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Resistance training is used to combat skeletal muscle function decline in older adults. Few studies have been designed specific for females, resulting in very limited treatment options for skeletal muscle atrophy in aging women. Here, we analyzed the gene expression profiles of skeletal muscle samples from sedentary young women, sedentary older women, and resistance-trained older women, using microarray data from public database. A total of 45 genes that were differentially expressed during female muscle aging and reversed by resistance training were identified. Functional and pathway enrichment analysis, protein–protein interaction network analysis, and receiver operating characteristic analysis were performed to reveal the key genes and pathways involved in the effects of resistance training on female muscle aging. The collagen genes COL1A1, COL3A1, and COL4A1 were identified important regulators of female muscle aging and resistance training, by modulating multiple signaling pathways, such as PI3 kinase-Akt signaling, focal adhesions, extracellular matrix-receptor interactions, and relaxin signaling. Interestingly, the expression of CDKN1A and TP63 were increased during aging, and further upregulated by resistance training in older women, suggesting they may negatively affect resistance training outcomes. Our findings provide novel insights into the molecular mechanisms of resistance training on female muscle aging and identify potential biomarkers and targets for clinical intervention. [ABSTRACT FROM AUTHOR]

• Endometriosis is a common gynecological disease with a significant economic burden. • Endometriosis is affected by differentially expressed genes and non-coding RNA. • Bioinformatic is a valuable tool to unveil the molecular basis underlying endometriosis. • Bioinformatic analysis revealed the potential biomarkers of endometriosis. Endometriosis is a common gynecological disease with a significant economic burden. Growing evidence has suggested the role of aberrant gene expression and epigenetic mechanisms in the pathogenesis of endometriosis. This study aims to identify potential key genes, epigenetic features, and regulatory networks in endometriosis using an integrated bioinformatic approach. Six microarray and RNA-sequencing datasets (GSE23339, GSE7305, GSE25628, GSE51981, GSE120103, GSE87809) were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) of each dataset were analyzed using the GEO2R tool, and their mRNA, miRNA, and lncRNA components were identified subsequently. The common DEGs between datasets were combined, and the Gene ontology (GO) and pathway enrichment were analyzed using the ShinyGo. The protein–protein interaction (PPI) network of DEGs, miRNA, and lncRNA was constructed using STRING and Cytoscape, and then the top 15 hub genes in the PPI network were identified using CytoHubba. A total of 551 common DEGs were identified from four or more studies, including 292 upregulated and 259 downregulated genes. Besides alterations in protein-coding genes (mRNA), 16 miRNA (5 upregulated and 11 downregulated) were identified from all studies, along with 12 lncRNA (10 upregulated and 2 downregulated) that were common in at least three studies. Enriched DEGs were mainly associated with extracellular matrix (ECM) interaction, P53 signaling pathway, and focal adhesion, which are suggested to play vital roles in the pathogenesis of endometriosis. Through PPI network construction of common DEGs, 178 nodes and 683 edges were obtained, from which 15 hub genes were identified, including CDK1, CCNB1, KIF11, CCNA2, BUB1B, DLGAP5, BUB1, TOP2A, ASPM, CEP55, CENPF, TPX2, CCNB2, KIFC, NCAPG. Our in-depth bioinformatics analysis reveals the critical molecular basis underlying endometriosis. The role of identified hub genes, miRNA, and lncRNA may also have an opportunity to be explored as potential biomarkers for endometriosis diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

Background: This study aimed to portray the atomic intelligence and prognostic implications of differentially expressed genes and their involvement in biological pathways in endometrial carcinoma, with a specific focus on the impacts of exercise on cancer. Methods: We utilized a multi-faceted approach, including volcano plots, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, Venn diagrams, protein-protein interaction networks, Kaplan-Meier survival analysis, Gene Set Variety Analysis, and single-cell transcriptomic analysis. Furthermore, we profiled tumor mutational scenes, assessed the prognostic value of immune-related features, and conducted a comprehensive examination of genetic variations and their impact on tumor mutational burden across different cancer types. Multidimensional genomic interactions and methylation elements were also investigated. Using real-time quantitative PCR and immunofluorescence staining, the effects of B-cell lymphoma 2 (BCL2) silencing on TNF-a and caspase-3 gene expression were evaluated. Results: Our study identified a noteworthy number of differentially expressed genes in endometrial carcinoma with potential links to athletic performance traits. BCL2 expression levels were found to be associated with survival outcomes, and its changeability across cancers was related to immune cell infiltration and immune checkpoint gene expression. Single-cell investigations uncovered cellular complexity within tumor microenvironments and critical biological pathways in BCL2-overexpressing cells. The expression flow and mutational effect of BCL2 in endometrial carcinoma were characterized, and the prognostic implications of immune-related features were assessed. Hereditary variations, including copy number variations and their relationship with gene expression and tumor mutational burden, were investigated. Multidimensional genomic transaction highlighted the essential role of regulatory genes in cancer pathogenesis. Silencing of the BCL2 gene significantly inhibited the proliferation of HEC-108 cells and promoted apoptosis, as evidenced by decreased TNF-a gene expression and increased caspase-3 gene expression. Immunofluorescence staining further confirmed these results. Conclusion: This study gives a point-by-point understanding of the atomic intelligence and prognostic implications in endometrial carcinoma and across various other cancers. BCL2's role as a modulatory factor within the tumor-resistant environment and its potential impact on disease prognosis and response to immunotherapy were underscored. The multidimensional genomic analysis provides insights into the complex interaction between genetic and epigenetic variables in cancer, which may shed light on future therapeutic strategies. This study indicates that silencing the BCL2 gene can significantly inhibit tumor cell proliferation and promote apoptosis through the regulation of the TNF-a and caspase-3 pathways. [ABSTRACT FROM AUTHOR]

Background: Endometriosis is a common cause of endometrial-type mucosa outside the uterine cavity with symptoms such as painful periods, chronic pelvic pain, pain with intercourse and infertility. However, the early diagnosis of endometriosis is still restricted. The purpose of this investigation is to identify and validate the key biomarkers of endometriosis. Methods: Next-generation sequencing dataset GSE243039 was obtained from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) between endometriosis and normal control samples were identified. After screening of DEGs, gene ontology (GO) and REACTOME pathway enrichment analyses were performed. Furthermore, a protein–protein interaction (PPI) network was constructed and modules were analyzed using the Human Integrated Protein–Protein Interaction rEference database and Cytoscape software, and hub genes were identified. Subsequently, a network between miRNAs and hub genes, and network between TFs and hub genes were constructed using the miRNet and NetworkAnalyst tool, and possible key miRNAs and TFs were predicted. Finally, receiver operating characteristic curve analysis was used to validate the hub genes. Results: A total of 958 DEGs, including 479 upregulated genes and 479 downregulated genes, were screened between endometriosis and normal control samples. GO and REACTOME pathway enrichment analyses of the 958 DEGs showed that they were mainly involved in multicellular organismal process, developmental process, signaling by GPCR and muscle contraction. Further analysis of the PPI network and modules identified 10 hub genes, including vcam1, snca, prkcb, adrb2, foxq1, mdfi, actbl2, prkd1, dapk1 and actc1. Possible target miRNAs, including hsa-mir-3143 and hsa-mir-2110, and target TFs, including tcf3 (transcription factor 3) and clock (clock circadian regulator), were predicted by constructing a miRNA-hub gene regulatory network and TF-hub gene regulatory network. Conclusions: This investigation used bioinformatics techniques to explore the potential and novel biomarkers. These biomarkers might provide new ideas and methods for the early diagnosis, treatment and monitoring of endometriosis. [ABSTRACT FROM AUTHOR]

