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Cancer stem cells (CSCs) have the potential to self-renew and induce cancer, which may contribute to a poor prognosis by enabling metastasis, recurrence, and therapy resistance. Hence, this study was performed to identify the association between CSC-related genes and triple-negative breast cancer (TNBC) development. Stemness gene sets were downloaded from StemChecker. Based on the online databases, a consensus clustering algorithm was conducted for unsupervised classification of TNBC samples. The variations between subtypes were assessed with regard to prognosis, tumor immune microenvironment (TIME), and chemotherapeutic sensitivity. The stemness-related gene signature was established and random survival forest analysis was employed to identify the core gene for validation experiments and tumor sphere formation assays. 499 patients with TNBC were classified into three subgroups and the Cluster 1 had a better OS than others. After that, WGCNA study was performed to identify genes important for Cluster 1 subtype. Out of all 8 modules, the subtype of Cluster 1 and the yellow module with 103 genes demonstrated the largest positive association. After that, a four-gene stemness-related signature was established. Based on the yellow module, the 39 potential pivotal genes were subjected to the random forest survival analysis to find out the gene that was relatively important for OS. KIF15 was confirmed as the targeted gene by LASSO and random survival forest analyses. In vitro experiments, the downregulation of KIF15 promoted the stemness of TNBC cells. The expression levels of stem cell markers Nanog, SOX2, and OCT4 were found to be elevated in TNBC cell lines after KIF15 inhibition. A stemness-associated risk model was constructed to forecast the clinical outcomes of TNBC patients. The downregulation of KIF15 expression in a subpopulation of TNBC stem cells may promote stemness and possibly TNBC progression., (© 2024. The Author(s).)

Low back pain (LBP) is largely attributed to intervertebral disc degeneration (IVDD), of which the endplate changes are an important component. However, the alterations in cell fate and properties within the endplates during degeneration remain unknown. Here, we firstly performed the single-cell RNA-sequencing analysis (scRNA-seq) of the cells focusing on degenerative human endplates. By unsupervised clustering of the 8,534 single-cell based on the gene expression, we identified nine distinct cell types. We employed Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis, and the single-cell regulatory network inference and clustering (SCENIC) to determine the enriched pathways and transcriptional activities across seven chondrocyte subpopulations. Furthermore, two cell fates of chondrocyte differentiation were found by trajectory analysis, one was enriched in inflammation-related genes, and the other was related to extracellular matrix (ECM). Additionally, the intercellular interactions of macrophages (MA) and chondrocytes, T cells/natural killer cells (T/NK) and chondrocytes were examined by ligand-receptor pairs analysis, showing the important regulative function of FN1 from MA and CD74 from T/NK during endplate degeneration. Overall, our findings provide novel perspectives on the endplate degeneration at the single-cell level and a whole-transcriptome size., (© 2024. The Author(s).)

A significant consequence of climate change is the rising incidence of wildfires. When wildfires occur close to wine grape (Vitis vinifera) production areas, smoke-derived volatile phenolic compounds can be taken up by the grape berries, negatively affecting the flavor and aroma profile of the resulting wine and compromising the production value of entire vineyards. Evidence for the permeation of smoke-associated compounds into grape berries has been provided through metabolomics; however, the basis for grapevines' response to smoke at the gene expression level has not been investigated in detail. To address this knowledge gap, we employed time-course RNA sequencing to observe gene expression-level changes in grape berries in response to smoke exposure. Significant increases in gene expression (and enrichment of gene ontologies) associated with detoxification of reactive compounds, maintenance of redox homeostasis, and cell wall fortification were observed in response to smoke. These findings suggest that the accumulation of volatile phenols from smoke exposure activates mechanisms that render smoke-derived compounds less reactive while simultaneously fortifying intracellular defense mechanisms. The results of this work lend a better understanding of the molecular basis for grapevines' response to smoke and provide insight into the origins of smoke-taint-associated flavor and aroma attributes in wine produced from smoke-exposed grapes., (© 2024. The Author(s).)

It is estimated that there are 544.9 million people suffering from chronic respiratory diseases in the world, which is the third largest chronic disease. Although there are various clinical treatment methods, there is no specific drug for chronic pulmonary diseases, including chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD) and idiopathic pulmonary fibrosis (IPF). Therefore, it is urgent to clarify the pathological mechanism and medication development. Single-cell transcriptome data of human and mouse from GEO database were integrated by "Harmony" algorithm. The data was standardized and normalized by using "Seurat" package, and "SingleR" algorithm was used for cell grouping annotation. The "Findmarker" function is used to find differentially expressed genes (DEGs), which were enriched and analyzed by using "clusterProfiler", and a protein interaction network was constructed for DEGs, and four algorithms are used to find the hub genes. The expression of hub genes were analyzed in independent human and mouse single-cell transcriptome data. Bulk RNA data were used to integrate by the "SVA" function, verify the expression levels of hub genes and build a diagnostic model. The L1000FWD platform was used to screen potential drugs. Through exploring the similarities and differences by integrated single-cell atlas, we found that the lung parenchymal cells showed abnormal oxidative stress, cell matrix adhesion and ubiquitination in COPD, corona virus disease 2019 (COVID-19), ILD and IPF. Meanwhile, the lung resident immune cells showed abnormal Toll-like receptor signals, interferon signals and ubiquitination. However, unlike acute pneumonia (COVID-19), chronic pulmonary disease shows enhanced ubiquitination. This phenomenon was confirmed in independent external human single-cell atlas, but unfortunately, it was not confirmed in mouse single-cell atlas of bleomycin-induced pulmonary fibrosis model and influenza virus-infected mouse model, which means that the model needs to be optimized. In addition, the bulk RNA-Seq data of COVID-19, ILD and IPF was integrated, and we found that the immune infiltration of lung tissue was enhanced, consistent with the single-cell level, UBA52, UBB and UBC were low expressed in COVID-19 and high expressed in ILD, and had a strong correlation with the expression of cell matrix adhesion genes. UBA52 and UBB have good diagnostic efficacy, and salermide and SSR-69071 can be used as their candidate drugs. Our study found that the disorder of protein ubiquitination in chronic pulmonary diseases is an important cause of pathological phenotype of pulmonary fibrosis by integrating scRNA-Seq and bulk RNA-Seq, which provides a new horizons for clinicopathology, diagnosis and treatment., (© 2024. The Author(s).)

Scenedesmus sp. is a species of the Scenedesmus genus within the phylum Chlorophyta, commonly found as a planktonic algal species in freshwater and known for its rapid growth rate. This study employs room-temperature, atmospheric-pressure plasma mutagenesis for the breeding of Scenedesmus sp., utilizing transcriptomic analysis to investigate the biosynthesis mechanism of triglycerides. Further analysis of differentially expressed genes in transcriptome by measuring the macroscopic biological indicators of mutant and original algal strains. The findings of the study suggest that the mutant strain's photosynthesis has been enhanced, leading to improved light energy utilization and CO 2 fixation, thereby providing more carbon storage and energy for biomass and lipid production. The intensification of glycolysis and the TCA (tricarboxylic acid) cycle results in a greater shift in carbon flux towards lipid accumulation. An elevated expression level of related enzymes in starch and protein degradation pathways may enhance acetyl CoA accumulation, facilitating a larger substrate supply for fatty acid production and thereby increasing lipid yield., (© 2024. The Author(s).)

Non-alcoholic Fatty Liver Disease (NAFLD), noted for its widespread prevalence among adults, has become the leading chronic liver condition globally. Simultaneously, the annual disease burden, particularly liver cirrhosis caused by NAFLD, has increased significantly. Neutrophil Extracellular Traps (NETs) play a crucial role in the progression of this disease and are key to the pathogenesis of NAFLD. However, research into the specific roles of NETs-related genes in NAFLD is still a field requiring thorough investigation. Utilizing techniques like AddModuleScore, ssGSEA, and WGCNA, our team conducted gene screening to identify the genes linked to NETs in both single-cell and bulk transcriptomics. Using algorithms including Random Forest, Support Vector Machine, Least Absolute Shrinkage, and Selection Operator, we identified ZFP36L2 and PHLDA1 as key hub genes. The pivotal role of these genes in NAFLD diagnosis was confirmed using the training dataset GSE164760. This study identified 116 genes linked to NETs across single-cell and bulk transcriptomic analyses. These genes demonstrated enrichment in immune and metabolic pathways. Additionally, two NETs-related hub genes, PHLDA1 and ZFP36L2, were selected through machine learning for integration into a prognostic model. These hub genes play roles in inflammatory and metabolic processes. scRNA-seq results showed variations in cellular communication among cells with different expression patterns of these key genes. In conclusion, this study explored the molecular characteristics of NETs-associated genes in NAFLD. It identified two potential biomarkers and analyzed their roles in the hepatic microenvironment. These discoveries could aid in NAFLD diagnosis and management, with the ultimate goal of enhancing patient outcomes., (© 2024. The Author(s).)

