Transcriptomic Analysis of Cardiac Tissues in a Rodent Model of Coronary Microembolization.

Purpose: Coronary microembolization (CME) can result in cardiac dysfunction, severe arrhythmias, and a reduced coronary flow reserve. Impairment of mitochondrial energy metabolism has been implicated in the progression and pathogenesis of CME; however, its role remains largely undetermined. This study aimed to explore alterations in mitochondria-related genes in CME. Methods: A rat model of CME was successfully established by injecting plastic microspheres into the left ventricle. The cardiac tissues of the two groups were sequenced and mitochondrial functions were assessed. Results: Using RNA-Seq, together with GO and KEGG enrichment analyses, we identified 3822 differentially expressed genes (DEGs) in CME rats compared to control rats, and 101 DEGs were mitochondria-related genes. Notably, 36 DEGs were up-regulated and 65 DEGs were down-regulated (CME vs control). In particular, the oxidative phosphorylation (OXPHOS) and mitochondrial electron transport were obviously down-regulated in the CME group. Functional analysis revealed that CME mice exhibited marked reductions in ATP and mitochondrial membrane potential (MMP), by contrast, the production of reactive oxygen species (ROS) was much higher in CME mice than in controls. Protein-protein interaction (PPI) and quantitative PCR (qPCR) validation suggested that eight hub genes including Cmpk2, Isg15, Acsl1, Etfb, Ndufa8, Adhfe1, Gabarapl1 and Acot13 were down-regulated in CME, whereas Aldh18a1 and Hspa5 were up-regulated. Conclusion: Our findings suggest that dysfunctions in mitochondrial activity and metabolism are important mechanisms for CME, and mitochondria-related DEGs may be potential therapeutic targets for CME.

Identification of Upregulating Genes, Transcription Factors, and miRNAs in Vitiligo. In silico Study.

Background: Depigmentation of specific areas of the skin is a persistent and long-lasting dermatologic disorder known as vitiligo, stemming from the impairment and disruption of melanocytes both structurally and functionally, leading to the loss of pigmentation in those regions. Aim: Our objective was to identify the pivotal genes and upstream regulators, transcription factors (TFs), microRNAs (miRNAs), and pathways implicated in the pathogenesis of vitiligo. Methods: An integrated analysis was conducted using microarray datasets on vitiligo obtained from the Gene Expression Omnibus (GEO) database. The functional annotation and potential pathways of differentially expressed genes (DEGs) were additionally investigated through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Various bioinformatics approaches were utilized, making use of publicly accessible databases to identify appropriate TFs and miRNAs. Results: Our investigation identified TYR, MLANA, TYRP1, PMEL, OCA2, SLC45A2, GPR143, DCT, TRPM1, and EDNRB as the most appropriate genes associated with vitiligo. Our suggestion is that the identified biological processes include developmental pigmentation (GO:0048066) and pigment metabolic processes (GO:0042440) as the most suitable biological processes. In contrast, the KEGG pathways that showed significance in our analysis are Tyrosine metabolism (Path: hsa00350) and Melanogenesis (Path: hsa04916). We hypothesized the involvement of ten TFs and 73 miRNAs in the regulation of genes related to vitiligo. Conclusion: TYR, MLANA, TYRP1, PMEL, OCA2, SLC45A2, GPR143, DCT, TRPM1, and EDNRB are the top ten genes that are pivotal in the progression and exhibition of vitiligo. The biological, cellular, molecular, and KEGG pathways of those genes has an imperative role in the pathogenesis of vitiligo. TFs and miRNAs that interact with this gene are listed, shedding light on the regulatory mechanisms governing the expression of these key genes in vitiligo.

Transcriptome analysis of Reticulitermes flaviceps exposed to Mentha spicata essential oil and carvone indicates a potential neurotoxic mechanism of action characterized by intracellular calcium influx mediated by dopamine receptors.