Visceral obesity (VO), characterized by excess fat around internal organs, is a recognized risk factor for gynecological tumors, including benign uterine leiomyoma (ULM) and malignant uterine leiomyosarcoma (ULS). Despite this association, the shared molecular mechanisms remain underexplored. This study utilizes an integrated bioinformatics approach to elucidate common molecular pathways and identify potential therapeutic targets linking VO, ULM, and ULS. We analyzed gene expression datasets from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs) in each condition. We found 101, 145, and 18 DEGs in VO, ULM, and ULS, respectively, with 37 genes overlapping across all three conditions. Functional enrichment analysis revealed that these overlapping DEGs were significantly enriched in pathways related to cell proliferation, immune response, and transcriptional regulation, suggesting shared biological processes. Protein–protein interaction network analysis identified 14 hub genes, of which TOP2A, APOE, and TYMS showed significant differential expression across all three conditions. Drug-gene interaction analysis identified 26 FDA-approved drugs targeting these hub genes, highlighting potential therapeutic opportunities. In conclusion, this study uncovers shared molecular pathways and actionable drug targets across VO, ULM, and ULS. These findings deepen our understanding of disease etiology and offer promising avenues for drug repurposing. Experimental validation is needed to translate these insights into clinical applications and innovative treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Mouse models of disease are commonly used to generate compelling data which are the basis for biological conviction in drug discovery. Systemic lupus erythematosus (SLE) is a debilitating autoimmune disease which can often lead to kidney failure, and there are many mouse models that claim to mimic the disease, but none can completely reproduce all aspects of human SLE. To effectively utilize these models for drug development, we must understand which biological similarities they share with human SLE patients. Here, we compared a select number of lupus mouse models to see how well immune pathways in kidney samples mimic human disease in kidney samples from lupus patients. The mouse models vary in the type and intensity of immune responses that were observed. Each mouse model shares various aspects of immune response with human SLE patients and should be utilized based on drug targets and shared biological pathways. Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease which can present with mixed organ involvement. Kidney involvement in lupus nephritis (LN) is a severe complication and major cause of mortality in SLE patients, second only to cardiovascular disease. While mouse models have helped uncover some molecular pathways involved in SLE/LN, we need a better understanding of the connection of these pathways and the immune cells involved in disease pathogenesis to develop new and effective therapies. Furthermore, models used for studying SLE/LN in mice have a heterogeneous immune response and may not always represent disease manifestations observed in patients. Identifying models that have shared pathways with human disease would allow for better translation for developing effective SLE/LN therapies. The molecular pathways of five different SLE/LN models (MRL/lpr, poly (I:C)-induced, interferon-α-induced, bm12 GvHD, and spontaneous NZB/W F1) were compared to characterize the immune response in mouse kidneys. These models demonstrated varied magnitudes in immune responses and proportions of innate vs. adaptive cell involvement. These findings were compared to human molecular pathways and cell types from public databases, including the Accelerating Medicine Partnership–Systemic Lupus Erythematosus Program (AMP-SLE), to help corelate mechanisms involved in mouse models to human disease. [ABSTRACT FROM AUTHOR]

Simple Summary: The Apis mellifera sinisxinyuan is a kind of western honeybee with strong cold hardiness. However, the cold tolerance mechanism of A. m. sinisxinyuan is still not clear. Here, we analyzed the supercooling point and transcriptome data of A. m. sinisxinyuan treated with different temperatures and speculated that honeybees increase their energy to resist cold stress through signaling transduction, hormone regulation, oxidative phosphorylation, and other processes to shivering thermogenesis and regulate their carbohydrate and lipid metabolism. This study provides insight into the cold tolerance mechanisms of honeybees. Honeybees are important pollinators worldwide that are closely related to agricultural production and ecological balance. The biological activities and geographical distribution of honeybees are strongly influenced by temperature. However, there is not much research on the cold tolerance of honeybees. The Apis mellifera sinisxinyuan, a kind of western honeybee, exhibits strong cold hardiness. Here, we determined that short-term temperature treatment could regulate the honeybee's cold tolerance ability by measuring the supercooling point of A. m. sinisxinyuan treated with different temperatures. Transcriptome data were analyzed between the treated and untreated honeybees. A total of 189 differentially expressed genes were identified. Among them, Abra, Pla1, rGC, Hr38, and Maf were differentially expressed in all comparisons. GO and KEGG analysis showed that the DEGs were enriched in molecular functions related to disease, signal transduction, metabolism, and the endocrine system's function. The main components involved were ribosomes, nucleosomes, proteases, and phosphokinases, among others. This study explored the formation and regulation mechanism of cold tolerance in honeybees, not only providing a theoretical basis for cultivating honeybees with excellent traits but also promoting research and practice on insect stress tolerance. [ABSTRACT FROM AUTHOR]

Gossypol (GP), a polyphenolic compound in cottonseed, has notable effects on female reproduction and the respiratory system in pigs. This study aimed to discern the alterations in gene expression within swine granulosa cells (GCs) when treated with two concentrations of GP (6.25 and 12.5 µM) for 72 h, in vitro. The analysis revealed significant changes in the expression of numerous genes in the GP-treated groups. A Gene Ontology analysis highlighted that the differentially expressed genes (DEGs) primarily pertained to processes such as the mitotic cell cycle, chromosome organization, centromeric region, and protein binding. Pathway analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) indicated distinct impacts on various pathways in response to different GP concentrations. Specifically, in the GP6.25 group, pathways related to the cycle oocyte meiosis, progesterone-mediated oocyte maturation, and p53 signaling were prominently affected. Meanwhile, in the GP12.5 group, pathways associated with PI3K-Akt signaling, focal adhesion, HIF-1 signaling, cell cycle, and ECM–receptor interaction showed significant alterations. Notably, genes linked to female reproductive function (CDK1, CCNB1, CPEB1, MMP3), cellular component organization (BIRC5, CYP1A1, TGFB3, COL1A2), and oxidation–reduction processes (PRDX6, MGST1, SOD3) exhibited differential expression in GP-treated groups. These findings offer valuable insights into the changes in GC gene expression in pigs exposed to GP. [ABSTRACT FROM AUTHOR]

Objective: To explore the role and relationship between oxidative stress and immune infiltration in idiopathic pulmonary fibrosis (IPF), and to predict the relevant therapeutic herbal medicines and active ingredients. Methods: GSE10667 gene expression profiles were downloaded from GEO database to obtain differential expression genes, differential expression of oxidative stress genes (DEOSGs) were identified in combination with oxidative stress genes. GSEA was used to evaluate the pathways and biological processes in IPF, and GO, KEGG and PPI network analysis were performed on DEOSGs. Candidate central genes were derived from PPI results and CytoHubba, and GSE110147 was validated as an independent group to identify central genes; in addition, the immune microenvironment of samples was evaluated using CIBERSORTF, and correlation between central gene levels and relative proportion of immune cells was explored; finally, therapeutic herbal medicines and components were predicted by central genes, and molecular docking verification was carried out. Results: A total of 51 DEOSGs, four central genes (ICAM-1, APOE, MMP-1, TGF- β2) were obtained; DEOSGs were mainly related to oxidative stress, immune response, etc; four central gene levels were closely correlated with 8 relative proportions of immune cells; therapeutic herbal medicines included 4 flavors such as Huangqi and Chuanxiong, and the active ingredients included 8 kinds of β-carotene, etc, the molecular docking results were stable. Conclusion: Oxidative stress and immune firing are exist in IPF, and oxidative stress may be recognized by immune cells or directly activate immune cells. [ABSTRACT FROM AUTHOR]

Objective: To investigate differentially expressed genes (DEGs) for neuropathic pain between sciatica and healthy controls. Method: The microarray dataset GSE150408 were downloaded from gene expression database (gene expression omnibus database, GEO). The DEGs were screened using the limma V3.42.0 (linear models for microarray data) package of the R software program(version 3.5.0). GEO terms and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis of DEGs were automatically completed and visualized by the clusterProiler V3.14.0. STRING was searched to identify and predict interactions between genes or proteins, to construct the protein to protein interaction. Result: A total of 424 DEGs were screened, including 233 up-regulated genes and 191 down-regulated genes. The result of GO enrichment indicated that for biological process, DEGs were significantly enriched in defense response, regulation of immune system process, cell activation, leukocyte activation. Regarding cell components, DEGs were significantly enriched in vesicles, secretory granules, tertiary granule. For molecular function, DEGs were significantly enriched in immune receptor activation, complement receptor activity and MAP kinase phosphatase activity. The result of KEGG pathway-enrichment indicated that DEGs were mainly enriched in transcriptional misregulation in cancer. Moreover, the GSEA analysis indicated that the most significant enriched gene sets included endocytosis, Epstein-Barr virus infection. PPI analysis were performed to explore the potential function of the DEGs. It showed that the degree of FCGR1A was the highest in up-regulated proteins and the highest in down-regulated proteins. These two proteins were the key nodes. Conclusion: It showed an inflammatory and immune characteristic in peripheral blood for neuropathic pain. AZU1, BPI, FCGR1A and SPTBN2 were the key genes in neuropathic pain. [ABSTRACT FROM AUTHOR]

The feather growth rate in chickens included early and late feathering. We attempted to characterize the genes and pathways associated with the feather growth rate in chickens that are not in agreement with Mendelian inheritance. Gene expression profiles in the hair follicle tissues of late-feathering cocks (LC), early-feathering cocks (EC), late-feathering hens (LH), and early-feathering hens (EH) were acquired using RNA sequencing (RNA-seq), mass spectrometry (MS), and quantitative reverse transcription PCR (qRT‑PCR). A total of 188 differentially expressed genes (DEGs) were ascertained in EC vs. LC and 538 DEGs were identified in EH vs. LH. We observed that 14 up-regulated genes and 9 down-regulated genes were screened both in EC vs. LC and EH vs. LH. MS revealed that 41 and 138 differentially expressed proteins (DEPs) were screened out in EC vs. LC and EH vs. LH, respectively. Moreover, these DEGs and DEPs were enriched in multiple feather-related pathways, including JAK-STAT, MAPK, WNT, TGF-β, and calcium signaling pathways. qRT-PCR assay showed that the expression of WNT8A was decreased in LC compared with EC, while ALK and GRM4 expression were significantly up-regulated in EH relative to LH. This study helps to elucidate the potential mechanism of the feather growth rate in chickens that do not conform to genetic law. [ABSTRACT FROM AUTHOR]

