B cell-specific overexpression of Fcrl5 enhanced antibody (Ab) production in both T cell-independent type 1 (TI1) and T cell-dependent (TD) responses.

Abiotic Ribose Synthesis Under Aqueous Environments with Various Chemical Conditions.

Ribose is the defining sugar in ribonucleic acid (RNA), which is often proposed to have carried the genetic information and catalyzed the biological reactions of the first life on Earth. Thus, abiological processes that yield ribose under prebiotic conditions have been studied for decades. However, aqueous environments required for the formation of ribose from materials available in quantity under geologically reasonable models, where the ribose formed is not immediately destroyed, remain unclear.

JAK inhibition during the early phase of SARS-CoV-2 infection worsens kidney injury by suppressing endogenous antiviral activity in mice.

Coronavirus disease 2019 (COVID-19) induces respiratory dysfunction as well as kidney injury. Although the kidney is considered a target organ of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and affected by the COVID-19-induced cytokine storm, the mechanisms of renal reaction in SARS-CoV-2 infection are unknown. In this study, a murine COVID-19 model was induced by nasal infection with mouse-adapted SARS-CoV-2 (MA10).

Adjuvant-free parenterally injectable vaccine platform that harnesses previously induced IgG as an antigen delivery carrier.

Subunit vaccines are among the most useful vaccine modalities; however, their low immunogenicity necessitates the addition of adjuvants. Although adjuvants improve immune responses induced by vaccines, they often cause adverse reactions. To address this, we developed an adjuvant-free subunit vaccine platform that uses pre-existing antibodies generated from past infections or vaccinations as carriers for the delivery of vaccine antigens.

Gap Junction Beta-2 p.Val84Met Can Cause Autosomal Dominant Syndromic Hearing Loss With Keratoderma.

In this study, we report a case of bilateral mild hearing loss and keratoderma caused by a gap junction beta-2 (GJB2) variant. The proband was a nine-year-old Japanese boy with bilateral mild hearing loss at birth. The proband's father, sister, paternal aunt, and cousins had mild sensorineural hearing loss.

Autoantibodies to nuclear valosin-containing protein-like protein: systemic sclerosis-specific antibodies revealed by in vitro human proteome.

Objectives: To identify and characterize undescribed systemic sclerosis (SSc)-specific autoantibodies targeting nucleolar antigens and to assess their clinical significance.

Methods: We conducted proteome-wide autoantibody screening (PWAS) against serum samples from SSc patients with nucleolar patterned anti-nuclear antibodies (NUC-ANAs) of specific antibodies (Abs) unknown, utilizing wet protein arrays fabricated from in vitro human proteome. Controls included SSc patients with already-known SSc-specific autoantibodies, patients with other connective tissue diseases and healthy subjects.

Novel Digenic Variants in and Causing X-Linked Alport Syndrome: A Case Report.

Introduction: Alport syndrome (AS) is a hereditary, progressive kidney disease characterized by structural abnormalities and dysfunction of the glomerular basement membrane (GBM). AS is classified as X-linked, autosomal, and digenic. The number of cases of digenic AS has increased, but the genotype-phenotype correlation of patient with digenic AS is still unclear.

Distribution of osteoprotegerin in unruptured intracranial aneurysms in humans: association with aneurysm wall protective remodeling.

Objective: Aneurysm wall inflammation is associated with lesion instability in unruptured intracranial aneurysms (UIAs). However, most UIAs remain unruptured during lifelong follow-ups because of simultaneous protective remodeling against the inflammatory response. The protective effects of osteoprotegerin (OPG) in intracranial and abdominal aortic aneurysms have been suggested using rodent models; however, the role of this protein in UIAs in humans remains unclear.

Intranasal immunization with an RBD-hemagglutinin fusion protein harnesses preexisting immunity to enhance antigen-specific responses.

Intranasal vaccines are anticipated to be powerful tools for combating many infectious diseases, including SARS-CoV-2, because they induce not only systemic immunity but also mucosal immunity at the site of initial infection. However, they are generally inefficient in inducing an antigen-specific immune response without adjuvants. Here, we developed an adjuvant-free intranasal vaccine platform that utilizes the preexisting immunity induced by previous infection or vaccination to enhance vaccine effectiveness.