Differentially Expressed Genes Research Articles

Disulfidptosis-related subtype and prognostic signature in prostate cancer

BackgroundDisulfidptosis refers to cell death caused by the accumulation and bonding of disulfide in the cytoskeleton protein of SLC7A11-high level cells under glucose deprivation. However, the role of disulfidptosis-related genes (DRGs) in prostate cancer (PCa) classification and regulation of the tumor microenvironment remains unclear.MethodsFirstly, we analyzed the expression and mutation landscape of DRGs in PCa. We observed the expression levels of SLC7A11 in PCa cells through in vitro experiments and assessed the inhibitory effect of the glucose transporter inhibitor BAY-876 on SLC7A11-high cells using CCK-8 assay. Subsequently, we performed unsupervised clustering of the PCa population and analyzed the differentially expressed genes (DEGs) between clusters. Using machine learning techniques to select a minimal gene set and developed disulfidoptosis-related risk signatures for PCa. We analyzed the tumor immune microenvironment and the sensitivity to immunotherapy in different risk groups. Finally, we validated the accuracy of the prognostic signatures genes using single-cell sequencing, qPCR, and western blot.ResultsAlthough SLC7A11 can increase the migration ability of tumor cells, BAY-876 effectively suppressed the viability of prostate cancer cells, particularly those with high SLC7A11 expression. Based on the DRGs, PCa patients were categorized into two clusters (A and B). The risk label, consisting of a minimal gene set derived from DEGs, included four genes. The expression levels of these genes in PCa were initially validated through in vitro experiments, and the accuracy of the risk label was confirmed in an external dataset. Cluster-B exhibited higher expression levels of DRG, representing lower risk, better prognosis, higher immune cell infiltration, and greater sensitivity to immune checkpoint blockade, whereas Cluster A showed the opposite results. These findings suggest that DRGs may serve as targets for PCa classification and treatment. Additionally, we constructed a nomogram that incorporates DRGs and clinical pathological features, providing clinicians with a quantitative method to assess the prognosis of PCa patients.ConclusionThis study analyzed the potential connection between disulfidptosis and PCa, and established a prognostic model related to disulfidptosis, which holds promise as a valuable tool for the management and treatment of PCa patients.

Transcriptional Modulation of Plant Defense Genes by a Bipartite Begomovirus Promotes the Performance of Its Whitefly Vector

The majority of plant viruses rely on insect vectors for inter-plant transmission. Amid virus transmission, vector-borne viruses such as begomoviruses may significantly modulate host plants in various ways and, in turn, plant palatability to insect vectors. While many case studies on monopartite begomoviruses are available, bipartite begomoviruses are understudied. More importantly, detailed elucidation of the molecular mechanisms involved is limited. Here, we report the mechanisms by which an emerging bipartite begomovirus, the Sri Lankan cassava mosaic virus (SLCMV), modulates plant defenses against whitefly. SLCMV infection of tobacco (Nicotiana tabacum) plants significantly downregulated defenses against whitefly, as whitefly survival and fecundity increased significantly on virus-infected plants when compared to the controls. We then profiled SLCMV-induced transcriptomic changes in plants and identified a repertoire of differentially expressed genes (DEGs). GO enrichment analysis of DEGs demonstrated that the term defense response was significantly enriched. Functional analysis of DEGs associated with defense response revealed that four downregulated DEGs, including putative late blight resistance protein homolog R1B-17 (R1B-17), polygalacturonase inhibitor-like (PGI), serine/threonine protein kinase CDL1-like (CDL1), and Systemin B, directly contributed to plant defenses against whitefly. Taken together, our findings elucidate the role of novel plant factors involved in the modulation of plant defenses against whitefly by a bipartite begomovirus and shed new light on insect vector–virus–host plant tripartite interactions.

Deciphering heart failure: an integrated proteomic and transcriptomic approach with experimental validation.

This study analyzed transcriptomic and proteomic data to identify molecular changes during heart failure (HF). Additionally,we embarked on an exploration of the prospect of therapeutic intervention through the manipulation of proteins implicated in ferroptosis. Three publicly available microarray datasets (GSE135055, GSE147236, GSE161472) profiling left ventricular samples from HF patients and healthy controls were obtained. Differentially expressed genes were identified in each dataset and cross-analyzed to determine shared gene signatures. Enrichment analysis of Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and gene set enrichment analysis were performed. Differentially expressed proteins were obtained from published proteomic studies and integrated with the transcriptomic results. To validate findings, a HF mouse model was generated and ferroptosis-related proteins were evaluated. Additionally, the effect of suppression of ferroptosis on hypoxia-induced ischemia model in HL-1 cardiomyocytes was assessed by knocking down Acyl-CoA synthetase long-chain family member 4 (ACSL4) using small interfering RNA (siRNA).Cross-analysis of differentially expressed genes (DEGs) in the GSE135055, GSE147236 and GSE161472 datasets revealed 224 up-regulated and 187 down-regulated potential genes which showed high enrichment in immune, inflammatory and metabolic pathways. Notably, four proteins, among them ACSL4, displayed consistent alterations at both the transcriptional and protein levels. In the HF mouse model, ACSL4 exhibited an elevation, whereas negative regulators of ferroptosis witnessed a decrement. Subsequently, knockdown of ACSL4 in a hypoxia-induced ischemic HL-1 cardiomyocyte cell model upregulated the expression of ferroptosis inhibitory protein and decreased the levels of reactive oxygen species (ROS), malondialdehyde (MDA)., and free iron and increased cell viability. Comprehensive multi-omics analysis revealed that the expression of the molecular target ACSL4 was increased in HF. Targeting ACSL4 to inhibit ferroptosis may represent a novel therapeutic strategy for HF treatment.