Pelophylax nigromaculatus is an important aquaculture economic animal in China, with an annual output of more than 80,000 tons in recent years. P. nigromaculatus demonstrates distinct sexual dimorphism, characterized by females being substantially larger than males. Consequently, the cultivation of female populations presents higher economic value. The RNA-Seq technology is harnessed in this study to delve into the sexual differentiation and reproductive mechanisms of these frogs. By analyzing the transcriptomes of mature testes and ovaries, 17.24 Gbp and 23.71 Gbp of clean data were obtained respectively. This analysis yielded 107,897 annotated genes, among which 8099 were differentially expressed; 4370 were upregulated and 3729 were downregulated in ovaries. GO and KEGG analyses highlighted 70 genes exhibiting sexual dimorphism. For validation, 13 differentially expressed genes were subjected to qRT-PCR, corroborating the results of transcriptome sequencing. Furthermore, the transcriptome analysis of P. nigromaculatus' sexual glands revealed 1,062,663 SNPs, with 676,172 (63.63%) and 386,491 (36.37%) being base conversion and base transversion sites, respectively. Utilizing excel for SNP site analysis, 35,406 SNPs were identified as significantly associated with the sex of P. nigromaculatus. In pursuit of sex-related markers, 100 SNP sites, aligning perfectly with male heterozygosity and female homozygosity, were randomly selected for amplification and sequencing. Through this approach, 134 SNPs were identified, 83 (61.94%) of which matched the transcriptome data. The findings of this study provide an invaluable resource for future functional research on sex-related genes of P. nigromaculatus and offer a foundation for the development of sex-related molecular markers. [ABSTRACT FROM AUTHOR]

For Atlantic salmon development, the most critical phase is the early development stage from egg to fry through alevin. However, the studies investigating the early development of Atlantic salmon based on RNA-seq are scarce and focus only on one stage of development. Therefore, using the RNA-seq technology, the assessment of different gene expressions of various early development stages (egg, alevin, and fry) was performed on a global scale. Over 22 GB of clean data was generated from 9 libraries with three replicates for each stage with over 90% mapping efficiency. A total of 5534 genes were differentially expressed, among which 19, 606, and 826 genes were specifically expressed in each stage, respectively. The transcriptome analysis showed that the number of differentially expressed genes (DEGs) increased as the Atlantic salmon progressed in development from egg to fry stage. In addition, gene ontology enrichment demonstrated that egg and alevin stages are characterized by upregulation of genes involved in spinal cord development, neuron projection morphogenesis, axonogenesis, and cytoplasmic translation. At the fry stage, upregulated genes were enriched in the muscle development process (muscle cell development, striated muscle cell differentiation, and muscle tissue development), immune system (defense response and canonical NF-kappaB signal transduction), as well as epidermis development. These results suggest that the early development of Atlantic salmon is characterized by a dynamic shift in gene expression and DEGs between different stages, which provided a solid foundation for the investigation of Atlantic salmon development. [ABSTRACT FROM AUTHOR]

Age-related hearing loss (ARHL) or presbycusis is associated with irreversible progressive damage in the inner ear, where the sound is transduced into electrical signal; but the detailed mechanism remains unclear. Here, we sought to determine the potential molecular mechanism involved in the pathogeneses of ARHL with bioinformatics methods. A single-cell transcriptome sequencing study was performed on the cochlear samples from young and aged mice. Detection of identified cell type marker allowed us to screen 18 transcriptional clusters, including myeloid cells, epithelial cells, B cells, endothelial cells, fibroblasts, T cells, inner pillar cells, neurons, inner phalangeal cells, and red blood cells. Cell-cell communications were analyzed between young and aged cochlear tissue samples by using the latest integration algorithms Cellchat. A total of 56 differentially expressed genes were screened between the two groups. Functional enrichment analysis showed these genes were mainly involved in immune, oxidative stress, apoptosis, and metabolic processes. The expression levels of crucial genes in cochlear tissues were further verified by immunohistochemistry. Overall, this study provides new theoretical support for the development of clinical therapeutic drugs. [ABSTRACT FROM AUTHOR]

Leishmaniasis is an infectious disease caused by protozoan parasites from different species of leishmania. The disease is transmitted by female sandflies that carry these parasites. In this study, datasets on leishmaniasis published in the GEO database were analyzed and summarized. The analysis in all three datasets (GSE43880, GSE55664, and GSE63931) used in this study has been performed on the skin wounds of patients infected with a clinical form of leishmania (Leishmania braziliensis), and biopsies have been taken from them. To identify differentially expressed genes (DEGs) between leishmaniasis patients and controls, the robust rank aggregation (RRA) procedure was applied. We performed gene functional annotation and protein-protein interaction (PPI) network analysis to demonstrate the putative functionalities of the DEGs. The study utilized Molecular Complex Detection (MCODE), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) to detect molecular complexes within the protein-protein interaction (PPI) network and conduct analyses on the identified functional modules. The CytoHubba plugin's results were paired with RRA analysis to determine the hub genes. Finally, the interaction between miRNAs and hub genes was predicted. Based on the RRA integrated analysis, 407 DEGs were identified (263 up-regulated genes and 144 down-regulated genes). The top three modules were listed after creating the PPI network via the MCODE plug. Seven hub genes were found using the CytoHubba app and RRA: CXCL10, GBP1, GNLY, GZMA, GZMB, NKG7, and UBD. According to our enrichment analysis, these functional modules were primarily associated with immune pathways, cytokine activity/signaling pathways, and inflammation pathways. However, a UBD hub gene is interestingly involved in the ubiquitination pathways of pathogenesis. The mirNet database predicted the hub gene's interaction with miRNAs, and results revealed that several miRNAs, including mir-146a-5p, crucial in fighting pathogenesis. The key hub genes discovered in this work may be considered as potential biomarkers in diagnosis, development of agonists/antagonist, novel vaccine design, and will greatly contribute to clinical studies in the future. [ABSTRACT FROM AUTHOR]

Background: Platycodon grandiflorum (P. grandiflorum) is a commonly used medicinal plant in China. Transcriptome sequencing studies of different tissues of P. grandiflorum have been widely conducted. However, studies on transcriptome sequencing and expression patterns of key genes in the saponin synthesis pathway of Tongcheng P. grandiflorum, a high-quality medicinal resource of different years, are relatively limited. Results: This study involved transcriptome sequencing and bioinformatics analysis of the roots from annual, biennial, and triennial P. grandiflorum in the Tongcheng area. After data filtering and assembly, we obtained 111.44 Gb of clean base data, including 742,880616 clean reads. We identified 5,156 differential expression unigenes between at least two sample groups, with differences noted among annual, biennial, and triennial P. grandiflorum plants. GO enrichment analysis annotated 3509, 1819, and 1393 DEGs in comparison TC1vsTC2, TC1vsTC3, and TC2vsTC3, respectively. Furthermore, KEGG enrichment analysis identified 16 genes encoding key enzymes in the terpene skeleton biosynthesis, sesquiterpene and triterpene biosynthesis pathways, including SE, AACT, FPPS, DXR, HMGR, HMGS, and DXS. The results of qRT-PCR experiments showed that most of the genes were most highly expressed in annual P. grandiflorum. Conclusions: The present study provided transcriptomic data from the roots of Tongcheng P. grandiflorum of different years, which provides critical bioinformatics data on the growth and development of P. grandiflorum, laying a foundation for further research on saponins and identifying key enzymes involved in this process across different growth stages. [ABSTRACT FROM AUTHOR]

Global food and nutritional security are being threatened by abiotic stresses such as drought, salinity, cold, and heat, owing to the rapid and deleterious effects of climate change. Millets represent an incredibly promising agricultural crop in terms of their potential to ensure global food security by virtue of their resiliency against climate change and escalating demand for nutritious food and feed. Considering their durability against climate change and the increasing demand for nutritional food and feed, millets, which refers to the diverse class of smallseeded C4 panicoid grasses, endure remarkable potential for safeguarding the world's food supply. With a rapid surge in the availability of genomic information through microarray and next-generation sequencing, transcriptomics facilitated the extensive examination and quantification of shifts brought about by abiotic stresses. This stipulates an imperative way of ascertaining the expression of vital genes. This technological advancement targeted toward deciphering the gene expression patterns underpinning the molecular mechanisms/pathways. Other techniques, for instance, genome-wide expression analysis which provides insights into the regulatory networks controlling the cellular processes, genome-wide location analysis which elucidates the control over genes by the transcriptional regulatory proteins, and genomic selection strengthens the reliability of stress tolerance predictions in millet breeding populations. This review emphasizes the impact of transcriptomics on millet improvement by collating the differentially expressed genes (DEGs), and transcription factors (TFs) specific to abiotic stress response in millets which could open advantageous avenues with intriguing opportunities in breeding cultivars for climate resilience. [ABSTRACT FROM AUTHOR]

