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Idiopathic pulmonary fibrosis (IPF) is a long-term condition with an unidentified cause, and currently there are no specific treatment options available. Alveolar epithelial type II cells (AT2) constitute a heterogeneous population crucial for secreting and regenerative functions in the alveolus, essential for maintaining lung homeostasis. However, a comprehensive investigation into their cellular diversity, molecular features, and clinical implications is currently lacking. In this study, we conducted a comprehensive examination of single-cell RNA sequencing data from both normal and fibrotic lung tissues. We analyzed alterations in cellular composition between IPF and normal tissue and investigated differentially expressed genes across each cell population. This analysis revealed the presence of two distinct subpopulations of IPF-related alveolar epithelial type II cells (IR_AT2). Subsequently, three unique gene co-expression modules associated with the IR_AT2 subtype were identified through the use of hdWGCNA. Furthermore, we refined and identified IPF-related AT2-related gene (IARG) signatures using various machine learning algorithms. Our analysis demonstrated a significant association between high IARG scores in IPF patients and shorter survival times (p-value < 0.01). Additionally, we observed a negative correlation between the percent predicted diffusing capacity for lung carbon monoxide (% DLCO) and increased IARG scores (cor = −0.44, p-value < 0.05). The cross-validation findings demonstrated a high level of accuracy (AUC > 0.85, p-value < 0.01) in the prognostication of patients with IPF utilizing the identified IARG signatures. Our study has identified distinct molecular and biological features among AT2 subpopulations, specifically highlighting the unique characteristics of IPF-related AT2 cells. Importantly, our findings underscore the prognostic relevance of specific genes associated with IPF-related AT2 cells, offering valuable insights into the advancement of IPF.

Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown cause, and the involvement of fibroblasts in its pathogenesis is well recognized. However, a comprehensive understanding of fibroblasts’ heterogeneity, their molecular characteristics, and their clinical relevance in IPF is lacking. In this study, we aimed to systematically classify fibroblast populations, uncover the molecular and biological features of fibroblast subtypes in fibrotic lung tissue, and establish an IPF-associated, fibroblast-related predictive model for IPF. Herein, a meticulous analysis of scRNA-seq data obtained from lung tissues of both normal and IPF patients was conducted to identify fibroblast subpopulations in fibrotic lung tissues. In addition, hdWGCNA was utilized to identify co-expressed gene modules associated with IPF-related fibroblasts. Furthermore, we explored the prognostic utility of signature genes for these IPF-related fibroblast subtypes using a machine learning-based approach. Two predominant fibroblast subpopulations, termed IPF-related fibroblasts, were identified in fibrotic lung tissues. Additionally, we identified co-expressed gene modules that are closely associated with IPF-fibroblasts by utilizing hdWGCNA. We identified gene signatures that hold promise as prognostic markers in IPF. Moreover, we constructed a predictive model specifically focused on IPF-fibroblasts which can be utilized to assess disease prognosis in IPF patients. These findings have the potential to improve disease prediction and facilitate targeted interventions for patients with IPF.

The Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9 (CRISPR/Cas9) system, an RNA-based adaptive immune system found in bacteria and archaea, has catalyzed the development and application of a new generation of gene editing tools. Numerous studies have shown that this system can precisely target a wide range of human genes, including those associated with diseases such as cancer. In cancer research, the intricate genetic mutations in tumors have promoted extensive utilization of the CRISPR/Cas9 system due to its efficient and accurate gene editing capabilities. This includes improvements in Chimeric Antigen Receptor (CAR)-T-cell therapy, the establishment of tumor models, and gene and drug target screening. Such progress has propelled the investigation of cancer molecular mechanisms and the advancement of precision medicine. However, the therapeutic potential of genome editing remains underexplored, and lingering challenges could elevate the risk of additional genetic mutations. Here, we elucidate the fundamental principles of CRISPR/Cas9 gene editing and its practical applications in tumor research. We also briefly discuss the primary challenges faced by CRISPR technology and existing solutions, intending to enhance the efficacy of this gene editing therapy and shed light on the underlying mechanisms of tumors.

The Malus crabapple is an important woody ornamental plant. The fading of petals during its development significantly affects their ornamental value. Petal color is related to anthocyanin content and miRNAs play an important role in the post-transcriptional regulation of anthocyanin synthesis. However, the mechanisms underlying miRNA regulation of petal fading have rarely been studied. Transcriptome and small RNA sequencing of petals from the blooming phases of Malus. ‘Indian Summer’ varieties S1 (small bud), S2 (initial-flowering), and S3 (late-flowering) allowed us to identify 230 known miRNAs and 17 novel miRNAs, including 52 differentially expressed miRNAs which targeted 494 genes and formed 823 miRNA–target pairs. Based on the target gene annotation results, miRNA–target pairs were screened that may be involved in the fading process of Malus crabapple petals through three different pathways: anthocyanin synthesis, transport, and degradation, involving mcr-miR858-MYB1\MYB5 and mcr-miR396-McCHI inhibiting anthocyanin synthesis; mcr-miR167, mcr-miR390, mcr-miR535, and mcr-miR858 inhibiting anthocyanin transport from the cytoplasm to the vacuole by targeting ABC transporter genes (ABCB, ABCC, ABCD, and ABCG); and mcr-miR398 targeting the superoxide dismutase genes (CZSOD2 and CCS) to accelerate anthocyanin degradation. These findings offer a novel approach to understanding the mechanism of petal fading and serve as a reference for other plants with floral fading.