Follicle-intrinsic and spatially distinct molecular programs drive follicle rupture and luteinization during ex vivo mammalian ovulation

During ovulation, the apical wall of the preovulatory follicle breaks down to facilitate gamete release. In parallel, the residual follicle wall differentiates into a progesterone-producing corpus luteum. Disruption of ovulation, whether through contraceptive intervention or infertility, has implications for women’s health. In this study, we harness the power of an ex vivo ovulation model and machine-learning guided microdissection to identify differences between the ruptured and unruptured sides of the follicle wall. We demonstrate that the unruptured side exhibits clear markers of luteinization after ovulation while the ruptured side exhibits cell death signals. RNA-sequencing of individual follicle sides reveals 2099 differentially expressed genes (DEGs) between follicle sides without ovulation induction, and 1673 DEGs 12 h after induction of ovulation. Our model validates molecular patterns consistent with known ovulation biology even though this process occurs in the absence of the ovarian stroma, vasculature, and immune cells. We further identify previously unappreciated pathways including amino acid transport and Jag-Notch signaling on the ruptured side and glycolysis, metal ion processing, and IL-11 signaling on the unruptured side of the follicle. This study yields key insights into follicle-inherent, spatially-defined pathways that underlie follicle rupture, which may further understanding of ovulation physiology and advance women’s health.

The SIRT6/BAP1/xCT signaling axis mediates ferroptosis in cisplatin-induced AKI

BackgroundCisplatin is extensively utilized in clinical settings for treating solid tumors; However, its use is restricted because of the kidney damage caused by side effects. Moreover, currently, no effective medications have been approved to prevent or treat acute kidney injury induced by cisplatin. Our research indicates that sirtuin 6 (SIRT6) can inhibit ferroptosis induced by cisplatin, and the use of SIRT6 agonists can alleviate acute kidney injury caused by cisplatin. MethodsAn animal model of cisplatin-induced acute kidney injury (AKI) was established, followed by RNA sequencing to identify potential differentially expressed genes (DEGs) and associated pathways. To explore the role of SIRT6 in this model, SIRT6 knockout mice were generated, and recombinant adeno-associated virus was employed to achieve SIRT6 overexpression in the mice. In vitro, cells were cultured in a cisplatin-containing medium to establish a cisplatin-induced cell model. The function of SIRT6 was further investigated by overexpressing or knocking down the gene using lentiviral plasmids. To elucidate the underlying molecular mechanisms, we employed RNA sequencing, performed bioinformatics analyses, and conducted chromatin immunoprecipitation assays. ResultsRNA sequencing and Western blot analyses revealed a significant reduction in SIRT6 expression in mice with cisplatin-induced acute kidney injury (AKI). Enhancing SIRT6 expression improved renal function, reduced ferroptosis, and mitigated kidney damage, whereas SIRT6 knockout exacerbated kidney injury and heightened ferroptosis. Mechanistically, RNA sequencing, bioinformatics analysis, and chromatin immunoprecipitation assays demonstrated that SIRT6 inhibits ferroptosis by reducing the acetylation of histone H4K9ac at the BAP1 promoter. Furthermore, in vitro studies demonstrated that the SIRT6 agonist UBCS039 can alleviate cisplatin-induced acute kidney injury, highlighting its potential therapeutic role in mitigating cisplatin's damaging effects. However, further research is needed to fully elucidate the underlying mechanisms and to validate these findings in vivo. ConclusionOur findings underscore the critical role of the SIRT6/BAP1/xCT axis in regulating ferroptosis, particularly via the downregulation of SIRT6, in the context of cisplatin-induced acute kidney injury (AKI). This suggests that SIRT6 could be a promising therapeutic target for treating cisplatin-induced AKI. However, additional research is required to explore the specific mechanisms and fully assess the therapeutic potential of SIRT6 in this context.