Siberian wildrye (Elymus sibiricus) is a xero-mesophytic forage grass with high nutritional quality and stress tolerance. Among its numerous germplasm resources, some possess superior drought resistance. In this study, we firstly investigated the physiological differences between the leaves of drought-tolerant (DT) and drought-sensitive (DS) genotypes under different field water contents (FWC) in soil culture. The results showed that, under drought stress, DT maintained a lower leaf water potential for water absorption, sustained higher photosynthetic efficiency, and reduced oxidative damage in leaves by efficiently maintaining the ascorbic acid-glutathione (ASA-GSH) cycle to scavenge reactive oxygen species (ROS) compared to DS. Secondly, using RNA sequencing (RNA-seq), we analyzed the gene expression profiles of DT and DS leaves under osmotic stress of hydroponics induced by PEG-6000. Through differential analysis, we identified 1226 candidate unigenes, from which we subsequently screened out 115/212 differentially expressed genes (DEGs) that were more quickly induced/reduced in DT than in DS under osmotic stress. Among them, Unigene0005863 (EsSnRK2), Unigene0053902 (EsLRK10) and Unigene0031985 (EsCIPK5) may be involved in stomatal closure induced by abscisic acid (ABA) signaling pathway. Unigene0047636 (EsCER1) may positively regulates the synthesis of very-long-chain (VLC) alkanes in cuticular wax biosynthesis, influencing plant responses to abiotic stresses. Finally, the contents of wax and cutin were measured by GC-MS under osmotic stress of hydroponics induced by PEG-6000. Corresponding to RNA-seq, contents of wax monomers, especially alkanes and alcohols, showed significant induction by osmotic stress in DT but not in DS. It is suggested that limiting stomatal and cuticle transpiration under drought stress to maintain higher photosynthetic efficiency and water use efficiency (WUE) is one of the critical mechanisms that confer stronger drought resistance to DT. This study provides some insights into the molecular mechanisms underlying drought tolerance in E. sibiricus. The identified genes may provide a foundation for the selection and breeding of drought-tolerant crops., (© 2024. The Author(s).)

Multiple investigations have demonstrated the crucial involvement of T-cell exhaustion (TEX) in anti-tumor immune response and their strong correlation with prognosis. This study aimed at creating a strong signature using TEX for gastric cancer through bioinformatics analysis and experimental validation. We utilized data from The Cancer Genome Atlas (TCGA) databases to retrieve RNA-seq data from patients with stomach adenocarcinoma (STAD). Genes related to TEX were discovered using gene set variance analysis (GSVA) and weighted gene correlation network analysis (WGCNA). Subsequently, prognostic signature based on TEX was developed using LASSO-Cox analysis. Relationship between key genes and immune cells were examined. Finally, biological function of a key TEX-related gene PTPRT in gastric cancer was verified by in vivo experiment. A total of 29 TEX-related biomarkers were screened by WGCNA and random forest. Among them, five core signatures (PTPRT, CAV2, PPIH, PRDM2, and FGF1), further identified by LASSO-Cox, were considered as strong predictors of prognosis for gastric cancer and associated with immune infiltration. PTPRT gene had the largest number of SNPs, with the most mutation types. In vivo experiments revealed that PTPRT overexpression significantly inhibited tumor malignant progression and accelerated apoptosis through stimulating the secretion of killer cytokines such as TNF-α and IFN-γ. In addition, flow cytometry revealed that PTPRT overexpression alleviated TEX by increasing the abundance of CD8+ T cells, with inhibition of cell surface PD-1 and Tim-3. The predictive prognostic value of TEX gene expression levels was evaluated in patients with gastric cancer, providing a new perspective for precision immuno-oncology studies., (© 2024. The Author(s).)

Lung adenocarcinoma (LUAD) is the dominant histotype of non-small cell lung cancer. Panoptosis, a comprehensive form of programmed cell death, is central to carcinogenesis. In this study, the expression of PANoptosis-related genes (PRGs) and their impact on the development, prognosis, tumor microenvironment, and treatment response of patients with lung adenocarcinoma (LUAD) were systematically evaluated. PRGs were selected from The Cancer Genome Atlas database and Genecards dataset using differential expression analysis. The signature of included PRGs was identified using univariate Cox regression analysis and LASSO regression analysis. Additionally, a nomogram was developed that includes signature and clinical information. Kaplan-Meier survival analysis and receiver operating characteristic curves were used to assess the predictive validity of these risk models. Finally, functional analysis of the selected PRGs in signature and analysis of immune landscape were also performed. Preliminary identification of 10 genes related to PANoptosis has significant implications for prognosis. Subsequently, seven related genes were integrated to classify LUAD patients into different survival risk groups. The prognostic risk score generated from the signature and the TNM stage were as independent prognostic factors and were utilized in creating a nomogram plot. Both the features and the nomogram plot showed accurate performance in predicting the overall survival of LUAD patients. The PRGs were enriched in several biological functions and pathways, and stratified studies were conducted on the differences in immune landscape between high-risk and low-risk groups based on their characteristics. Ultimately, our evaluation focused on the differences in drug treatment efficacy between the high-risk and low-risk groups, providing a foundation for future research directions. Potential associations between PRGs and patient prognosis in LUAD have been identified in this study. Potential biomarkers for clinical application could be considered for the prognostic predictors identified in this study., (© 2024. The Author(s).)

Liver cancer is the fourth leading cause of cancer-related deaths with a steadily increasing rate worldwide, as a well-known hallmark of liver cancer, metabolic alterations are related to liposomal changes, a common characteristic of primary liver cancers based on recent lipidomics studies. Peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated transcription factor with important lipid homeostasis function, therefore we aimed to understand the molecular mechanisms and pathways that activate PPARα after using PPAR-α agonist WY-14643 and identify candidate biomarkers related to PPARα activity and evaluate their effects in liver cancer. The data from differently expressed genes (DEGs) between liver cancer tissue from obese subjects alone and liver tissue after treatment were evaluated by DESeq2 and module genes were analyzed using weighted gene co-expression network analysis (WGCNA). Final candidate genes were identified by intersecting genes among highly ranked DEGs and the brown module, which demonstrated a significant negative correlation with drug treatments. We conducted a protein-protein interaction network, and KEGG enrichment analysis, and core hub genes (CD40, CXCL9, CXCL10, TNFSF14, GBP2, GBP3, APOL3, CLDN1) were identified using the cyto-hubba plugin, among them we focused on GBP2 that plays key roles in oncogenesis and evaluate its expressional with clinical outcomes. In conclusion, the WGCNA-based co-expression network identified GBP2 as one of the hub genes with a negative relation with PPARα agonist treatments. higher expression of GBP2 was closely associated with HCC progression. Therefore, GBP2 might be a potential candidate for the study of PPARα activity in HCC., (© 2024. The Author(s).)

Abnormal expression of circRNAs has been observed in different types of carcinomas, and they play significant roles in the biology of these cancers. Nevertheless, the clinical relevance and functional mechanisms of the majority of circRNAs implicated in breast cancer progression remain unclear. The primary objective of our investigation is to uncover new circRNAs in breast cancer and elucidate the underlying mechanisms by which they exert their effects. The circRNA expression profile data for breast cancer and RNA-sequencing data were acquired from distinct public databases. Differentially expressed circRNAs and mRNA were identified through fold change filtering. The establishment of the competing endogenous RNAs (ceRNAs) network relied on the interplay between circular RNAs, miRNAs, and mRNAs. The hub genes were identified from the protein-protein interaction (PPI) regulatory network using the CytoHubba plugin in Cytoscape. Moreover, the expression levels and prognostic value of these hub genes in the PPI network were assessed using the GEPIA and Kaplan-Meier plotter databases. Fluorescence in situ hybridization (FISH) was used to identified the expression and intracellular localization of hsa_circ_0059665 by using the tissue microarray. Transwell analysis and CCK-8 analysis were performed to assess the invasion, migration, and proliferation abilities of breast cancer cells. Additionally, we investigated the interactions between hsa_circ_0059665 and miR-602 through various methods, including FISH, RNA-binding protein immunoprecipitation (RIP), and luciferase reporter assay. Rescue experiments were conducted to determine the potential regulatory role of hsa_circ_0059665 in breast cancer progression. A total of 252 differentially expressed circRNAs were identified. Among them, 246 circRNAs were up-regulated, while 6 circRNAs were down-regulated. Based on prediction and screening of circRNA-miRNA and miRNA-mRNA binding sites, we constructed a network consisting of circRNA-miRNA-mRNA interactions. In addition, we constructed a Protein-Protein Interaction (PPI) network and identified six hub genes. Moreover, the expression levels of these six hub genes in breast cancer tissues were found to be significantly lower. Furthermore, the survival analysis results revealed a significant correlation between low expression levels of KIT, FGF2, NTRK2, CAV1, LEP and poorer prognosis in breast cancer patients. The FISH experiment results indicated that hsa_circ_0059665 exhibits significant downregulation in breast cancer, and its decreased expression is linked to poor prognosis in breast cancer patients. Functional in vitro experiments revealed that overexpression of hsa_circ_0059665 can inhibit proliferation, migration and invasion abilities of breast cancer cells. Further molecular mechanism studies showed that hsa_circ_0059665 exerts its anticancer gene role by acting as a molecular sponge for miR-602. In our study, we constructed and analyzed a circRNA-related ceRNA regulatory network and found that hsa_circ_0059665 can act as a sponge for miR-602 and inhibit the proliferation, invasion and migration of breast cancer cells., (© 2024. The Author(s).)