The destructive bacterial wilt disease caused by Ralstonia solanacearum leads to substantial losses in tomato production worldwide. RNA‐seq is a powerful technology to decipher various biological processes of host–pathogen interactions by analysing differentially expressed genes (DEGs). In the current study, we used RNA‐seq to analyse the transcriptome changes during the interaction of R. solanacearum and susceptible tomato leaves at the time point of 24 h. Gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to annotate functions of DEGs in tomato plants. DEGs related to plant and pathogen interaction pathways, photosynthesis pathways and hormone signalling pathways were further analysed. Our results revealed that R. solanacearum inoculation activated plant defence response pathways to induce a number of core defence genes against bacterial invasion, inhibited expression of genes related to photosynthesis processes and activated the salicylic acid (SA) signalling pathway to induce defence responses. We quantified SA and jasmonic acid (JA) contents after bacterial inoculation. SA treatment alleviated plant disease symptoms and induced immune‐related reactive oxygen species (ROS) bursts in tomato leaves. The extent of disease symptoms was much greater in SlNPR1‐silenced plants than wild‐type plants. Together, our results will provide a better understanding of the mechanisms of plant induced defences against bacterial invasion and provide a theoretical basis for breeding resistance of tomato against R. solanacearum in future. [ABSTRACT FROM AUTHOR]

Background: Proliferative diabetic retinopathy (PDR) is a severe complication of diabetes, and understanding its molecular mechanisms is crucial. Endoplasmic reticulum (ER) stress has been implicated in various diseases, including diabetic complications. This study aims to elucidate ER stress-related biomarkers in PDR, providing insights into the underlying molecular pathways. Methods: We analyzed two independent PDR datasets, GSE102485 and GSE60436. The GSE102485 dataset (22 PDR and 3 normal samples) was the primary dataset for comprehensive analyses, including differential expression, functional enrichment, PPI network construction, immune cell infiltration, and drug prediction. The GSE60436 dataset (6 PDR and 3 normal samples) was used for validation. In vitro experiments using human umbilical vein endothelial cells (HUVECs) in a high-glucose environment were conducted to validate key bioinformatics outcomes. Western blotting assessed protein levels of ER stress markers (TRAM1 and TXNIP). Results: Differential expression analysis identified 2451 genes, including 328 ER stress-related genes. Functional analysis revealed enrichment in ER stressrelated processes and pathways. Hub genes (BCL2, CCL2, IL-1b, TLR4, TNF, TP53) were identified, and immune infiltration analysis showed altered immune cell proportions. Validation in GSE60436 and in vitro confirmed ER stress gene dysregulation. Drug prediction suggested potential small molecules targeting ER stress markers. Conclusion: This study provides a comprehensive molecular characterization of ER stress in PDR, highlighting altered biological processes, immune changes, and potential therapeutic targets. The identified hub genes and small molecules offer avenues for further investigation and therapy development, enhancing understanding of PDR pathogenesis and aiding targeted intervention creation. [ABSTRACT FROM AUTHOR]

Liriomyza trifolii (Burgess) (Diptera: Agromyzidae) is a polyphagous insect that is widely known for its invasiveness. Understanding the adaptation of L. trifolii to different host plants is critical in formulating effective approaches for integrated pest management (IPM). In this study, the effects of various host plants on L. trifolii were investigated by age‐stage, two‐sex life tables and transcriptome analysis. Our results show that the growth rate of immature L. trifolii on sponge gourd increased significantly relative to bean, but mortality was high. Mature L. trifolii adapted to sponge gourd had significantly increased longevity as compared to flies adapted to bean but exhibited reduced fecundity. The net reproductive rate, the intrinsic rate of increase, and the finite rate of increase of L. trifolii adapted to sponge gourd were significantly lower than those of flies adapted to bean. Transcriptome analysis showed the presence of 150 up‐ and 617 downregulated differentially expressed genes in L. trifolii adapted to sponge gourd as compared to flies adapted to bean. Genes encoding glutathione‐S‐transferase, cytochrome P450, and trypsin were significantly downregulated in L. trifolii adapted to sponge gourd as compared to bean. This study provides valuable insight into host plant effects on L. trifolii and provides a basis for the subsequent development of IPM measures such as push and pull, crop rotation, and biopesticide development. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is a malignant neoplasm which is classified into various types defined by underlying molecular factors such as estrogen receptor positive (ER+), progesterone receptor positive (PR+), human epidermal growth factor positive (HER2+) and triple negative (TNBC). Early detection of ER+ and TNBC is crucial in the choice of diagnosis and appropriate treatment strategy. Here we report the key genes associated to ER+ and TNBC using RNA-Seq analysis and machine learning models. Three ER+ and TNBC RNA seq datasets comprising 164 patients in-toto were selected for standard NGS hierarchical data processing and data analyses protocols. Enrichment pathway analysis and network analysis was done and finally top hub genes were identified. To come with a reliable classifier which could distinguish the distinct transcriptome patterns associated to ER+ and TNBC, ML models were built employing Naïve Bayes, SVM and kNN. 1730 common DEG's exhibiting significant logFC values with 0.05 p-value threshold were identified. A list of top ten hub genes were screened on the basis of maximal clique centrality (MCC) which included CDC20, CDK1, BUB1, AURKA, CDCA8, RRM2, TTK, CENPF, CEP55 and NDC80.These genes were found to be involved in crucial cell cycle pathways. k-Nearest Neighbor (kNN) model was observed to be best classifier with accuracy 84%, specificity 66% and sensitivity 95% to differentiate between ER+ and TNBC RNA-Seq transcriptomes. Our screened list of 10 hub genes can thus help unearth novel molecular signatures implicated in ER+ and TNBC onset, prognosis and design of novel protocols for breast cancer diagnostics and therapeutics. [ABSTRACT FROM AUTHOR]

Objective: Sago palm (Metroxylon sagu Rottb.) is one of the most important economic crops abundantly found in Mukah, Sarawak, Malaysia. The robustness of the palm triggered the Sarawak government's selection as one of the state's commodity crops, with the opening of several sago palm plantations. However, stunted (non-trunking) palms were reported in several sago palm plantations despite attaining a maturity period of more than ten years after cultivation. Research targeting this problem has been conducted in various fields, yet information on molecular mechanisms is still scarce. This study aimed to determine the genes responsible for sago palm's normal phenotype (trunking) by attaining leaf transcriptomes from samples of all trunking sago palms from different sago palm plantations. Data description: The conventional CTAB method was employed in the present investigation to extract total RNA from leaf tissues. Transcriptome sequencing was conducted on the Illumina NovaSeq 6000 platform. Differential expression analysis was performed using the DESeq2 package. A total of 6,119 differentially expressed genes, comprising 4,384 downregulated and 1,735 upregulated genes, were expressed in all three sago palm datasets. The datasets provide insights into the commonly expressed genes among trunking sago palms. [ABSTRACT FROM AUTHOR]

Inflammatory Bowel Disease (IBD) is believed to be a risk factor for Small Intestinal Neuroendocrine Tumors (SI-NET) development; however, the molecular relationship between IBD and SI-NET has yet to be elucidated. In this study, we use a systems biology approach to uncover such relationships. We identified a more similar transcriptomic-wide expression pattern between Crohn's Disease (CD) and SI-NET whereas a higher proportion of overlapping dysregulated genes between Ulcerative Colitis (UC) and SI-NET. Enrichment analysis indicates that extracellular matrix remodeling, particularly in epithelial-mesenchymal transition and intestinal fibrosis mediated by TIMP1, is the most significantly dysregulated pathway among upregulated genes shared between both IBD subtypes and SINET. However, this remodeling occurs through distinct regulatory molecular mechanisms unique to each IBD subtype. Specifically, myofibroblast activation in CD and SI-NET is mediated through IL-6 and ciliary-dependent signaling pathways. Contrarily, in UC and SI-NET, this phenomenon is mainly regulated through immune cells like macrophages and the NCAM signaling pathway, a potential gut-brain axis in the context of these two diseases. In both IBD and SINET, intestinal fibrosis resulted in significant metabolic reprogramming of fatty acid and glucose to an inflammatory- and cancer-inducing state. This altered metabolic state, revealed through enrichment analysis of downregulated genes, showed dysfunctions in oxidative phosphorylation, gluconeogenesis, and glycogenesis, indicating a shift towards glycolysis. Also known as the Warburg effect, this glycolytic switch, in return, exacerbates fibrosis. Corresponding to enrichment analysis results, network construction and subsequent topological analysis pinpointed 7 protein complexes, 17 hub genes, 11 microRNA, and 1 transcription factor related to extracellular matrix accumulation and metabolic reprogramming that are candidate biomarkers in both IBD and SI-NET. Together, these biological pathways and candidate biomarkers may serve as potential therapeutic targets for these diseases. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