Reticulitermes flaviceps is an economically important pest in agriculture, forestry, and construction. Recent studies have shown an increase in research focusing on the anti-termite properties of plant essential oils, however, there remains a lack of information regarding the specific molecular mechanism involved. In this study, RNA-seq analysis was conducted on termites exposed to Mentha spicata essential oil (EO) and carvone, leading to the discovery of various genes that were expressed differentially under different treatment conditions. Numerous genes that exhibited a response to M. spicata EO and carvone found to be associated with stress-related pathways, such as drug metabolism cytochrome P450, glutathione metabolism, fatty acid metabolism, citric acid cycle, neuroactive ligand-receptor interaction, cell apoptosis, the AMPK signalling pathway, the mTOR signalling pathway, the longevity regulation pathway, ubiquitin-mediated protein hydrolysis, and the calcium signalling pathway. The up-regulation of genes (SPHK) associated with calcium channels, such as SPHK, indicates a potential mechanism of neurotoxicity, while the up-regulation of apoptosis-associated genes, including ACTB_G1, PYG, SQSTM1, RNF31, suggests a potential mechanism of cytotoxicity. The metabolism of M. spicata EO induces oxidative stress, elevates free Ca2+ levels in mitochondria, and initiates the generation of reactive oxygen species (ROS), ultimately resulting in programmed cell necrosis and apoptosis, as well as facilitating cellular autophagy. The monoterpenes exhibited neurotoxic and cytotoxic effects on R. flaviceps and could be exploited to advance termiticide development and eco-friendly termite control.

Dynamic Transcriptome Profile Analysis of Mechanisms Related to Melanin Deposition in Chicken Muscle Development.

The pectoral muscle is an important component of skeletal muscle. The blackness of pectoral muscles can directly affect the economic value of black-boned chickens. Although the genes associated with melanogenesis in mammals and birds have been thoroughly investigated, only little is known about the key genes involved in muscle hyperpigmentation during embryonic development. Here, we analyzed melanin deposition patterns in the pectoral muscle of Yugan black-boned chickens and compared differentially expressed genes (DEGs) between the muscles of Wenchang (non-black-boned chickens) and Yugan black-boned chickens on embryonic days 9, 13, 17, and 21. Melanin pigments were found to gradually accumulate in the muscle fibers over time. Using RNA-seq, there were 40, 97, 169, and 94 genes were identified as DEGs, respectively, between Yugan black-boned chicken muscles and Wenchang chickens at embryonic day 9, 13, 17, and 21 stages (fold change ≥2.0, false discovery rate (FDR) < 0.05). Thirteen DEGs, such as MSTRG.720, EDNRB2, TYRP1, and DCT, were commonly identified among the time points observed. These DEGs were mainly involved in pigmentation, melanin biosynthetic and metabolic processes, and secondary metabolite biosynthetic processes. Pathway analysis of the DEGs revealed that they were mainly associated with melanogenesis and tyrosine metabolism. Moreover, weighted gene co-expression network analysis (WGCNA) was used to detect core modules and central genes related to melanogenesis in the muscles of black-boned chickens. A total of 24 modules were identified. Correlation analysis indicated that one of them (the orange module) was positively correlated with muscle pigmentation traits (r > 0.8 and p < 0.001). Correlations between gene expression and L* values of the breast muscle were investigated in Yugan and Taihe black-boned chickens after hatching. The results confirmed that EDNRB2, GPNMB, TRPM1, TYR, and DCT expression levels were significantly associated with L* values (p < 0.01) in black-boned chickens (p < 0.05). Our results suggest that EDNRB2, GPNMB, TRPM1, TYR, and DCT are the essential genes regulating melanin deposition in the breast muscle of black-boned chickens. MSTRG.720 is a potential candidate gene involved in melanin deposition in the breast muscles of Yugan black-boned chickens.

Transcriptome analysis of four types of gonadal tissues in largemouth bass (Micropterus salmoides) to reveal its sex-related genes.

The sex determination system of largemouth bass (Micropterus salmoides, LMB) is XX/XY; however, the underlying molecular mechanisms involved in early sex differentiation, gonadal development, and exogenous hormone-induced sex reversal remain unknown. In this study, LMB at 15 days post-hatching (dph) were fed diets containing 20 mg/kg of 17α-methyltestosterone (17α-MT) or 30 mg/kg of 17ß-estradiol (17ß-E2) for 60 days, respectively. Serum steroid levels, histological observations of the gonads, and identification of sex-specific markers were employed to screen the gonads of 60-day-old normal female fish (XX-F), normal male fish (XY-M), 17ß-E2 induced pseudo-female fish (XY-F), and 17α-MT-induced pseudo-male fish (XX-M) for transcriptome sequencing in order to uncover genes and pathway involved in the process of sexual reversal. The results from histology and serum sex steroid hormone analysis showed that both 17α-MT and 17ß-E2 were capable of inducing sex reversal of LMB at 15 dph. Transcriptome results revealed a total of 2,753 genes exhibiting differential expression, and the expression pattern of these genes in the gonads of XX-M or XY-F resembled that of normal females or males. The male sex-biased genes that are upregulated in XX-M and downregulated in XY-F are referred to as key genes for male reversal, while the female sex-biased genes that are upregulated in XY-F and downregulated in XX-M are referred to as key genes for female reversal. Finally, 12 differentially expressed genes (DEGs) related to male sex reversal were screened, including star2, cyp17a, cyp11b1, dmrt1, amh, sox9a, katnal1, spata4, spata6l, spata7, spata18 and foxl3. 2 DEGs (foxl2a and cyp19a1b) were found to be associated with female sex reversal. The changes in these genes collectively influence the direction of sex differentiation of LMB. Among them, star2, dmrt1 and cyp19a1b with significantly altered expression levels may play potentially crucial role in the process of gender reversal. The expression patterns of 21 randomly selected genes were verified using qRT-PCR which confirmed the reliability and accuracy of the RNA-seq results. These findings not only enhance our understanding of the molecular basis underlying sex reversal but also provide crucial data support for future breeding research on unisexual LMB.

