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The rapid growth of large-scale spatial gene expression data demands efficient and reliable computational tools to extract major trends of gene expression in their native spatial context. Here, we used stability-driven unsupervised learning (i.e., staNMF) to identify principal patterns (PPs) of 3D gene expression profiles and understand spatial gene distribution and anatomical localization at the whole mouse brain level. Our subsequent spatial correlation analysis systematically compared the PPs to known anatomical regions and ontology from the Allen Mouse Brain Atlas using spatial neighborhoods. We demonstrate that our stable and spatially coherent PPs, whose linear combinations accurately approximate the spatial gene data, are highly correlated with combinations of expert-annotated brain regions. These PPs yield a brain ontology based purely on spatial gene expression. Our PP identification approach outperforms principal component analysis and typical clustering algorithms on the same task. Moreover, we show that the stable PPs reveal marked regional imbalance of brainwide genetic architecture, leading to region-specific marker genes and gene coexpression networks. Our findings highlight the advantages of stability-driven machine learning for plausible biological discovery from dense spatial gene expression data, streamlining tasks that are infeasible by conventional manual approaches.

MOTIVATION: Protein-protein interaction (PPI) networks provide valuable insights into the function of biological systems. Aligning multiple PPI networks may expose relationships beyond those observable by pairwise comparisons. However, assessing the biological quality of multiple network alignments is a challenging problem. RESULTS: We propose two new measures to evaluate the quality of multiple network alignments using functional information from Gene Ontology (GO) terms. When aligning multiple real PPI networks across species, we observe that both measures are highly correlated with objective quality indicators, such as common orthologs. Additionally, our measures strongly correlate with an alignments ability to predict novel GO annotations, which is a unique advantage over existing GO-based measures. AVAILABILITY AND IMPLEMENTATION: The scripts and the links to the raw and alignment data can be accessed at https://github.com/kimiayazdani/GO_Measures.git.

Network alignment aims to uncover topologically similar regions in the protein-protein interaction (PPI) networks of two or more species under the assumption that topologically similar regions tend to perform similar functions. Although there exist a plethora of both network alignment algorithms and measures of topological similarity, currently no gold standard exists for evaluating how well either is able to uncover functionally similar regions. Here we propose a formal, mathematically and statistically rigorous method for evaluating the statistical significance of shared GO terms in a global, 1-to-1 alignment between two PPI networks. Given an alignment in which k aligned protein pairs share a particular GO term g, we use a combinatorial argument to precisely quantify the p-value of that alignment with respect to g compared to a random alignment. The p-value of the alignment with respect to all GO terms, including their inter-relationships, is approximated using the Empirical Browns Method. We note that, just as with BLASTs p-values, this method is not designed to guide an alignment algorithm towards a solution; instead, just as with BLAST, an alignment is guided by a scoring matrix or function; the p-values herein are computed after the fact, providing independent feedback to the user on the biological quality of the alignment that was generated by optimizing the scoring function. Importantly, we demonstrate that among all GO-based measures of network alignments, ours is the only one that correlates with the precision of GO annotation predictions, paving the way for network alignment-based protein function prediction.

Biological interpretation of metabolomic datasets often ends at a pathway analysis step to find the over-represented metabolic pathways in the list of statistically significant metabolites. However, definitions of biochemical pathways and metabolite coverage vary among different curated databases, leading to missed interpretations. For the lists of genes, transcripts and proteins, Gene Ontology (GO) terms over-presentation analysis has become a standardized approach for biological interpretation. But, GO analysis has not been achieved for metabolomic datasets. We present a new knowledgebase (KB) and the online tool, Gene Ontology Analysis by the Integrated Data Science Laboratory for Metabolomics and Exposomics (IDSL.GOA) to conduct GO over-representation analysis for a metabolite list. The IDSL.GOA KB covers 2393 metabolic GO terms and associated 3144 genes, 1,492 EC annotations, and 2621 metabolites. IDSL.GOA analysis of a case study of older versus young female brain cortex metabolome highlighted 82 GO terms being significantly overrepresented (FDR

Rationale: Shiduqing Capsules, a well‐known Chinese patent medicine, are widely used clinically for the treatment of pruritus. However, to date, there is a lack of research on its pharmacological substances and mechanisms of action. Methods: In the current study, the chemical components of Shiduqing Capsules were identified using UHPLC‐QE‐Orbitrap‐MS technology. Molecular network analysis was employed to identify structurally similar compounds to the known chemical components. The potential molecular targets of the active ingredients were predicted using the SwissTargetPrediction website. The identified targets were further analyzed using gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis through the DAVID database. Molecular docking was used to validate the network pharmacology results. Results: Ultimately, A total of 51 chemical components of Shiduqing Capsules were identified. Molecular network analysis identified 21 flavonoids and 13 terpenoids. The core targets of these ingredients include TP53, AKT1, and STAT3. GO and KEGG enrichment analysis revealed 1,371 different biological functions and 177 signaling pathways. Molecular docking confirmed the high affinity between multiple core active ingredients of Shiduqing Capsules and pruritus targets. Conclusion: In conclusion, the effective ingredients of Shiduqing Capsules exert a multifaceted therapeutic effect on pruritus through multiple targets and pathways. [ABSTRACT FROM AUTHOR]

Antisocial behavior (ASB) infringes on the rights of others and significantly disrupts social order. Studies have shown that ASB is phenotypically associated with various psychiatric disorders. However, these studies often neglected the importance of genetic foundations. This study utilized genome-wide association studies and pleiotropy analysis to explore the genetic correlation between ASB and psychiatric disorders. Linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL) methods were employed to assess genetic correlations, and the PLACO method was used for pleiotropy analysis. Functional annotation and biological pathway analysis of identified pleiotropic genes were performed using enrichment analysis. Furthermore, Mendelian randomization (MR) analysis was conducted to validate these causal relationships. LDSC and HDL analysis showed that significant positive genetic correlations were between ASB and attention deficit hyperactivity disorder (ADHD), schizophrenia (SCZ), major depressive disorder (MDD), and post-traumatic stress disorder (PTSD). Multiple potential pleiotropic genetic loci were identified, particularly the FOXP2 and MDFIC genes located at the 7q31.1 locus. Enrichment analysis showed that these pleiotropic genes are highly expressed in several brain regions (such as the hypothalamus, cerebellar hemisphere, cortex, and amygdala) and immune-related cells. MR analysis further confirmed the causal effects ADHD, SCZ, and MDD on ASB risk. This study reveals significant genetic correlations and potential causal mechanisms between ASB and various psychiatric disorders. The MR analysis confirmed the causal effects of psychiatric disorders on ASB. These findings deepen our understanding of the genetic architecture of psychiatric disorders and ASB. • There are genetic links between ASB and disorders like ADHD, MDD, SCZ, and PTSD. • The pleiotropic loci like FOXP2 and MDFIC at 7q31.1, linking ASB with psychiatric disorders. • There are causal links between ADHD, SCZ, MDD, and ASB. [ABSTRACT FROM AUTHOR]

A debate in conservation genomics centers on whether to conserve small, fragmented populations independently or blend them through translocations from larger populations. Translocations of red grouse (Lagopus scotica) from Great Britain to supplement the Irish population have been suggested. We incorporate a variety of genetic datasets to address this. We used genome wide data from 23 contemporary and historic red grouse from Great Britain and Ireland. We also investigate microsatellite data, sequence candidate pigmentation genes, and assess phenotypic color variation. Genomic data indicate higher inbreeding in Irish grouse relative to an English population and significant divergence for genomic (FST = 0.095) and microsatellite (FST = 0.03) markers. Contemporary Ne was seven times smaller in the Irish population compared to the English. We identified divergent regions linked to pigmentation, immune response, and food intake. We show phenotypic differences in plumage color and sequence divergence among coding regions in the melanin pathway including MC1R (FST from genomic data of 0.3). The two populations thus appear locally adapted and this divergence between the source and target population when used for conservation translocations can swamp locally adapted alleles and/or introduce maladapted genotypes, leading to outbreeding depression. While it is important to avoid inbreeding by sustaining larger populations, our research emphasizes the need for practitioners to consider population divergence and local adaptation. We advocate against translocations between Ireland and Britain as a conservation strategy in this particular case and underscore the importance of prioritizing local populations where possible. [ABSTRACT FROM AUTHOR]

[Display omitted] • MPTP is unable to induce anxiety-like behaviors and motor deficit in LXRα-/- mice. • Knockout of LXRα leads to dopaminergic neurons loss in substantia nigra. • LXRα ablation prevents MPTP-induced augmentation of glial cells reaction. • LXRα ablation alters pro-inflammatory cytokines releases. Parkinson's disease (PD) is the second most common neurodegenerative disorder whose etiology remains unknown. The immune system has been implicated in hallmarks of PD including aggregation of α-synuclein and death of dopaminergic neurons in the substantia nigra. As a core regulator of immune response and inflammation, liver X receptors (LXRs) have been shown to have protective effects in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. With two isoforms of LXRs (LXRα and LXRβ) expressed in the brain, their roles and distributions in this tissue remain largely unexplored. Here, we used MPTP to mimic symptoms and biomedical changes seen in PD in LXRα-/- and wild-type mice to investigate the role of LXRα in the etiology and progression of PD. We found that MPTP is unable to induce motor deficits, anxiety-like behavior in LXRα-/- mice, which has been seen in WT mice. Gene ontology analysis of RNA sequencing revealed that knockout of LXRα led to enrichment of the process, including immune response and inflammation in the midbrain. In addition, MPTP did not lead to dopaminergic neuron death in the striatum and substantia nigra in LXRα-/- mice, the basal GFAP protein level, and pro-inflammatory cytokines were elevated in LXRα-/- mice. Lastly, the microglia activation and astrogliosis caused by MPTP intoxication we found in WT mice were abolished in LXRα-/- mice. To sum up, we conclude that LXRα is a critical regulator in MPTP intoxication and may play a unique role in astrogliosis seen in the neuroinflammation of PD. [ABSTRACT FROM AUTHOR]