One of the sensitive markers for autoimmune thyroid disease (AITD) clinical identification is thyroid-stimulating hormone receptor antibodies (TRAbs). To quickly distinguish TRAb with distinct antigenic epitopes, a straightforward and uncomplicated technique has not yet been created. The objective of this study is to search for molecular diagnostic targets for different types of AITD {Graves' disease (GD), Graves' orbitopathy (GO), GD with third-degree goiter [GD(3)], hypothyroidism combined with positive TRAb [HT(TRAb+)]} as molecular diagnostic targets. Following action on thyroid cells, differential genes (DEGs) generated by TRAb with distinct antigenic epitopes were detected and identified by RNA sequencing (RNA-Seq), bioinformatics analysis, and quantitative reverse transcription-polymerase chain reaction (RT-qPCR) in the serum of patients with AITD. Using the 5-ethynyl-2′-deoxyuridine (EdU) assay, the effect of coculturing thyroid cells with different antigenic TRAb epitopes on the cells' capacity to proliferate was investigated. Bioinformatics analysis and RT-qPCR validation identified one GD key gene alpha 2-HS glycoprotein (AHSG), two GO key genes [adrenoceptor alpha 1D (ADRA1D) and H2B clustered histone 18 (H2BC18)], two GD(3) key genes [suppressor of cytokine signaling 1 (SOCS1) and cytochrome b-245 beta (CYBB)], and one HT(TRAb+) key gene (MASP2). Correlation analysis and ROC curves showed that the abovementioned genes could be used as molecular diagnostic targets for different types of AITD. Finally, EdU results showed that TRAb inhibited thyroid cell proliferation in the HT(TRAb+) group compared with the normal control group, whereas the remaining three groups promoted thyroid cell proliferation, with a statistically significant difference (P < 0.05). We identified six key genes for different types of AITD, which have diagnostic value for different types of AITD. Meanwhile, we found that TRAbs with different antigenic epitopes in AITD have different biological functions. NEW & NOTEWORTHY: We identified six molecular targets of different types of AITD [GD, GO, GD(3), and HT(TRAb+)], which have diagnostic value for different types of AITD. Meanwhile, we found that TRAb with different antigenic epitopes extracted from the sera of patients with AITD had different biological functions, which also provided a new idea for further research on the mechanism of action of TRAb with different antigenic epitopes in AITD. [ABSTRACT FROM AUTHOR]

Low temperature is a significant abiotic stress factor that not only impacts plant growth, development, yield, and quality but also constrains the geographical distribution of numerous wild plants. Kohlrabi (Brassica oleracea L. var. caulorapa L.) belongs to the Brassicaceae family and has a short growing period. In this study, a total of 196,642 unigenes were obtained from kohlrabi seedlings at low temperatures; of these, 52,836 unigenes were identified as differentially expressed genes. Transcription factor family members ARR-B, C3H, B3-ARF, etc. that had a high correlation with biochemical indicators related to low temperature were identified. A total of nineteen BocARR-B genes (named BocARR-B1–BocARR-B19) were obtained, and these genes were distributed unevenly across seven chromosomes. Nineteen BocARR-B genes searched four conserved motifs and were divided into three groups. The relative expression level analysis of 19 BocARR-B genes of kohlrabi showed obvious specificity in different tissues. This study lays a foundation and provides new insight to explain the low-temperature resistance mechanism and response pathways of kohlrabi. It also provides a theoretical basis for the functional analysis of 19 BocARR-B transcription factor gene family members. [ABSTRACT FROM AUTHOR]

LMNA-related dilated cardiomyopathy (DCM) is an autosomal-dominant genetic condition with cardiomyocyte and conduction system dysfunction often resulting in heart failure or sudden death. The condition is caused by mutation in the Lamin A/C (LMNA) gene encoding Type-A nuclear lamin proteins involved in nuclear integrity, epigenetic regulation of gene expression, and differentiation. The molecular mechanisms of the disease are not completely understood, and there are no definitive treatments to reverse progression or prevent mortality. We investigated possible mechanisms of LMNA-related DCM using induced pluripotent stem cells derived from a family with a heterozygous LMNA c.357-2A>G splice-site mutation. We differentiated one LMNA-mutant iPSC line derived from an affected female (Patient) and two non-mutant iPSC lines derived from her unaffected sister (Control) and conducted single-cell RNA sequencing for 12 samples (four from Patients and eight from Controls) across seven time points: Day 0, 2, 4, 9, 16, 19, and 30. Our bioinformatics workflow identified 125,554 cells in raw data and 110,521 (88%) high-quality cells in sequentially processed data. Unsupervised clustering, cell annotation, and trajectory inference found complex heterogeneity: ten main cell types; many possible subtypes; and lineage bifurcation for cardiac progenitors to cardiomyocytes (CMs) and epicardium-derived cells (EPDCs). Data integration and comparative analyses of Patient and Control cells found cell type and lineage-specific differentially expressed genes (DEGs) with enrichment, supporting pathway dysregulation. Top DEGs and enriched pathways included 10 ZNF genes and RNA polymerase II transcription in pluripotent cells (PP); BMP4 and TGF Beta/BMP signaling, sarcomere gene subsets and cardiogenesis, CDH2 and EMT in CMs; LMNA and epigenetic regulation, as well as DDIT4 and mTORC1 signaling in EPDCs. Top DEGs also included XIST and other X-linked genes, six imprinted genes (SNRPN, PWAR6, NDN, PEG10, MEG3, MEG8), and enriched gene sets related to metabolism, proliferation, and homeostasis. We confirmed Lamin A/C haploinsufficiency by allelic expression and Western blot. Our complex Patient-derived iPSC model for Lamin A/C haploinsufficiency in PP, CM, and EPDC provided support for dysregulation of genes and pathways, many previously associated with Lamin A/C defects, such as epigenetic gene expression, signaling, and differentiation. Our findings support disruption of epigenomic developmental programs, as proposed in other LMNA disease models. We recognized other factors influencing epigenetics and differentiation; thus, our approach needs improvement to further investigate this mechanism in an iPSC-derived model. [ABSTRACT FROM AUTHOR]

Endometrial carcinoma is one of most common malignant tumors in women, and ferroptosis is closely related to the development and treatment of endometrial carcinoma. The aim of this study was to screen ferroptosis-related genes associated with endometrial carcinoma and predict targeted drugs through bioinformatics. 761 differentially expressed genes were obtained by the dataset GSE63678 from the GEO database, and most of the genes were enriched in the KEGG_CELL_CYCLE and KEGG_OOCYTE_MEIOSIS signaling pathways. 22 ferroptosis-differentially expressed genes were obtained by intersection with the FerrDb database. These genes were involved in biological processes including macromolecular complex assembly and others, and involved in signal pathways including glutathione metabolism, p53 signaling pathway and others. CDKN2A, IDH1, NRAS, TFRC and GOT1 were obtained as hub genes by PPI network analysis. GEPIA showed that CDKN2A, IDH1, NRAS and TFRC were significantly expressed in endometrial carcinoma. Immunohistochemical results showed that CDKN2A, NRAS and TFRC were significantly expressed in endometrial carcinoma clinical tissue samples. The ROC constructed by TCGA database showed that CDKN2A, NRAS and TFRC had significant value in the diagnosis of endometrial carcinoma, and all had prognostic efficacy. 136,572-09-3 BOSS and others were identified as potential targeted drugs for endometrial carcinoma targeting ferroptosis. Our study has shown that ferroptosis-related genes CDKN2A, NRAS and TFRC are diagnostic markers of endometrial carcinoma, and 136,572-09-3 BOSS, methyprylon BOSS, daunorubicin CTD 00005752, nitroglycerin BOSS and dUTP BOSS, IRON BOSS, Imatinib mesylate BOSS, 2-Butanone BOSS, water BOSS, and L-thyroxine BOSS may be potential therapeutic drugs. [ABSTRACT FROM AUTHOR]