Comparative physiological and transcriptomic analyses reveal genotype specific response to drought stress in Siberian wildrye (Elymus sibiricus).

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

The consistently up-regulated expression of NLRP3 in severe asthma patients from mRNA microarray and ovalbumin-induced mouse model of asthma.

Background: Severe asthma (SA) is a chronic lung disease, resistant to current treatments, symbolized by repeated symptoms of reversible airflow obstruction, airway hyper-responsiveness, and inflammation. The aim of this study was to identify genes exhibiting differential expression in individuals without asthma and SA patients. We aimed to pinpoint hub differentially expressed genes (DEGs) by utilizing a mouse model of asthma sensitized to ovalbumin (OVA). Methods: Microarray data for SA were acquired from the Gene Expression Omnibus (GEO) databases. DEGs were identified, and functional enrichment analyses were carried out. STRING and Cytoscape were utilized to design a protein-protein interaction (PPI) network and conduct module analysis. An OVA-induced asthma mice model was established. Lung tissue from the mice was collected for quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemistry (IHC) to assess the expression of DEGs. Results: A total of 545 DEGs were identified, among which 172 genes were upregulated in SA patients compared to healthy controls. The nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) was significantly up-regulated in SA patients [adjusted P value (Padj) =0.001]. Analysis of lung tissue using qRT-PCR, western blot, and IHC revealed higher expression of NLRP3 in OVA-induced asthma mice compared to the control group. Enrichment analysis suggests the involvement of NLRP3 in pathways related to pyroptosis, c-type lectin receptor signaling, and NOD-like receptor signaling. Conclusions: Through bioinformatics analysis, we identified a multitude of DEGs that could potentially contribute significantly to the development of SA. Notably, our findings highlight NLRP3 as a potential pivotal player in asthma pathogenesis, underscoring its prospective utility as a biomarker for SA.

RNA-seq analyses on gametogenic tissues of alfalfa (Medicago sativa) revealed plant reproduction- and ploidy-related genes.

BACKGROUND: In alfalfa (Medicago sativa), the coexistence of interfertile subspecies (i.e. sativa, falcata and coerulea) characterized by different ploidy levels (diploidy and tetraploidy) and the occurrence of meiotic mutants capable of producing unreduced (2n) gametes, have been efficiently combined for the establishment of new polyploids. The wealth of agronomic data concerning forage quality and yield provides a thorough insight into the practical benefits of polyploidization. However, many of the underlying molecular mechanisms regarding gene expression and regulation remained completely unexplored. In this study, we aimed to address this gap by examining the transcriptome profiles of leaves and reproductive tissues, corresponding to anthers and pistils, sampled at different time points from diploid and tetraploid Medicago sativa individuals belonging to progenies produced by bilateral sexual polyploidization (dBSP and tBSP, respectively) and tetraploid individuals stemmed from unilateral sexual polyploidization (tUSP). RESULTS: Considering the crucial role played by anthers and pistils in the reduced and unreduced gametes formation, we firstly analyzed the transcriptional profiles of the reproductive tissues at different stages, regardless of the ploidy level and the origin of the samples. By using and combining three different analytical methodologies, namely weighted-gene co-expression network analysis (WGCNA), tau (τ) analysis, and differentially expressed genes (DEGs) analysis, we identified a robust set of genes and transcription factors potentially involved in both male sporogenesis and gametogenesis processes, particularly in crossing-over, callose synthesis, and exine formation. Subsequently, we assessed at the same floral stage, the differences attributable to the ploidy level (tBSP vs. dBSP) or the origin (tBSP vs. tUSP) of the samples, leading to the identification of ploidy and parent-specific genes. In this way, we identified, for example, genes that are specifically upregulated and downregulated in flower buds in the comparison between tBSP and dBSP, which could explain the reduced fertility of the former compared to the latter materials. CONCLUSIONS: While this study primarily functions as an extensive investigation at the transcriptomic level, the data provided could represent not only a valuable original asset for the scientific community but also a fully exploitable genomic resource for functional analyses in alfalfa.