The in vitro generation of spermatogonial stem cells (SSCs) from embryonic stem cells (ESCs) offers a viable approach for addressing male infertility. A multitude of molecules participate in this intricate process, which requires additional elucidation. Despite the decline in SSCs in aged testes, SSCs are deemed immortal since they can multiply for three years with repeated transplantation. Nonetheless, the examination of aging is challenging due to the limited quantity and absence of precise indicators. Using a microarray, we assessed genome-wide transcripts (about 55,000 transcripts) of fibroblasts and SSCs. The WGCNA approach was then used to look for SSC-specific transcription factors (TFs) and hub SSC-specific genes based on ATAC-seq, DNase-seq, RNA-seq, and microarray data from the GEO databases as well as gene expression data (RNA-seq and microarray data). The microarray analysis of three human cases with different SSCs revealed that 6 genes were upregulated, and the expression of 23 genes was downregulated compared to the normal case in relation to aging genes. To reach these results, online assessments of Enrich Shiny GO, STRING, and Cytoscape were used to forecast the molecular and functional connections of proteins before identifying the master routes. The biological process and molecular function keywords of cell–matrix adhesion, telomerase activity, and telomere cap complex were shown to be significantly altered in upregulated differentially expressed genes (DEGs) by the functional enrichment analysis. According to our preliminary research, cell-specific TFs and TF-mediated GRNs are involved in the creation of SSCs. In order to maximize the induction efficiency of ESC differentiation into SSCs in vitro, hub SSC-specific genes and important SSC-specific TFs were identified, and sophisticated network regulation was proposed. According to our research, these genes and the hub proteins that they interact with may be able to shine a light on the pathophysiologies of infertility and aberrant germ cells. [ABSTRACT FROM AUTHOR]

Regarding the limited information on species protein differences between sheep, goat, and cow milk, we analyzed the differentially expressed proteins in sheep, goat, and cow milk and their functional differences using label-free proteomics technology to identify potential biomarkers. In all, 770 proteins and 2,914 peptide segments were identified. Statistical analysis showed significant differences in the relative abundances of the 74 proteins among sheep, goat, and cow milk. CSN3 and LALBA can be used as potential biomarkers for goat milk, XDH can be used as a potential biomarker for cow milk, and CTSB and BPIFB1 can be used as potential biomarkers for sheep milk. Functional analysis using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes showed that these significantly different proteins were enriched by different pathways, including thyroid hormone synthesis and glycerol phospholipid metabolism. The data revealed differences in the amounts and physiological functions of the milk proteins of different species, which may provide an important basis for research on the nutritional composition of dairy products and adulteration identification technology. The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. [ABSTRACT FROM AUTHOR]

• Eggplant is a rich source of health-promoting phenolic acids, mainly chlorogenic acid (CGA). • CGA has various health benefits. • Study identified and analyzed key genes involved in the CGA biosynthesis pathway of eggplant. • This study highlights the potential of engineering the CGA biosynthesis pathway of eggplant. Eggplant (Solanum melongena L.) is a rich source of health-promoting phenolic acids, mainly chlorogenic acid (CGA), and trace elements. CGA has been shown to have antioxidant, anti-inflammatory, neuroprotective, cardioprotective, anticancer, and antidiabetic properties. The natural genome of eggplants contains essential genes for beneficial traits like drought tolerance, disease resistance, and high concentrations of medicinal substances. Transcriptomic analysis of eggplant overexpressing the hydroxycinnamoyl CoA quinate hydroxycinnamoyl transferase (HQT) gene revealed upregulation of 2165 genes, including three similar to HQT and cinnamate-4-hydroxylase (C4H). Sequence similarity analysis showed homology to caffeoyl-CoA O-methyltransferases, key enzymes in the phenylpropanoid pathway leading to CGA biosynthesis. Gene ontology and KEGG pathway analysis identified 5 highly upregulated glycosyltransferase family 43 genes (650.3-fold change). Glycosyltransferases like UDP-glucose:cinnamate glucosyltransferase and cinnamate-glucose 4′-O-glucosyltransferase are crucial for CGA production in eggplant. qRT-PCR validated the potential upregulation of HQT and C4H in transgenic eggplants. Comparative analysis revealed eggplant has the highest CGA content (5–8.1 g/kg dry weight) among vegetables, with foliar CGA acting as a natural insecticide. CGA offers antioxidant, hypoglycemic, antiviral, and hepatoprotective benefits to humans. This study highlights the role of HQT and C4H in elevating the medicinal properties of eggplant through CGA biosynthesis pathway engineering. [ABSTRACT FROM AUTHOR]

RNA methylation modification influences various processes in the human body and has gained increasing attention from scholars. Predicting genes associated with RNA methylation pathways can significantly aid biologists in studying RNA methylation processes. Several prediction methods have been investigated, but their performance is still limited by the scarcity of positive samples. To address the challenge of data imbalance in RNA methylation-associated gene prediction tasks, this study employed a generative adversarial network to learn the feature distribution of the original dataset. The quality of synthetic samples was controlled using the Classifier Two-Sample Test (CTST). These synthetic samples were then added to the data blocks to mitigate class distribution imbalance. Experimental results demonstrated that integrating the synthetic samples generated by our proposed model with the original data enhances the prediction performance of various classifiers, outperforming other oversampling methods. Moreover, gene ontology (GO) enrichment analyses further demonstrate the effectiveness of the predicted genes associated with RNA methylation pathways. The model generating gene samples with PyTorch is available at https://github.com/heyheyheyheyhey1/WGAN-GP_RNA_methylation [ABSTRACT FROM AUTHOR]

Huanglongbing (HLB) is the most devastating disease of citrus. Although no citrus species are known to be immune to HLB, some (e.g., Persian lime [Citrus latifolia]) have a high level of tolerance. Differentially expressed genes in the WRKY transcription factor (TF) family have been identified in another tolerant citrus, suggesting an association with such tolerance. Therefore, here we searched for the conserved WRKY domain of WRKY family members in the transcriptome of C. latifolia infected with HLB, characterized the identified ClWRKY genes, and determined which were differentially expressed in leaves with HLB symptoms; 177 transcripts with the WRKY domain were identified, and 32 ClWRKY genes were characterized for conserved motifs, gene ontology, and coexpression networks among the 32 ClWRKY genes. These genes were thus shown to be involved in response to external stimuli and biotic and abiotic stresses. Four differentially expressed ClWRKY genes (ClWRKY20, 23, 47, and 65) were identified in the transcriptome and validated by qRT-PCR. The possible roles of these genes in the tolerance of C. latifolia to HLB are discussed based on the function of homologs of these genes in other plant species. These WRKY genes could contribute to the genetic improvement of susceptible citrus to manage HLB. [ABSTRACT FROM AUTHOR]

Major Depressive Disorder (MDD) is a heterogenous and etiologically complex disease often presenting with divergent appetitive phenotypes including Hyperphagic MDD (characterized by an increased appetite) and Hypophagic MDD (characterized by a decrease in appetite) which are closely related to comorbidities, including cardiometabolic disorders. Hyperphagia is associated with atypical depression, decreased stress-hormone signaling, a pro-inflammatory status, hypersomnia, and poorer clinical outcomes. Yet, our understanding of associated biological correlates of Hyperphagic and Hypophagic MDD remain fragmented. We performed an exploratory study on peripheral blood RNA profiling using bulk RNAseq in unmedicated individuals with Hyperphagic and Hypophagic MDD (n = 7 and n = 13, respectively). At baseline, we discovered an increased expression of TADA2B in hyperphagic MDD with the significant enrichment of 72 gene ontology pathways mainly related to inflammation. In addition, we used the Maastricht Acute Stress Task to uncover stress-related transcriptomic profiles in Hyper- and Hypophagic MDD and discovered the upregulation of CCDC196 and the downregulation of SPATA33 in hyperphagic MDD. Gene ontology enrichment analysis after stress exposure showed pathways related to ribosomal activity. Limitations: The present findings are tempered primarily by the limited sample size, which requires independent replication of this exploratory study. However, stringent methods controlling for false positive findings mitigate the risk associated with sample size limitations. Limitations notwithstanding, findings suggest that hyper- and hypophagic MDD is associated with divergent RNA expression profiles in peripheral blood that are amplified by exposure to a controlled stress test. Our findings in a well-controlled study provide evidence for peripheral markers of a relevant endophenotype of MDD. [ABSTRACT FROM AUTHOR]