Lateral organ boundaries domain (LBD) proteins are plant-specific transcription factors involved in various transcriptional regulation processes. We identified a total of 37 GbLBD genes in ginkgo, and based on gene structure and phylogenetic analysis, the GbLBD gene family was classified into class I (33, with the largest number of Id genes (16)) and class II (4). The ginkgo LBD gene was also analyzed regarding its chromosomal distributions, gene duplications, promoters, and introns/exons. In addition, gene expression profiling and real-time quantitative PCR analysis showed that the expression of 14 GbLBD genes differed in six different tissues and three developmental stages. The GbLBD gene of class II were highly expressed relative to the class I gene in all tissues and developmental stages, while class Id gene were generally at low levels or were not expressed, especially in seed developmental stages. The expression pattern analysis of cold/drought treatment and IAA/ABA hormone treatment showed that abiotic stress treatment could significantly induce the expression of GbLBD gene, of which class II genes played a key role in stress treatment. Our study provides a solid foundation for further evolutionary and functional analysis of the ginkgo LBD gene family.

The gibberellic acid-stimulated Arabidopsis (GASA) gene family plays an important regulatory role in the growth and development of plants. In this study, we identified 19 GASA genes using bioinformatics-based methods in Populus trichocarpa, and these PtGASA genes could be divided into three categories based on their phylogenetic relationships. Based on an analysis of the structure and motifs of these genes, it was concluded that PtGASA class II members are more conserved than class I and class III members are, and the results of collinearity analysis showed that members of class II are collinearly related in poplar. Expression analysis of Populus trichocarpa roots, stems, and leaves showed that most of the PtGASA genes are expressed at higher levels in the stems or roots than in the leaves; a similar expression pattern was found in Vitis vinifera, indicating that the GASA-family members mainly play a role in the morphogenesis of poplar. Considering the phenomenon of gene amplification, we found that the higher the similarity of homologous genes was, the more similar the expression patterns. This study represents the first whole-genome identification and expression-profile analysis of the GASA-gene family in poplar, a model species, laying a foundation for functional studies of poplar GASA genes and serving as a reference for related research on other woody plant species.

Although grape-seed proanthocyanidin extract (GSPE) demonstrates strong anti-oxidant activity, little research has been done to clearly reveal the protective effects on the hepatotoxicity caused by zearalenone (ZEN). This study is to explore the protective effect of GSPE on ZEN-induced oxidative damage of liver in Kunming mice and the possible protective molecular mechanism of GSPE. The results indicated that GSPE could greatly reduce the ZEN-induced increase of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities. GSPE also significantly decreased the content of MDA but enhanced the activities of antioxidant enzymes SOD and GSH-Px. The analysis indicated that ZEN decreased both mRNA expression levels and protein expression levels of nuclear erythroid2-related factor2 (Nrf2). Nrf2 is considered to be an essential antioxidative transcription factor, as downstream GSH-Px, -glutamyl cysteine synthetase (-GCS), hemeoxygenase-1 (HO-1), and quinone oxidoreductase 1 (NQO1) decreased simultaneously, whereas the pre-administration of GSPE groups was shown to elevate these expressions. The results indicated that GSPE exerted a protective effect on ZEN-induced hepatic injury and the mechanism might be related to the activation of the Nrf2/ARE signaling pathway. [ABSTRACT FROM AUTHOR]

The aim was to investigate the prevention of grape seed proanthocyanidin extract (GSPE) on the subchronic immune injury induced by aflatoxin B1 (AFB1) and the possible ameliorating effect of GSPE in mice. The subchronic AFB1-induced immune injury mice model was set up with the continuous administration of 100 μg/kg body weight (BW) AFB1 for six weeks by intragastric administration. Then, intervention with different doses (50 and 100 mg/kg BW) of GSPE was conducted on mice to analyze the changes of body weight, immune organ index, antioxidant capability of spleen, serum immunoglobulin content, and the expression levels of inflammatory cytokines. The prevention of GSPE on the immune injury induced by AFB1 was studied. The GSPE could relieve the AFB1-induced reduction of body weight gain and the atrophy of the immune organ. The malondialdehyde (MDA) level of the spleen in the AFB1 model group significantly increased, but levels of catalase (CAT), glutathione (GSH), glutathione peroxidase (GSH-PX), and superoxide dismutase (SOD) significantly decreased. The GSPE could significantly inhibit the oxidative stress injury of the spleen induced by AFB1. AFB1 exposure could not significantly change the contents of IgA, IgG, or IgM. AFB1 significantly improved the expression of interleukin 1β (IL-1β), IL-6, tumor necrosis factor α (TNF-α), and interferon (IFN-). Additionally, GSPE could decrease the expression of these four proinflammatory factors to different degrees and inhibit the inflammatory reaction of mice. The results suggest that GSPE alleviates AFB1-induced oxidative stress and significantly improves the immune injury of mice induced by AFB1. [ABSTRACT FROM AUTHOR]