DEFENSE NO DEATH 1 (DND1) is a cyclic nucleotide-gated ion channel protein. Earlier, it was shown that the silencing of DND1 in the potato (Solanum tuberosum L.) leads to resistance to late blight, powdery mildew, and gray mold diseases. At the same time, however, it can reduce plant growth and cause leaf necrosis. To obtain knowledge of the molecular events behind the pleiotropic effect of DND1 downregulation in the potato, metabolite and transcriptome analyses were performed on three DND1 silenced lines of the cultivar 'Désirée.' A massive increase in the salicylic acid content of leaves was detected. Concentrations of jasmonic acid and chlorogenic acid and their derivatives were also elevated. Expression of 1866 genes was altered in the same way in all three DND1 silenced lines, including those related to the synthesis of secondary metabolites. The activation of several alleles of leaf rust, late blight, and other disease resistance genes, as well as the induction of pathogenesis-related genes, was detected. WRKY and NAC transcription factor families were upregulated, whereas bHLHs were downregulated, indicating their central role in transcriptome changes. These results suggest that the maintenance of the constitutive defense state leads to the reduced growth of DND1 silenced potato plants., (© 2024. The Author(s).)

Oxidative stress plays a pivotal role in the pathogenesis of diabetic erectile dysfunction, while specific mechanisms have not been illuminated. The study aims to reveal the genetic expression patterns of oxidative stress in diabetic erectile dysfunction. Transcriptome data of diabetic erectile dysfunction and oxidative stress-related genes (OSRGs) in the Gene Expression Omnibus database were downloaded and analyzed based on differential expression. Functional enrichment analyses were conducted to clarify the biological functions. A protein interaction framework was established, and significant gene profiles were validated in the cavernous endothelial cells, clinical patients, and rat models. A miRNA-OSRGs network was predicted and validated. The results were analyzed using Student's t-test. The analysis screened 203 differentially expressed OSRGs (p < 0.05), which had a close association with oxidoreductase activities, glutathione metabolism, and autophagy. A four-gene signature comprised of EPS8L2 (p = 0.044), GSTA3 (p = 0.015), LOX (p < 0.001) and MGST1 (p = 0.002) was well validated and regarded as the hub OSRGs. Compared with the control group, notable increases and decreases were observed in the expressions of GSTA3 (3.683 ± 0.636 vs. 0.416 ± 0.507) and LOX (2.104 ± 1.895 vs. 18.804 ± 2.751) in the validated diabetic erectile dysfunction group. The hub OSRGs-related miRNAs participated in smooth muscle cell proliferation. Besides, miR-125a-3p (p = 0.034) and miR-138-2-3p (p = 0.012) were validated as promising oxidative stress-related miRNA biomarkers. Our findings revealed the genetic alternations of oxidative stress in diabetic erectile dysfunction. These results will be instructive to explore the molecular landscape and the potential treatment for diabetic erectile dysfunction., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Colorectal cancer is caused by a sequence of somatic genomic alterations affecting driver genes in core cancer pathways 1 . Here, to understand the functional and prognostic impact of cancer-causing somatic mutations, we analysed the whole genomes and transcriptomes of 1,063 primary colorectal cancers in a population-based cohort with long-term follow-up. From the 96 mutated driver genes, 9 were not previously implicated in colorectal cancer and 24 had not been linked to any cancer. Two distinct patterns of pathway co-mutations were observed, timing analyses identified nine early and three late driver gene mutations, and several signatures of colorectal-cancer-specific mutational processes were identified. Mutations in WNT, EGFR and TGFβ pathway genes, the mitochondrial CYB gene and 3 regulatory elements along with 21 copy-number variations and the COSMIC SBS44 signature correlated with survival. Gene expression classification yielded five prognostic subtypes with distinct molecular features, in part explained by underlying genomic alterations. Microsatellite-instable tumours divided into two classes with different levels of hypoxia and infiltration of immune and stromal cells. To our knowledge, this study constitutes the largest integrated genome and transcriptome analysis of colorectal cancer, and interlinks mutations, gene expression and patient outcomes. The identification of prognostic mutations and expression subtypes can guide future efforts to individualize colorectal cancer therapy., (© 2024. The Author(s).)

Preeclampsia (PE) is a heterogeneous disease that seriously affects the health of mothers and fetuses. Lack of detection assays, its diagnosis and intervention are often delayed when the clinical symptoms are atypical. Using personalized pathway-based analysis and machine learning algorithms, we built a PE diagnosis model consisting of nine core pathways using multiple cohorts from the Gene Expression Omnibus database. The model showed an area under the receiver operating characteristic (AUROC) curve of 0.959 with the data from the placental tissue samples in the development cohort. In the two validation cohorts, the AUROCs were 0.898 and 0.876, respectively. The model also performed well with the maternal plasma data in another validation cohort (AUROC: 0.815). Moreover, we identified tyrosine-protein kinase Lck (LCK) as the hub gene in this model and found that LCK and pLCK proteins were downregulated in placentas from PE patients. The pathway-level model for PE can provide a novel direction to develop molecular diagnostic assay and investigate potential mechanisms of PE in future studies., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

The development of intracerebral hemorrhage (ICH) is a dynamic process and intervention during the acute phase of ICH is critical for subsequent recovery. Therefore, it is crucial to screen potential signature genes and therapeutic target genes in the acute phase of ICH. In this study, based on the results of mRNA sequencing in mouse ICH and mRNA sequencing of human ICH from online databases, top five potential signature genes after ICH, Tyrobp, Itgb2, Tlr2, Ptprc and Itgam, were screened. Quantitative PCR results showed higher mRNA expression of Tyrobp, Itgb2, Tlr2, Ptprc, and Itgam in the 1-, 3- and 5-day mouse ICH groups compared to the sham-operated group. Immune infiltration correlation analysis shows that the top-ranked signature gene, Tyrobp, is negatively correlated with M2 macrophages and plasma cells, and Western blot analysis shows higher expression of the Tyrobp protein in the 1-, 3-, and 5-day mouse ICH groups compared to the sham-operated group. Furthermore, immunohistochemistry revealed that TYROBP protein expression was significantly higher in human ICH tissues than in normal brain tissues. Our results suggest that Tyrobp is a signature gene in the acute phase of ICH and may be a potential target for the treatment of the acute phase of ICH., (© 2024. The Author(s).)

Systemic lupus erythematosus (SLE) is a multifactorial disease characterized by the convergence of genetic, immunological, and viral elements resulting in a complex interaction of both internal and external factors. The role of the Epstein-Barr virus (EBV) and human endogenous retroviruses (HERV-E) as triggers and maintenance elements in the pathogenesis of SLE has been widely recognized. Previous studies have independently evaluated the effects of EBV and HERV-E in this disease. In this work, for the first time, these viral factors are jointly investigated in SLE patients. This study aimed at assessing the differential expression of immune regulatory genes and the incidence of specific viral pathogens (EBV and HERV-E), alongside the detailed characterization of surface markers in T- and B-lymphocytes in patients with SLE and control participants. A comparative analysis between patients with SLE and control participants was performed, evaluating the expression of phenotypic markers and genes involved in the immune response (TNF-α, IL-2, IL-6, IL-10, IFNG, TLR3), as well as HERV-E gag and EBV viral genes (LMP1 and BZLF1).A significant association between SLE and EBV was found in this study. A notable increase in EBV LMP1 gene expression was observed in patients with SLE . Also, a significant overexpression of HERV-E was observed, in addition to a considerable increase in the distribution of the cell surface marker CD27 + on T- and B-lymphocytes, observed in individuals with SLE compared to the control group. This study provides evidence regarding the role that EBV virus plays in lymphocytes in the context of SLE, highlighting how both the virus and the host gene expression may influence disease pathogenesis by altering immune regulatory pathways mediated by TNF-α, IFN-γ, and IL-10, as well as parallel overexpression of HERV-E gag. The decrease in TLR3 could indicate a compromised antiviral response, which could facilitate viral reactivation and contribute to disease activity., (© 2024. The Author(s).)

