Multi-omics uncovers transcriptional programs of gut-resident memory CD4+ T cells in Crohn's disease.

Tissue-resident memory T cells (TRM) remain in nonlymphatic barrier tissues for extended periods and are deeply involved in immune memory at the site of inflammation. Here, we employed multilayered single-cell analytic approaches including chromatin, gene, and protein profiling to characterize a unique CD4+ TRM subset present in the inflamed gut mucosa of Crohn's disease patients. We identified two key transcription factors, RUNX2 and BHLHE40, as regulators of pathologically relevant CD4+ TRM.

Fecal microbiota transplantation for Crohn's disease-like intestinal lesions arising after allogeneic stem cell transplantation.

Several cases of inflammatory bowel disease (or similar gastrointestinal lesions) arising after allogeneic hematopoietic stem cell transplantation have been reported, but the effect of intestinal dysbiosis on development of these lesions remains unclear. We performed fecal microbiota transplantation (FMT) and 16S rRNA microbiome analysis in a patient who developed Crohn's disease-like lesions after allogeneic transplantation. A 62-year-old woman underwent haploidentical stem cell transplantation from her daughter to treat double-hit lymphoma relapsed after chimeric antigen receptor T-cell therapy, and achieved remission without developing acute graft-versus-host disease.

Molecular epidemiological surveillance for non-tuberculous mycobacterial pulmonary disease: a single-center prospective cohort study.

Unlabelled: Bacterial species cultured from sputum change during treatment or observation for non-tuberculous mycobacterial pulmonary disease; however, strain-level changes remain unrecognized. Variable number tandem repeat typing is a standard technique for strain identification; nonetheless, its labor-intensive and time-consuming nature limits routine clinical use. Therefore, we aimed to elucidate species-subspecies and strain dynamics in non-tuberculous mycobacteria and develop a simple sequence-based strain-level determination method.

A nonactivating mutation in the β3 cytoplasmic region causes macrothrombocytopenia with an impaired αIIbβ3/RhoA pathway.

Almost all mutations of or identified in congenital macrothrombocytopenia induce constitutive activation of αIIbβ3. However, whether concomitant αIIbβ3 activation is essential for macrothrombocytopenia development remains unknown. Recently, we identified the β3(R760C) mutation that does not induce αIIbβ3 activation in a patient with macrothrombocytopenia.

A retrospective observational study of the nosocomial outbreak caused by human rhinovirus A34.

Background: Past reports of nosocomial outbreak due to human rhinovirus (HRV) in adults are limited. We report a case of nosocomial outbreak of HRV-A34 in a long-term care facility with a literature review.

Methods: Multiplex real-time polymerase chain reaction assay (Allplex™ RV Essential Assay) was used for the detection of HRV.

Deciphering state-dependent immune features from multi-layer omics data at single-cell resolution.

Current molecular quantitative trait locus catalogs are mostly at bulk resolution and centered on Europeans. Here, we constructed an immune cell atlas with single-cell transcriptomics of >1.5 million peripheral blood mononuclear cells, host genetics, plasma proteomics and gut metagenomics from 235 Japanese persons, including patients with coronavirus disease 2019 (COVID-19) and healthy individuals.

Spatial transcriptomics identifies SPARC as a prognostic marker in interstitial lung diseases.

Interstitial lung diseases (ILDs) encompass a diverse group of pulmonary disorders, with progressive fibrosis leading to poor prognosis. Here we aimed to identify key molecules involved in progressive fibrosis across various ILDs, using spatial transcriptomics (ST). ST analysis (Visium) was performed on lung cryobiopsy specimens from five patients with various ILDs.

Identifying genetic variations in 89 associated with severe invasive infections.

causes mild human infections as well as life-threatening invasive diseases. Since the mutations known to enhance virulence to date account for only half of the severe invasive infections, additional mechanisms/mutations need to be identified. Here, we conducted a genome-wide association study of 89 strains to comprehensively identify pathology-related bacterial genetic factors (single-nucleotide polymorphisms [SNPs], indels, genes, or k-mers).

OTUD3 prevents ulcerative colitis by inhibiting microbiota-mediated STING activation.