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This study aimed to identify the combined genetic profiles and evaluate the potential mechanism underlying the occurrence of this complication. Methods: The Gene Expression Omnibus (GEO) database was used to obtain the gene expression profiles of psoriasis (GSE30999) and vitiligo (GSE75819), and common differentially expressed genes (DEGs) were identified using GEO2R. DEGs were analyzed using functional enrichment analysis, protein-protein interaction (PPI) network and module construction, hub gene identification, and co-expression analysis. And hub genes were identified using Cytoscape software, and the gene expression of hub genes were validated in psoriasis (GSE13355) and vitiligo (GSE65127) datasets and immunohistochemistry at the clinical sample. Results: A total of 164 common DEGs with the same trend (137 upregulated and 27 downregulated) were selected for subsequent analysis. Functional analysis emphasized the important roles of the cell cycle and mitotic cell division, cytoskeletal reorganization, and chromatin remodeling in the complications of these two diseases. Fourteen important hub genes were identified, including BUB1, CEP55, CDK1, TOP2A, CENPF, PBK, MELK, CCNB2, MAD2L1, NUSAP1, TTK, NEK2, CDKN3, and PTTG1. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) may be an important immune checkpoint in the pathogenesis of the comorbidities. Conclusion: Our study identified hub genes and potential mechanisms underlying psoriasis and vitiligo complications. And we proposed a new spatio-temporal theory and the probable immune checkpoint for the pathogenesis of the comorbidity which may provide new ideas for the further research. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) has seriously affected the quality of traditional Chinese medicinal material Salvia miltiorrhiza in recent years, threatening human health. The physiological and metabolic profiles of S. miltiorrhiza in response to Cd stress have been revealed in previous studies. However, transcriptional and post-transcriptional regulation in response to different degrees of Cd (0, 25, 50, and 100 mg/kg) stress in S. miltiorrhiza remains unclear. Here, transcriptome atlas in S. miltiorrhiza under different degrees of Cd Stress was unveiled using RNA sequencing (RNA-seq). These results showed that the profiles of gene expression were different in the response to Cd treatment. Defense response-related biological processes were involved in differentially expressed genes (DEGs). In total, 1966 genes were identified as transcription factors (TFs) with seven expressed trends. Retained intron (RI) was the major phenomenon. Targeted genes of intron splicing factors were identified via weighted gene co-expression network analysis (WGCNA). All of these indicated that transcriptional and post-transcriptional regulations were involved in response to Cd stress in S. miltiorrhiza. Our study will provide the most comprehensive resource for studying heavy metals in traditional Chinese medicine plants. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the leading commonly diagnosed cancer in the world, with complex mechanisms underlying its development. There is an urgent need to enlighten key genes as potential therapeutic targets crucial to advancing BC treatment. This study sought to investigate the influence of doxorubicin (DOX) on identified key genes consistent across numerous BC datasets obtained through bioinformatic analysis. To date, a meta-analysis of publicly available coding datasets for expression profiling by array from the Gene Expression Omnibus (GEO) has been carried out. Differentially Expressed Genes (DEGs) identified using GEO2R revealed a total of 23 common DEGs, including nine upregulated genes and 14 downregulated genes among the datasets of three platforms (GPL570, GPL6244, and GPL17586), and the commonly upregulated DEGs, showed significant enrichment in the cell cycle in KEGG analysis. The top nine genes, NUSAP1, CENPF, TPX2, PRC1, ANLN, BUB1B, AURKA, CCNB2, and CDK-1, with higher degree values and MCODE scores in the cytoscape program, were regarded as hub genes. The hub genes were activated in disease states commonly across all the subclasses of BC and correlated with the unfavorable overall survival of BC patients, as verified by the GEPIA and UALCAN databases. qRT-PCR confirmed that DOX treatment resulted in reduced expression of these genes in BC cell lines, which reinforces the evidence that DOX remains an effective drug for BC and suggests that developing modified formulations of doxorubicin to reduce toxicity and resistance, could enhance its efficacy as an effective therapeutic option for BC. [ABSTRACT FROM AUTHOR]

Simple Summary: The oriental river prawn, Macrobrachium nipponense, is a widely distributed species in freshwater and low-salinity estuarine regions of China and other Asian countries. This species has become an important commercial commodity in China because of its high nutritional value and palatability. There are significant differences in growth between male and female M. nipponense. The aim of this study was to determine the hepatopancreas transcriptome differences between sex-related size differences in M. nipponense. We identified four genes associated with sex-related size differences, as well as six closely related metabolic pathways. The results indicated the molecular mechanism underlying the sex-related size differences and identified key genes and metabolic pathways. This data will be invaluable to support explanations of individual differences between male and female prawns. Macrobrachium nipponense, a commercially popular crustacean species within the Chinese context, is recognized for its exceptional nutritional composition and palatability. There are significant differences in growth between male and female M. nipponense. Herein, transcriptomics was used to determine the hepatopancreas transcriptome differences between sex-related size differences in M. nipponense. We identified 974 differentially expressed genes (DEGs) between the SHE (female) and BHE (male) groups, which were validated using RT-qPCR. The genes encoding matrix metalloproteinase-9 (MM9), Ribosome-binding protein 1 (RBP1), Aly/REF export factor 2, and hematological and neurological expressed 1 (HN1) may play a role in modulating the sex-related size differences observed in M. nipponense. Clusters of orthologous groups and gene ontology functional analysis demonstrated that the DEGs for sex-related size in M.nipponense were associated with various biological functions. The Kyoto Encyclopedia of Genes and Genomes pathways analysis demonstrated that upregulated DEGs were mainly enriched in lysine biosynthesis, tryptophan metabolism, and lysine degradation pathways, whereas the downregulated DEGs were mainly enriched in ascorbate and aldarate metabolism, retinol metabolism, and drug metabolism-cytochrome P450 pathways. The results indicated the molecular mechanism underlying the sex-related size differences and identified key genes. This data will be invaluable to support explanations of individual differences between male and female prawns. [ABSTRACT FROM AUTHOR]

Glioblastoma multiforme (GBM) is a malignant tumour with a poor prognosis. Therefore, potential treatment strategies and novel therapeutic targets have gained increased attention. Our data showed that the ethanol extract of Vanilla planifolia stem (VAS) significantly decreased the viability and the colony formation of GBM cells. Moreover, VAS induced the cleavage of MAP1LC3, a marker of autophagy. Further RNA‐seq and bioinformatic analysis revealed 4248 differentially expressed genes (DEGs) between VAS‐treated GBM cells and the control cells. Protein–protein interactions between DEGs with fold changes less than −3 and more than 5 were further analysed, and we found that 16 and 9 hub DEGs, respectively, were correlated with other DEGs. Further qPCR experiments confirmed that 14 hub DEGs was significantly downregulated and 9 hub DEGs was significantly upregulated. In addition, another significantly downregulated DEG, p21‐activated kinase 6 (PAK6), was correlated with the overall survival of GBM patients. Further validation experiments confirmed that VAS significantly reduced the mRNA and protein expression of PAK6, which led to the abolition of cell viability and colony formation. These findings demonstrated that VAS reduced cell viability, suppressed colony formation and induced autophagy and revealed PAK6 and other DEGs as potential therapeutic targets for GBM treatment. [ABSTRACT FROM AUTHOR]

Aims: This study examined the relationship between obesity (OB) and osteoporosis (OP), aiming to identify shared genetic markers and molecular mechanisms to facilitate the development of therapies that target both conditions simultaneously. Methods: Using weighted gene co-expression network analysis (WGCNA), we analyzed datasets from the Gene Expression Omnibus (GEO) database to identify co-expressed gene modules in OB and OP. These modules underwent Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and protein-protein interaction analysis to discover Hub genes. Machine learning refined the gene selection, with further validation using additional datasets. Single-cell analysis emphasized specific cell subpopulations, and enzyme-linked immunosorbent assay (ELISA), protein blotting, and cellular staining were used to investigate key genes. Results: WGCNA revealed critical gene modules for OB and OP, identifying the Toll-like receptor (TLR) signalling pathway as a common factor. TLR2 was the most significant gene, with a pronounced expression in macrophages. Elevated TLR2 expression correlated with increased adipose accumulation, inflammation, and osteoclast differentiation, linking it to OP development. Conclusion: Our study underscores the pivotal role of TLR2 in connecting OP and OB. It highlights the influence of TLR2 in macrophages, driving both diseases through a pro-inflammatory mechanism. These insights propose TLR2 as a potential dual therapeutic target for treating OP and OB. Cite this article: Bone Joint Res 2024;13(10):573–587.

Aegilops tauschii is a wild diploid goat-grass which occupies a vast range in Central Eurasia and comprises three different gene-pools: TauL1, TauL2, and TauL3. Multivariate statistical analysis of the transcriptomes from the leaf tissue of 40 A. tauschii accessions, 18 of TauL1, 20 of TauL2, and 2 of TauL3, revealed that the gene-pools of A. tauschii distinctly and essentially differ in their genetic expression patterns. Statistically significant differential gene expression of 2349, 376, and 272 were observed between TauL1 and TauL2; TauL1 and TauL3; TauL2 and TauL3, respectively. These findings indicate substantial adaptive intraspecies divergence in A. tauschii.

To elucidate the genetic factors contributing to melon resistance against Phelipanche aegyptiaca and comprehend the role of differentially resistant materials in responding to changes in P. aegyptiaca parasitisation, we investigated the P. aegyptiaca-resistant line K16 and the susceptible line K27. The parasitism rate of P. aegyptiaca was assessed at 25 days. Results revealed significant differences in parasitisation rates between K16 (15.35%) and K27 (34.2%). We compared inoculated K16 and K27 to their respective controls through transcriptome analysis and contrasted inoculated K16 with inoculated K27. Eight hundred eighteen genes exhibited differential expression across all comparisons. Gene ontology (GO) functional enrichment analysis revealed that differentially expressed genes were significantly enriched in nitrate transport and assimilation, cellular components, extracellular regions, binding and enzyme activities. KEGG pathway enrichment underscored the importance of phytohormone signaling, phenylpropanoid biosynthesis, linolenic acid and linoleic acid metabolism, cyanoamino acid metabolism and nitrogen metabolism in the interaction between melon and P. aegyptiaca. Nine genes potentially associated with P. aegyptiaca resistance were identified, encoding cytochrome protein P450, peroxidases, β-glucosidase, acyltransferase family proteins, histidine phosphotransfer protein, and D-type cyclins. This study aims to provide insights into the mechanism of P. aegyptiaca parasitism on melons and offers implications for breeding resistant varieties