Genetic Adaptations of Soybean to Cold Stress Reveal Key Insights Through Transcriptomic Analysis

Low temperatures greatly restrict the development, growth, and productivity of soybeans, with their effects differing across various cultivars. The present work investigated the transcriptome and physiological reactions of two soybean cultivars, namely “KD52” exhibiting cold tolerance and “DS17” displaying cold sensitivity, to cold stress across a precisely defined period. The soybean plants were subjected to cold treatment at 6 °C for durations of 0, 2, 4, and 8 h. A comparative physiological marker study revealed distinct reactions to cold stress in the two cultivars. The findings showed that increased malondialdehyde levels provided evidence of DS17’s heightened vulnerability to lipid peroxidation and membrane degradation. In contrast, the KD52 cultivar exhibited increased activities of antioxidant enzymes, including peroxidase and superoxide dismutase, in response to cold exposure, suggesting a strong antioxidant defense system against oxidative stress. The transcriptomic analysis revealed dynamic responses, mapping 54,532 genes. Within this group, a total of 234 differentially expressed genes (DEGs) were found to be consistently changed at several time intervals, showing unique expression patterns across the two cultivars. Analysis of the association between these important DEGs and the physiological indicators revealed candidate genes that may be involved in controlling oxidative damage and antioxidant defenses. Some key genes showed a progressive rise in expression over time in both cultivars, with a more significant acceleration in KD52, and are probably involved in promoting adaptation processes during extended periods of cold exposure. The identification of improved defense mechanisms in KD52, together with the identification of crucial genes, offers great prospects for enhancing the cold stress resilience of soybean.

Nppb contributes to Sepsis-Induced myocardial injury by regulating Senescence-Related genes

BackgroundSepsis, a systemic inflammatory condition, is a leading cause of mortality due to cardiovascular injury. Sepsis and cellular senescence are closely related, yet the specific mechanisms are still unclear. This study aims to identify a novel therapeutic target for mitigating sepsis-induced myocardial injury. MethodsWe initially assessed serum inflammatory markers and myocardial injury indicators in septic mice. This involved observing inflammatory cell infiltration in ventricular muscle tissue, assessing cardiac function, and recording electrocardiograms. We examined the expression of connexin 40 (Cx40) and connexin 43 (Cx43) and analyzed mitochondrial structures in ventricular tissues. A conditional heart-specific Nppb knockout mouse model was then developed in mice to evaluate these changes. Ventricular tissues were analyzed via mRNA sequencing to identify differentially expressed genes (DEGs), which were cross-referenced with senescence-related genes to identify key hub genes. The expression and distribution of hub genes were subsequently analyzed by single-cell analysis. Finally, the expression of the senescence-related gene CCL2, along with cardiac structure and function, was validated in a conditional heart-specific Nppb knockout sepsis mouse model. ResultsMyocardial injury severity positively correlated with serum brain natriuretic peptide (BNP) in septic mice. Conditional heart-specific Nppb knockout improved myocardial injury outcomes in mice with sepsis. The DEGs identified in the conditional heart-specific Nppb knockout model overlapped with senescence-related genes, identifying seven upregulated genes associated with inflammation, cardiac contraction and apoptotic pathways. Single-cell analysis confirmed high CCL2 levels and an increased macrophage presence correlating with sepsis progression. Conditional heart-specific Nppb knockout reduced CCL2 levels, which were associated with improved cardiac structure and function. ConclusionThis study confirms that conditional heart-specific Nppb knockout reduces CCL2 expression, thereby ameliorating myocardial injury in septic mice. Targeting Nppb to regulate the senescence-related gene CCL2 may represent an effective strategy for treating myocardial injury in septic patients.

Ustekinumab affects myofibroblast metabolism to alleviate intestinal fibrosis by targeting KDELC1 in Crohn’s disease through multi-machine learning combined with single-cell sequencing analysis

BackgroundUstekinumab (UST), a biologic against interleukin (IL)-12/23, is commonly used to treat Crohn’s disease (CD). Myofibroblast (MF) is known as one of the most important factors causing intestinal fibrosis, and UST has been reported to alleviate this condition. However, the genetic mechanisms underlying UST’s effects on CD remain unclear. This study uses bioinformatics tools to analyze the genes and potential pathways affected by UST in CD, with a focus on its anti-fibrosis effects, providing insights into new therapeutic targets.MethodsThe data downloaded from the Gene Expression Omnibus (GEO) database were analyzed to screen for differentially expressed genes (DEGs). Various machine learning strategies, including the least absolute shrinkage and selection operator (LASSO), support vector machine (SVM), and random forest (RF), were employed to screen for key genes among the DEGs. Functional and pathway enrichment analyses were conducted, and key genes associated with myofibroblast (MF) activity were screened. Finally, endoscopic surgical specimens from CD patients and healthy participants were collected to assess the expression levels of collagen and key genes in intestinal tissues using hematoxylin–eosin (H&E), Masson staining, and immunohistochemistry.ResultsA total of 1,341 DEGs associated with CD were identified. Among them, 738 genes showed low expression in healthy populations but high expression in patients with CD, reduced expression after the treatment of UST. In contrast, 603 genes exhibited high expression in healthy individuals, showed low expression in CD patients, and increased expression after UST treatment. Functional and pathway analysis showed that DEGs were mainly concentrated in response to foreign biological stimuli and bacterial-derived molecules. DEGs are mainly enriched in chemokines, TNF, IL-17, and other signaling pathways. Seven key genes were identified: NCRNA00236, LOC730101, ORP3, XG, UBFD1, KDELC1, and RBP7. Single-cell analysis revealed that KDELC1 was closely related to MF activity. MFs with high KDELC1 expression were significantly enriched in biological functions, signaling pathways, and metabolic processes that promote fibrosis. The experiment showed that UST treatment helped maintain the integrity of intestinal tissue structure, reducing the expression levels of collagen I, KDELC1, and the severity of intestinal fibrosis. The functional and pathway analysis reiterated that DEGs were largely focused on responses to foreign biological stimuli and bacterial-derived molecules, as well as signaling pathways such as chemokines, TNF, and IL-17. Of the identified genes, KDELC1 showed a particularly strong correlation with MF activity in single-cell analysis (R = 0.33, p = 3.2e-07). MFs with high KDELC1 expression were closely linked to pathways promoting fibrosis progression, including TGF-β, epithelial-mesenchymal transformation, TNF/NF-κB, and related metabolic pathways such as vitamin B6 and arginine.ConclusionKDELC1 plays a key role in regulating multiple biological functions, including signaling pathways related to MF. UST alleviates intestinal fibrosis by targeting KDELC1, thereby influencing intramuscular fat metabolism and intercellular communication.