Unlocking the Transcriptional Reprogramming Repertoire between Variety-Dependent Responses of Grapevine Berries to Infection by Aspergillus carbonarius.

Aspergillus carbonarius causes severe decays on berries in vineyards and is among the main fungal species responsible for grape contamination by ochratoxin A (OTA), which is the foremost mycotoxin produced by this fungus. The main goal of this study was to investigate at the transcriptome level the comparative profiles between two table grape varieties (Victoria and Fraoula, the white and red variety, respectively) after their inoculation with a virulent OTA-producing A. carbonarius strain. The two varieties revealed quite different transcriptomic signatures and the expression profiles of the differential expressed genes (DEGs) highlighted distinct and variety-specific responses during the infection period. The significant enrichment of pathways related to the modulation of transcriptional dynamics towards the activation of defence responses, the triggering of the metabolic shunt for the biosynthesis of secondary metabolites, mainly phenylpropanoids, and the upregulation of DEGs encoding phytoalexins, transcription factors, and genes involved in plant-pathogen interaction and immune signaling transduction was revealed in an early time point in Fraoula, whereas, in Victoria, any transcriptional reprogramming was observed after a delay. However, both varieties, to some extent, also showed common expression dynamics for specific DEG families, such as those encoding for laccases and stilbene synthases. Jasmonate (JA) may play a critical modulator role in the defence machinery as various JA-biosynthetic DEGs were upregulated. Along with the broader modulation of the transcriptome that was observed in white grape, expression profiles of specific A. carbonarius genes related to pathogenesis, fungal sporulation, and conidiation highlight the higher susceptibility of Victoria. Furthermore, the A. carbonarius transcriptional patterns directly associated with the regulation of the pathogen OTA-biosynthesis gene cluster were more highly induced in Victoria than in Fraoula. The latter was less contaminated by OTA and showed substantially lower sporulation. These findings contribute to uncovering the interplay beyond this plant-microbe interaction.

FHL1: A novel diagnostic marker for papillary thyroid carcinoma.

Although there are clear morphologic criteria for the diagnosis of papillary thyroid carcinoma (PTC), when the morphology is untypical or overlaps, accurate diagnostic indicators are necessary. Since few studies investigated the role of down-regulated genes in PTC, this article aims to further explore the molecular markers associated with PTC. We conducted bioinformatics analysis of gene microarrays of PTC and normal adjacent tissues. Besides, quantitative real-time quantitative polymerase chain reaction array and immunohistochemical staining were used to investigate the expression of the major down-regulated genes. The results indicated that several important down-regulated genes, including TLE1, BCL2, FHL1, GHR, KIT, and PPARGC1A were involved in the process of PTC. Compared to normal adjacent tissues, the mRNA expression of the major genes was down-regulated in PTC (p＜0.05). Immunohistochemically, FHL1 shows negative or low expression in PTC tissues (p＜0.05). BCL2 did not show a significant difference between PTC and normal thyroid tissues (p > 0.05). TLE1, KIT, PPARGC1A and GHR showed negative expression in both tumor and normal tissues. These results suggested that FHL1 could serve as a novel tumor marker for precise diagnosis of PTC.

Comparative global profiling of Perilla leaf and stem via transcriptomics and metabolomics.