Ulcerative colitis (UC) develops through a complicated interaction between the host and microbiota. Intestinal fibroblasts are believed to play crucial roles in the pathogenesis of UC, but the influence of the host-microbiota interaction on the pathophysiology of intestinal fibroblasts remains poorly understood. Here, we demonstrate that OTU deubiquitinase 3 (OTUD3) suppresses pathologic activation of fibroblasts exposed to microbial cyclic GMP-AMP (3'3'-cGAMP) in the colon by deubiquitinating stimulator of interferon genes (STING).

Transmission of maternal oral pathobionts to the infant gut predisposes offspring to exacerbated enteritis.

Infants acquire maternal microbes from various body sites, which become early colonizers of the infant gut. Consequently, disruption of healthy maternal microbiota, particularly maternal gut dysbiosis, can influence the composition of offspring's gut microbiota and affect their health outcomes. However, the effects of non-gut maternal microbes on infant health and disease remain largely unexplored.

Microbiota-driven antitumour immunity mediated by dendritic cell migration.

Gut microbiota influence the antitumour efficacy of immune checkpoint blockade, but the mechanisms of action have not been fully elucidated. Here, we show that a new strain of the bacterial genus Hominenteromicrobium (designated YB328) isolated from the faeces of patients who responded to programmed cell death 1 (PD-1) blockade augmented antitumour responses in mice. YB328 activated tumour-specific CD8 T cells through the stimulation of CD103CD11b conventional dendritic cells (cDCs), which, following exposure in the gut, migrated to the tumour microenvironment.

Differences in gut microbiome between autosomal dominant polycystic kidney disease with and without intracranial aneurysms.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by cyst formation in the kidneys, and is associated with an elevated risk of intracranial aneurysms (IAs). Although a family history is a recognized risk factor for IAs in patients with ADPKD, emerging research suggests that gut microbiome composition may influence IA development. We investigated the relationship between the gut microbiome and the development of IA in patients with ADPKD.

Lung microbiota of patients with ARDS due to coronavirus disease 2019 receiving ECMO.

Diversity of the microbiota, which is essential for lower airway homeostasis, is greatly altered in acute respiratory distress syndrome (ARDS). Extracorporeal membrane oxygenation (ECMO) is the ultimate protective treatment for the lungs of patients with severe ARDS, but little is known about its effect on the lung microbiota of these patients. To evaluate the effect of ECMO on the lung microbiota of ARDS patients, we performed 16S rRNA and fungal ITS1 profiling and shotgun sequencing on bronchoalveolar lavage fluid (BALF) collected from ARDS patients due to COVID-19.

Pathogenic mechanism of extracranial arteriovenous malformations: insights from clinical, pathological, and genetic analyses.

Extracranial arteriovenous malformations (AVMs) are rare aggressive vascular malformations, and half of AVMs harbor mutations in the RAS/RAF/MAPK pathway. AVMs consist of abnormal networks of small vessels formed between arteries and veins. Although the abnormal small-vessel networks are considered to cause AVM progression, the underlying mechanisms remain poorly understood.

Antisense oligonucleotide targeting nicotinamide N-methyltransferase exhibits antitumor effects.

Nicotinamide N-methyltransferase (NNMT) is one of the methyltransferase family genes. It consumes S-adenosyl-l-methionine (SAM), which is required for DNA methylation and histone methylation for epigenetic regulation, to produce 1-methylnicotinamide from nicotinamide, a source of NAD, thus affecting energy metabolism and epigenetics. Recent studies have shown that is highly expressed in cancer tissues, mainly in the stroma, and worsens prognosis.

Oral Pathobiont Streptococcus Anginosus Is Enriched in the Gut of Stroke Patients and Predicts 2-Year Cardiovascular Outcome.

Background: Several cross-sectional studies have implicated gut dysbiosis caused by an abundance of oral commensals in stroke, but the effect on long-term prognosis is still unknown. Therefore, we longitudinally investigated oral pathobionts in the gut and their clinical relevance to stroke.

Methods And Results: We analyzed the salivary and gut microbiomes collected from 189 acute stroke and 55 non-stroke subjects, and found that Streptococcus anginosus was significantly more abundant in both the saliva (median [IQR], 0.