Weighted Gene Co-Expression Network Analysis Uncovers Critical Genes and Pathways Involved in Soybean Response to Soybean Mosaic Virus

Background: Soybean mosaic virus (SMV) is a globally prevalent and detrimental virus that belongs to the Potyvirus genus. Pathogenic viruses of this genus are typically linear in shape, with dimensions ranging between 630 and 750 nm, and are composed of single-stranded RNA and proteins. We have developed an SMV-resistant soybean line, Dongnong 93-046, which has no significant changes in disease resistance identification in the adult plants and has neat grains with no obvious brown or black markings. To explore the defense mechanisms of soybean against SMV, we performed comparative transcriptomic sequencing of the leaves between the Dongnong 93-046 inoculated with SMV at 8 h (T) and the non-inoculated control (C) on the HiSeq2000 platform. In addition, we performed non-targeted metabolomic sequencing of leaves from the treatment and control groups. Results: We identified a total of 41,189 differentially expressed genes (DEGs). A total of 9809 differentially expressed genes (DEGs) met the criteria of |Log2FC (Fold Change)| ≥ 1 and adjusted p-value ≤ 0.001. Among the 41,189 DEGs identified, 9196 exhibited FPKM values greater than 10. KEGG pathway enrichment analysis of the 9809 DEGs revealed significant enrichment of genes involved in resistance-related pathways such as plant–pathogen interaction, linoleic acid metabolism, mitogen-activated protein kinase (MAPK) signaling pathway, and plant hormone signaling transduction. Functional analysis using MapMan software identified multiple DEGs that were associated with pathways such as jasmonate synthesis and phenylpropanoid biosynthesis. Weighted gene co-expression network analysis (WGCNA) using the differential metabolites and the 9196 DEGs revealed a strong correlation between gene clusters within the Turquoise module and the content of jasmonate-related metabolites. Further functional enrichment analysis of the 894 genes within the gene clusters showed a significant and repeated enrichment of pathways related to plant–pathogen interaction, linoleic acid metabolism, and plant hormone signaling transduction. Subsequent focused pathway analysis identified key genes involved in plant hormone signaling transduction pathways, such as the jasmonate ZIM domain protein Glyma.16G010000, the gene Glyma.01G235600 encoding the essential diterpene reductase required for jasmonate synthesis in the jasmonate biosynthesis pathway, and the transcription factor Glyma.02G232600 involved in the plant–pathogen interaction pathway, among others. This study provides a theoretical framework for understanding the resistance mechanism of soybean cultivar Dongnong 93-046 against the SMV N1 strain, offers potential gene resources for breeding soybean varieties with resistance to SMV, and paves the way for new strategies to control SMV infection, enhance resistance, and improve crop yield and quality.

C6 and KLRG2 are pyroptosis subtype-related prognostic biomarkers and correlated with tumor-infiltrating lymphocytes in lung adenocarcinoma