To evaluate the prognostic significance of the maximum standardized uptake value (SUVmax) in nasopharyngeal carcinoma (NPC), establish a gene signature that correlates with SUVmax, and explore the underlying biological behaviors associated with these correlations for the prediction of clinical outcomes. A cohort of 726 patients with NPC was examined to identify correlations between SUVmax and various clinical variables. RNA sequencing was performed to identify genes related to SUVmax, and these genes were used to develop an SUV signature. Additionally, transcriptome enrichment analysis was conducted to investigate the potential biological behaviors underlying the observed correlations. Higher SUVmax was associated with an increased tumor burden and worse prognosis. The SUV signature, which consisted of 10 genes, was positively correlated with SUVmax, and it predicted worse survival outcomes. This signature was highly expressed in malignant epithelial cells and associated with hypoxia and resistance to radiotherapy. Additionally, the signature was negatively correlated with immune function. SUVmax is a valuable prognostic indicator in NPC, with higher values predicting worse outcomes. The SUV signature offers further prognostic insights, linking glucose metabolism to tumor aggressiveness, treatment resistance, and immune function, and it could represent a potential biomarker for NPC., (© 2024. The Author(s).)

The limited understanding of the molecular mechanism underlying MYCN-amplified (MNA) neuroblastoma (NB) has hindered the identification of effective therapeutic targets for MNA NB, contributing to its higher mortality rate compared to MYCN non-amplified (non-MNA) NB. Therefore, a comprehensive analysis integrating metabolomics and transcriptomics was conducted to systematically investigate the MNA NB. Metabolomics analysis utilized plasma samples from 28 MNA NB patients and 68 non-MNA NB patients, while transcriptomics analysis employed tissue samples from 15 MNA NB patients and 37 non-MNA NB patients. Notably, joint metabolomics and transcriptomics analysis was performed. A total of 46 metabolites exhibited alterations, with 21 displaying elevated levels and 25 demonstrating reduced levels in MNA NB. In addition, 884 mRNAs in MNA NB showed significant changes, among which 766 mRNAs were higher and 118 mRNAs were lower. Joint-pathway analysis revealed three aberrant pathways involving glycerolipid metabolism, purine metabolism, and lysine degradation. This study highlights the substantial differences in metabolomics and transcriptomics between MNA NB and non-MNA NB, identifying three abnormal metabolic pathways that may serve as potential targets for understanding the molecular mechanisms underlying MNA NB., (© 2024. The Author(s).)

Alzheimer's disease is the predominant form of dementia, and disulfidptosis is the latest reported mode of cell death that impacts various disease processes. This study used bioinformatics to analyze genes associated with disulfidptosis in Alzheimer's disease comprehensively. Based on the public datasets, the differentially expressed genes associated with disulfidptosis were identified, and immune cell infiltration was investigated through correlation analysis. Subsequently, hub genes were determined by a randomforest model. A prediction model was constructed using logistic regression. In addition, the drug-target affinity was predicted by a graph neural network model, and the results were validated by molecular docking. Five hub genes (PPEF1, NEUROD6, VIP, NUPR1, and GEM) were identified. The gene set showed significant enrichment for AD-related pathways. The logistic regression model demonstrated an AUC of 0.952, with AUC values of 0.916 and 0.864 in validated datasets. The immune infiltration analysis revealed significant heterogeneity between the Alzheimer's disease and control groups. High-affinity drugs for hub genes were identified. Through our study, a disease prediction model was constructed using potential biomarkers, and drugs targeting the genes were predicted. These results contribute to further understanding of the molecular mechanisms underlying Alzheimer's disease., (© 2024. The Author(s).)

Colorectal cancer (CRC) is one of most common tumors worldwide, causing a prominent global health burden. Cell senescence is a complex physiological state, characterized by proliferation arrest. Here, we investigated the role of cellular senescence in the heterogeneity of CRC. Based on senescence-associated genes, CRC samples were classified into different senescence patterns with different survival, cancer-related biological processes and immune cell infiltrations. A senescence-related model was then developed to calculate the senescence-related score to comprehensively explore the heterogeneity of each CRC sample such as stromal activities, immunoreactivities and drug sensitivity. Single-cell analysis revealed there were different immune cell infiltrations between low and high senescence-related model genes enrichment groups, which was confirmed by multiplex immunofluorescence staining. Pseudotime analysis indicated model genes play a pivotal role in the evolution of B cells. Besides, intercellular communication modeled by NicheNet showed tumor cells with higher enrichment of senescence-related model genes highly expressed CXCL2/3 and CCL3/4, which attracted immunosuppressive cell infiltration and promoted tumor metastasis. Finally, top 6 hub genes were identified from senescence-related model genes by PPI analysis. And RT-qPCR revealed the expression differences of hub genes between normal and CRC cell lines, indicating to some extent the clinical practicability of senescence-related model. To sum up, our study explores the impact of cellular senescence on the prognosis, TME and treatment of CRC based on senescence patterns. This provides a new perspective for CRC treatment., (© 2024. The Author(s).)

Identifying and breeding cattle that are more feed efficient is of great benefit to beef production. Additionally, it is crucial that genes contributing to feed efficiency are robust across varying management settings including dietary source as well as being relevant across contrasting breeds of cattle. The aim of this study was to determine miRNAs that are contributing to the expression of residual feed intake (RFI) across two breeds and dietary sources. miRNA profiling was undertaken in Longissimus dorsi tissue of Charolais and Holstein-Friesian steers divergent for RFI phenotype following two contrasting consecutive diets (high-forage and high-concentrate). Ten miRNA were identified as differentially expressed (adj. P < 0.1) across the breed and diet contrasts examined. Of particular interest was the differential expression of miR-2419-5p and miR-2415-3p, both of which were up-regulated in the Low-RFI Charolais steers across each dietary phase. Pathway analysis of target mRNA genes of differentially expressed miRNA revealed enrichment (P < 0.05) for pathways including metabolic related pathways, insulin receptor signalling, adipogenesis as well as pathways related to skeletal muscle growth. These results provide insight into the skeletal muscle miRNAome of beef cattle and their potential molecular regulatory mechanisms relating to feed efficiency in beef cattle., (© 2024. The Author(s).)

Bronchopulmonary dysplasia (BPD) is the most common sequela of prematurity and is characterized by alveolar simplification and lung angiogenesis failure. The aim of this study was to explore the immune signatures of BPD. Differentially expressed gene analysis and immune infiltration analysis were conducted to identify key immune cell types and related genes by using the mRNA-seq dataset GSE25286. The expression patterns of key genes were validated in the scRNA-seq dataset GSE209664 and in experiments. The cell-cell crosstalk of key immune cells was explored with CellChat. We found that differentially expressed genes between BPD mice and controls were mostly enriched in leukocyte migration and M1 macrophages were highly enriched in BPD lungs. Hub genes (Cybb, Papss2, F7 and Fpr2) were validated at the single-cell level, among which the downregulation of Cybb was most closely related to macrophage infiltration. The reduced mRNA and protein levels of Cybb were further validated in animal experiments. Colocalization analysis of Cybb and macrophage markers demonstrated a significant decrease of Cybb in M1 macrophages. Cell-cell crosstalk found that alveolar epithelial cells interacted actively with macrophages through MIF-(CD74 + CD44) signalling. In conclusion, M1 macrophages played important roles in promoting BPD-like lung injury, which was correlated with a specific reduction of Cybb in macrophages and the potential activation of MIF signalling., (© 2024. The Author(s).)

Soil salinization, a prevalent form of environmental stress, leads to significant soil desertification and impacts agricultural productivity by altering the internal soil environment, slowing cellular metabolism, and modifying cellular architecture. This results in a marked reduction in both the yield and diversity of crops. Maize, which is particularly susceptible to salt stress, serves as a critical model for studying these effects, making the elucidation of its molecular responses essential for crop improvement strategies. This study focuses on the phytochrome-interacting factor 3 (PIF3), previously known for its role in freezing tolerance, to assess its function in salt stress tolerance. Utilizing two transcript variants of maize ZmPIF3 (ZmPIF3.1 and ZmPIF3.2), we engineered Arabidopsis transgenic lines to overexpress these variants and analyzed their phenotypic, physiological, biochemical, and transcriptomic responses to salt stress. Our findings reveal that these transgenic lines displayed not only enhanced salt tolerance but also improved peroxide decomposition and reduced cellular membrane damage. Transcriptome analysis indicated significant roles of hormonal and Ca 2+ signaling pathways, along with key transcription factors, in mediating the enhanced salt stress response. This research underscores a novel role for ZmPIF3 in plant salt stress tolerance, offering potential avenues for breeding salt-resistant crop varieties., (© 2024. The Author(s).)