Perilla (Perilla frutescens L.) is a time-honored herbal plant with widespread applications in both medicine and culinary practices around the world. Profiling the essential organs and tissues with medicinal significance on a global scale offers valuable insights for enhancing the yield of desirable compounds in Perilla and other medicinal plants. In the present study, genome-wide RNA-sequencing (RNA-seq) and assessing the global spectrum of metabolites were carried out in the two major organs/tissues of stem (PfST) and leaf (PfLE) in Perilla. The results showed a total of 18,490 transcripts as the DEGs (differentially expressed genes) and 144 metabolites as the DAMs (differentially accumulated metabolites) through the comparative profiling of PfST vs PfLE, and all the DEGs and DAMs exhibited tissue-specific trends. An association analysis between the transcriptomics and metabolomics revealed 14 significantly enriched pathways for both DEGs and DAMs, among which the pathways of Glycine, serine and threonine metabolism (ko00260), Glyoxylate and dicarboxylate metabolism (ko00630), and Glucagon signaling pathway (ko04922) involved relatively more DEGs and DAMs. The results of qRT-PCR assays of 18 selected DEGs confirmed the distinct tissue-specific characteristics of all identified DEGs between PfST and PfLE. Notably, all eight genes associated with the flavonoid biosynthesis/metabolism pathways exhibited significantly elevated expression levels in PfLE compared to PfST. This observation suggests a heightened accumulation of metabolites related to flavonoids in Perilla leaves. The findings of this study offer a comprehensive overview of the organs and tissues in Perilla that have medicinal significance.

Differences in T cell-associated serum markers between ischemic cardiomyopathy and dilated cardiomyopathy.

Background: Ischemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) have similar clinical manifestations but differ in pathogenesis. We aimed to identify T cell-associated serum markers that can be used to distinguish between ICM and DCM. Methods: We identified differentially expressed genes (DEGs) with transcriptome sequencing data in GSE116250, and then conducted enrichment analysis of DEGs in the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Protein-protein interaction (PPI) networks were used to analyze the relationship between T cells-related genes and identify hub genes. Enzyme-linked immunosorbent assay (ELISA) kits were used to detect T cell-associated proteins in serum, and receiver operating characteristic (ROC) curves were used to evaluate the diagnostic efficacy of these serum markers. Results: Using the limma package and Venn plots, we found that the non-failing donors (NFD) and DCM groups shared many of the same DEGs and DEGs-enriched functions compared to the ICM group, which were involved in T cell activation and differentiation, among other functions. Subsequently, the immune cell score showed no difference between NFD and DCM, but they were significantly different from ICM patients in CD8 T cells CD4 T cells memory resting and activated, T cells follicular helper, and M1 macrophage. After analyzing T cell-associated DEGs, it was found that 4 DEGs encoding secreted proteins were highly expressed in the ICM group compared with the NFD and DCM groups, namely chemokine (C-C motif) ligand 21 (CCL21), interleukin (IL)-1ß, lymphocyte-activation gene 3 (LAG3), and vascular cell adhesion molecule-1 (VCAM-1). Importantly, the serum levels of CCL21, IL-1ß, LAG3, and VCAM-1 in ICM patients were all significantly higher than those in DCM patients. The ROC curves showed that the area under the curve (AUC) values of serum CCL21, IL-1ß, LAG3, and VCAM-1 were 0.775, 0.868, 0.934, and 0.903, respectively. Conclusions: We have identified four T cell-associated serum markers, CCL21, IL-1ß, LAG3, and VCAM-1, as potential diagnostic serum markers that differentiate ICM from DCM.

Role of 14-3-3 protein family in the pathobiology of EBV in immortalized B cells and Alzheimer's disease.

Background and Aims: Several studies have revealed that Epstein-Barr virus (EBV) infection raised the likelihood of developing Alzheimer's disease (AD) via infecting B lymphocytes. The purpose of the current investigation was to assess the possible association between EBV infection and AD. Methods: The microarray datasets GSE49628, GSE126379, GSE122063, and GSE132903 were utilized to extract DEGs by using the GEO2R tool of the GEO platform. The STRING tool was used to determine the interaction between the DEGs, and Cytoscape was used to visualize the results. The DEGs that were found underwent function analysis, including pathway and GO, using the DAVID 2021 and ClueGo/CluePedia. By using MNC, MCC, Degree, and Radiality of cytoHubba, we identified seven common key genes. Gene co-expression analysis was performed through the GeneMANIA web tool. Furthermore, expression analysis of key genes was performed through GTEx software, which have been identified in various human brain regions. The miRNA-gene interaction was performed through the miRNet v 2.0 tool. DsigDB on the Enrichr platform was utilized to extract therapeutic drugs connected to key genes. Results: In GEO2R analysis of datasets with |log2FC|≥ 0.5 and p-value <0.05, 8386, 10,434, 7408, and 759 genes were identified. A total of 141 common DEGs were identified by combining the extracted genes of different datasets. A total of 141 nodes and 207 edges were found during the PPI analysis. The DEG GO analysis with substantial alterations disclosed that they are associated to molecular functions and biological processes, such as positive regulation of neuron death, autophagy regulation of mitochondrion, response of cell to insulin stimulus, calcium signaling regulation, organelle transport along microtubules, protein kinase activity, and phosphoserine binding. Kyoto Encyclopedia of Genes and Genomes analysis discovered the correlation between the DEGs in pathways of neurodegeneration: multiple disease, cell cycle, and cGMP-PKG signaling pathway. Finally, YWHAH, YWHAG, YWHAB, YWHAZ, MAP2K1, PPP2CA, and TUBB genes were identified that are strongly linked to EBV and AD. Three miRNAs, i.e., hsa-mir-15a-5p, hsa-let-7a-5p, and hsa-mir-7-5p, were identified to regulate most of hub genes that are associated with EBV and AD. Further top 10 significant therapeutic drugs were predicted. Conclusion: We have discovered new biomarkers and therapeutic targets for AD, as well as the possible biological mechanisms whereby infection with EBV may be involved in AD susceptibility for the first time.