Pyroptosis plays an important role in lung adenocarcinoma (LUAD). In this study, we aimed to explore the pyroptosis-related gene (PRG) expression pattern and to identify promising pyroptosis-related biomarkers to improve the prognosis of LUAD. The gene expression profiles and clinical information of LUAD patients were downloaded from the Cancer Genome Atlas (TCGA), and validation cohort information was extracted from the Gene Expression Omnibus database. Gene expression data were analyzed using the limma package and visualized using the ggplot2 package as well as the pheatmap package in R software. Functional enrichment analysis was also performed for the 44 differentially expressed PRGs (DEPRGs). Then, consensus clustering revealed pyroptosis-related tumor subtypes, and differentially expressed genes (DEGs) were screened according to the subtypes. Next, univariate Cox and multivariate Cox regression analyses were used to identify independent prognostic PRGs. After overlapping DEGs and the Lasso regression analysis-based prognostic genes, the predictive risk model was established and validated. Correlation analysis between PRGs and clinicopathological variables was also explored. Finally, the TIMER and TISIDB databases were used to further explore the correlation analysis between immune cell infiltration levels, the risk score, and clinicopathological variables in the predictive risk model. A total of 52 genes from the PubMed were identified as PRGs, and 44 of the 52 genes were pooled as DEPRGs. The most significant GO term was “collagen trimer” (P = 2.46E-13), and KEGG analysis results indicated that 44 DEPRGs were significantly enriched in Salmonella infection (P < 0.001). Then, consensus clustering analysis divided LUAD patients into two clusters, and a total of 79 DEGs were identified according to these cluster subtypes. Subsequently, univariate and multivariate Cox regression analyses were used to identify 12 genes that could serve as independent prognostic indicators and we also performed Lasso regression analysis and screened 23 DEGs. After overlapping 23 DEGs and 12 genes, only 4 (KLRG2, MAPK4, C6 and SFRP5) of 12 genes were selected for the further exploration of the prognostic pattern. Survival analysis results indicated that this risk model effectively predicted the prognosis (P < 0.001). Combined with the correlation analysis results between the 4 genes and clinicopathological variables, C6 and KLRG2 were screened as prognostic genes. In this study, we constructed a predictive risk model and identified two pyroptosis subtype-related gene expression patterns to improve the prognosis of LUAD. Understanding the subtypes of LUAD is helpful for accurately characterizing the LUAD and developing personalized treatment.

Identification of key signaling pathways and novel computational drug target for oral cancer, metabolic disorders and periodontal disease

AimDue to conventional endocrinological methods, there is presently no shared work available, and no therapeutic options have been demonstrated in oral cancer (OC) and periodontal disease (PD), type 2 diabetes (T2D), and obese patients. The aim of this study is to determine the similar molecular pathways and potential therapeutic targets in PD, OC, T2D, and obesity that may be used to anticipate the progression of the disease. MethodsFour Gene Expression Omnibus (GEO) microarray datasets (GSE29221, GSE15773, GSE16134, and GSE13601) are used for finding differentially expressed genes (DEGs) for T2D, obese, and PD patients with OC in order to explore comparable pathways and therapeutic medications. Gene ontology (GO) and pathway analysis were used to investigate the functional annotations of the genes. The hub genes were then identified using protein-protein interaction (PPI) networks, and the most significant PPI components were evaluated using a clustering approach. ResultsThese three gene expression-based datasets yielded a total of seven common DEGs. According to the GO annotation, the majority of the DEGs were connected with the microtubule cytoskeleton structure involved in mitosis. The KEGG pathways revealed that the concordant DEGs are connected to the cell cycle and progesterone-mediated oocyte maturation. Based on topological analysis of the PPI network, major hub genes (CCNB1, BUB1, TTK, PLAT, and AHNAK) and notable modules were revealed. This work additionally identified the connection of TF genes and miRNAs with common DEGs, as well as TF activity. ConclusionPredictive drug analysis yielded concordant drug compounds involved with T2D, OC, PD, and obesity disorder, which might be beneficial for examining the diagnosis, treatment, and prognosis of metabolic disorders and Oral cancer.

Oviduct epithelial spheroids during in vitro culture of bovine embryos mitigate oxidative stress, improve blastocyst quality and change the embryonic transcriptome

BackgroundIn vitro embryo production is increasingly used for genetic improvement in cattle but bypasses the oviduct environment and exposes the embryos to oxidative stress with deleterious effects on further development. Here we aimed to examine the effect of oviduct epithelial spheroids (OES) on embryo development and quality in terms of morphology and gene expression during two co-culture times (4 days: up to embryonic genome activation at 8–16 cell stage vs. 7 days: up to blastocyst stage) and under two oxygen levels (5% vs. 20%).MethodsBovine presumptive zygotes produced by in vitro fertilization (day 0) using in-vitro matured oocytes were cultured in droplets of synthetic oviductal fluid (SOF) medium with or without (controls) OES for 4 or 7 days under 5% or 20% oxygen (4 treated and 2 control groups). Cleavage rates were evaluated on day 2 and blastocyst rates on days 7–8. Expanded blastocysts on days 7–8 were evaluated for total cell numbers and gene expression analysis by RNA-sequencing.ResultsUnder 20% oxygen, blastocyst rates and total cell numbers were significantly higher in the presence of OES for 4 and 7 days compared to controls (P < 0.05), with no difference according to the co-culture time. Under 5% oxygen, the presence of OES did not affect blastocyst rates but increased the number of cells per blastocyst after 7 days of co-culture (P < 0.05). Both oxygen level and OES co-culture had a significant impact on the embryonic transcriptome. The highest number of differentially expressed genes (DEGs) was identified after 7 days of co-culture under 20% oxygen. DEGs were involved in a wide range of functions, including lipid metabolism, membrane organization, response to external signals, early embryo development, and transport of small molecules among the most significantly impacted.ConclusionOES had beneficial effects on embryo development and quality under both 5% and 20% oxygen, mitigating oxidative stress. Stronger effects on embryo quality and transcriptome were obtained after 7 than 4 days of co-culture. This study shows the impact of OES on embryo development and reveals potential molecular targets of OES-embryo dialog involved in response to stress and early embryonic development.