Herpes simplex virus 1 evades APOBEC1-mediated immunity via its uracil-DNA glycosylase in mice.

Herpes simplex virus 1 (HSV-1) is the most common cause of viral encephalitis, which can be lethal or result in severe neurological defects despite antiviral therapy. The apolipoprotein B messenger-RNA editing enzyme, catalytic polypeptide-like (APOBEC) group of proteins can act as viral restriction factors. How HSV-1 evades this intrinsic immune mechanism is unclear.

Molecular epidemiology of human sapovirus based on the surveillance of wastewater and patients with acute gastroenteritis in Osaka, Japan.

Wastewater-based epidemiology has recently emerged as a promising tool for determining the prevalence of infectious diseases in a community. In the present study, human sapoviruses (HuSaVs) detected in wastewater collected weekly from January 2023 to March 2024 were analyzed using qPCR and next-generation sequencing (NGS), and the results were compared with those from clinical surveillance samples obtained from patients with acute gastroenteritis (AGE) in Osaka Prefecture, Japan. The detection trend of HuSaV in wastewater agreed with the clinical surveillance data in that HuSaV genomes increased in the cold season.

mlstverse-web: advancing real-time identification of mycobacteria from sputum using targeted sequencing NALC-Seq.

The identification of mycobacteria, including Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacteria (NTM), remains a critical challenge in clinical and public health settings due to their pathogenicity and increasing drug resistance. Traditional diagnostic methods, such as PCR and mass spectrometry, are limited by species detectability and prolonged culture requirements. To address these limitations, this study introduces a novel approach, named NALC-Seq, which integrates next-generation sequencing (NGS) and target capture sequencing for the direct and comprehensive identification of mycobacteria from sputum samples.

Identification of 2 Novel Species, Mycobacterium novusgordonae and M. shingordonae.

We identified 2 novel species, Mycobacterium novusgordonae and M. shingordonae, from sputum specimens of pulmonary disease patients in Japan. Genetic and biochemical analyses revealed a close relationship with M.

A comprehensive analysis of antimicrobial resistance of clinical 89 in Japan.

Objectives: is involved in a wide range of diseases, including pharyngitis and life-threatening invasive infections. Increasing prevalence of antimicrobial resistance (AMR) has been reported worldwide in various bacteria, limiting the use of antibiotics in infection cases. The present study investigated the AMR of most prevalent types, including 89 strains in Japan.

Karyotype evolution of myelodysplastic syndrome and acute myeloid leukemia with TP53 mutations.

To clarify karyotype evolution of myelodysplastic syndrome or acute myeloid leukemia with TP53 mutations (MDS/AML-TP53), we analyzed G-banding of bone marrow aspiration samples of eight patients with MDS/AML-TP53 and visualized the evolutions as phylogenetic trees. With very few exceptions, the initial roots of these trees and all branches longitudinally had -5/5q- and -7/7q- in common. Time series data of the karyotypes obtained in six patients showed highly complex karyotype evolutions, such as combined branched, linear, parallel, and macro-evolutions.

Transcriptome signature in the blood of neuromyelitis optica spectrum disorder under steroid tapering.

Background: The advent of biologics has significantly transformed treatment strategies for neuromyelitis optica spectrum disorder (NMOSD). However, there are no biomarkers that predict relapses associated with steroid tapering; therefore, it is critical to identify potential indicators of disease activity. In this study, we collected peripheral blood mononuclear cells (PBMCs) from NMOSD patients during steroid tapering and performed bulk RNA sequencing to analyze changes in immune dynamics caused by steroid reduction.

Intestinal Foxl1+ cell-derived CXCL12 maintains epithelial homeostasis by modulating cellular metabolism.

Several mesenchymal cell populations are known to regulate intestinal stem cell (ISC) self-renewal and differentiation. However, the influences of signaling mediators derived from mesenchymal cells other than ISC niche factors on epithelial homeostasis remain poorly understood. Here, we show that host and microbial metabolites, such as taurine and gamma-aminobutyric acid (GABA), act on PDGFRαhigh Foxl1high sub-epithelial mesenchymal cells to regulate their transcription.