Explore the vast range of titles available.

The hallmark features of type 2 mucosal immunity include intestinal tuft and goblet cell expansion initiated by tuft cell activation. How infectious agents that induce type 2 mucosal immunity are detected by tuft cells is unknown. Published microarray analysis suggested that succinate receptor 1 (Sucnr1) is specifically expressed in tuft cells. Thus, we hypothesized that the succinate–Sucnr1 axis may be utilized by tuft cells to detect certain infectious agents. Here we confirmed that Sucnr1 is specifically expressed in intestinal tuft cells but not in other types of intestinal epithelial cells, and demonstrated that dietary succinate induces tuft and goblet cell hyperplasia via Sucnr1 and the tuft cell-expressed chemosensory signaling elements gustducin and Trpm5. Conventional mice with a genetic Sucnr1 deficiency (Sucnr1 −/−) showed diminished immune responses to treatment with polyethylene glycol and streptomycin, which are known to enhance microbiota-derived succinate, but responded normally to inoculation with the parasitic worm Nippostrongylus brasiliensis that also produces succinate. Thus, Sucnr1 is required for microbiota-induced but not for a generalized worm-induced type 2 immunity.

Meteorin-like (Metrnl) is a newly identified secreted protein that plays important roles in metabolic and inflammation-related diseases. Our study aimed to evaluate serum Metrnl levels and establish their relationship with vascular calcification (VC) in hemodialysis (HD) patients. In total, 313 HD patients and 41 healthy individuals, as controls, were included. Serum levels of Metrnl and other clinical and laboratory parameters were compared. VC was evaluated based on the abdominal aortic calcification (AAC) scores. HD patients were divided into a high-AAC score group (AAC score ≥ 4) and a low-AAC score group (AAC score < 4). HD patients had higher serum Metrnl levels than the controls (0.52 ± 0.26 ng/ml vs. 0.24 ± 0.11 ng/ml,  < 0.001). Serum Metrnl concentrations were significantly higher in HD patients in the high-AAC score group than in those in the low-AAC score group (0.55 ± 0.27 vs. 0.49 ± 0.24 ng/ml,  = 0.041). Multivariate logistic regression revealed that serum Metrnl, age, diabetes mellitus, serum total carbon dioxide ( CO ) and serum intact parathyroid hormone (iPTH) were significant independent determinants of high AAC scores. The results herein provide the first clinical evidence of the association between serum Metrnl and VC in HD patients. Higher Metrnl levels, older age, diabetes mellitus, and higher serum CO and iPTH levels are independent determining factors for high AAC scores in HD patients.

Leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5) and its homologs (e.g., Lgr6) mark adult stem cells in multiple tissues. Recently, we and others have shown that Lgr5 marks adult taste stem/progenitor cells in posterior tongue. However, the regenerative potential of Lgr5-expressing (Lgr5 ⁺) cells and the identity of adult taste stem/progenitor cells that regenerate taste tissue in anterior tongue remain elusive. In the present work, we describe a culture system in which single isolated Lgr5 ⁺ or Lgr6 ⁺ cells from taste tissue can generate continuously expanding 3D structures (“organoids”). Many cells within these taste organoids were cycling and positive for proliferative cell markers, cytokeratin K5 and Sox2, and incorporated 5-bromo-2’-deoxyuridine. Importantly, mature taste receptor cells that express gustducin, carbonic anhydrase 4, taste receptor type 1 member 3, nucleoside triphosphate diphosphohydrolase-2, or cytokeratin K8 were present in the taste organoids. Using calcium imaging assays, we found that cells grown out from taste organoids derived from isolated Lgr5 ⁺ cells were functional and responded to tastants in a dose-dependent manner. Genetic lineage tracing showed that Lgr6 ⁺ cells gave rise to taste bud cells in taste papillae in both anterior and posterior tongue. RT-PCR data demonstrated that Lgr5 and Lgr6 may mark the same subset of taste stem/progenitor cells both anteriorly and posteriorly. Together, our data demonstrate that functional taste cells can be generated ex vivo from single Lgr5 ⁺ or Lgr6 ⁺ cells, validating the use of this model for the study of taste cell generation. Significance Taste tissue regenerates continuously throughout the life span in mammals. Here, using lineage tracing and a culture system, we show that leucine-rich repeat-containing G protein-coupled receptor 5-expressing and leucine-rich repeat-containing G protein-coupled receptor 6-expressing taste stem/progenitor cells generate mature taste cells in vivo and ex vivo. Importantly, our ex vivo studies show that single-progenitor cells can generate all mature taste cell types and that differentiated taste cells form in the absence of innervation. This ex vivo model mimics the development of taste bud cells in taste papillae, recapitulates the process of taste renewal from adult taste stem cells to mature taste cells, and provides a means to study the regulation of taste cell generation and to understand the origins and cell lineage relationships within taste buds.