Gene Expression Profiling and Immune Pathway Dysregulation in Ribonucleoprotein Autoantibody-Positive Systemic Lupus Erythematosus Patients

Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by immune dysregulation and chronic inflammation across various organ systems. While anti-dsDNA and anti-Sm antibodies are commonly associated with SLE, the presence of anti-RNP antibodies is often linked to unique gene expression profiles and immune responses. This study aims to investigate the gene expression profiles in ribonucleoprotein (RNP) autoantibody-positive SLE patients by analyzing publicly available transcriptomic data. Methods: This study analyzed transcriptomic data from the GEO dataset GSE61635, which includes gene expression profiles from 79 anti-RNP-positive SLE patients and 30 healthy controls. Differentially expressed genes (DEGs) were identified using the GEO2R tool with a p-value &lt; 0.05 and |log2fold change| &gt; 1. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Tissue-specific and cell-type enrichment analyses highlighted the involvement of immune tissues. Results: A total of 1891 DEGs were identified between anti-RNP-positive SLE patients and healthy controls. Among the identified DEGs, SLC4A1 and EPB42 were notably downregulated, while PIP4K2A was highly upregulated. Enrichment analyses revealed significant dysregulation in antiviral response and immune regulation pathways. PPI network analysis highlighted key hub genes, suggesting a heightened antiviral state in these patients. Tissue-specific enrichment and cell-type enrichment identified the bone marrow and immune tissues as being highly affected by the altered gene expression. Additionally, gene frequency analysis highlighted RASD2 as being recurrently significant across multiple studies. Conclusions: The findings suggest that anti-RNP-positive SLE patients exhibit distinct gene expression and immune dysregulation profiles, particularly in antiviral and immune regulation pathways. These results provide insights into the molecular mechanisms driving SLE in this patient subset and may guide future therapeutic interventions.

Transcriptome analysis of tilapia streptococcus agalactiae in response to baicalin.

Streptococcus agalactiae (S. agalactiae) is a highly pathogenic bacterial pathogen in aquatic animals. Our previous study has demonstrated the significant inhibitory effect of baicalin on β-hemolytic/cytolytic activity, which is a key virulence factor of S. agalactiae. In this study, we aimed to elucidate the mechanism underlying baicalin's inhibition of S. agalactiae β-hemolytic/cytolytic activity by transcriptomic analysis. Bacteria were exposed to 39.06µg/mL baicalin for 6h, and their β-hemolytic/cytolytic activities were assessed using blood plates. Then, the differentially expressed genes (DEGs) were identified and characterized by RNA sequencing (RNA-Seq), and further confirmed using the qRT-PCR. A total of 10 DEGs with 7 significantly up-regulated and 3 significantly down-regulated, were found to be affected significantly under baicalin treatment. These DEGs were associated with 5 biological processes, 5 cellular components, and 3 molecular functions. They were primarily enriched in 3 pathways: lacD and lacC in galactose metabolism, lrgA and lrgB in the two-component system, and ribH/rib4 in riboflavin metabolism. These suggested that baicalin might inhibit the conversion of pyruvate to acetyl-CoA and malonyl-CoA, which are crucial precursors for β-hemolysin/cytolysin synthesis, and result in the accumulation of pyruvate, suppress the expressions of pyruvate cell membrane channel protein genes lrgA and lrgB. Baicalin could compensatory up-regulate the expressions of tryptophan/tyrosine ABC transporter family genes, ABC.X4.A, ABC.X4.P, and ABC.X4.S by inhibiting the expression of cyl A/B in cyl operons. Moreover, it hinders the conversion of D-glucose 1-phosphate to the dTDP-L-rhamnose pathway and leads to a deficiency of L-rhamnose, an important precursor for β-hemolysin/cytolysin synthesis.

Dual RNA-Seq Unveils Candidate Key Virulence Genes of Vibrio harveyi at the Early Stage of Infection in Hybrid Grouper (♀ Epinephelus polyphekadion × ♂ E. fuscoguttatus)