Purpose: Menopause is associated with a decrease in smell discrimination ability. This study assessed the impact of black cohosh on hippocampal (HC) and hypothalamic (HT) gene expression profiles in rats, to understand, if herbal treatment has an impact on neurologic changes due to menopause and whether this could address a decrease in smell discrimination. Methods: HC and HT tissues from female Sprague Dawley rats (total n = 19) were analyzed at three different life stages: intact tissues of the HC (n = 4) and the HT (n = 4), oophorectomized tissues 3 months after oophorectomy (OVX) of the HC (n = 4) and the HT (n = 3), and tissues after treatment with an isopropanolic extract (iCR) from the rhizomes of black cohosh (60 mg/kg) for 3 months after OVX of the HC (n = 2) and the HT (n = 2). Main outcome measures: To reveal underlying biological processes a gene set enrichment analysis (GSEA) was performed. Results: The GSEA revealed gene ontology terms that were significantly enriched, including several genes associated with the olfactory system, indicating biological processes regulated by treatment with iCR. Six olfactory receptor genes were further analyzed by another GSEA, demonstrating the possibility of iCR treatment to compensate for oophorectomy-induced changes. Conclusion: Findings suggest that herbal treatment, such as iCR, has an esteeming impact on HC and HT genes that are changed through menopause. Further studies are needed to suggest black cohosh as a treatment option for decreased smell discrimination. [ABSTRACT FROM AUTHOR]

Central nervous system diseases pose a significant threat to human health. Clinical observations have demonstrated that celabenzine, the primary active component of the natural plant ginseng, can potentially alleviate cognitive dysfunction in patients with central nervous system disorders. However, the specific mechanisms of its action remain unclear. The PubMed database was used to identify the targets of celabenzine. Subsequently, a Venn diagram of intersecting targets was constructed by utilizing the identified central nervous system injury targets. Additionally, Cytoscape software (version 3.7.2) was used to construct active ingredient-target and Protein-protein interaction networks. The Metascape database was used to perform Gene Ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Molecular docking was performed on active ingredients and target genes. Network pharmacology analysis revealed that celabenzine shares 175 intersecting targets with central nervous system damage, manifesting its effects through PI3K-Akt and MAPK signaling pathways and proteoglycans in the cancer pathway. Celabenzine demonstrates a strong binding affinity with its target gene, RhoA, indicating stable binding. This study was accomplished using network pharmacology and bioinformatics. Our findings suggested that celabenzine shows its protective effects against central nervous system damage by modulating the RhoA gene. [ABSTRACT FROM AUTHOR]

Introduction: The proteome profile of the female Tenualosa ilisha (Hamilton, 1822), a species of great ecological and economic importance, across various age groups was investigated to comprehend the functional dynamics of the serum proteome for conservation and aquaculture, as well as sustain the population. Methods: Advanced liquid chromatography-tandem mass spectrometry LC-MS/MS-based proteomic data were analysed and submitted to the ProteomeXchange Consortium via PRIDE (PRoteomics IDEntifications database). Bioinformatics analysis of serum proteome have been done and it showed different proteins associated with GO Gene Ontology () terms, and the genes associated with enriched KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways (such as phagosome, mTOR, Apelin signalling pathways, herpes simplex virus) implicated in immune responses. Results: The expression levels of important immunological proteins, such as those involved in cellular defence and inflammatory responses, were significantly different age-dependently. In this study, we annotated 952, 494, 415, and 282 proteins in year classes IV, III, II, and I Hilsa, respectively, and analysed their Protein-Protein Interaction (PPI) networks based on their functional characteristics. From year classes I to IV, new proteins appeared and were more than three-fold. Notably, class I hilsa displayed a lower abundance of proteins than class IV hilsa. Discussion: This is the first study, to the best of our knowledge, to report the analysis of the serum proteome of hilsa at different developmental stages, and the results can help improve the understanding of the mechanisms underlying the different changes in protein enrichment during migration in hilsa. This analysis also offers crucial insights into the immune system for hilsa conservation and management. [ABSTRACT FROM AUTHOR]

The purpose of this study is to explore the potential molecular mechanism of Bidentis Bipinnatae Herba against gastric cancer by using network pharmacology methods, molecular docking, and cellular experimental validation. Medicinal plants related to gastric cancer were queried through TCMSP, SymMap, and Herb databases. The TCSMP database (drug-likeness ≥ 0.18) was used to retrieve the bioactive constituents. TCSMP, SwissTargetPrediction, and Herb databases were used to retrieve the target genes, and Cytoscape software was used to construct the "active ingredient-target" network. After protein interaction analysis using String 11.0 platform, the hub genes were screened using CytoHubba. The obtained hub genes were uploaded to the cBioPortal for pathway enrichment. The genes involved in gastric cancer-related RTK-RAS pathway were molecularly docked and experimentally validated. Bidentis Bipinnatae Herba was common to TCMSP, SymMap, and Herb databases. A total of nine active ingredients were obtained in Bidentis Bipinnatae Herba, acting on 192 targets. Seven hub genes were obtained from these target genes and enriched in the RTK-RAS pathway in gastric cancer. MAPK1 and EGFR had good molecular docking results with their corresponding chemicals. Cellular experiments showed that the treatment of luteolin, quercetin, and Okanin reduced the expression of EGFR in AGS cells; the treatment of luteolin and quercetin could reduce the expression of MAPK1. Bidentis Bipinnatae Herba contained active components, which may be anti-gastric cancer in a multi-target (MAPK1 and EGFR) manner. [ABSTRACT FROM AUTHOR]

The study focusing on developing an artificial neural network (ANN) model in accordance with genetic characteristics of osteosarcoma (OS) to accurately speculate OS cases. In the present study, we identified 467 DEGs through differentially acting gene investigation and that 345 exist suppressed and 122 exist stimulated. The resultant of GO enrichment analysis displayed the functions mainly included T cell activation, secretory granule lumen, antioxidant property etc. The pathways identified in the differentially acting genes (DAGs) were greatly interacted with Phagosome, Staphylococcus aureus infection, Human T − cell leukemia virus 1 infection, etc. Next, we found out top ten hub DEGs (HDEGs) by PPI network analysis. In addition, through the validation of ANN itself and Test set samples, it was proved that the prediction performance of our constructed ANN model is accurate and reliable. Finally, the penetration of immune cells and its interaction with target CDEGs were examined, and variations in penetration of 22 types of immune cells amongst different classes were found, additionally correlation amongst immune cells and between immune cells and target CDEGs. Furthermore, we analyzed the expression of the top two CDEGs (YES1 and MFNG) in OS tissues and normal tissues, also the interrelationship among the activity of YES1 and MFNG in OS tissues and clinicopathological properties of OS cases. Furthermore, the correlation analysis between the top two CDEGs and immune infiltrating cells was performed in OS tissues. Our research results revealed that CDEGs-based ANN model is effective at predicting OS patients, which facilitates early diagnosis and treatment of OS. [ABSTRACT FROM AUTHOR]

Objective: Obesity‐associated insulin resistance (IR) is responsible for considerable morbidity and mortality globally. Despite vast genomic data, many areas, from pathogenesis to management, still have significant knowledge gaps. We aimed to characterize visceral adipose tissue (VAT) in obesity and IR through a multi‐omics approach. Methods: We procured data on VAT samples from the Gene Expression Omnibus (GEO) for the following two groups: 1) populations with obesity (n = 34) versus those without (n = 26); and 2) populations with obesity and IR (n = 15) versus those with obesity but without IR (n = 15). Gene set enrichment, protein‐protein interaction network construction, hub gene identification, and drug‐gene interactions were performed, followed by regulatory network prediction involving transcription factors (TFs) and microRNAs (miRNAs). Results: Interleukin signaling pathways, cellular differentiation, and regulation of immune response revealed a significant cross talk between VAT and the immune system. Other findings include cancer pathways, neurotrophin signaling, and aging. A total of 10 hub genes, i.e., STAT1, KLF4, DUSP1, EGR1, FOS, JUN, IL2, IL6, MMP9, and FGF9, 24 TFs, and approved hub gene‐targeting drugs were obtained. A total of 10 targeting miRNAs (e.g., hsa‐miR‐155‐5p, hsa‐miR‐34a‐5p) were associated with obesity and IR‐related pathways. Conclusions: Our multi‐omics integration method revealed hub genes, TFs, and miRNAs that can be potential targets for investigation in VAT‐related inflammatory processes and IR, therapeutic management, and risk stratifications. [ABSTRACT FROM AUTHOR]

The edible flower of Hemerocallis citrina Baroni, commonly known as “Huang Huacai” in China, has anti‐depressant effects. However, targets and molecular mechanisms of Hemerocallis citrina Baroni edible flowers (HEF) in depression treatment are still unclear. The potential anti‐depression targets in HEF were identified by the intersecting results from typical drug databases. The network construction and Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis were carried out for core targets. The molecular docking was conducted to predict the binding affinity between the active components and the central targets. The intersecting results indicated that there were 24 active components in HEF, with 449 anti‐depression targets identified. After screening through degree centrality (DC), betweenness centrality (BC), and closeness centrality (CC), 166 core targets were determined. Tumor protein 53 (TP53) and interleukin 6 (IL‐6) had the highest degree values. The results of GO enrichment analysis associated with anti‐depression revealed that the biological processes were negative regulation of osteoclast differentiation and positive regulation of phosphorus metabolic process. KEGG enrichment analysis results revealed that pathways, such as the phosphatidylinositol 3‑kinase‐protein kinase B (PI3K‐Akt) signaling pathway and mitogen‐activated protein kinase (MAPK) signaling pathway, were primarily associated with anti‐depression. Molecular docking results indicated that the top 10 active ingredients in HEF could bind to the central targets. This study applied network pharmacology to unveil the potential anti‐depressive mechanisms of HEF, providing a theoretical basis for further exploration of the effective components in H. citrina edible flower parts. [ABSTRACT FROM AUTHOR]