Oral squamous cell carcinoma (OSCC) has an extremely poor prognosis. Recent studies have suggested that mitophagy-related genes (MRGs) are closely correlated with the development and occurrence of cancer, but the role they play in oral cancer has not yet been explained.We conducted a comprehensive analysis of integrated single-cell and bulk RNA sequencing (RNA-seq) data retrieved from Gene Expression Omnibus (GEO) datasets and The Cancer Genome Atlas (TCGA) database. Multiple methods were combined to provide a comprehensive understanding of the genetic expression patterns and biology of OSCC, such as analysis of pseudotime series, CellChat cell communication, immune infiltration, Gene Ontology (GO), LASSO Cox regression, gene set variation analysis (GSVA), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), Tumor Mutation Burden (TMB) and drug sensitivity assessments. The findings of this study demonstrated significantly greater activity of MRGs in NK cells than in other cells in OSCC. A reliable prognostic model was developed using 12 candidate genes strongly associated with mitochondrial autophagy. T stage, N stage and risk score were revealed as independent prognostic factors. Distinctively enriched pathways and immune cells were observed in different risk groups. Notably, low-risk patients were more responsive to chemotherapy. In addition, a nomogram model with excellent predictive ability was established by combining the risk scores and clinical features. The activity of MRGs suggest the potential for the development of new targeted therapies. The construction of a robust prognostic model also provides reference value for individualized prediction and clinical decision-making in patients with OSCC., (© 2024. The Author(s).)

Uveitis is characterised by breakdown of the blood-retinal barrier (BRB), allowing infiltration of immune cells that mediate intraocular inflammation, which can lead to irreversible damage of the neuroretina and the loss of sight. Treatment of uveitis relies heavily on corticosteroids and systemic immunosuppression due to limited understanding of disease pathogenesis. We performed single-cell RNA-sequencing of retinas, as well as bulk RNA-sequencing of retinal pigment epithelial (RPE) cells from mice with experimental autoimmune uveitis (EAU) versus healthy control. This revealed that the Th1/Th17-driven disease induced strong gene expression changes in response to inflammation in rods, cones, Müller glia and RPE. In particular, Müller glia and RPE cells were found to upregulate expression of chemokines, complement factors, leukocyte adhesion molecules and MHC class II, thus highlighting their contributions to immune cell recruitment and antigen presentation at the inner and outer BRB, respectively. Additionally, ligand-receptor interaction analysis with CellPhoneDB revealed key interactions between Müller glia and T cell / natural killer cell subsets via chemokines, galectin-9 to P4HB/TIM-3, PD-L1 to PD-1, and nectin-2/3 to TIGIT signalling axes. Our findings elucidate mechanisms contributing to breakdown of retinal immune privilege during uveitis and identify novel targets for therapeutic interventions., (© 2024. The Author(s).)

Bariatric surgery is an approved treatment for obesity that consistently improves metabolic syndrome, with well-documented beneficial effects on dyslipidemia, cardiovascular risk, nonalcoholic fatty liver disease and glucose homeostasis. In this study, we determined the differential expression genes in three periods after bariatric surgery: short-term (4-months), medium-term (1- and 2-years), and long-term (5-years) periods. Two microarray profiles were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by comparing the expression of adipose tissue genes before surgery compared to short, medium and long-term periods following surgery. Shared DEGs for the medium-term were evaluated by comparing the DEGs for both 1 and 2 years. 165, 65, and 59 DEGs were identified in short-medium-long periods. The protein-protein interactions were analyzed by STRING. A co-expression network was constructed by mapping the DEGs onto the GeneMANIA plugin of Cytoscape. Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) and wikipathway analysis were done for each group of DEGs. Interleukin-8 receptor activity, complement receptor activity and opsonin receptor activity/N-formyl peptide receptor activity in GO Function enrichment and cellular response to interleukin-8, positive regulation of hippocampal neuron apoptotic process, and positive regulation of hippocampal neuron apoptotic process in GO Process showed the best scores in short-, medium-, and long-term periods, respectively. Eight genes, including CCL2 (Chemokine ligand 2), CXCR4 (CXC motif chemokine receptor 4), EGR2 (Early Growth Response 2), FPR1 (Formyl Peptide Receptor 1), IL6 (interleukin-6), RGS2 (regulator of gene protein signaling2), SELPLG (Selectin P Ligand), and THBS1 (Thrombospondin 1) were identified as shared DEGs in the three periods after surgery. Importantly, results of DAVID database analysis showed 7, 6, 4, and 4 of these genes have roles in immune/ cancer/cardiovascular diseases, type 2 diabetes, myocardial infarct, and atherosclerosis, respectively., (© 2024. The Author(s).)

Liver fibrosis is a chronic liver disease with progressive wound healing reaction caused by liver injury. Currently, there is no FDA approved drugs for liver fibrosis. Human adipose mesenchymal stem cells (hADSCs) have shown remarkable therapeutic effects in liver diseases. However, few studies have evaluated the therapeutic role of hADSCs in liver fibrosis, and the detailed mechanism of action is unknown. Here, we investigated the in vitro and in vivo anti-fibrosis efficacy of hADSCs and identified important metabolic changes and detailed mechanisms through transcriptomic and metabolomic analyses. We found that hADSCs could inhibit the proliferation of activated hepatic stellate cells (HSCs), promote their apoptosis, and effectively inhibit the expression of pro-fibrotic protein. It can significantly reduce collagen deposition and liver injury, improve liver function and alleviate liver inflammation in cirrhotic mouse models. In addition, transcriptome analysis revealed that the key mechanism of hADSCs against liver fibrosis is the regulation of AGE-RAGE signaling pathway. Metabolic analysis showed that hADSCs influenced changes of metabolites in lipid metabolism. Therefore, our study shows that hADSCs could reduce the activation of hepatic stellate cells and inhibit the progression of liver fibrosis, which has important potential in the treatment of liver fibrosis as well as other refractory chronic liver diseases., (© 2024. The Author(s).)

Our study probed the differences in ion channel gene expression in the endometrium of women with Recurrent Implantation Failure (RIF) compared to fertile women. We analyzed the relative expression of genes coding for T-type Ca2+, ENaC, CFTR, and KCNQ1 channels in endometrial samples from 20 RIF-affected and 10 control women, aged 22-35, via microarray analysis and quantitative real-time PCR. Additionally, we examined DNA methylation in the regulatory region of KCNQ1 using ChIP real-time PCR. The bioinformatics component of our research included Gene Ontology analysis, protein-protein interaction networks, and signaling pathway mapping to identify key biological processes and pathways implicated in RIF. This led to the discovery of significant alterations in the expression of ion channel genes in RIF women's endometrium, most notably an overexpression of CFTR and reduced expression of SCNN1A, SCNN1B, SCNN1G, CACNA1H, and KCNQ1. A higher DNA methylation level of KCNQ1's regulatory region was also observed in RIF patients. Gene-set enrichment analysis highlighted a significant presence of genes involved with ion transport and membrane potential regulation, particularly in sodium and calcium channel complexes, which are vital for cation movement across cell membranes. Genes were also enriched in broader ion channel and transmembrane transporter complexes, underscoring their potential extensive role in cellular ion homeostasis and signaling. These findings suggest a potential involvement of ion channels in the pathology of implantation failure, offering new insights into the mechanisms behind RIF and possible therapeutic targets., (© 2024. The Author(s).)

Neutrophil infiltration plays a key role in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). However, pertinent mechanisms remain poorly elucidated. Here, we obtained the data from gene expression omnibus (GEO) and gene set enrichment analysis (GSEA) to identify and validate neutrophil-associated hub genes in CRSwNP. We found that four neutrophil-associated hub genes, namely ICAM1, IL-1β, TYROBP, and BCL2A1, were markedly upregulated and positively correlated with neutrophil infiltration levels in patients with CRSwNP. Subsequently, this was confirmed by real-time quantitative PCR. In conclusion, we identified the role of neutrophil infiltration in the pathophysiology of CRSwNP, which may be the potential targets for the diagnosis and treatment of CRSwNP., (© 2024. The Author(s).)

Yaks live in the Qinghai-Tibet Plateau for a long time where oxygen is scarce, but can ensure the smooth development of testis and spermatogenesis. The key lies in the functional regulation of the Sertoli cells under hypoxia. In this study, we sequenced yak Sertoli cells cultured in normal oxygen concentration (Normoxia) and treated with low oxygen concentration (Hypoxia) by whole transcriptomics, and screened out 194 differentially expressed mRNAs (DEmRNAs), 934 differentially expressed LncRNAs (DELncRNAs) and 129 differentially expressed miRNAs (DEmiRNAs). GO and KEGG analysis showed that these differential genes were mainly concentrated in PI3K-AKT, MAPK, RAS, and other signaling pathways, and were associated with glucose metabolism, tight junction, steroid hormone synthesis, cell fusion, and immunity of yak Sertoli cells. We constructed the gene interaction network of yak Sertoli cells in hypoxia and screened out the relationship pairs related to glucose metabolism and tight junction. The results suggested that the changes in energy metabolism, tight junction, and immune regulation of yak Sertoli cells under hypoxia might provide favorable conditions for spermatogenesis. This study provides data for further study on the role of non-coding RNA in testis development and spermatogenesis of yak., (© 2024. The Author(s).)

