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Pelvic organ prolapse (POP) is a prevalent disease among women, and immune cell and telomere have potential associations with the pathogenesis of POP. The identification and validation of immune cell-related genes (ICRGs) and telomere-related genes (TRGs) in POP are of great significance for elucidating its mechanisms, screening diagnostic key genes, and identifying therapeutic targets. In this study, first, ICRGs were obtained based on immune infiltration and WGCNA; key genes related to immune cell and telomere in POP were identified from public-database transcriptome data through differential expression analysis, machine learning, expression level analysis and ROC analysis. Subsequently, a comprehensive analysis including nomogram construction, correlation analysis, GSEA, molecular regulatory network construction, and drug prediction explored the molecular mechanisms of these key genes in POP. We identified 864 differentially expressed genes (DEGs), including 833 upregulated and 31 downregulated genes. The intersection of DEGs, telomere-related genes (TRGs), and immune cell-related genes (ICRGs) yielded six candidate genes. Machine learning further pinpointed CCNL1 and NAMPT as key biomarkers, which were significantly upregulated in POP samples (p < 0.05) and validated by RT-qPCR. Subsequently, a comprehensive analysis revealed their diagnostic potential via a nomogram (AUC: 0.847), a strong positive correlation (r = 0.78, p < 0.001), and enrichment in pathways such as ubiquitin-mediated proteolysis (GSEA). Molecular regulatory network construction predicted interactions with 21 key nodes and 28 interactions, and drug prediction identified 14 potential therapeutic compounds. These findings provide a theoretical basis for understanding POP pathogenesis and identifying novel therapeutic targets. This study identifies CCNL1 and NAMPT as novel immune- and telomere-related biomarkers for POP. These findings provide potential targets for diagnostic development and lay a computational foundation for future therapeutic strategies, although experimental validation is required to confirm their causal roles.

Given that electroacupuncture (EA) is a promising yet mechanistically unclear intervention for IBS, and considering the anterior cingulate cortex (ACC)'s crucial role in visceral pain and emotion within the gut-brain axis, this study aims to investigate the transcriptomic alterations in the ACC of a rat IBS model and to evaluate the potential therapeutic effects of EA administered at the acupoints Tianshu (ST25) and Zusanli (ST36). Rats subjected to water avoidance stress (WAS) were evaluated for IBS symptoms, including increased anxiety-like behavior, abnormal abdominal muscle activity, and elevated abdominal withdrawal reflex (AWR) scores-a validated measure of visceral hypersensitivity. The effect of EA at ST25 and ST36 was assessed on these symptoms, and the transcriptomic profile of the ACC was analyzed after WAS and EA treatment using RNA sequencing and subsequent validation by real-time PCR. The stress model induced significant IBS-like symptoms, including visceral hypersensitivity and anxiety-like behavior. EA at ST25 and ST36 significantly ameliorated these behavioral and physiological deficits. Notably, transcriptomic profiling of the ACC linked this behavioral improvement to central modulation, revealing dysregulation of 3 key genes involved in many pathways. RT-PCR validated the expression changes in 3 selected candidate genes, further supporting their role in EA's therapeutic effects. EA alleviates IBS symptoms in rats, potentially through transcriptomic reprogramming in the ACC, which provides novel mechanistic insight into how peripheral acupuncture may exert central actions to treat IBS.

Sepsis is an infection-induced systemic inflammatory response syndrome. T cell remodeling and senescence are linked to sepsis, so identifying T cell-related genes (TCRGs) and senescence-related genes (SRGs) as biomarkers is crucial for elucidating mechanisms, diagnosis, and targeted therapy. TCRGs were derived from single-cell sequencing data. Biomarkers were screened via differential expression analysis, machine learning, and expression analysis of public transcriptome data. Molecular mechanisms were explored through artificial neural network (ANN), GSEA, immune infiltration analysis, and drug prediction, with RT-qPCR validation in clinical samples. PATZ1, SIN3B, BLK, and MTHFD2 were identified. MTHFD2 was upregulated in sepsis, while the other three were downregulated (P < 0.001); MTHFD2 showed no significant difference in validation (P > 0.05). The ANN had high prediction accuracy. These genes were enriched in phosphatidylinositol signaling, hematopoietic cell lineage, and DNA replication. Immune infiltration analysis revealed correlations between the biomarkers and immune cells (e.g., PATZ1 with CD8 T cells/neutrophils). Emetine, latamoxef, and dihydroergotamine bound stably to the biomarkers. PATZ1, SIN3B, BLK, and MTHFD2, as T cell and senescence-related biomarkers in sepsis, offered valuable insights into sepsis pathogenesis and targeted therapy.

Background Recently, Zika virus (ZIKV) re-emerged in India and was potentially associated with microcephaly. However, the molecular mechanisms underlying ZIKV pathogenesis remain to be explored. Results Herein, we performed a comprehensive RNA-sequencing analysis on ZIKV-infected JEG-3, U-251 MG, and HK-2 cells versus corresponding uninfected controls. Combined with a series of functional analyses, including gene annotation, pathway enrichment, and protein–protein interaction (PPI) network analysis, we defined the molecular characteristics induced by ZIKV infection in different tissues and invasion time points. Data showed that ZIKV infection and replication in each susceptible organ commonly stimulated interferon production and down-regulated metabolic-related processes. Also, tissue-specific immune responses or biological processes (BPs) were induced after ZIKV infection, including GnRH signaling pathway in JEG-3 cells, MAPK signaling pathway in U-251 MG cells, and PPAR signaling pathway in HK-2 cells. Of note, ZIKV infection induced delayed antiviral interferon responses in the placenta-derived cell lines, which potentially explains the molecular mechanism by which ZIKV replicates rapidly in the placenta and subsequential vertical transmission occurs. Conclusions Together, these data may provide a systemic insight into the pathogenesis of ZIKV infection in distinct human tissue-derived cell lines, which is likely to help develop prophylactic and therapeutic strategies against ZIKV infection.