Methylation, a key epigenetic modification, is essential for regulating gene expression and protein function without altering the DNA sequence, contributing to various biological processes, including gene transcription, embryonic development, and cellular functions. Methylation encompasses DNA methylation, RNA methylation and histone modification. Recent research indicates that DNA methylation is vital for establishing and maintaining normal brain functions by modulating the high-order structure of DNA. Alterations in the patterns of DNA methylation can exert significant impacts on both gene expression and cellular function, playing a role in the development of numerous diseases, such as neurological disorders, cardiovascular diseases as well as cancer. Our current understanding of the etiology of neurological diseases emphasizes a multifaceted process that includes neurodegenerative, neuroinflammatory, and neurovascular events. Epigenetic modifications, especially DNA methylation, are fundamental in the control of gene expression and are critical in the onset and progression of neurological disorders. Furthermore, we comprehensively overview the role and mechanism of DNA methylation in in various biological processes and gene regulation in neurological diseases. Understanding the mechanisms and dynamics of DNA methylation in neural development can provide valuable insights into human biology and potentially lead to novel therapies for various neurological diseases. [ABSTRACT FROM AUTHOR]

Although the European flounder is frequently used in research and has economic importance, there is still lack of comprehensive transcriptome data for this species. In the present research we show RNA-Seq data from ten selected organs of P. flesus female inhabiting brackish waters of the Gulf of Gdańsk (southern Baltic Sea). High throughput Next Generation Sequencing technology NovaSeq 6000 was used to generate 500 M sequencing reads. These were mapped against European flounder reference genome and reads extracted from the mapping were assembled producing 61k reliable contigs. Gene ontology (GO) terms were assigned to the majority of annotated contigs/unigenes based on the results of PFAM, PANTHER, UniProt and InterPro protein databases searches. BUSCOs statistics for eukaryota, metazoa, vertebrata and actinopterygii databases showed that the reported transcriptome represents a high level of completeness. The data set can be successfully used as a tool in design of experiments from various research fields including biology, aquaculture and toxicology. [ABSTRACT FROM AUTHOR]

The therapeutic approach to thymic cysts remains a subject of controversy. Predicted biomarkers for identifying thymic cysts and thymoma (THYM) are crucial. In this research, patients diagnosed with thymic cysts (MTC, n = 6) and thymoma (B1, n = 6; B3, n = 6) were enrolled. Proteins of superior quality were subjected to TMT labeling and UPLC-MS, and differentially expressed proteins (DEPs) were identified. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interactive network analyses were applied to the DEPs. Some key differentially expressed genes(DEGs) were corroborated through GEPIA 32. The pan-cancer expression levels of key DEGs remarkably linked with prognosis were determined utilizing The University of ALabama at Birmingham CANcer data analysis Portal (UALCAN). Eventually, 49 DEPs were identified in the B1 vs. MTC comparison (17 upregulated and 32 downregulated), 27 in the B3 vs. MTC comparison (8 upregulated and 19 downregulated), and 38 in the B3 vs. B1 comparison (9 upregulated and 29 downregulated). IL13RA1 (down), galectin-3 binding protein (LGALS3BP)(up), PRCSH (down), C3 (down), MXRA5 (down), TNN (down), CFHR1 (down), SUN3 (down) were jointly altered in both B1 vs. NZ and B3 vs. NZ. GEPIA validated that LGALS3BP was significantly upregulated in thymoma patients. In conclusion, LGALS3BP might be an essential biomarker to identify thymoma from the thymic cyst. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Whole‐exome sequencing (WES) studies have revealed that germline de novo variants (gDNVs) contribute to the genetic etiology of schizophrenia. However, the contribution of mosaic DNVs (mDNVs) to the risk of schizophrenia remains to be elucidated. In the present study, we systematically investigated the gDNVs and mDMVs that contribute to the genetic etiology of schizophrenia in a Japanese population.We performed deep WES (depth: 460×) of 73 affected offspring and WES (depth: 116×) of 134 parents from 67 families with schizophrenia. Prioritized rare nonsynonymous gDNV and mDNV candidates were validated using Sanger sequencing and ultra‐deep targeted amplicon sequencing (depth: 71,375×), respectively. Subsequently, we performed a Gene Ontology analysis of the gDNVs and mDNVs to obtain biological insights. Lastly, we selected DNVs in known risk genes for psychiatric and neurodevelopmental disorders.We identified 62 gDNVs and 98 mDNVs. The Gene Ontology analysis of mDNVs implicated actin filament and actin cytoskeleton as candidate biological pathways. There were eight DNVs in known risk genes: splice region gDNVs in AKAP11 and CUL1; a frameshift gDNV in SHANK1; a missense gDNV in SRCAP; missense mDNVs in CTNNB1, GRIN2A, and TSC2; and a nonsense mDNV in ZFHX4.Our results suggest the potential contributions of rare nonsynonymous gDNVs and mDNVs to the genetic etiology of schizophrenia. This is the first report of the mDNVs in schizophrenia trios, demonstrating their potential relevance to schizophrenia pathology. [ABSTRACT FROM AUTHOR]

Introduction: "Peroxisome Proliferator-Activated Receptors" (PPARs) belong to the class of transcription factors (TF) identified as Nuclear Receptors (NR). Upon activation by peroxisome proliferators (PPs), PPARs modulate a diverse range of genes, consequently regulating intra-cellular lipid metabolism, glucose uptake, apoptosis, and cell proliferation. Subsequent to the heterodimerization of Retinoid X Receptors (RXR) with PPARs induced by the binding of activators to PPARs, facilitates the binding of the resulting complex to Peroxisome Proliferator- Activated Receptors Response Elements (PPRE), with a consensus sequence 5'AGGTCANAGGTCA-3', and regulate the transcription of the targeted genes. Methods: A comprehensive screening of PPREwithin the whole human genome was performed using the Genome Workbench and UCSC Genome Browser to find the associated genes. Subsequently, the kinase subset was isolated fromthe extracted list of PPRE-related genes. Functional enrichment of the kinases was performed using FunRich, ToppGene, and ShinyGO. Network analysis and enrichment studies were then further performed using NDEx to elucidate these identified kinases' connections and significance. Additionally, the disease association of the PPRE kinases was analyzed using DisGeNET data in R studio and the COSMIC dataset. Results: A comprehensive analysis of 1002 PPRE sequences within the human genome (T2T), yielded the identification of 660 associated genes, including 29 kinases. The engagement of these kinases in various biological pathways, such as apoptosis, platelet activation, and cytokine pathways, revealed from the functional enrichment analysis, illuminates the multifaceted role of PPAR in the regulation of cellular homeostasis and biological processes. Network analysis reveals the kinases interact with approximately 5.56% of the Human Integrated Protein-Protein Interaction rEference (HIPPIE) network. Disease association analysis using DisGeNET and COSMIC datasets revealed the significant roles of these kinases in cellular processes and disease modulation. Discussion: This study elucidates the regulatory role of PPAR-associated genes and their association with numerous biological pathways. The involvement of the kinases with disease-related pathways highlights new potential for the development of therapeutic strategies designed for disease management and intervention. [ABSTRACT FROM AUTHOR]

Traditional gene set enrichment analyses are typically limited to a few ontologies and do not account for the interdependence of gene sets or terms, resulting in overcorrected p-values. To address these challenges, we introduce mulea, an R package offering comprehensive overrepresentation and functional enrichment analysis. mulea employs a progressive empirical false discovery rate (eFDR) method, specifically designed for interconnected biological data, to accurately identify significant terms within diverse ontologies. mulea expands beyond traditional tools by incorporating a wide range of ontologies, encompassing Gene Ontology, pathways, regulatory elements, genomic locations, and protein domains. This flexibility enables researchers to tailor enrichment analysis to their specific questions, such as identifying enriched transcriptional regulators in gene expression data or overrepresented protein domains in protein sets. To facilitate seamless analysis, mulea provides gene sets (in standardised GMT format) for 27 model organisms, covering 22 ontology types from 16 databases and various identifiers resulting in almost 900 files. Additionally, the muleaData ExperimentData Bioconductor package simplifies access to these pre-defined ontologies. Finally, mulea's architecture allows for easy integration of user-defined ontologies, or GMT files from external sources (e.g., MSigDB or Enrichr), expanding its applicability across diverse research areas. mulea is distributed as a CRAN R package downloadable from https://cran.r-project.org/web/packages/mulea/ and https://github.com/ELTEbioinformatics/mulea. It offers researchers a powerful and flexible toolkit for functional enrichment analysis, addressing limitations of traditional tools with its progressive eFDR and by supporting a variety of ontologies. Overall, mulea fosters the exploration of diverse biological questions across various model organisms. [ABSTRACT FROM AUTHOR]

The calmodulin-binding transcription activator (CAMTA) family contributes to stress responses in many plant species. The Oryza sativa ssp. japonica genome harbors seven CAMTA genes; however, intraspecific variation and functional roles of this gene family have not been determined. Here, we comprehensively evaluated the structure and characteristics of the CAMTA genes in japonica rice using bioinformatics approaches and RT-qPCR. Within the CAMTA gene and promoter sequences, 527 single nucleotide polymorphisms were retrieved from 3,024 rice accessions. The CAMTA genes could be subdivided into 5–14 haplotypes. Association analyses between haplotypes and phenotypic traits, such as grain weight and salt stress parameters, identified phenotypic differences between rice subpopulations harboring different CAMTA haplotypes. Co-expression analyses and the identification of CAMTA-specific binding motifs revealed candidate genes regulated by CAMTA. A Gene Ontology functional enrichment analysis of 690 co-expressed genes revealed that CAMTA genes have key roles in defense responses. An interaction analysis identified 30 putative CAMTA interactors. Three genes were identified in co-expression and interaction network analyses, suggesting that they are potentially regulated by CAMTAs. Based on all information obtained together with the phenotypes of the CRISPR-Cas9 knockout mutant lines of three OskCAMTA genes generated, CAMTA1 likely plays important roles in the response to salt stress in rice. Overall, our findings suggest that the CAMTA gene family is involved in development and the salt stress response and reveal candidate target genes, providing a basis for further functional characterization. [ABSTRACT FROM AUTHOR]