Drosophila suzukii lay eggs in soft-skinned, ripening fruits, making this insect a serious threat to berry production. Since its 2008 introduction into North America, growers have used insecticides, such as pyrethroids and spinosads, as the primary approach for D. suzukii management, resulting in development of insecticide resistance in this pest. This study sought to identify the molecular mechanisms conferring insecticide resistance in these populations. We sequenced the transcriptomes of two pyrethroid- and two spinosad-resistant isofemale lines. In both pyrethroid-resistant lines and one spinosad-resistant line, we identified overexpression of metabolic genes that are implicated in resistance in other insect pests. In the other spinosad-resistant line, we observed an overexpression of cuticular genes that have been linked to resistance. Our findings enabled the development of molecular diagnostics that we used to confirm persistence of insecticide resistance in California, U.S.A. To validate these findings, we leveraged D. melanogaster mutants with reduced expression of metabolic or cuticular genes that were found to be upregulated in resistant D. suzukii to demonstrate that these genes are involved in promoting resistance. This study is the first to characterize the molecular mechanisms of insecticide resistance in D. suzukii and provides insights into how current management practices can be optimized., (© 2024. The Author(s).)

Recently, we have reported that extracellular vesicles (EVs) from the bone marrow mesenchymal stromal cells (BM-MSC) of aplastic anemia (AA) patients inhibit hematopoietic stem and progenitor cell (HSPC) proliferative and colony-forming ability and promote apoptosis. One mechanism by which AA BM-MSC EVs might contribute to these altered HSPC functions is through microRNAs (miRNAs) encapsulated in EVs. However, little is known about the role of BM-MSC EVs derived miRNAs in regulating HSPC functions in AA. Therefore, we performed miRNA profiling of EVs from BM-MSC of AA (n = 6) and normal controls (NC) (n = 6) to identify differentially expressed miRNAs. The Integrated DEseq2 analysis revealed 34 significantly altered mature miRNAs, targeting 235 differentially expressed HSPC genes in AA. Hub gene analysis revealed 10 HSPC genes such as IGF-1R, IGF2R, PAK1, PTPN1, etc., which are targeted by EV miRNAs and had an enrichment of chemokine, MAPK, NK cell-mediated cytotoxicity, Rap1, PI3k-Akt, mTOR signalling pathways which are associated with hematopoietic homeostasis. We further showed that miR-139-5p and its target, IGF-1R (hub-gene), might regulate HSPC proliferation and apoptosis, which may serve as potential therapeutic targets in AA. Overall, the study highlights that AA BM-MSC EV miRNAs could contribute to impaired HSPC functions in AA., (© 2024. The Author(s).)

Metabolic disorders such as insulin resistance and type 2 diabetes are associated with brain dysfunction and cognitive deficits, although the underpinning molecular mechanisms remain elusive. Epigenetic factors, such as non-coding RNAs, have been reported to mediate the molecular effects of nutrient-related signals. Here, we investigated the changes of miRNA expression profile in the hippocampus of a well-established experimental model of metabolic disease induced by high fat diet (HFD). In comparison to the control group fed with standard diet, we observed 69 miRNAs exhibiting increased expression and 63 showing decreased expression in the HFD mice's hippocampus. Through bioinformatics analysis, we identified numerous potential targets of the dysregulated miRNAs, pinpointing a subset of genes regulating neuroplasticity that were targeted by multiple differentially modulated miRNAs. We also validated the expression of these synaptic and non-synaptic proteins, confirming the downregulation of Synaptotagmin 1 (SYT1), calcium/calmodulin dependent protein kinase I delta (CaMK1D), 2B subunit of N-methyl-D-aspartate glutamate receptor (GRIN2B), the DNA-binding protein Special AT-Rich Sequence-Binding Protein 2 (SATB2), and RNA-binding proteins Cytoplasmic polyadenylation element-binding protein 1 (CPEB1) and Neuro-oncological ventral antigen 1 (NOVA1) in the hippocampus of HFD mice. In summary, our study offers a snapshot of the HFD-related miRNA landscape potentially involved in the alterations of brain functions associated with metabolic disorders. By shedding light on the specific miRNA-mRNA interactions, our research contributes to a deeper understanding of the molecular mechanisms underlying the effects of HFD on the synaptic function., (© 2024. The Author(s).)

The EphA family belongs to a large group of membrane receptor tyrosine kinases. Emerging evidence indicates that the EphA family participates in tumour occurrence and progression. Nonetheless, the expression patterns and prognostic values of the nine EphAs in non-small cell lung cancer (NSCLC) have rarely been studied before. In the current study, we comprehensively analysed the expression and prognostic role of EphA family members by different means. The Cancer Genome Atlas and Gene Expression Profiling Interactive Analysis databases were used to investigate the expression of EphAs in NSCLC. The cBioPortal database was applied to analyse the prognostic values and genetic mutations of EphAs.We discovered that the expression of EphA10 was significantly higher in NSCLC tissues than in adjacent noncancerous tissues, and survival analyses showed that a higher level of EphA10 predicted poor prognosis. Further exploration into the role of EphA10 by ESTIMATE, CIBERSORT, and ssGSEA analysis found that it was also related to immune infiltration and higher expression of targets of ICI targets. In conclusion, this study revealed that among the EphA family members, EphA10 played an oncogenic role and was a promising biomarker for poor prognosis and better immunotherapy response in NSCLC., (© 2024. The Author(s).)

MicroRNAs (miRNAs) are important regulators of gene expression and are involved in bacterial pathogenesis and host-pathogen interactions. In this study, we investigated the function of miRNAs in the regulation of host responses to Pasteurella multocida infection. Using next-generation sequencing, we analyzed miRNA expression pattern and identified differentially expressed miRNAs in Pasteurella multocida-infected goat lungs. In addition, we investigated the function of differentially expressed miRNAs andtheir targeted signaling pathways in bacterial infection processes. The results showed that Pasteurella multocida infection led to 69 significantly differentially expressed miRNAs, including 28 known annotated miRNAs with miR-497-3p showing the most significant difference. Gene target prediction and functional enrichment analyses showed that the target genes were mainly involved in cell proliferation, regulation of the cellular metabolic process, positive regulation of cellular process, cellular senescence, PI3K-Akt signaling pathway, FoxO signaling pathway and infection-related pathways. In conclusion, these data provide a new perspective on the roles of miRNAs in Pasteurella multocida infection., (© 2024. The Author(s).)

Bone marrow-derived mesenchymal stem cells (BMSCs) exhibit multi-lineage differentiation potential and robust proliferative capacity. The late stage of differentiation signifies the functional maturation and characterization of specific cell lineages, which is crucial for studying lineage-specific differentiation mechanisms. However, the molecular processes governing late-stage BMSC differentiation remain poorly understood. This study aimed to elucidate the key biological processes involved in late-stage BMSC differentiation. Publicly available transcriptomic data from human BMSCs were analyzed after approximately 14 days of osteogenic, adipogenic, and chondrogenic differentiation. Thirty-one differentially expressed genes (DEGs) associated with differentiation were identified. Pathway enrichment analysis indicated that the DEGs were involved in extracellular matrix (ECM)-receptor interactions, focal adhesion, and glycolipid biosynthesis, a ganglion series process. Subsequently, the target genes were validated using publicly available single-cell RNA-seq data from mouse BMSCs. Lamc1 exhibited predominant distribution in adipocytes and osteoblasts, primarily during the G2/M phase. Tln2 and Hexb were expressed in chondroblasts, osteoblasts, and adipocytes, while St3gal5 was abundantly distributed in stem cells. Cell communication analysis identified two receptors that interact with LAMCI. q-PCR results confirmed the upregulation of Lamc1, Tln2, Hexb, and St3gal5 during osteogenic differentiation and their downregulation during adipogenic differentiation. Knockdown of Lamc1 inhibited adipogenic and osteogenic differentiation. In conclusion, this study identified four genes, Lamc1, Tln2, Hexb, and St3gal5, that may play important roles in the late-stage differentiation of BMSCs. It elucidated their interactions and the pathways they influence, providing a foundation for further research on BMSC differentiation., (© 2024. The Author(s).)

