Characterization of DMRT1 variants for testis determination and differentiation in emu.

Introduction: DMRT1 on the Z chromosome is a conserved male sex-determining gene in birds. In chickens, a representative model species of Neognathae, the function of DMRT1 has been well characterized. In contrast, Palaeognathae species such as the emu possess less differentiated sex chromosomes and thus provide a valuable system for investigating avian sex determination, yet molecular studies remain limited.

Identification and replication of sex-dimorphic protein quantitative trait loci across multiple ancestries and their associations with diseases.

Males and females exhibit differences in proteome profiles associated with disease risk. However, sex-dimorphic protein quantitative trait loci (SD-pQTL) and their effects on sex differences in health disorders have not been thoroughly investigated. We conducted a sex-stratified, genome-wide association study on 2,922 proteins using data from 30,272 individuals of Caucasian ancestry from the UK Biobank and compared the estimated effects on protein levels of these variants in the men and women to identify SD-pQTLs.

Clonal diversity shapes the tumour microenvironment leading to distinct immunotherapy responses in metastatic urothelial carcinoma.

Repeated oncogenic mutations and polyclonal proliferation are evident in cancers. However, little is known about the polyclonal principles governing the systemic cancerous lineage during immunotherapy. Here, we examine a unique autopsy case of metastatic urothelial carcinoma that exhibits different treatment responses to anti-PD-1 therapy at each tumor site.

2,3-Pyridinedicarboxylate is associated with shorter recurrence-free survival in patients with hypopharyngeal squamous cell carcinoma.

Introduction: Metabolites are associated with the biology of cancer; however, no metabolites related to prognosis have been identified in head and neck cancer. This study aimed to identify metabolites associated with prognosis in patients with hypopharyngeal squamous cell carcinoma (HPSCC).

Methods: Fifty-two patients who underwent surgery for HPSCC were included and randomly divided into test and validation cohorts of 26 patients each for further metabolome analysis using capillary electrophoresis/mass spectrometry on tumor and non-tumor tissues of the hypopharynx.

Restoration of the gut-microbiota-liver axis after hepatitis C virus eradication.

Background & Aims: We previously reported altered intestinal environmental features during HCV infection. Here, we aimed to characterize the gut-microbiota-liver axis in patients with chronic hepatitis C after a sustained virological response (SVR).

Methods: A total of 174 patients with HCV infection were enrolled in a cross-sectional study: 95 with chronic hepatitis (CH-HCV group) and 79 with cirrhosis or hepatocellular carcinoma (LC/HCC-HCV group).

Phased genome assemblies and pangenome graphs of human populations of Japan and Saudi Arabia.

The selection of a reference sequence in genome analysis is critical, as it serves as the foundation for all downstream analyses. Recently, the pangenome graph has been proposed as a data model that incorporates haplotypes from multiple individuals. Here we present JaSaPaGe, a pangenome graph reference for Saudi Arabian and Japanese populations, both of which have been significantly underrepresented in previous genomic studies.

Giant extrachromosomal element "Inocle" potentially expands the adaptive capacity of the human oral microbiome.

Survival strategy of bacteria is expanded by extrachromosomal elements (ECEs). However, their genetic diversity and functional roles for adaptability are largely unknown. Here, we discover a novel family of intracellular ECEs using 56 saliva samples by developing an efficient microbial DNA extraction method coupled with long-read metagenomics assembly.

Inhibition of Scarb1 on Endothelial Cells Attenuates Pressure Overload-induced Heart Failure Progression.

Inappropriate endothelial cell (EC) interactions contribute to heart failure; however, their precise mechanisms remain poorly understood. This study investigated EC-fibroblast interactions mediated by Scarb1 using single-cell RNA-sequencing analysis in a mouse heart failure model. ECs exhibited inflammatory and fibrotic gene expression, with Scarb1-mediated fibroblast-EC interactions driving disease progression.

Bidirectional anti-tumor and immunological strategies by targeting GARP-TGF-β axis in adult T-cell leukemia/lymphoma.