Mpox, caused by the Mpox virus (MPXV), emerged globally in 2022 with the Clade IIb strain, presenting a critical public health challenge. While MPXV is primarily characterized by fever and rash, gastrointestinal (GI) complications, such as diarrhea and proctitis, have also been observed. This study is a reanalysis of GSE219036 without own data and focuses on the impact of MPXV infection on the colon, using human-induced pluripotent stem cell-derived colon organoids as a model. We applied a tailored statistical framework for RNA-seq data, Generalized Linear Models with Quasi-Likelihood F-tests and Relaxed Magnitude–Altitude Scoring (GLMQL-RMAS), to identify differentially expressed genes (DEGs) across MPXV clades: MPXV I (Zr-599 Congo Basin), MPXV IIa (Liberia), and MPXV IIb (2022 MPXV). Through a novel methodology called Cross-RMAS, we ranked genes by integrating statistical significance and biological relevance across all clades. Machine learning analysis using the genes identified by Cross-RMAS, demonstrated 100% accuracy in differentiating between the different MPXV strains and mock samples. Furthermore, our findings reveal that MPXV Clade I induces the most extensive alterations in gene expression, with significant upregulation of stress response genes, such as HSPA6 and FOS, and downregulation of genes involved in cytoskeletal organization and vesicular trafficking, such as PSAP and CFL1. In contrast, Clade IIb shows the least impact on gene expression. Through Gene Ontology (GO) analysis, we identified pathways involved in protein folding, immune response, and epithelial integrity that are disrupted in infected cells, suggesting mechanisms by which MPXV may contribute to GI symptoms. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) is a complex and highly variable disease, ranking among the top five cancers diagnosed globally, and a leading cause of cancer-related deaths. Emerging from stomach lining cells amid chronic inflammation, it often advances to preneoplastic stages. Late-stage diagnoses and treatment challenges highlight the critical need for early detection and innovative biomarkers, motivating this study's focus on identifying theranostic markers through gene ontology analysis. By exploring deregulated biological processes, this study aims to uncover insights into cancer progression and associated markers, potentially identifying novel theranostic candidates in GC. Using public data from The Human Protein Atlas, this study pinpointed 299 prognostic genes, delineating 171 with unfavorable prognosis and 128 with favorable prognosis. Functional enrichment and protein–protein interaction analyses, supported by RNAseq results and conducted via Metascape and Cytoscape, highlighted five genes (vWF, FN1, THBS1, PCDH7, and F5) with promising theranostic potential. Notably, FN1 and THBS1 exhibited significant promise, with FN1 showing a 370% expression increase in cancerous tissue, and it is possible that FN1 can also indicate the stratification status in GC. While further validation is essential, these findings provide new insights into molecular alterations in GC and potential avenues for clinical application of theranostic markers. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusion Bipolar disorder (BD) is a common psychiatric disorder characterized by alterations between manic/hypomanic and depressive states. Rare pathogenic copy number variations (CNVs) that overlap with exons of synaptic genes have been associated with BD. However, no study has comprehensively explored CNVs in synaptic genes associated with BD. Here, we evaluated the relationship between BD and rare CNVs that overlap with synaptic genes, not limited to exons, in the Japanese population.Using array comparative genome hybridization, we detected CNVs in 1839 patients with BD and 2760 controls. We used the Synaptic Gene Ontology database to identify rare CNVs that overlap with synaptic genes. Using gene‐based analysis, we compared their frequencies between the BD and control groups. We also searched for synaptic gene sets related to BD. The significance level was set to a false discovery rate of 10%.The RNF216 gene was significantly associated with BD (odds ratio, 4.51 [95% confidence interval, 1.66–14.89], false discovery rate < 10%). The BD‐associated CNV that corresponded with RNF216 also partially overlapped with the minimal critical region of the 7p22.1 microduplication syndrome. The integral component of the postsynaptic membrane (Gene Ontology:0099055) was significantly associated with BD. The CNV overlapping with the intron region of GRM5 in this gene set showed a nominal significant association between cases and controls (P < 0.05).We provide evidence that CNVs in RNF216 and postsynaptic membrane–related genes confer a risk of BD, contributing to a better understanding of the pathogenesis of BD. [ABSTRACT FROM AUTHOR]

In vivo , the temperature inside preovulatory follicles of cows is approximately 1 °C lower than rectal temperature. However, standard bovine oocyte in vitro maturation (IVM) protocols use 38.5 °C based on rectal temperature. This study evaluated the effect of reducing IVM temperature to 37.5 °C on the proteomic profile of oocytes compared to the routine 38.5 °C. Nuclear maturation rate and cumulus cell (CC) expansion (30 COCs per group, 21 replicates) were assessed by observing the first polar body and using a subjective scoring method (0–4). Total nitrite concentrations in the culture medium were measured using the Griess method. Differential proteomics was performed using LC-MS/MS on pooled oocyte samples (500 matured oocytes per group, three replicates), followed by gene ontology enrichment, protein-protein interaction, and putative miRNA target analyses. No significant differences were observed between the groups in nuclear maturation, CC expansion, or nitrite concentration (P > 0.05). A total of 806 proteins were identified, with 7 up-regulated and 12 down-regulated in the treatment group compared to the control. Additionally, 12 proteins were unique to the control group, and 8 were unique to the treatment group. IVM at 37.5 °C resulted in the upregulation of proteins involved in protein folding and GTP binding, and the downregulation of enzymes with oxidoreductase activity and proteins involved in cytoskeletal fiber formation. Furthermore, 43 bovine miRNAs potentially regulating these genes (DES, HMOX2, KRT75, FARSA, IDH2, CARHSP1) were identified. We conclude that IVM of bovine oocytes at 37.5 °C induces significant proteomic changes without impacting nuclear maturation, cumulus cell expansion, or nitrite concentration in the IVM medium. • Temperature reduction during IVM altered the proteomic profile but did not affect nuclear maturation. • The total nitrite concentration in the IVM medium of COCs was similar between groups cultured at 38.5 °C and 37.5 °C • Proteomic analysis identified 12 unique proteins in the control group and 8 unique proteins in the treatment group • IVM at 37.5 °C resulted in the upregulation of proteins involved in protein folding and GTP binding. • 43 bovine miRNAs were found to potentially regulate key genes affected by the temperature change during IVM of bovine oocytes. [ABSTRACT FROM AUTHOR]

Sacha Inchi (Plukenetia volubilis) oil press-cake (SIPC) represents a new source of proteins of high biological value, with promissory food applications. However, knowledge of these proteins remains limited. In this study, a Sacha Inchi protein concentrate (SPC) was extracted from the SIPC, and proteomic analysis was performed to identify the major alkaline-soluble proteins. The electrophoretic profile highlighted the efficacy of alkaline pH and moderate temperature to extract the major proteins, from which a group of proteins, not previously reported, were registered. LC-MS/MS analyses produced abundant high-quality fragmentation spectra. Utilizing the Euphorbiaceae database (DB), 226 proteins were identified, with numerous well-assigned spectra remaining unidentified. PEAKS Studio v11.5 software generated 1819 high-quality de novo peptides. Data are available via ProteomeXchange with identifier PXD052665. Gene ontology (GO) classification allowed the identification of sequenced proteins associated with biological processes, molecular functions, and cellular components in the seed. Consequently, the principal alkali-soluble proteins from SPC were characterized through derived functional analysis, covering 24 seed-storage-, 27 defense-, and 12 carbohydrate- and lipid-metabolism-related proteins, crucial for human nutrition due to their sulfur-containing amino acids, antioxidant properties, and oil yields, respectively. This research makes a significant contribution to the current understanding of the Sacha Inchi proteome and offers valuable insights for its potential applications in the food industry. [ABSTRACT FROM AUTHOR]

Background: DNA methylation plays a critical role in asthma development, but differences in DNA methylation among adults with varying asthma severity are less well-defined. Objective: To examine how DNA methylomic patterns differ among adults with asthma based on asthma severity and airway inflammation. Methods: Peripheral blood T cells from 35 adults with asthma in Beijing, China, were serially collected over time (130 samples total) and analyzed for global DNA methylation using the Illumina MethylationEPIC Array. Differential methylation was compared among subjects with varying airway inflammation and severity, as measured by fraction of exhaled nitric oxide, forced expiratory volume in one second (FEV1), and Asthma Control Test (ACT) scores. Results: Significant differences in DNA methylation were noted among subjects with different degrees of airway inflammation and asthma severity. These differences in DNA methylation were annotated to genes that were enriched in pathways related to asthma or T cell function and included gene ontology categories related to MHC class II assembly, T cell activation, interleukin (IL)-1, and IL-12. Genes related to P450 drug metabolism, glutathione metabolism, and developmental pathways were also differentially methylated in comparisons between subjects with high vs low FEV1 and ACT. Notable genes that were differentially methylated based on asthma severity included RUNX3, several members of the HLA family, AGT, PTPRC, PTPRJ, and several genes downstream of the JAK2 and TNF signaling pathway. Conclusion: These findings demonstrate how adults with asthma of varying severity possess differences in peripheral blood T cell DNA methylation that contribute to differences in clinical indices of asthma. [ABSTRACT FROM AUTHOR]