To investigate the function of age-related genes in different subtypes of asthma based on bioinformatics analysis.

Asthma is a heterogeneous airway inflammatory disease that can be classified according to the inflammatory phenotype. The pathogenesis, clinical features, response to hormone therapy, and prognosis of different inflammatory phenotypes differ significantly. This condition also refers to age-related chronic ailments. Here, we intend to identify the function of aging-related genes in different inflammatory phenotypes of asthma using bioinformatic analyses. Initially, the research adopted the GSEA analysis to understand the fundamental mechanisms that govern different inflammatory phenotypes of asthma pathogenesis and use the CIBERSORT algorithm to assess the immune cell composition. The differentially expressed genes (DEGs) of eosinophilic asthma (EA), neutrophilic asthma (NA), and paucigranulocytic asthma (PGA) were identified through the limma R package. Aging-related genes, screened from multiple databases, were intersected with DEGs of asthma to obtain the asthma-aging-related DEGs. Then, the GO and KEGG pathway enrichment analyses showed that the NA- and EA-aging-related DEGs are involved in the various cytokine-mediated signaling pathways. PPI network and correlation analysis were performed to identify and evaluate the correlation of the hub genes. Further, the clinical characteristics of asthma-aging-related DEGs were explored through ROC analysis. 3 and 12 aging-related DEGs in EA and NA patients show high diagnostic accuracy, respectively (AUC >0.7). This study provided valuable insights into aging-related gene therapy for phenotype-specific asthma. Moreover, the study suggests that effective interventions against asthma may operate by disrupting the detrimental cycle of "aging induces metabolic diseases, which exacerbate aging".

Identifying key pathogenic mechanisms and potential intervention targets for recurrence after laryngeal cancer treatment through bioinformatics screening.

Background: Laryngeal cancer (LC), a prevalent malignant tumor of the head and neck, is characterized by a high rate of postoperative recurrence and significant treatment challenges upon recurrence, severely impacting patients' quality of life. There is a pressing need for effective biomarkers in clinical practice to predict the risk of LC recurrence and guide the development of personalized treatment plans. This study uses bioinformatics methods to explore potential biomarkers for LC recurrence, focusing on key genes and exploring their functions and mechanisms of action in LC recurrence. The aim is to provide new perspectives and evidence for clinical diagnosis, prognostic evaluation, and targeted treatment of LC. Methods: Gene expression profiles from the GSE25727 data set in the Gene Expression Omnibus database were analyzed to detect the differentially expressed genes (DEGs) between the tumor tissues of postoperative recurrent and non-recurrent early stage LC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were also conducted. A protein-protein interaction (PPI) network and transcription factor (TF)-DEG-microRNA (miRNA) network were developed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, with key genes selected using the Molecular Complex Detection (MCODE) plugin. A Gene Set Enrichment Analysis (GSEA) was carried out to investigate the possible mechanisms of the key genes. A retrospective analysis was conducted using the clinical data of 83 LC patients. Immunohistochemical staining was used to examine the transcription level of the key genes in the LC tumor tissues and the factors affecting postoperative recurrence. Results: A total of 248 upregulated and 34 downregulated DEGs were identified in the GSE25727 data set. The PPI network analysis identified a significant module and five candidate genes (i.e., RRAGA, SLC38A9, WDR24, ATP6V1B1, and LAMTOR3). The construction of the TF-DEG-miRNA network indicated that ATP6V1B1 might be regulated by one TF and interact with 17 miRNAs. The KEGG and GSEA analyses suggested that ATP6V1B1 may influence LC recurrence through the involvement of pro-inflammatory and pro-fibrotic mediators, glutathione metabolism, matrix metalloproteinases, immune regulation, and lymphocyte interactions. The recurrence rate of the 83 LC patients included in the study was 19.3% (16/83). The immunohistochemistry results indicated that ATP6V1B1 was highly expressed in patients with recurrent LC. The univariate and multivariate logistic regression analyses revealed that tumor stage T3 (P=0.04), tumor stage T4 (P=0.01), and a high expression of ATP6V1B1 (P=0.02) were risk factors for recurrence after surgical treatment in LC patients. Conclusions: The key genes and signaling pathways identified through the bioinformatics screening provide insights into the potential mechanisms of the pathogenesis of LC. ATP6V1B1 may promote the recurrence of LC by weakening the immune phenotype. Our findings provide a theoretical basis for further research into clinical diagnostics and treatment strategies for LC.