Much remains unknown about the reproductive physiology of southern white rhinoceros (SWR) and the effect of ovarian stimulation prior to ovum pickup (OPU) have not been fully elucidated. Granulosa cells (GC) provide valuable insight into follicle growth and oocyte maturation status. The goals of this study were to evaluate transcriptomic changes in GC from three stages of follicle development and to identify biomarkers possibly associated with follicular growth and maturation as a result of ovarian stimulation. GC collected from SWRs following OPU were assigned stages based upon follicle size. Total RNA was isolated, and cDNA libraries were prepared and sequenced on a NovaSeq 6000. All bioinformatics analyses were performed utilizing the Galaxy web platform. Reads were aligned to CerSimCot1.0, and the manual curation was performed with EquCab3.0. Overall, 39,455 transcripts (21,612 genes) were identified across follicle stages, and manual curation yielded a 61% increase in gene identification from the original annotation. Granulosa cells from preovulatory follicles expressed the highest number of unique transcripts. The following seven biomarkers were determined based upon cluster analysis and patterns of expression: COL1A1, JMY, FBXW11, NRG1, TMPO, MACIR and COL4A1. These data can be used to potentially evaluate the effects of different ovarian stimulation protocols on follicle dynamics, improve OPU results, and support conservation efforts in this species., (© 2024. The Author(s).)

Lumbar disc herniation (LDH) is a common clinical spinal disorder, yet its etiology remains unclear. We aimed to explore the role of cuproptosis-related genes (CRGs) and identify potential diagnostic biomarkers. Our analysis involved interrogating the GSE124272 and GSE150408 datasets for differential gene expression profiles associated with CRGs and immune characteristics. Molecular clustering was performed on LDH samples, followed by expression and immune infiltration analyses. Using the WGCNA algorithm, specific genes within CRG clusters were identified. After selecting the most predictive genes from the optimal model, four machine learning models were constructed and validated. This study identified nine CRGs associated with copper-regulated cell death. Two copper-containing molecular clusters linked to death were detected in LDH samples. Elevated expression and immune infiltration levels were found in LDH patients, particularly in CRG cluster C2. Utilizing XGB, five genes were identified for constructing a diagnostic model, achieving an area under the curve values of 0.715. In conclusion, this research provides valuable insights into the association between LDH and copper-regulated cell death, alongside proposing a promising predictive model., (© 2024. The Author(s).)

Type 2 diabetes (T2D) and Clear-cell renal cell carcinoma (ccRCC) are both complicated diseases which incidence rates gradually increasing. Population based studies show that severity of ccRCC might be associated with T2D. However, so far, no researcher yet investigated about the molecular mechanisms of their association. This study explored T2D and ccRCC causing shared key genes (sKGs) from multiple transcriptomics profiles to investigate their common pathogenetic processes and associated drug molecules. We identified 259 shared differentially expressed genes (sDEGs) that can separate both T2D and ccRCC patients from control samples. Local correlation analysis based on the expressions of sDEGs indicated significant association between T2D and ccRCC. Then ten sDEGs (CDC42, SCARB1, GOT2, CXCL8, FN1, IL1B, JUN, TLR2, TLR4, and VIM) were selected as the sKGs through the protein-protein interaction (PPI) network analysis. These sKGs were found significantly associated with different CpG sites of DNA methylation that might be the cause of ccRCC. The sKGs-set enrichment analysis with Gene Ontology (GO) terms and KEGG pathways revealed some crucial shared molecular functions, biological process, cellular components and KEGG pathways that might be associated with development of both T2D and ccRCC. The regulatory network analysis of sKGs identified six post-transcriptional regulators (hsa-mir-93-5p, hsa-mir-203a-3p, hsa-mir-204-5p, hsa-mir-335-5p, hsa-mir-26b-5p, and hsa-mir-1-3p) and five transcriptional regulators (YY1, FOXL1, FOXC1, NR2F1 and GATA2) of sKGs. Finally, sKGs-guided top-ranked three repurposable drug molecules (Digoxin, Imatinib, and Dovitinib) were recommended as the common treatment for both T2D and ccRCC by molecular docking and ADME/T analysis. Therefore, the results of this study may be useful for diagnosis and therapies of ccRCC patients who are also suffering from T2D., (© 2024. The Author(s).)

Endometrial cancer (EC) is associated with significant risk factors such as polycystic ovarian syndrome (PCOS) and sedentary behavior. In our study, we aim to employ machine learning algorithms to investigate the potential molecular processes that underlie their interaction and explore their respective roles in the diagnosis and immunotherapy of EC. The GEO database provides access to microarray data, which was utilized in this study to identify gene expression modules associated with PCOS and sedentary behavior, using weighted gene expression network analysis (WGCNA). Cluego software was then employed to investigate the energy enrichment of shared pathways in both PCOS and sedentary individuals, and differential gene analysis was used to confirm another two databases. The miRNAs-mRNAs controlled network was constructed to verify the pathway. The immune-related factors of the shared pathway in EC were then analyzed. Finally, to validate our findings, we conducted cell experiments using EC cell lines (AN3CA, KLE, Ishikawa, RL95-2, and HEC-1A). We found that increased intracellular aromatic compound anabolism is a common feature of both PCOS and sedentary individuals. We then developed a disease pathway model that was based on the common genetic characteristics of PCOS and sedentary behavior. We utilized pathway typing in EC samples and found a significant survival difference between the two subgroups, with the upregulated expression type exhibiting an immune-hot phenotype. Finally, the experimental results confirmed the expression of the hub gene (NAA15) in EC. The findings of our study suggest that genes related to the intracellular aromatic compound metabolic pathway can be used for immunotherapy of EC., (© 2024. The Author(s).)

Cadmium, a common metal pollutant, has been demonstrated to induce type 2 diabetes by disrupting pancreatic β cells function. In this study, transcriptome microarray was utilized to identify differential gene expression in oxidative damage to pancreatic β cells following cadmium exposure. The results indicated that a series of mRNAs, LncRNAs, and miRNAs were altered. Of the differentially expressed miRNAs, miR-29a-3p exhibited the most pronounced alteration, with an 11.62-fold increase relative to the control group. Following this, the target gene of miR-29a-3p was identified as Col3a1 through three databases (miRDB, miRTarbase and Tarbase), which demonstrated a decrease across the transcriptome microarray. The upstream target gene of miR-29a-3p was identified as NONMMUT036805, with decreased expression observed in the microarray. Finally, the expression trend of NONMMUT036805/miR-29a-3p/Col3a1 was reversed following NAC pretreatment. This was accompanied by a reduction in oxidative damage indicators, MDA/ROS/GSH-Px appeared to be negatively affected to varying degrees. In conclusion, this study has demonstrated that multiple RNAs are altered during cadmium exposure-induced oxidative damage in pancreatic β cells. The NONMMUT036805/miR-29a-3p/Col3a1 axis has been shown to be involved in this process, which provides a foundation for the identification of potential targets for cadmium toxicity intervention., (© 2024. The Author(s).)

This study aimed to develop a prognostic risk model based on immune-related long non-coding RNAs (lncRNAs). By analyzing the expression profiles of specific long non-coding RNAs, the objective was to construct a predictive model to accurately assess the survival prognosis of breast cancer (BC) patients. This effort seeks to provide personalized treatment strategies for patients and improve clinical outcomes. Based on the median risk value, 300 samples of triple-negative BC (TNBC) patients were rolled into a high-risk group (HR group, n = 140) and a low-risk group (LR group, n = 160). Multivariate Cox (MVC) analysis was performed by combining the patient risk score and clinical information to evaluate the prognostic value of the prognostic risk (PR) model. A total of 371 immune-related lncRNAs associated with the prognosis of TNBC were obtained from 300 TNBC samples. Nine associated with prognosis were obtained by univariate Cox (UVC) analysis, and 3 (AC090181.2, LINC01235, and LINC01943) were selected by MVC analysis for the construction of TNBC PR model. Survival analysis showed a great difference in TNBC patients in different groups (P < 0.001). The receiver operator characteristic (ROC) curve showed the model possessed a good area under ROC curve (AUC), which was 0.928. The patient RS jointing with clinical information as well as the MVC analysis revealed that RS was an independent risk factor (IRF) for prognosis of TNBC (P < 0.05, HR = 1.033286). Therefore, the lncRNAs associated with TNBC immunity can be screened by bioinformatics analysis, and the established PR model of TNBC could better predict the prognosis of patients with TNBC, exhibiting a high application value in clinic., (© 2024. The Author(s).)

Isomalto/malto-polysaccharides (IMMPs) are a novel type of soluble dietary fibres with a prebiotic potential promoting growth of beneficial microbes in the gut. However, the mode of action of IMMPs remains unknown. Previous studies on IMMPs showed an increase in total bacteria, especially lactobacilli, and higher production of short chain fatty acids (SCFA) when IMMPs were fed to rats or used during in vitro fermentation. Here we used metatranscriptomics to investigate how IMMPs with different amounts of α - (1 → 6) glycosidic linkages affected microbial function during incubation with human fecal inoculum. We showed that active microbial community dynamics during fermentation varied depending on the type of IMMP used and that the observed changes were reflected in the community gene expression profiles. Based on metatranscriptome analysis, members of Bacteroides, Lactobacillus and Bifidobacterium were the predominant degraders of IMMPs, and the increased gene expression in these bacteria correlated with high amounts of α - (1 → 6) glycosidic linkages. We also noted an increase in relative abundance of these bacteria and an activation of pathways involved in SCFA synthesis. Our findings could provide a baseline for more targeted approaches in designing prebiotics for specific bacteria and to achieve more controlled modulation of microbial activity towards desired health outcomes., (© 2024. The Author(s).)