Background: Nelore cattle play a key role in tropical production systems due to their resilience to harsh conditions, such as heat stress and seasonally poor nutrition. Monitoring their genetic diversity is essential to manage the negative impacts of inbreeding. Traditionally, inbreeding and inbreeding depression are assessed by pedigree-based coefficients (F), but recently, genetic markers have been preferred for their precision in capturing the inbreeding level and identifying animals at risk of reduced productive and reproductive performance. Hence, we compared the inbreeding and inbreeding depression for productive and reproductive performance traits in Nelore cattle using different inbreeding coefficient estimation methods from pedigree information (FPed), the genomic relationship matrix (FGRM), runs of homozygosity (FROH) of different lengths (> 1 Mb (genome), between 1 and 2 Mb - FROH 1−2; 2–4 Mb FROH 2−4 or > 8 Mb FROH >8) and excess homozygosity (FSNP). Results: The correlation between FPed and FROH was lower when the latter was based on shorter segments (r = 0.15 with FROH 1−2, r = 0.20 with FROH 2−4 and r = 0.28 with FROH 4−8). Meanwhile, the FPed had a moderate correlation with FSNP (r = 0.47) and high correlation with FROH >8 (r = 0.58) and FROH−genome (r = 0.60). The FROH−genome was highly correlated with inbreeding based on FROH>8 (r = 0.93) and FSNP (r = 0.88). The FGRM exhibited a high correlation with FROH−genome (r = 0.55) and FROH >8 (r = 0.51) and a lower correlation with other inbreeding estimators varying from 0.30 for FROH 2−4 to 0.37 for FROH 1−2. Increased levels of inbreeding had a negative impact on the productive and reproductive performance of Nelore cattle. The unfavorable inbreeding effect on productive and reproductive traits ranged from 0.12 to 0.51 for FPed, 0.19–0.59 for FGRM, 0.21–0.58 for FROH−genome, and 0.19–0.54 for FSNP per 1% of inbreeding scaled on the percentage of the mean. When scaling the linear regression coefficients on the standard deviation, the unfavorable inbreeding effect varied from 0.43 to 1.56% for FPed, 0.49–1.97% for FGRM, 0.34–2.2% for FROH−genome, and 0.50–1.62% for FSNP per 1% of inbreeding. The impact of the homozygous segments on reproductive and performance traits varied based on the chromosomes. This shows that specific homozygous chromosome segments can be signs of positive selection due to their beneficial effects on the traits. Conclusions: The low correlation observed between FPed and genomic-based inbreeding estimates suggests that the presence of animals with one unknown parent (sire or dam) in the pedigree does not account for ancient inbreeding. The ROH hotspots surround genes related to reproduction, growth, meat quality, and adaptation to environmental stress. Inbreeding depression has adverse effects on productive and reproductive traits in Nelore cattle, particularly on age at puberty in young bulls and heifer calving at 30 months, as well as on scrotal circumference and body weight when scaled on the standard deviation of the trait. [ABSTRACT FROM AUTHOR]

Background: The genetic basis underlying spawning abilities in the Pacific white shrimp, Penaeus vannamei, remains largely unexplored. To investigate genetic variations potentially related to reproductive performance, a systematic bioinformatic analysis was conducted to identify structural variations (SVs) with different polymorphic spectra in P. vannamei with high fertility (HF) and low fertility (LF). Results: A total of 2,323 and 1,859 SV events were identified exclusively in the HF and LF groups, respectively. These SVs were mapped to 277 genes in the HF group and 231 genes in the LF group. Gene Ontology (GO) enrichment analysis based on SNPs (single nucleotide polymorphism) and SVs revealed several neural-related processes, suggesting the importance of neural regulation in reproduction. Notably, we identified a set of promising genes, including Cttn, Spast, Ppp4c, Spire1, Lhcgr, and Ftz-f1, which may enhance fertility in shrimp. Conclusion: In conclusion, this study is the first to establish a link between SVs and reproductive traits in P. vannamei. The promising genes discovered have the potential to serve as crucial markers for enhancing reproductive traits through targeted genotyping. [ABSTRACT FROM AUTHOR]

Background: The extracellular pH (pHe) is known to be acidic. We investigated the effect of mild (pHe 6.8) and severe (pHe 5.9) acidosis on gene expression in mouse B16-BL6 melanoma cells using cDNA microarray analysis and compared them with the acidic pHe dependence of human tumors. Methods: B16-BL6 cells were treated with pHe 7.4 (control), pHe 6.8, and pHe 5.9. The mRNA expression was analyzed by using the cDNA microarray. Heat map, volcano plot, and gene ontology enrichment analysis were performed. The data were compared with the gene signatures of published data GSE52031 and GSE8401 and compared with the pathological staging by GEPIA2, and the prognostic signature of proteins was searched by the Human Protein Atlas database. If the acidic pHe-induced and -reduced genes were correlated with shortened and prolonged survival times, respectively, and also correlated with pathological staging, we defined it as "hit" and counted the sum of hit points of eight types of tumors such as breast, colorectal, prostate, gastric, liver, prostate, lung, and head and neck and melanoma. Results: Gene expression was differentially and commonly regulated by both pHes. The number of genes upregulated fourfold or more at pHe 6.8 and 5.9 only for 25 and 131 genes, respectively, and 85 genes were common. The number of genes downregulated fourfold or less at pHe 6.8 and 5.9 only for 63 and 82 genes, respectively, and 118 genes were common. Compared with human mRNA expression data (GSE8401), there is no correlation with the overall pattern of the signature. In seven types of cancer (breast, colorectal, gastric, liver, prostate, lung, and head and neck) and melanoma, the relationship between acidic pHemodulated gene expression and overall survival was evaluated. As a result, acidic pHe dependency contributing to prognosis was higher in colorectal, lung, and head and neck cancers and lower in prostate cancer. Conclusion: Tumor classification based on response to extracellular acidic pHe will provide new insights into chemotherapy strategy for patients with tumors. [ABSTRACT FROM AUTHOR]

Climatic changes pose a continuing danger to food production, impacting people's livelihoods worldwide. Salt and drought stresses have significantly impeded global maize output. RNA editing (RE) is a post-transcriptional process and has a unique function in regulating responses to environmental stimuli. The function of RNA editing sites (RES) in maize plants exposed to salt and water stresses has not been well investigated. In this study, two maize genotypes, sensitive to salt (SS) and resistant to salt (ST) were used. We investigated how salt and water stressors impact RNA editing sites in the whole mRNA derived from the maize nuclear genome. The average alignment rate was 90% for SS and 80% for ST genotypes when compared to the reference genome. Most of the editing events were non-synonymous codon alterations, and the trend in amino acid modifications was mostly hydrophobic. When we compared the root and shoot samples from the treated and control groups, we found that both groups had twelve different types of REs including A/C, A/G (A/I), A/T, C/A, C/G, C/T (C/U), G/A, G/C, G/T, T/A, T/C, and T/G. The treated samples showed an overall improvement in RE efficiency. Gene Ontology analysis showed that the mapped genes participated in several biological processes and molecular activities. The analysis of the whole genome's encoded RNA-edited genes showed that 26 sites were altered from C to T (C to U) in the genes ZemaCp023, ZemaCp001, and Zm00001eb437010. Three A/G (A/I) REs were exclusively linked to ZemaCp001. These results will serve as a foundation for identifying RES in other crops and will also be helpful in the development of salt and water tolerance in maize. [ABSTRACT FROM AUTHOR]

Background: Soft tissue sarcoma (STS) represents highly multifarious malignant tumors that often occur in adolescents and have a poor prognosis. The basement membrane, as an ancient cellular matrix, was recently proven to play a vital role in developing abundant tumors. The relationship between basement membrane‐related genes and STS remains unknown. Methods: Consensus clustering was employed to identify subgroups related to differentially expressed basement membrane‐related genes. Cox and least absolute shrinkage and selection operator regression analyses were utilized to construct this novel signature. Then, we established a nomogram and calibration curve, including the risk score and available clinical characteristics. Finally, we carried out functional enrichment analysis and immune microenvironment analysis to investigate enriched pathways and the tumor immune microenvironment related to the novel signature. Results: A prognostic predictive signature consisting of eight basement membrane‐related genes was established. Kaplan–Meier survival curves demonstrated that the patients in the high‐risk group had a poor prognosis. Independent analysis illustrated that this risk model could be an independent prognostic predictor. We validated the accuracy of our signature in the validation data set. In addition, gene set enrichment analysis and immune microenvironment analysis showed that patients with low‐risk scores were enriched in some pathways associated with immunity. Finally, in vitro experiments showed significantly differential expression levels of these signature genes in STS cells and PSAT1 could promote the malignant behavior of STS. Conclusions: The novel signature is a promising prognostic predictor for STS. The present study may improve the prognosis and enhance individualized treatment for STS in the future. [ABSTRACT FROM AUTHOR]