Date palm transcriptome analysis provides new insights on changes in response to high salt stress of colonized roots with the endophytic fungus Piriformospora indica.

Salinity is a significant threat that causes considerable yield losses in date palm. The root endophytic fungus Piriformospora indica has proven effective in providing salt stress tolerance to host plants. However, the underlying molecular mechanism facilitating the date palm's response to P. indica inoculation, and its involvement in the salt stress tolerance, remains unknown. In this study, the colonization of P. indica on date palm seedlings exposed to saline conditions was observed through confocal microscopy, and its impact on gene expressions was evaluated using the transcriptomic analysis. Our findings show that P. indica colonization reinforced the cortical cells, prevented them from plasmolysis and cell death under salinity. The RNAseq analysis produced clean reads ranging from 62,040,451 to 3,652,095 across the treatment groups, successfully assembling into 30,600 annotated genes. Out of them, the number of differentially expressed genes (DEGs) varied across the treatments: i.e., 2523, 2031, and 1936 DEGs were upregulated, while 2323, 959, and 3546 were downregulated in Salt, Fungi, and Fungi+Salt groups, respectively. Furthermore, principal component analysis based on transcriptome profiles revealed discrete clustering of samples from different treatment groups. KEGG and GO pathways enrichment analysis highlighted variation in the number and types of enriched pathways among the treatments. Our study indicated variations in gene expression related to plant hormone biosynthesis and signal transduction (auxin, abscisic acid, gibberellin, and ethylene), ABC transporters, sodium/hydrogen exchanger, cation HKT transporter, transcription factors such as WRKY and MYBs, and the plant immune system (lipoxygenase and jasmonate) of the date palm seedlings. By characterizing the transcriptome of date palm roots under salt stress and with colonization of P. indica, the present findings provide valuable perspectives on the molecular mechanisms responsible for inducing salinity stress tolerance in plants.

Host response to influenza infections in human blood: association of influenza severity with host genetics and transcriptomic response.

Introduction: Influenza virus infections are a major global health problem. Influenza can result in mild/moderate disease or progress to more severe disease, leading to high morbidity and mortality. Severity is thought to be primarily driven by immunopathology, but predicting which individuals are at a higher risk of being hospitalized warrants investigation into host genetics and the molecular signatures of the host response during influenza infections. Methods: Here, we performed transcriptome and genotype analysis in healthy controls and patients exhibiting mild/moderate or severe influenza (ICU patients). A unique aspect of our study was the genotyping of all participants, which allowed us to assign ethnicities based on genetic variation and assess whether the variation was correlated with expression levels. Results: We identified 169 differentially expressed genes and related molecular pathways between patients in the ICU and those who were not in the ICU. The transcriptome/genotype association analysis identified 871 genes associated to a genetic variant and 39 genes distinct between African-Americans and Caucasians. We also investigated the effects of age and sex and found only a few discernible gene effects in our cohort. Discussion: Together, our results highlight select risk factors that may contribute to an increased risk of ICU admission for influenza-infected patients. This should help to develop better diagnostic tools based on molecular signatures, in addition to a better understanding of the biological processes in the host response to influenza.

Cataloging the Genetic Response: Unveiling Drought-Responsive Gene Expression in Oil Tea Camellia (Camellia oleifera Abel.) through Transcriptomics.