Olfactory dysfunction (OD) is a common nasal disease, particularly prevalent among the elderly population, significantly impacting the affected individuals’ quality of life. This review focuses on the influence of aging and chronic inflammation on olfactory dysfunction, presenting insights from both the peripheral and central olfactory systems. By exploring the molecular mechanisms and pathological changes underlying the occurrence of olfactory dysfunction in relation to age-related diseases and chronic inflammation conditions, we aim to provide a comprehensive theoretical foundation for further research and offer valuable insights for more effective treatment of olfactory dysfunction.

Brain damage caused by acute hypoxia is associated with the physiological activities of mitochondria. Although mitochondria being dynamically regulated, our comprehensive understanding of the response of specific brain cell types to acute hypoxia remains ambiguous. Tumor necrosis factor receptor-associated protein 1 (TRAP1), a mitochondrial-based molecular chaperone, plays a role in controlling mitochondrial movements. Herein, we demonstrated that acute hypoxia significantly alters mitochondria morphology and functionality in both in vivo and in vitro brain injury experiments. Summary-data-based Mendelian Randomization (SMR) analyses revealed possible causative links between mitochondria-related genes and hypoxia injury. Advancing the protein-protein interaction network and molecular docking further elucidated the associations between TRAP1 and mitochondrial dynamics. Furthermore, it was shown that TRAP1 knockdown levels variably affected the expression of key mitochondrial dynamics proteins (DRP1, FIS1, and MFN1/2) in primary hippocampal neurons, astrocytes, and BV-2 cell, leading to changes in mitochondrial structure and function. Understanding the function of TRAP1 in altering mitochondrial physiological activity during hypoxia-induced acute brain injury could help serve as a potential therapeutic target to mitigate neurological damage.

TOPLESS/TOPLESS-RELATED (TPR) proteins are conserved transcriptional co-repressors vital for plant growth and development. However, the functions of soybean TPR ( GmTPR ) gene family members and their roles in photoperiod responses remain largely unexplored. In this study, we identified 12 TPR genes in the soybean genome, distributed across 11 chromosomes. Phylogenetic analysis classified GmTPRs into three subfamilies (Class I–III) by comparing them with Arabidopsis TPR proteins. Collinearity analysis revealed that 6 GmTPR genes are collinear with 3 AtTPR genes, resulting in 10 pairs of collinear genes, with no tandem duplications found. Analysis of physicochemical properties, motif composition, and gene structure indicated significant differences among GmTPR members. Subcellular localization confirmed that GmTPRs predominantly reside in the nucleus, suggesting regulatory functions. Additionally, analysis of cis-regulatory elements revealed significant enrichment of light-responsive elements in GmTPR promoters, indicating possible regulation by light. Tissue-specific expression analysis showed that GmTPR genes are mainly expressed in flowers and seeds. RNA-seq and RT-qPCR analyses revealed distinct expression patterns of GmTPRs between long and short photoperiods, highlighting their responsiveness to photoperiod changes. This study provides a comprehensive analysis of the GmTPR family, emphasizing their critical role in photoperiod responses.

The olfactory epithelium (OE) undergoes life-long renewal and regeneration. This process is supported by the globose basal cells (GBC) during the homeostatic state, as well as horizontal basal cells (HBC) during severe damage. Inflamm-aging refers to the low-grade, chronic and progressive state of heightened pro-inflammation associated with aging. However, the impact of inflamm-aging on OE homeostasis, regeneration, and the inflammatory microenvironment is not fully understood. In this study using mouse models, we elucidate the role of interleukin-17a (IL-17a) in OE regeneration and olfactory function. Our findings implicate that inflamm-aging in aged OE promotes the recruitment and activation of immune cells, accompanied by crosstalk between HBC and T cells. Elevated expression of IL-17a in aged OE triggers inflammatory signals and impairs olfactory function. Administration of IL-17a inhibitor Y-320 or neutralizing antibody promotes sensory neuronal regeneration and reverses age-related respiratory metaplasia in OE. Co-culturing mouse OE organoids with Th17 cells impairs neuronal generation and enhances the transformation towards respiratory cells, while neutralizing antibody against IL-17a alleviates neuronal loss and respiratory transformation. Additionally, conditional knockout of IL-17a in T cells facilitates OE regeneration by promoting HBC recruitment and differentiation into GBC. Collectively, our study identifies a function of IL-17a in OE regeneration and age-related deficits in olfactory function, providing evidence for further investigation of IL-17a as a possible therapeutic target against presbyosmia. The olfactory epithelium (OE) undergoes changes during aging and this may affect inflammatory responses and immune cell infiltration. Here the authors look at the effect of aging on OE and how this involves cross talk between T cells and horizontal basal cells involving Il17a expression in OE which is increased in aging and inhibition of IL-17a function reduces respiratory metaplasia.