In adult T-cell leukemia/lymphoma (ATL), tumor cells show a regulatory T-cell (Treg)-type phenotype, which influences their tumor immunity. However, our knowledge of what molecular events are involved in pathogenesis is still missing. Here, we took advantage of this unique phenotype and screened whole transcriptome data from primary ATL cells to search for effective therapeutic targets.

STEMIN transcription factor drives selective chromatin remodeling for gene activation within a relaxed chromatin during reprogramming in the moss Physcomitrium patens.

Land plants exhibit remarkable cellular plasticity, readily reprogramming differentiated cells into stem cells in response to internal and external stimuli. While chromatin remodeling is crucial for cellular reprogramming, its interplay with gene expression during reprogramming into stem cells remains elusive. In the moss Physcomitrium patens, wounding induces reprogramming of leaf cells facing wounded cells to change into chloronema apical stem cells through the activation of the AP2/ERF transcription factor STEMIN.

Induced lung epithelial-like cells derived by direct reprogramming rescue influenza virus-induced lung injury in mice.

We recently reported that a combination of four transcription factors (Nkx2-1, Foxa1, Foxa2, and Gata6) directly reprograms mouse embryonic fibroblasts (MEFs) into differentiated self-renewable alveolar epithelial-like cells in a serum-free 3D organoid system. Here, we aimed to generate induced pulmonary epithelial-like cells in serum-containing culture (iPULsSC) using the same four transcription factors in a serum-containing 3D culture system. We found that the global gene expression profile of iPULsSC was similar to that of alveolar epithelial type II (AT2) and alveolar type I (AT1) cells.

Single-cell spatial analysis with Xenium reveals anti-tumour responses of CXCL13 + T and CXCL9+ cells after radiotherapy combined with anti-PD-L1 therapy.

Background: The standard treatment for unresectable non-small cell lung cancer (NSCLC) is anti-PD-L1 therapy combined with chemoradiotherapy (anti-PD-L1-CRT). Although some patients achieve complete cancer eradication and cure, more than half of patients retain persistent cancer cells. Our research aimed to unravel the nuanced mechanisms involved in both immune attack and evasion induced by anti-PD-L1-CRT with single cell spatial transcriptome.

Clinicopathologic, Cellular, and Molecular Analyses of Pulmonary Neuroendocrine Carcinoma With High Expression of Hepatocyte Nuclear Factor 4 Alpha.

Pulmonary neuroendocrine carcinoma (NEC), including small cell carcinoma (SCLC) and large cell neuroendocrine carcinoma (LCNEC), is highly aggressive and has a poor prognosis. The molecular subtyping of NECs has recently attracted attention, and we identified a new NEC subtype, the hepatocyte nuclear factor 4α (HNF4α) subtype. HNF4α, a transcription factor associated with gastrointestinal differentiation, and TTF-1 are mutually and exclusively expressed in lung adenocarcinomas; however, the characteristics of HNF4α-high NEC and TTF-1-high NEC have yet to be compared.

Distinct follicular T cell subsets regulate lymphoma progression and outcomes.

Follicular lymphoma (FL) is characterized by the expansion of neoplastic follicle structures and is suggested to have a distinctive form of T cell immunity. However, the heterogeneity and role of follicular T cells beyond T follicular helper (T) cells remain largely unexplored in FL. Here, we performed multi-omics analyses of follicular T cells in FL leveraging pan-cancer single-cell mapping, spatially resolved single-cell transcriptomics and multiplex protein profiling, and functional characterization.

Trajectory analysis reveals an uncommitted neuroblastic state in MYCN-driven neuroblastoma development.

Background: Understanding the factors that determine the spontaneous regression of pre-cancerous lesions is critical to advancing cancer prevention. Neuroblastoma, a pediatric cancer, undergoes spontaneous regression more frequently than other types of cancer.

Methods: Here, we analyzed the transcriptomic features of spontaneous regression in pre-cancerous neuroblasts using Th-MYCN mice, an animal model that closely resembles human neuroblastoma.