Vibrio harveyi is a major bacterial pathogen that causes disease in aquaculture animals worldwide. Although V. harveyi consistently harbors a range of traditional virulence genes, it remains unclear which specific genes are crucial for virulence at different infection stages. Dual RNA-seq is a cutting-edge RNA sequencing technology that is ideal for investigating the gene expression patterns of pathogens within the host, which is highly effective in identifying key virulence genes. In previous artificial infection experiments, we have identified the liver of hybrid grouper (♀ Epinephelus polyphekadion × ♂ E. fuscoguttatus) as the main target organ for pathogenic V. harveyi GDH11385 during the initial infection phase. To further explore the key virulence factors of V. harveyi at the early stage of infection, the liver of the hybrid grouper infected with strain GDH11385 was analyzed here by dual RNA-seq. The transcriptome data were compared with that of in vitro cultured bacteria. The results showed that 326 and 1140 DEGs (differentially expressed genes) were significantly up- and down-regulated, respectively, at 4 h post-infection (hpi). Further pathway enrichment analyses revealed that these up-regulated DEGs in vivo were mainly enriched in siderophore biosynthesis and transport, type VI secretion system (T6SS), flagellar assembly, glycolysis/gluconeogenesis, and ribosome. Notably, all genes involved in the metabolism and utilization of vibrioferrin (a carboxylate class of siderophore produced by Vibrio), and most of the genes within one of three T6SSs, were significantly up-regulated in vivo. This indicates that siderophore-dependent iron competition and T6SS-mediated delivery of virulence factors are vital for the successful colonization of V. harveyi at the early stage of infection. This study provides more precise clues to reveal the virulence mechanism of V. harveyi during the initial phase of infection.

Elevated CO2 enhances growth and cyanide assimilation in nitrogen-deficient rice: A transcriptome and metabolomic perspective

Plants face multiple challenges from environmental pollutants and higher emissions of atmospheric CO2. Therefore, a hydroponic-based experiment was used to explore the combined effects of elevated [CO2] (700 ppm) and exogenous cyanide (CN−) (3.0 mg CN/L) on rice seedlings under nitrogen deficiency, utilizing metabonomic and transcriptomic analysis. Elevated [CO2] significantly improved the growth of CN−-treated rice seedlings compared to those with ambient [CO2] (350 ppm), and it also significantly affected CN− assimilation. Transcriptome analysis revealed distinct impacts on differentially expressed genes (DEGs) across treatments and tissues. KEGG analysis showed variability in DEGs enriched in amino acid (AA) and energy metabolism pathways due to elevated [CO2] and CN−. Metabonomic indicated that higher input of [CO2] and exogenous CN− more severely impacted energy metabolism elements than the individual species of AAs. Positive synergistic effects of elevated [CO2] and CN− were observed for glutamine and asparagine in shoots, and methionine in roots, wherein negative effects were noted for phenylalanine in shoots, and phenylalanine, valine, and alanine in roots. Meanwhile, positive effects on fumarate in shoots and α-ketoglutarate and succinate in roots were also found. Overall, elevated [CO2] enhanced growth in CN−-treated rice seedlings under nitrogen deficiency by altering AA and energy metabolism. This is the first attempt to provide new evidence of [CO2]-based gaseous fertilization as an energy-saving strategy for rice plants fed with biodegradable N-containing pollutants as a supporting N source under N deficient conditions.

Identification of Biomarkers and Molecular Pathways Implicated in Smoking and COVID-19 Associated Lung Cancer Using Bioinformatics and Machine Learning Approaches

Lung cancer (LC) is a significant global health issue, with smoking as the most common cause. Recent epidemiological studies have suggested that individuals who smoke are more susceptible to COVID-19. In this study, we aimed to investigate the influence of smoking and COVID-19 on LC using bioinformatics and machine learning approaches. We compared the differentially expressed genes (DEGs) between LC, smoking, and COVID-19 datasets and identified 26 down-regulated and 37 up-regulated genes shared between LC and smoking, and 7 down-regulated and 6 up-regulated genes shared between LC and COVID-19. Integration of these datasets resulted in the identification of ten hub genes (SLC22A18, CHAC1, ROBO4, TEK, NOTCH4, CD24, CD34, SOX2, PITX2, and GMDS) from protein-protein interaction network analysis. The WGCNA R package was used to construct correlation network analyses for these shared genes, aiming to investigate the relationships among them. Furthermore, we also examined the correlation of these genes with patient outcomes through survival curve analyses. The gene ontology and pathway analyses were performed to find out the potential therapeutic targets for LC in smoking and COVID-19 patients. Moreover, machine learning algorithms were applied to the TCGA RNAseq data of LC to assess the performance of these common genes and ten hub genes, demonstrating high performances. The identified hub genes and molecular pathways can be utilized for the development of potential therapeutic targets for smoking and COVID-19-associated LC.

Development and drought escape response in Arabidopsis thaliana are regulated by AtPLC1 in response to abscisic acid.