Computational pharmacogenomics can potentially identify new indications for already approved drugs and pinpoint compounds with similar mechanism-of-action. Here, we used an integrated drug repositioning approach based on transcriptomics data and structure-based virtual screening to identify compounds with gene signatures similar to three known proteasome inhibitors (PIs; bortezomib, MG-132, and MLN-2238). In vitro validation of candidate compounds was then performed to assess proteasomal proteolytic activity, accumulation of ubiquitinated proteins, cell viability, and drug-induced expression in A375 melanoma and MCF7 breast cancer cells. Using this approach, we identified six compounds with PI properties ((-)-kinetin-riboside, manumycin-A, puromycin dihydrochloride, resistomycin, tegaserod maleate, and thapsigargin). Although the docking scores pinpointed their ability to bind to the β5 subunit, our in vitro study revealed that these compounds inhibited the β1, β2, and β5 catalytic sites to some extent. As shown with bortezomib, only manumycin-A, puromycin dihydrochloride, and tegaserod maleate resulted in excessive accumulation of ubiquitinated proteins and elevated HMOX1 expression. Taken together, our integrated drug repositioning approach and subsequent in vitro validation studies identified six compounds demonstrating properties similar to proteasome inhibitors., (© 2024. The Author(s).)

Heart failure (HF) is a terminal condition of multiple cardiovascular disorders. Cancer is a deadly disease worldwide. The relationship between HF and cancer remains poorly understood. The Gene Expression Omnibus database was used to download the RNA sequencing data of 356 patients with hypertrophic cardiomyopathy-induced HF and non-HF. A co-expression network was established through the weighted correlation network analysis (WGCNA) to identify hub genes of HF and cancer. Cox risk analysis was performed to predict the prognostic risks of HF hub genes in pan-cancer. HF was linked to immune response pathway by the analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). A positive correlation was observed between the expression levels of 4 hub genes and the infiltration of CD8 + T-cells in pan-cancer. 4 hub genes were identified as beneficial prognostic factors in several cancers. Western blotting and real-time polymerase chain reaction validated the high expression of GZMM, NKG7, and ZAP70 in both mice and patients with HF compared to control groups. Our study highlights the shared immune pathogenesis of HF and cancer and provides valuable insights for developing novel therapeutic strategies, offering new opportunities for improving the management and treatment outcomes of both HF and cancer., (© 2024. The Author(s).)

Clear cell renal cell carcinoma (ccRCC) is characterized by a high incidence and mortality rate. Despite advancements in therapeutic interventions, the prognosis for renal cancer patients remains suboptimal. Of late, methylation modifications have emerged as promising molecular targets for tumor assessment and treatment, yet their potential has not been fully investigated in the context of ccRCC. Transcriptomic and clinical data were extracted from The Cancer Genome Atlas, Gene Expression Omnibus, and ArrayExpress databases, leading to the identification of 57 methylation-related genes (MRGs). Utilizing DESeq2 analysis, Cox regression analysis, and the LASSO regression algorithm, a Methylation-Related Risk Score (MARS) was constructed. Cluster analysis, Gene Ontology (GO) analysis, clinical feature analysis, immune infiltration analysis, and mutation analysis were further employed to evaluate the model. Our investigation identified six pivotal prognostic MRGs and established a risk score predicated on m6A/m5C/m1A/m7G regulatory factors. This score was validated across two external cohorts and can be utilized to assess individual immune infiltration statuses and predict responses to immunotherapy. Moreover, cluster analysis delineated two distinct m6A/m5C/m1A/m7G gene clusters. We have developed and validated a robust prognostic signature based on genes associated with m6A, m5C, m1A, and m7G modifications. This gene signature demonstrates significant prognostic value in assessing survival outcomes, clinical characteristics, immune infiltration, and responses to immunotherapy in ccRCC patients. This finding provides valuable insights for refining precision treatment strategies., (© 2024. The Author(s).)

Osteosarcoma (OS) is the most common primary malignant tumour of the bone with high mortality. Here, we comprehensively analysed the hypoxia signalling in OS and further constructed novel hypoxia-related gene signatures for OS prediction and prognosis. This study employed Gene Set Enrichment Analysis (GSEA), Weighted correlation network analysis (WGCNA) and Least absolute shrinkage and selection operator (LASSO) analyses to identify Stanniocalcin 2 (STC2) and Transmembrane Protein 45A (TMEM45A) as the diagnostic biomarkers, which further assessed by Receiver Operating Characteristic (ROC), decision curve analysis (DCA), and calibration curves in training and test dataset. Univariate and multivariate Cox regression analyses were used to construct the prognostic model. STC2 and metastasis were devised to forge the OS risk model. The nomogram, risk score, Kaplan Meier plot, ROC, DCA, and calibration curves results certified the excellent performance of the prognostic model. The expression level of STC2 and TMEM45A was validated in external datasets and cell lines. In immune cell infiltration analysis, cancer-associated fibroblasts (CAFs) were significantly higher in the low-risk group. And the immune infiltration of CAFs was negatively associated with the expression of STC2 (P < 0.05). Pan-cancer analysis revealed that the expression level of STC2 was significantly higher in Esophageal carcinoma (ESCA), Head and Neck squamous cell carcinoma (HNSC), Kidney renal clear cell carcinoma (KIRC), Lung squamous cell carcinoma (LUSC), and Stomach adenocarcinoma (STAD). Additionally, the higher expression of STC2 was associated with the poor outcome in those cancers. In summary, this study identified STC2 and TMEM45A as novel markers for the diagnosis and prognosis of osteosarcoma, and STC2 was shown to correlate with immune infiltration of CAFs negatively., (© 2024. The Author(s).)

Alzheimer's disease (AD) is a prevalent neurodegenerative disorder afflicting the elderly population worldwide. The identification of potential gene candidates for AD holds promises for diagnostic biomarkers and therapeutic targets. Employing a comprehensive strategy, this study integrated transcriptomic data from diverse data sources, including microarray and single-cell datasets from blood and tissue samples, enabling a detailed exploration of gene expression dynamics. Through this thorough investigation, 19 notable candidate genes were found with consistent expression changes across both blood and tissue datasets, suggesting their potential as biomarkers for AD. In addition, single cell sequencing analysis further highlighted their specific expression in excitatory and inhibitory neurons, the primary functional units in the brain, underscoring their relevance to AD pathology. Moreover, the functional enrichment analysis revealed that three of the candidate genes were downregulated in synaptic signaling pathway. Further validation experiments significantly showed reduced levels of rabphilin-3A (RPH3A) in 3xTg-AD model mice, implying its role in disease pathogenesis. Given its role in neurotransmitter exocytosis and synaptic function, further investigation into RPH3A and its interactions with neurotrophic proteins may provide valuable insights into the complex molecular mechanisms underlying synaptic dysfunction in AD., (© 2024. The Author(s).)

Evolution of unisexual flowers involves extreme changes in floral development. Spinach is one of the species to discern the formation and evolution of dioecy. MADS-box gene family is involved in regulation of floral organ identity and development and in many other plant developmental processes. However, there is no systematic analysis of MADS-box family genes in spinach. A comprehensive genome-wide analysis and transcriptome profiling of MADS-box genes were undertaken to understand their involvement in unisexual flower development at different stages in spinach. In total, 54 MADS-box genes found to be unevenly located across 6 chromosomes and can be divided into type I and type II genes. Twenty type I MADS-box genes are subdivided into Mα, Mβ and Mγ subgroups. While thirty-four type II SoMADSs consist of 3 MIKC*, and 31 MIKC C -type genes including sixteen floral homeotic MADS-box genes that are orthologous to the proposed Arabidopsis ABCDE model of floral organ identity determination, were identified in spinach. Gene structure, motif distribution, physiochemical properties, gene duplication and collinearity analyses for these genes are performed in detail. Promoters of both types of SoMADS genes contain mainly MeJA and ABA response elements. Expression profiling indicated that MIKCc genes exhibited more dynamic and intricate expression patterns compared to M-type genes and the majority of type-II genes AP1, SVP, and SOC1 sub-groups showed female flower-biased expression profiles, suggesting their role in carpel development, while PI showed male-biased expression throughout flower developmental stages, suggesting their role in stamen development. These results provide genomic resources and insights into spinach dioecious flower development and expedite spinach improvement., (© 2024. The Author(s).)