Aims: Perioperative neurocognitive disorders (PND), including postoperative delirium (POD) and postoperative cognitive dysfunction (POCD), are common following anesthesia and surgery in older patients and significantly increase morbidity and mortality. However, the underlying mechanism of PND is unclear. Our study aims to analyze the differentially expressed genes (DEGs) in excitatory neurons and investigate the role of hippocampal glutamatergic synaptic alterations in sevoflurane‐induced cognitive dysfunction in aged mice. Methods: We performed single‐nucleus RNA sequencing (snRNA‐seq) technology to examine the alterations of excitatory neurons in hippocampus induced by sevoflurane in aged mice. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEGs were performed in excitatory neurons. At last, immunofluorescence staining was used to validate sevoflurane‐induced alternation of glutamatergic synapses in the hippocampus of aged mice. Results: This study demonstrates that DEGs in excitatory neurons are associated with reduction of glutamatergic synapses and cognitive dysfunction. After immunofluorescence staining validation, we also confirmed that sevoflurane anesthesia decreased the density of glutamatergic synapses in the hippocampus of aged mice. Conclusions: Our findings demonstrated a key role of hippocampal glutamatergic synaptic alterations in sevoflurane‐induced cognitive dysfunction in aged mice. [ABSTRACT FROM AUTHOR]

Endometrial carcinoma is a common malignancy among peri-menopausal and menopausal females, even among some women of reproductive age. The treatment approach to endometrial cancer is a platinum-based regimen combined with paclitaxel, which may be unsatisfactory. A copper-mediated binding of lipoylated constituents of tricarboxylic acid cycle has been found recently, which brings about lethal protein stress and cell death, a phenomenon termed cuproptosis. As an innovative method of cell death, cuproptosis could be designed for cancer treatment and many aspects remain unaddressed. In our study, clinical, genomic, and mutational profiles of uterine corpus endometrial carcinoma (UCEC) patients were obtained from The Cancer Genome Atlas and cuproptosis-related genes and long non-coding RNAs (lncRNAs) were acquired thereafter. Co-expression and Cox regression analyses led to the development of a prognostic signature. Patients were separated into two groups (high- and low-risk groups) and survival analysis, risk score calculation, multivariate Cox analysis, and subgroup validation were implemented to determine the utility of the signature. Differentially expressed genes (DEGs) between the two groups were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Immune-related functional analysis and tumor mutation burden (TMB) analysis were performed. Three independent high-risk cuproptosis-related lncRNAs were finally confirmed and incorporated into the prognostic model, including BX322234.1, LINC01545 and LINC01224. Areas under the curve for 1-, 3- and 5- year survival were 0.717, 0.688 and 0.714, respectively. The risk model served as an independent factor to predict prognosis. Patients with high-risk and low TMB tended to have poor prognoses. Enrichment analysis demonstrated that DEGs were mostly associated with immune responses. In conclusion, the three high-risk cuproptosisrelated lncRNAs could predict the prognosis of UCEC patients with higher power, where patients with high-risk and low TMB are prone to have the worst prognosis, which broadens the pattern of clinical treatment and applications. [ABSTRACT FROM AUTHOR]

Advanced cervical cancer (CESC) is a common gynecological malignancy that threatens females' lives and existing treatments remain ineffective. This study focused on discovering potential biomarkers for the prognosis of CESC patients and exploring potential curative mechanisms and possible therapeutic directions. Based on the gene expression profile and CESC patient survival data in The Cancer Genome Atlas (TCGA) database, prognostic signatures were obtained and using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses to understand related gene functions, functional and pathway enrichment of potential biomarkers. Gene set enrichment analysis and gene set variation analysis were performed to understand further the biological characteristics and regulatory networks of potential biomarker expression levels on the prognosis of CESC. Immune infiltration analysis to comprehend the functional correlation between potential biomarkers and immune cells and the receiver operating characteristic (ROC) curves to assess the degree of CESC differentiation identification by prognostic signature and hazard score in predicting patient prognosis. Brain-Specific Angiogenesis Inhibitor 1-Associated Protein 2-Like Protein 1 (BAIAP2L1) and secreted phosphoprotein 1 (SPP1) (hazard ratio (HR) >1) were highly expressed in tumor tissues as CESC risk factors, while DES (Desmin) and EF-Hand Calcium Binding Domain 1 (EFCAB1) (HR <1) were expressed at low levels in tumor tissues as prognostic protective factors. SPP1 had the highest positive correlation with Macrophages M0 and IL3RA had the highest positive correlation with T cells CD8. Patients with high expression of the risk factor gene SPP1 had a significant reduction in overall survival (OS) time, whereas those with high expression of the protective factor gene interleukin-3 receptor alpha chain (IL3RA) had a long OS time. Our results showed that the prognostic signature, either risk or protective factors, have a great effect on the prognosis of CESC, and understanding the role of these genes in the development of CESC may provide new directions. [ABSTRACT FROM AUTHOR]

Background: Diffuse large B-cell lymphoma (DLBCL) is globally recognized as the most prevalent and aggressive subtype of non-Hodgkin lymphoma. While conventional treatments are effective initially, the disease can become resistant or relapse over time. This study aimed to examine the differentially expressed genes at the transcriptome level and molecular pathways in DLBCL patients. Methods: This investigation utilized RNA sequencing analysis to compare differentially expressed gene samples from five diffuse large B-cell lymphoma patients with two healthy volunteers. These participants were admitted to UKM Medical Center, Kuala Lumpur between 2019 and 2020. The differentially expressed genes were identified using the DESeq2 R package (version 1.10.1) using a negative binomial distribution model. The obtained P values were corrected with the Benjamin and Hochberg method and identified using a False Discovery Rate threshold of <0.05, with log2 fold change (FC) of ≥2 or ≤-2. Results: Results showed 73 differentially expressed genes between the two groups, among which 70 genes were downregulated, and three genes were upregulated. The differentially expressed genes analyzed with the Reactome pathway were significantly associated with the downregulation of antimicrobial humoral response (P<0.001), neutrophil degranulation (P<0.001), chemokine receptors bind chemokines (P=0.028), defensins (P=0.028) and metabolism of angiotensinogen (P=0.040). Conclusion: These findings suggest that the identified pathways may contribute to cancer progression and weaken the immune response in diffuse large B-cell lymphoma patients. This study offers fresh insights into previously undiscovered downstream targets and pathways modulated by diffuse large B-cell lymphoma. [ABSTRACT FROM AUTHOR]

Marine Heat Waves (MHWs) occurrence has been increasing in the Mediterranean Sea. The effects of field simulated MHWs of different intensity (medium and high temperature) on the transcriptome expression of the endemic seagrass Posidonia oceanica were evaluated considering different origins of the plant. The aim of the study was reached through a common garden transplant experiment in the North-west of Sardinia (Italy), where two P. oceanica meadows characterized by different thermal regimes (cold and warm) were chosen. MHWs were simulated in front of a power plant, that creates a natural laboratory by releasing warm water in the sea. Differential gene expression and GO enrichment analyses highlighted differences in the transcriptomic profiles of plants from cold and warm environments suggesting that the MHWs induced different levels of stress due to different tolerance to the heat event. Plants from both origins activated processes to achieve protein homeostasis, but only cold plants activated an antioxidant defense and altered sugar metabolism, both indicators of heat stress. Within plants of the same origin, a different response to MHW intensity was also detected: while warm plants showed the most complex response at high temperature rather than at medium temperature, cold plants seemed to better cope with the medium temperature intensity rather than with high temperature. [ABSTRACT FROM AUTHOR]

Objective • Smoking stands as a significant factor contributing to aberrations in bone metabolism, while microRNAs are intricately linked to the regulation of bone metabolism. This study aimed to identify cotinine- responsive microRNAs (miRNAs) and downstream regulatory pathways of their target genes involved in the regulation of osteoblastic cells, providing a foundation for new treatments targeting miRNAs for the bone metabolism imbalance induced by smoking. Methods • Primary osteoblastic cells of Sprague-Dawley rats were cultured through a modified enzymatic digestion method from the cranial bone of neonatal rats and stimulated with a high concentration of cotinine (1000 ng/ mL) for 7 days. Then, miRNA gene chip technology was utilized to detect the changes in miRNA expression profiles in cotinine-stimulated osteoblastic cells, and differential expression profiles of cotinine-responsive miRNAs in osteoblastic cells were identified. Real-time polymerase chain reaction was used to detect the levels of significantly differentially expressed miRNAs in rat osteoblastic cells. Gene ontology (GO) and Kyoto encyclopedia of Genes and Genomes (KEGG) pathway analyses were utilized to predict target genes of these miRNAs to reveal the potential biological functions and pathways. Results • We identified 6 statistically differentially expressed miRNAs in the miRNA microarray analysis, of which 3 were upregulated and 3 were downregulated. We chose bone metabolism-related miRNAs as the miRNAs of interest. Quantitative real-time polymerase chain reaction was used to detect the expression levels of the differentially expressed miRNAs, and only miR-210 was significantly upregulated (3.34-fold), consistent with the microarray data. GO and KEGG pathway analyses of predicted miR-210 target genes revealed that miR-210 might participate in numerous signaling pathways, such as the RAS, Rap, PI3K-Akt, and calcium signaling pathways. Conclusion • We found that the strongly upregulated miR-210 may play an important regulatory role in osteoblast cells’ biological behavior and bone formation function. The GO analysis results showed that miR-210 mainly involved protein binding, transporter activity, growth factor binding, and ion channel activity. According to the results of the KEGG analysis, miR-210 might negatively regulate the PI3K-Akt signaling pathway, thus affecting the proliferation of osteoblastic cells. These findings suggest that miR-210 may be a potential target for regulating the imbalance of bone metabolism caused by smoking, offering a new direction for clinical treatment of patients with bone metabolism-related diseases. [ABSTRACT FROM AUTHOR]