Drought stress is a critical environmental factor that significantly impacts plant growth and productivity. However, the transcriptome analysis of differentially expressed genes in response to drought stress in Camellia oleifera Abel. is still unclear. This study analyzed the transcriptome sequencing data of C. oleifera under drought treatments. A total of 20,674 differentially expressed genes (DEGs) were identified under drought stress, with the number of DEGs increasing with the duration of drought. Specifically, 11,793 and 18,046 DEGs were detected after 8 and 15 days of drought treatment, respectively, including numerous upregulated and downregulated genes. Gene Ontology (GO) enrichment analysis showed that the DEGs were primarily involved in various biological processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that carbon metabolism, glyoxylate and dicarboxylate metabolism, proteasome, glycine, serine, and threonine metabolism were the main affected pathways. Among the DEGs, 376 protein kinases, 42 proteases, 168 transcription factor (TF) genes, and 152 other potential functional genes were identified, which may play significant roles in the drought response of C. oleifera. The expression of relevant functional genes was further validated using quantitative real-time PCR (qRT-PCR). These findings contribute to the comprehension of drought tolerance mechanisms in C. oleifera and bolster the identification of drought-resistant genes for molecular breeding purposes.

Toxicity Evaluation and Transcriptome Analysis of Yellowstripe Goby (Mugilogobius chulae) in Response to 2,7-Dibromocarbazole Exposure during Early Development.

Polyhalogenated carbazoles (PHCZs) are a class of nitrogen-containing heterocyclic compounds that are widely distributed throughout the marine environment and sediment. These compounds share structural and toxicity similarities with dioxins. However, our understanding of the toxicological effects of PHCZs on marine organisms and their underlying molecular mechanisms remains limited. In this study, we employed the marine model organism Mugilogobius chulae as the experimental subject and selected 2,7-dibromocarbazole (2,7-DBCZ), a compound known for its high toxicity and detection frequency, to conduct both an acute toxicity test and transcriptome analysis on M. chulae embryos. Our findings revealed that the 96 h median lethal concentration (LC50) of 2,7-DBCZ for M. chulae embryos was 174 µg/L, with a median effective concentration (EC50) resulting in pericardial edema deformity of 88.82 µg/L. Transcriptome analysis revealed significant impacts on various systems in M. chulae embryos following exposure to 2,7-DBCZ, including the sensory, cardiovascular, immune, and endocrine systems. Furthermore, this compound perturbed signaling pathways such as phototransduction, protein folding and processing, amino acid metabolism, lipid transport, and exogenous compound metabolism. Notably, transcript abundance of the CYP1A gene associated with the activation of the AhR signaling pathway, similar to dioxin-like compounds, was 18.18 times higher than that in the control group. This observation suggests that M. chulae embryos mount a stress response when exposed to PHCZs. In summary, this study contributes to our understanding of the toxicological implications of PHCZ in marine fish and offers a theoretical foundation for risk assessment and regulatory frameworks for PHCZs in the marine environment.

Molecular mechanisms regulating glucose metabolism in quinoa (Chenopodium quinoa Willd.) seeds under drought stress.

BACKGROUND: Abiotic stress seriously affects the growth and yield of crops. It is necessary to search and utilize novel abiotic stress resistant genes for 2.0 breeding programme in quinoa. In this study, the impact of drought stress on glucose metabolism were investigated through transcriptomic and metabolomic analyses in quinoa seeds. Candidate drought tolerance genes on glucose metabolism pathway were verified by qRT-PCR combined with yeast expression system. RESULTS: From 70 quinoa germplasms, drought tolerant material M059 and drought sensitive material M024 were selected by comprehensive evaluation of drought resistance. 7042 differentially expressed genes (DEGs) were indentified through transcriptomic analyses. Gene Ontology (GO) analysis revealed that these DEGs were closely related to carbohydrate metabolic process, phosphorus-containing groups, and intracellular membrane-bounded organelles. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis detected that DEGs were related to pathways involving carbohydrate metabolisms, glycolysis and gluconeogenesis. Twelve key differentially accumulated metabolites (DAMs), (D-galactose, UDP-glucose, succinate, inositol, D-galactose, D-fructose-6-phosphate, D-glucose-6-phosphate, D-glucose-1-phosphate, dihydroxyacetone phosphate, ribulose-5-phosphate, citric acid and L-malate), and ten key candidate DEGs (CqAGAL2, CqINV, CqFrK7, CqCELB, Cqbg1x, CqFBP, CqALDO, CqPGM, CqIDH3, and CqSDH) involved in drought response were identified. CqSDH, CqAGAL2, and Cqß-GAL13 were candidate genes that have been validated in both transcriptomics and yeast expression screen system. CONCLUSION: These findings provide a foundation for elucidating the molecular regulatory mechanisms governing glucose metabolism in quinoa seeds under drought stress, providing insights for future research exploring responses to drought stress in quinoa.