Abstract Background Endometriosis is a common cause of endometrial-type mucosa outside the uterine cavity with symptoms such as painful periods, chronic pelvic pain, pain with intercourse and infertility. However, the early diagnosis of endometriosis is still restricted. The purpose of this investigation is to identify and validate the key biomarkers of endometriosis. Methods Next-generation sequencing dataset GSE243039 was obtained from the Gene Expression Omnibus database, and differentially expressed genes (DEGs) between endometriosis and normal control samples were identified. After screening of DEGs, gene ontology (GO) and REACTOME pathway enrichment analyses were performed. Furthermore, a protein–protein interaction (PPI) network was constructed and modules were analyzed using the Human Integrated Protein–Protein Interaction rEference database and Cytoscape software, and hub genes were identified. Subsequently, a network between miRNAs and hub genes, and network between TFs and hub genes were constructed using the miRNet and NetworkAnalyst tool, and possible key miRNAs and TFs were predicted. Finally, receiver operating characteristic curve analysis was used to validate the hub genes. Results A total of 958 DEGs, including 479 upregulated genes and 479 downregulated genes, were screened between endometriosis and normal control samples. GO and REACTOME pathway enrichment analyses of the 958 DEGs showed that they were mainly involved in multicellular organismal process, developmental process, signaling by GPCR and muscle contraction. Further analysis of the PPI network and modules identified 10 hub genes, including vcam1, snca, prkcb, adrb2, foxq1, mdfi, actbl2, prkd1, dapk1 and actc1. Possible target miRNAs, including hsa-mir-3143 and hsa-mir-2110, and target TFs, including tcf3 (transcription factor 3) and clock (clock circadian regulator), were predicted by constructing a miRNA-hub gene regulatory network and TF-hub gene regulatory network. Conclusions This investigation used bioinformatics techniques to explore the potential and novel biomarkers. These biomarkers might provide new ideas and methods for the early diagnosis, treatment and monitoring of endometriosis.

Abstract Age-related hearing loss (ARHL) or presbycusis is associated with irreversible progressive damage in the inner ear, where the sound is transduced into electrical signal; but the detailed mechanism remains unclear. Here, we sought to determine the potential molecular mechanism involved in the pathogeneses of ARHL with bioinformatics methods. A single-cell transcriptome sequencing study was performed on the cochlear samples from young and aged mice. Detection of identified cell type marker allowed us to screen 18 transcriptional clusters, including myeloid cells, epithelial cells, B cells, endothelial cells, fibroblasts, T cells, inner pillar cells, neurons, inner phalangeal cells, and red blood cells. Cell-cell communications were analyzed between young and aged cochlear tissue samples by using the latest integration algorithms Cellchat. A total of 56 differentially expressed genes were screened between the two groups. Functional enrichment analysis showed these genes were mainly involved in immune, oxidative stress, apoptosis, and metabolic processes. The expression levels of crucial genes in cochlear tissues were further verified by immunohistochemistry. Overall, this study provides new theoretical support for the development of clinical therapeutic drugs.

Abstract Leishmaniasis is an infectious disease caused by protozoan parasites from different species of leishmania. The disease is transmitted by female sandflies that carry these parasites. In this study, datasets on leishmaniasis published in the GEO database were analyzed and summarized. The analysis in all three datasets (GSE43880, GSE55664, and GSE63931) used in this study has been performed on the skin wounds of patients infected with a clinical form of leishmania (Leishmania braziliensis), and biopsies have been taken from them. To identify differentially expressed genes (DEGs) between leishmaniasis patients and controls, the robust rank aggregation (RRA) procedure was applied. We performed gene functional annotation and protein-protein interaction (PPI) network analysis to demonstrate the putative functionalities of the DEGs. The study utilized Molecular Complex Detection (MCODE), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) to detect molecular complexes within the protein-protein interaction (PPI) network and conduct analyses on the identified functional modules. The CytoHubba plugin’s results were paired with RRA analysis to determine the hub genes. Finally, the interaction between miRNAs and hub genes was predicted. Based on the RRA integrated analysis, 407 DEGs were identified (263 up-regulated genes and 144 down-regulated genes). The top three modules were listed after creating the PPI network via the MCODE plug. Seven hub genes were found using the CytoHubba app and RRA: CXCL10, GBP1, GNLY, GZMA, GZMB, NKG7, and UBD. According to our enrichment analysis, these functional modules were primarily associated with immune pathways, cytokine activity/signaling pathways, and inflammation pathways. However, a UBD hub gene is interestingly involved in the ubiquitination pathways of pathogenesis. The mirNet database predicted the hub gene’s interaction with miRNAs, and results revealed that several miRNAs, including mir-146a-5p, crucial in fighting pathogenesis. The key hub genes discovered in this work may be considered as potential biomarkers in diagnosis, development of agonists/antagonist, novel vaccine design, and will greatly contribute to clinical studies in the future.

Abstract Background Platycodon grandiflorum (P. grandiflorum) is a commonly used medicinal plant in China. Transcriptome sequencing studies of different tissues of P. grandiflorum have been widely conducted. However, studies on transcriptome sequencing and expression patterns of key genes in the saponin synthesis pathway of Tongcheng P. grandiflorum, a high-quality medicinal resource of different years, are relatively limited. Results This study involved transcriptome sequencing and bioinformatics analysis of the roots from annual, biennial, and triennial P. grandiflorum in the Tongcheng area. After data filtering and assembly, we obtained 111.44 Gb of clean base data, including 742,880616 clean reads. We identified 5,156 differential expression unigenes between at least two sample groups, with differences noted among annual, biennial, and triennial P. grandiflorum plants. GO enrichment analysis annotated 3509, 1819, and 1393 DEGs in comparison TC1vsTC2, TC1vsTC3, and TC2vsTC3, respectively. Furthermore, KEGG enrichment analysis identified 16 genes encoding key enzymes in the terpene skeleton biosynthesis, sesquiterpene and triterpene biosynthesis pathways, including SE, AACT, FPPS, DXR, HMGR, HMGS, and DXS. The results of qRT-PCR experiments showed that most of the genes were most highly expressed in annual P. grandiflorum. Conclusions The present study provided transcriptomic data from the roots of Tongcheng P. grandiflorum of different years, which provides critical bioinformatics data on the growth and development of P. grandiflorum, laying a foundation for further research on saponins and identifying key enzymes involved in this process across different growth stages.

Abstract Objective Sago palm (Metroxylon sagu Rottb.) is one of the most important economic crops abundantly found in Mukah, Sarawak, Malaysia. The robustness of the palm triggered the Sarawak government’s selection as one of the state’s commodity crops, with the opening of several sago palm plantations. However, stunted (non-trunking) palms were reported in several sago palm plantations despite attaining a maturity period of more than ten years after cultivation. Research targeting this problem has been conducted in various fields, yet information on molecular mechanisms is still scarce. This study aimed to determine the genes responsible for sago palm’s normal phenotype (trunking) by attaining leaf transcriptomes from samples of all trunking sago palms from different sago palm plantations. Data description The conventional CTAB method was employed in the present investigation to extract total RNA from leaf tissues. Transcriptome sequencing was conducted on the Illumina NovaSeq 6000 platform. Differential expression analysis was performed using the DESeq2 package. A total of 6,119 differentially expressed genes, comprising 4,384 downregulated and 1,735 upregulated genes, were expressed in all three sago palm datasets. The datasets provide insights into the commonly expressed genes among trunking sago palms.

Abstract 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.

Abstract Breast cancer (BC) is a malignant neoplasm which is classified into various types defined by underlying molecular factors such as estrogen receptor positive (ER+), progesterone receptor positive (PR+), human epidermal growth factor positive (HER2+) and triple negative (TNBC). Early detection of ER+ and TNBC is crucial in the choice of diagnosis and appropriate treatment strategy. Here we report the key genes associated to ER+ and TNBC using RNA-Seq analysis and machine learning models. Three ER+ and TNBC RNA seq datasets comprising 164 patients in-toto were selected for standard NGS hierarchical data processing and data analyses protocols. Enrichment pathway analysis and network analysis was done and finally top hub genes were identified. To come with a reliable classifier which could distinguish the distinct transcriptome patterns associated to ER+ and TNBC, ML models were built employing Naïve Bayes, SVM and kNN. 1730 common DEG’s exhibiting significant logFC values with 0.05 p-value threshold were identified. A list of top ten hub genes were screened on the basis of maximal clique centrality (MCC) which included CDC20, CDK1, BUB1, AURKA, CDCA8, RRM2, TTK, CENPF, CEP55 and NDC80.These genes were found to be involved in crucial cell cycle pathways. k-Nearest Neighbor (kNN) model was observed to be best classifier with accuracy 84%, specificity 66% and sensitivity 95% to differentiate between ER+ and TNBC RNA-Seq transcriptomes. Our screened list of 10 hub genes can thus help unearth novel molecular signatures implicated in ER+ and TNBC onset, prognosis and design of novel protocols for breast cancer diagnostics and therapeutics.