The objectives of this investigation were to identify differentially expressed circular RNAs (circRNAs) in the hypothalamus of goats with high and low prolificacy and construct a circRNA-mRNA regulatory network to uncover key potential circRNAs that influence goat prolificacy. Transcriptome analysis was performed on hypothalamus samples from low-prolificacy (n = 5) and high-prolificacy (n = 6) Chuanzhong black goats to identify circRNAs that influence prolificacy in these goats. Differential expression analysis identified a total of 205 differentially expressed circRNAs, comprising 100 upregulated and 105 downregulated circRNAs in the high-prolificacy group compared with the low-prolificacy group. Enrichment analysis of these differentially expressed circRNAs indicated significant enrichment in Gene Ontology terms associated with mammalian oogenesis, negative regulation of neurotransmitter secretion, reproductive developmental processes, hormone-mediated signaling pathways, and negative regulation of hormone secretion. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted significant enrichment in the oxytocin signaling pathway, GnRH signaling pathway, and hormone-mediated oocyte maturation. The hypothalamus of low- and high-prolificacy goats contains circular RNAs (circRNAs), including chicirc_063269, chicirc_097731, chicirc_017440, chicirc_049641, chicirc_008429, chicirc_145057, chicirc_030156, chicirc_109497, chicirc_030156, chicirc_176754, and chicirc_193363. Chuanzhong black goats have the potential to influence prolificacy by modulating the release of serum hormones from the hypothalamus. A circRNA-miRNA regulatory network was constructed, which determined that miR-135a, miR-188-3p, miR-101-3p, and miR-128-3p may interact with differentially expressed circRNAs, thereby regulating reproductive capacity through the hypothalamic-pituitary-gonadal axis. The results of this study enhance our knowledge of the molecular mechanisms that regulate prolificacy in Chuanzhong black goats at the hypothalamic level. [ABSTRACT FROM AUTHOR]

Alfalfa species Medicago sativa L. (MS) and Medicago falcata L. (MF), globally prominent perennial leguminous forages, hold substantial economic value. However, our comprehension of the molecular mechanisms governing their resistance to cold stress remains limited. To address this knowledge gap, we scrutinized and compared MS and MF cold-stress responses at the molecular level following 24 h and 120 h low-temperature exposure (4 °C). Our study revealed that MF had superior physiological resilience to cold stress compared with MS, and its morphology was healthier under cold stress, and its malondialdehyde content and superoxide dismutase activity increased, first, and then decreased, while the soluble sugar content continued to accumulate. Transcriptome analysis showed that after 120 h of exposure, there were different gene-expression patterns between MS and MF, including 1274 and 2983 genes that were continuously up-regulated, respectively, and a total of 923 genes were included, including star cold-resistant genes such as ICE1 and SIP1. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed numerous inter-species differences in sustained cold-stress responses. Notably, MS-exclusive genes included a single transcription factor (TF) gene and several genes associated with a single DNA repair-related pathway, whereas MF-exclusive genes comprised nine TF genes and genes associated with 14 pathways. Both species exhibited high-level expression of genes encoding TFs belonging to AP2-EREBP, ARR-B, and bHLH TF families, indicating their potential roles in sustaining cold resistance in alfalfa-related species. These findings provide insights into the molecular mechanisms governing cold-stress responses in MS and MF, which could inform breeding programs aimed at enhancing cold-stress resistance in alfalfa cultivars. [ABSTRACT FROM AUTHOR]

Simple Summary: Nasopharyngeal carcinoma (NPC) is a head and neck cancer that is mainly found in Southeast Asia and North Africa. Most patients with NPC are diagnosed at an advanced stage, which increases the risk of recurrence and metastasis. A cohort of 41 NPC tumor samples from Morocco and North Africa were analyzed using shotgun proteomics. Within the cohort, three proteomically defined clusters were identified. We also examined sex and stage differences from a proteomic perspective. In total, 59 and 26 differentially abundant proteins were identified between male and female patients and patients with early and advanced stages within the cohort. Data were then compared to 21 healthy controls from a prior study. Across the two datasets, 6532 proteins were identified, of which 1507 proteins were differentially abundant between patients and controls. Differentially abundant proteins between tumor and healthy samples included PI3K, MAPK, BCL2, and PPIA proteins, which are involved in various biological pathways related to cell proliferation and growth. This study lays a foundation for both mechanistic and biomarker studies into NPC in Morocco and North African populations. Background: Nasopharyngeal carcinoma (NPC) is a distinct cancer of the head and neck that is highly prevalent in Southeast Asia and North Africa. Though an extensive analysis of environmental and genetic contributors has been performed, very little is known about the proteome of this disease. A proteomic analysis of formalin-fixed paraffin-embedded (FFPE) tissues can provide valuable information on protein expression and molecular patterns for both increasing our understanding of the disease and for biomarker discovery. To date, very few NPC proteomic studies have been performed, and none focused on patients from Morocco and North Africa. Methods: Label-free Liquid Chromatography–Tandem Mass Spectrometry (LC-MS/MS) was used to perform a proteomic analysis of FFPE tissue samples from a cohort of 41 NPC tumor samples of Morocco and North Africa origins. The LC-MS/MS data from this cohort were analyzed alongside 21 healthy controls using MaxQuant 2.4.2.0. A differential expression analysis was performed using the MSstats package in R. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotations were carried out using the DAVID bioinformatic tool. Results: 3341 proteins were identified across our NPC cases, revealing three main clusters and five DEPs with prognostic significance. The sex disparity of NPC was investigated from a proteomic perspective in which 59 DEPs were found between males and females, with significantly enriched terms associated with the immune response and gene expression. Furthermore, 26 DEPs were observed between patients with early and advanced stages of NPC with a significant cluster related to the immune response, implicating up-regulated DEPs such as IGHA, IGKC, and VAT1. Across both datasets, 6532 proteins were quantified between NPC patients and healthy controls. Among them, 1507 differentially expressed proteins (DEPs) were observed. GO and KEGG pathway analyses showed enriched terms of DEPs related to increased cellular activity, cell proliferation, and survival. PI3K and MAPK proteins as well as RAC1 BCL2 and PPIA were found to be overexpressed between cancer tissues and healthy controls. EBV infection was also one of the enriched pathways implicating its latent genes like LMP1 and LMP2 that activate several proteins and signaling pathways including NF-Kappa B, MAPK, and JAK-STAT pathways. Conclusion: Our findings unveil the proteomic landscape of NPC for the first time in the Moroccan population. These studies additionally may provide a foundation for identifying potential biomarkers. Further research is still needed to help develop tools for the early diagnosis and treatment of NPC in Moroccan and North African populations. [ABSTRACT FROM AUTHOR]

In mammalian females, the transition from dormancy in primordial follicles to follicular development is critical for maintaining ovarian function and reproductive longevity. In mice, the quiescent primary oocyte of the primordial follicle contains a Balbiani body (B-body), an organelle aggregate comprised of a spherical structure of Golgi complexes. Here we show that the structure of the B-body is maintained by microtubules and actin. The B-body stores mRNA-capping enzyme and 597 mRNAs associated with mRNA-decapping enzyme 1 A (DCP1A). Gene ontology analysis results indicate that proteins encoded by these mRNAs function in enzyme binding, cellular component organization and packing of telomere ends. Pharmacological depolymerization of microtubules or actin led to B-body disassociation and nascent protein synthesis around the dissociated B-bodies within three hours. An increased number of activated developing follicles were observed in ovaries with prolonged culture and the in vivo mouse model. Our results indicate that the mouse B-body is involved in the activation of dormant primordial follicles likely via translation of the B-body-associated RNAs in primary oocytes. Balbiani body-mediated RNA storage and translational regulation is involved in primary oocyte quiescence in mice, providing new insights into the molecular mechanisms of ovarian reserve maintenance in mammals. [ABSTRACT FROM AUTHOR]

Objective: Asthma and gastroesophageal reflux disease (GERD) often occur simultaneously, with GERD being a comorbidity of asthma. This study aimed to explore the biological markers related to asthma and GERD by bioinformatics analysis. Methods: Initially, gene expression datasets for asthma and GERD were obtained from the Gene Expression Omnibus database, and subsequent differential expression analysis yielded 620 differentially expressed genes (DEGs) for asthma and 2367 DEGs for GERD. The intersection of these two gene sets yielded a total of 84 DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that these genes may be involved in steroid hormone secretion and cellular stress response. Five hub genes (PTGDR2, CPA3, FCER1A, TPSAB1, and IL1RL1) were identified by a protein–protein interaction (PPI) network analysis and topological algorithm. Results: Enrichment analysis results indicated that hub genes may be involved in hormone secretion and disease development, particularly in regulating the renin–angiotensin system and systemic arterial blood pressure. PTGDR2, CPA3, TPSAB1, and IL1RL1 were upregulated in both asthma and GERD patient groups, while FCER1A was upregulated in asthma patients but downregulated in GERD patients. Through drug prediction, 22 drugs targeting hub genes PTGDR2, FCER1A, and TPSAB1 were identified. By constructing a transcription factor (TF)-target gene network, we found that eight TFs may regulate the expression of PTGDR2, FCER1A, and IL1RL1. Conclusion: Hence, Asthma and GERD were related to steroid hormone secretion and the renin–angiotensin system. [ABSTRACT FROM AUTHOR]