AtPLC1 plays a critical role in plant growth, development, and response to drought stress. Phosphoinositide-specific phospholipase C (PI-PLC) hydrolyzes substrates to generate secondary messengers crucial for plant growth, development, and stress responses. Drought escape (DE) response is an adaptive strategy that plants employ under drought conditions. The expression levels of the flower meristem-specific gene APETALA 1 and flowering regulatory genes FLOWERING LOCUS T and SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 were downregulated in plc1, and FLOWERING LOCUS C was upregulated. The flowering time of the plc1flc double mutant was earlier than that of the wild type. Transcriptome analysis revealed that the Gene Ontology of differentially expressed genes (DEGs) was enriched in abscisic acid (ABA) response signaling, and Kyoto Encyclopedia of Genes and Genomes analysis revealed differential gene expression annotated to plant hormone signaling pathways. Our experiments show that AtPLC1 is upregulated by ABA in Arabidopsis. Under ABA induction and water stress, wild-type plants exhibit a DE response, and the DE response in plc1 disappears. Expression levels of ABA signaling pathway transcription factors ABA-responsive element-binding factors 3 (ABF3) and ABF4 were downregulated in plc1. In conclusion, our study suggests that AtPLC1 participates in regulating plant growth and development and participates in the DE response through the regulation of ABA signaling pathway transcription factors ABF3/ABF4. The study enhances our comprehension of the role of AtPLC1 in plant development and drought stress, providing a theoretical foundation for further investigation into DE responses.

Acute-phase innate immune responses in SIVmac239-infected Mamu-B*08+ Indian rhesus macaques may contribute to the establishment of elite control

IntroductionSpontaneous control of chronic-phase HIV/SIV viremia is often associated with the expression of specific MHC class I allotypes. HIV/SIV-specific CD8+ cytotoxic T lymphocytes (CTLs) restricted by these MHC class I allotypes appear to be critical for viremic control. Establishment of the elite controller (EC) phenotype is predictable in SIVmac239-infected Indian rhesus macaques (RMs), with approximately 50% of Mamu-B*08+ RMs and 20% of Mamu-B*17+ RMs becoming ECs. Despite extensive characterization of EC-associated CTLs in HIV/SIV-infected individuals, the precise mechanistic basis of elite control remains unknown. Because EC and non-EC viral load trajectories begin diverging by day 14 post-infection, we hypothesized that hyperacute innate immune responses may contribute to viremic control.MethodsTo gain insight into the immunological factors involved in the determination of EC status, we vaccinated 16 Mamu-B*08+ RMs with Vif and Nef to elicit EC-associated CTLs, then subjected these 16 vaccinees and an additional 16 unvaccinated Mamu-B*08+ controls to repeated intrarectal SIVmac239 challenges. We then performed whole-blood transcriptomic analysis of all 32 SIVmac239-infected Mamu-B*08+ RMs and eight SIVmac239-infected Mamu-B*08– RMs during the first 14 days of infection.ResultsVaccination did not provide protection against acquisition, but peak and setpoint viremia were significantly lower in vaccinees relative to controls. We did not identify any meaningful correlations between vaccine-induced CTL parameters and SIVmac239 acquisition rate or chronic-phase viral loads. Ultimately, 13 of 16 vaccinees (81%) and 7 of 16 controls (44%) became ECs (viremia ≤ 10,000 vRNA copies/mL plasma for ≥ 4 weeks). We identified subsets of immunomodulatory genes differentially expressed (DE) between RM groupings based on vaccination status, EC status, and MHC class I genotype. These DE genes function in multiple innate immune processes, including the complement system, cytokine/chemokine signaling, pattern recognition receptors, and interferon-mediated responses.DiscussionA striking difference in the kinetics of differential gene expression among our RM groups suggests that Mamu-B*08-associated elite control is characterized by a robust, rapid innate immune response that quickly resolves. These findings indicate that, despite the association between MHC class I genotype and elite control, innate immune factors in hyperacute SIV infection preceding CTL response development may facilitate the establishment of the EC phenotype.

Transcriptomic Analysis of the Combined Effects of Methyl Jasmonate and Wounding on Flavonoid and Anthraquinone Biosynthesis in Senna tora.

Jasmonates, including jasmonic acid (JA) and its derivatives such as methyl jasmonate (MeJA) or jasmonly isoleucine (JA-Ile), regulate plant responses to various biotic and abiotic stresses. In this study, we applied exogenous MeJA onto Senna tora leaves subjected to wounding and conducted a transcriptome deep sequencing analysis at 1 (T1), 3 (T3), 6 (T6), and 24 (T24) h after MeJA induction, along with the pretreatment control at 0 h (T0). Out of 18,883 mapped genes, we identified 10,048 differentially expressed genes (DEGs) between the T0 time point and at least one of the four treatment times. We detected the most DEGs at T3, followed by T6, T1, and T24. We observed the upregulation of genes related to JA biosynthesis upon exogenous MeJA application. Similarly, transcript levels of genes related to flavonoid biosynthesis increased after MeJA application and tended to reach their maximum at T6. In agreement, the flavonols kaempferol and quercetin reached their highest accumulation at T24, whereas the levels of the anthraquinones aloe-emodin, emodin, and citreorosein remained constant until T24. This study highlights an increase in flavonoid biosynthesis following both MeJA application and mechanical wounding, whereas no significant influence is observed on anthraquinone biosynthesis. These results provide insights into the distinct regulatory pathways of flavonoid and anthraquinone biosynthesis in response to MeJA and mechanical wounding.