Prognostic Significance of Preoperative Serum CA19-9-to-CEA Ratio in Stage I-III Colorectal Cancer Post-Resection.

During colorectal cancer (CRC) surveillance, tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9), play important roles in the diagnosis, prediction, and monitoring of tumors. Herein, we devised a novel combined index comprising the CA19-9-to-CEA ratio and investigated its prognostic value in patients with stage I-III CRC after resection. This retrospective study included 306 patients who underwent radical resection between 2011 and 2020.

Direct reprogramming of mouse fibroblasts into self-renewable alveolar epithelial-like cells.

Direct reprogramming is a breakthrough technology that can alter the fate of cells without the passage of stem cells. However, direct reprogramming of somatic cells into pulmonary alveolar epithelial cells has not yet been achieved. Here, we report the direct reprogramming of mouse tail tips and embryonic fibroblasts into induced pulmonary alveolar epithelial-like cells (iPULs) using four transcription factor-coding genes (Nkx2-1, Foxa1, Foxa2, and Gata6) and three-dimensional culture.

The Masc-PSI complex directly induces male-type doublesex splicing in silkworms.

The WZ sex determination system is found in a diverse range of animals, including lepidopteran insects. In the silkworm Bombyx mori, the masculinizing protein Masculinizer (BmMasc) induces the production of the male-type Bombyx mori doublesex (Bmdsx), which is the master genetic switch of B. mori sex differentiation.

In vivo transition in chromatin accessibility during differentiation of deep-layer excitatory neurons in the neocortex.

During neuronal differentiation, gene transcription patterns change in response to both intrinsic and extrinsic cues. Chromatin regulation at regulatory elements plays a key role in this process. However, how chromatin accessibility evolves in vivo in cortical neurons remains unclear.

Ligand-Receptor Interactions Between Squamous and Endothelial Cells Induce Head and Neck Squamous Cell Carcinoma.

Advances in narrowband imaging (NBI) have revealed that squamous epithelial lesions form alongside changes in squamous epithelial cells and intrapapillary capillary loops (IPCLs) in the head and neck. However, the molecular interactions between squamous epithelial cells and endothelial cells (ECs) that promote IPCL proliferation are unclear. This study aimed to identify the mechanisms of cooperation between parenchymal squamous cells and stromal IPCLs during the formation of head and neck squamous cell carcinoma (SCC).

Novel body component score predicts long-term survival in patients with stage I-III colorectal cancer following radical resection.

Background: In gastrointestinal cancer, the relationship among skeletal muscle, subcutaneous and visceral fat mass, and prognosis is gaining attention. Herein, we developed a body component score (BCS) to comprehensively evaluate total body composition in patients with stage I-III colorectal cancer (CRC) and examined its relationship with long-term prognosis.

Methods: This retrospective study included 300 patients with CRC who underwent curative colorectal resection in 2010-2019.

Dissecting cross-population polygenic heterogeneity across respiratory and cardiometabolic diseases.

Biological mechanisms underlying multimorbidity remain elusive. To dissect the polygenic heterogeneity of multimorbidity in twelve complex traits across populations, we leveraged biobank resources of genome-wide association studies (GWAS) for 232,987 East Asian individuals (the 1st and 2nd cohorts of BioBank Japan) and 751,051 European individuals (UK Biobank and FinnGen). Cross-trait analyses of respiratory and cardiometabolic diseases, rheumatoid arthritis, and smoking identified negative genetic correlations between respiratory and cardiometabolic diseases in East Asian individuals, opposite from the positive associations in European individuals.

Immersive Virtual Reality for Reducing Intraoperative Pain: A Pilot Randomized Controlled Trial.

Background/aim: In this study, we aimed to evaluate the effect of virtual reality (VR) therapy on pain, anxiety, and other outcomes in patients with cancer undergoing central venous (CV) port placement.

Patients And Methods: We conducted a single-center randomized controlled trial with 10 adults with cancer undergoing CV port placement. Participants were randomized into the VR group (n=5), which received VR therapy with the Therapeia VR system (xCura), or the control group (n=5), which underwent conventional procedures.