Taste cells undergo constant turnover throughout life; however, the molecular mechanisms governing taste cell generation are not well understood. Using RNA-Seq, we systematically surveyed the transcriptome landscape of taste organoids at different stages of growth. Our data show the staged expression of a variety of genes and identify multiple signaling pathways underlying taste cell differentiation and taste stem/progenitor cell proliferation. For example, transcripts of taste receptors appear only or predominantly in late-stage organoids. Prior to that, transcription factors and other signaling elements are upregulated. RNA-Seq identified a number of well-characterized signaling pathways in taste organoid cultures, such as those involving Wnt, bone morphogenetic proteins (BMPs), Notch, and Hedgehog (Hh). By pharmacological manipulation, we demonstrate that Wnt, BMPs, Notch, and Hh signaling pathways are necessary for taste cell proliferation, differentiation and cell fate determination. The temporal expression profiles displayed by taste organoids may also lead to the identification of currently unknown transducer elements underlying sour, salt, and other taste qualities, given the staged expression of taste receptor genes and taste transduction elements in cultured organoids.

This study systematically measured gross hair weight and hair length traits across five body regions of 759 Tianzhu White Yak individuals. The BSL trait exhibited moderate heritability, while the BL trait demonstrated high heritability (h2 = 0.450). All other traits showed low heritability. GWASs were conducted using whole-genome resequencing data comprising 22,566,255 high-quality SNP loci. The MLM model identified 519 genome-wide significant loci and 767 chromosome-wide significant loci. Chromosome 6 harbored the highest number of significant SNP loci, while the remaining significant loci were distributed across multiple autosomes. Strong long-range linkage disequilibrium (r2 > 0.7) was observed between numerous significant SNPs on chromosome 6 associated with Gw and HL traits. A total of 73 candidate genes were annotated, including FGF5, CFAP299, and PRDM8. Functional enrichment analysis based on the GO and KEGG databases revealed significant enrichment in cytoplasm and the MAPK signaling pathway. Sanger sequencing results revealed that mutations in the FGF5, CFAP299, PRDM8, ANTXR2, and GPHB5 genes significantly affected the Gw, HL, and BSL traits of Tianzhu White Yak (p < 0.01). Linkage disequilibrium analysis indicated strong linkage disequilibrium (r2 > 0.6) among Sanger-sequenced SNP loci on the same chromosome. From a biological perspective, multiple candidate genes such as FGF5 and CFAP299 are involved in hair follicle cycle regulation, cell proliferation, and metabolic control, suggesting its potential role in hair follicle development and hair shaft growth. This study identifies candidate loci and genes for gross hair weight and hair length traits in Tianzhu White Yak, contributing to elucidating the genetic mechanisms underlying hair production performance.

( ) genes are crucial for regulating flowering time in plants. While the biological importance of the ( ) gene family has been recognized in , a systematic analysis of these genes in soybean is lacking. Characterizing genes in soybean will help uncover their roles in flowering regulation, offering valuable insights for improving soybean adaptation. In this study, we identified 16 genes in soybean, naming them based on their relationship to the genes in . These genes are unevenly distributed across thirteen chromosomes. Phylogenetic analysis categorizes Frigida-like proteins from , soybean, and rice into four distinct subfamilies (I-IV). Our findings indicate that eight GmFRLs arose from whole-genome duplication (WGD) events, alongside two tandem duplication events. Gene structure analysis confirmed that all GmFRL members contain Frigida domains. Additionally, promoter analysis revealed numerous cis-acting elements related to photoperiodic response, suggesting their significant role in soybean's light response mechanisms. RNA-seq data demonstrated variable expression levels of genes across tissues, including flower, leaf, pod, and seed, and other tissues, while subcellular localization and qPCR analyses further support their vital role in light responsiveness in soybean. In summary, our comprehensive analysis offers valuable insights into the evolution and potential functions of genes, emphasizing their significance in photoperiodic responses and establishing a foundation for further research on the GmFRL family.