As a carnivorous fish, the cannibalism are prone to happen in the early seedling stage in Dongting catfish (Silurus asotus), especailly when there is not enough food, which resulting in the low survival rate of Dongting catfish. To find clues to improve the survival rate of Dongting catfish offspring, the comparative transcriptomics analysis were conducted between normal and malformed larval fish, as well as normal larval fish before and after first food intake. In normal and malformed larval fish groups, a total of 881 differential genes were identified, including 634 up-regulated genes and 247 down-regulated genes. From these genes related to growth hormone synthesis and secretion were screened out as SLA isoform X1, SOCS3, STAT1b, JUNB, respectively. In the group of larval fish before and after the first food intake, 4901 up-regulated genes and 3660 down-regulated genes were found, from which the differential genes related to protein digestion and absorption pathway and pancreatic secretion pathway were screened out as cathepsin D precursor, elastase 2 like precursor, elastase 2 precursor, LPL isoform X1, CTRB1 precursor, CTRL precursor, CPA precursor, FABP, SLC15A1, CEL tandem duplicate 2 precursor. The differential genes screened for association with amino acid metabolism were ASAOC precursor, PLD3, NDPKs, trehalase, UMP-CMP kinase, L-amino-acid oxidase, PLB1, FALDH isoform X2, PLA2 precursor, glucokinase. Meanwhile, nine differential genes were selected for qPCR verification. The results confirmed that the relative expression trends of these genes were consistent with those found in the transcriptome. These findings provide an important reference for developing strategies to enhance the survival rate of Dongting catfish at early seedling stage.

ABSTRACTParkinson’s disease (PD) often results in hippocampal dysfunction, which leads to cognitive and emotional challenges and synaptic irregularities. This study attempted to assess behavioral anomalies and identify differentially expressed genes (DEGs) within the hippocampus of a hemiparkinsonian rat model to potentially uncover novel genetic candidates linked to hippocampal dysfunction. Striatal 6-hydroxydopamine (6-OHDA) infusions were performed unilaterally in the brains of adult SD rats, while dopaminergic impairments were verified in rats with 6-OHDA-lesioned striata. RNA sequencing and gene expression analysis unveiled 1018 DEGs in the ipsilateral rat hippocampus following 6-OHDA infusion: 631 genes exhibited upregulation, while 387 genes were downregulated (with FDR-adjusted p-value 1.5). Gene ontology analysis of DEGs indicated that alterations in the hippocampi of 6-OHDA-lesioned rats were primarily associated with synaptic signaling, axon development, behavior, postsynaptic membrane, synaptic membrane, neurotransmitter receptor activity, and peptide receptor activity. The Kyoto Encyclopedia of Genes and Genomes analysis of DEGs demonstrated significant enrichment of the neuroactive ligand–receptor interaction, calcium signaling pathway, cAMP signaling pathway, axon guidance, and notch signaling pathway in rat hippocampi that had been subjected to striatal 6-OHDA infusion. STRING analysis confirmed a notable upregulation of eight hub genes (Notch3, Gng4, Itga3, Grin2d, Hgf, Fgf11, Htr3a, and Col6a2), along with a significant downregulation of two hub genes (Itga11 and Plp1), as validated by reverse transcription-quantitative polymerase chain reaction. This study provides a comprehensive transcriptomic profile of the hippocampi in a hemiparkinsonian rat model, thereby offering insights into the signaling pathways underlying hippocampal dysfunction.

Macrobrachium rosenbergii is an economically important crustacean worldwide. Based on the important role of the androgenic gland (AG) in sex determination in crustaceans, this study comparatively analyzed the transcriptomes of AG and ovary tissues using Illumina sequencing technology. A total of 91,810 unigenes were generated from the six libraries after splicing and assembly, and 28,516 (31.1%) were annotated by BLASTx comparison with Nr and other databases. A total of 20,793 differentially expressed genes including 105 potentially related to sex determination and sex differentiation were identified in both tissues, of which 69 were upregulated in the ovary, 19 were upregulated in AG, 12 were ovary-specific, and 5 were AG-specific. This study screened out differentially expressed genes related to sex determination and differentiation by comparing the transcriptome expression differences between the ovary and AG of M. rosenbergii, accumulating important data for further studies on the mechanisms of sex determination and differentiation in M. rosenbergii. [ABSTRACT FROM AUTHOR]

Diabetic cardiomyopathy (DbCM) is one of the most common vascular complications of diabetes, and can cause heart failure and threaten the life of patients. The pathogenesis is complex, and key genes have not fully identified. In this study, bioinformatics analysis was used to predict DbCM-related gene targets. Published datasets from the NCBI Gene Expression Omnibus with accession numbers GSE62203 and GSE197850 were selected for analysis. Differentially expressed genes (DEGs) were identified by the online tool GEO2R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the DAVID online database. Protein–protein interaction network construction and hub gene identification were performed using STRING and Cytoscape. We used 30 mM and 1 μM hydrocortisone-stimulated AC16 cells as an in vitro model of diabetic cardiomyopathy. Quantitative real-time PCR (qRT-PCR) was performed to validate the expression levels of hub genes. A total of 73 common DEGs were identified in both datasets, including 47 upregulated and 26 downregulated genes. GO and KEGG pathway enrichment analyses revealed that the DEGs were significantly enriched in metabolism, hypoxia response, apoptosis, cell proliferation regulation, and cytoplasmic and HIF signalling pathways. The top 10 hub genes were LDHA, PGK1, SLC2A1, ENO1, PFKFB3, EGLN1, MYC, PDK1, EGLN3 and BNIP3. In our in vitro study, we found that PGK1, SLC2A1, PFKFB3, EGLN1, MYC, EGLN3 and BNIP3 were upregulated, ENO1 was downregulated, and LDHA was unchanged. Except for PGK1 and ENO1, these hub genes have been previously reported to be involved in DbCM. In summary, we identified DEGs and hub genes and first reported PGK1 and ENO1 in DbCM, which may serve as potential candidate genes for DbCM targeted therapy. [ABSTRACT FROM AUTHOR]

Background: Asthma, a prevalent chronic respiratory disorder, remains enigmatic, notwithstanding considerable advancements in our comprehension. Continuous efforts are crucial for discovering novel molecular targets and gaining a comprehensive understanding of its pathogenesis. Materials and methods: In this study, we analyzed gene expression data from 212 individuals, including asthma patients and healthy controls, to identify 267 differentially expressed genes, among which C1orf64 and C7orf26 emerged as potential key genes in asthma pathogenesis. Various bioinformatics tools, including differential gene expression analysis, pathway enrichment, drug target prediction, and single-cell analysis, were employed to explore the potential roles of the genes. Results: Quantitative PCR demonstrated differential expression of C1orf64 and C7orf26 in the asthmatic airway epithelial tissue, implying their potential involvement in asthma pathogenesis. GSEA enrichment analysis revealed significant enrichment of these genes in signaling pathways associated with asthma progression, such as ABC transporters, cell cycle, CAMs, DNA replication, and the Notch signaling pathway. Drug target prediction, based on upregulated and downregulated differential expression, highlighted potential asthma treatments, including Tyrphostin-AG-126, Cephalin, Verrucarin-a, and Emetine. The selection of these drugs was based on their significance in the analysis and their established anti-inflammatory and antiviral invasion properties. Utilizing Seurat and Celldex packages for single-cell sequencing analysis unveiled disease-specific gene expression patterns and cell types. Expression of C1orf64 and C7orf26 in T cells, NK cells, and B cells, instrumental in promoting hallmark features of asthma, was observed, suggesting their potential influence on asthma development and progression. Conclusion: This study uncovers novel genetic aspects of asthma, highlighting potential therapeutic pathways. It exemplifies the power of integrative bioinformatics in decoding complex disease patterns. However, these findings require further validation, and the precise roles of C1orf64 and C7orf26 in asthma warrant additional investigation to validate their therapeutic potential. [ABSTRACT FROM AUTHOR]

Abstract Objective Gastric cancer (GC) is one of the most common malignancies worldwide and it is considered the fourth most common cause of cancer death. This study aimed to find critical genes/pathways in GC pathogenesis to be used as biomarkers or therapeutic targets. Methods Differentially expressed genes were explored between human gastric cancerous and noncancerous tissues, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analyses were done. Hub genes were identified based on the protein–protein interaction network constructed in the STRING database with Cytoscape software. The hub genes were selected for further investigation using GEPIA2 and DrugBank databases. Results Ten overexpressed hub genes in GC were identified in the current study, including FN1, TP53, IL-6, CXCL5, ELN, ADAMTS2, WISP1, MMP2, CTGF, and THBS1. The study demonstrated the PI3K-Akt pathway's central involvement in GC, with pronounced alterations in essential components. Survival analysis revealed significant correlations between CTGF, FN1, IL-6, THBS1, and WISP1 overexpression and reduced overall survival times in GC patients. Conclusion A mutual interplay emerged, where PI3K-Akt signaling could upregulate certain genes, forming feedback loops and intensifying cancer phenotypes. The interconnected overexpression of genes and the PI3K-Akt pathway fosters gastric tumorigenesis, suggesting therapeutic potential. DrugBank analysis identified limited FDA-approved drugs, advocating for further exploration while targeting these hub genes could reshape GC treatment. The identified genes could be novel diagnostic/prognostic biomarkers or potential therapeutic targets for GC, but further clinical validation is required.