Spinal cord injury (SCI) is a severely disabling disease. Hyperactivation of neuroinflammation is one of the main pathophysiological features of secondary SCI, with phospholipid metabolism playing an important role in regulating inflammation. Phospholipase D (PLD), a critical lipid-signaling molecule, is known to be involved in various physiological processes, including the regulation of inflammation. Despite this knowledge, the specific role of PLD in SCI remains unclear. In this study, we constructed mouse models of SCI and administered PLD inhibitor (FIPI) treatment to investigate the efficacy of PLD. Additionally, transcriptome sequencing and protein microarray analysis of spinal cord tissues were conducted to further elucidate its mechanism of action. The results showed that PLD expression increased after SCI, and inhibition of PLD significantly improved the locomotor ability, reduced glial scarring, and decreased the damage of spinal cord tissues in mice with SCI. Transcriptome sequencing analysis showed that inhibition of PLD altered gene expression in inflammation regulation. Subsequently, the protein microarray analysis of spinal cord tissues revealed variations in numerous inflammatory factors. Biosignature analysis pointed to an association with immunity, thus confirming the results obtained from transcriptome sequencing. Collectively, these observations furnish compelling evidence supporting the anti-inflammatory effect of FIPI in the context of SCI, while also offering important insights into the PLD function which may be a potential therapeutic target for SCI.

A lobed leaf is a common trait in plants, but it is very rare in Lauraceae plants, including species of Phoebe. In the study of germplasm resources of Phoebe neurantha, we found lobed leaf variant seedlings, and the variation could be inherited stably. Studying the lobed leaf mechanism of P. neurantha var. lobophylla can offer insight into the leaf development mechanism of woody plants. RNA-seq and small RNA-seq analysis results showed that a total of 8091 differentially expressed genes (DEGs) and 16 differentially expressed miRNAs were identified in P. neurantha var. lobophylla. Considering previous research results, a leaf margin morphological development related miRNA, pne-miRNA319a, was primary identified as a candidate miRNA. Target gene prediction showed that a total of 2070 genes were predicted to be the target genes of differentially expressed miRNAs. GO enrichment analysis of differentially expressed target genes suggested that PnTCP2 is related to lobed leaf formation. The TRV-VIGS gene silencing of PnTCP2 led to lobed leaves in P. neurantha seedlings. The downregulation of PnTCP2 led to lobed leaves. The yeast two-hybrid test and bimolecular fluorescence complementation test confirmed that the PnTCP2 protein interacted with the PnLBD41 protein. Based on the expression analysis of gene-silenced leaves and RNA-seq and small RNA-seq analysis results, pne- miRNA319a and PnLBD41 might also play important roles in this process. In conclusion, PnTCP2 plays an important and vital role in the formation of the lobed leaves of P. neurantha var. lobophylla.

Mandarin fish ( Siniperca chuatsi ) can adapt to artificial diets, with the improvement of domestication level. However, the effects of artificial diets on the muscle health of fish are unclear. In this study, 480 homogenous-sized mandarin fish (initial weight of 25.1 ± 0.1 g) were randomly divided into two groups and fed with artificial diets or live prey fish for eight weeks. The transcriptome sequencing analysis identified that artificial diets primarily affected glucose metabolism, lipid metabolism, and immune system in the muscle. Furthermore, artificial diets induced excessive glycogen accumulation in the muscle by increasing the mRNA expression of gluconeogenesis-related genes and decreasing the mRNA expression of glycolysis-related genes. Meanwhile, artificial diets significantly increased triglyceride accumulation in the muscle by upregulating the activity of fatty acid synthetase and the mRNA expression of lipid synthesis-related genes, including srebp1 , fas , and plin2 . Artificial diets significantly increased the level of malondialdehyde, leading to oxidative stress in the muscle. Besides, artificial diets also upregulated the mRNA expression of pro-inflammation cytokines, including il-1β , ifn-γ , and tnfα . In conclusion, artificial diets disrupted glucose and lipid metabolism and induced oxidative stress and inflammation in the muscle of mandarin fish.

Trichoderma is a filamentous fungus that is widely distributed in nature. As a biological control agent of agricultural pests, Trichoderma species have been widely studied in recent years. This study aimed to understand the inhibitory mechanism of Trichoderma virens ZT05 on Rhizoctonia solani through the side-by-side culture of T. virens ZT05 and R. solani. To this end, we investigated the effect of volatile and nonvolatile metabolites of T. virens ZT05 on the mycelium growth and enzyme activity of R. solani and analyzed transcriptome data collected from side-by-side culture. T. virens ZT05 has a significant antagonistic effect against R. solani. The mycelium of T. virens ZT05 spirally wraps around and penetrates the mycelium of R. solani and inhibits the growth of R. solani. The volatile and nonvolatile metabolites of T. virens ZT05 have significant inhibitory effects on the growth of R. solani. The nonvolatile metabolites of T. virens ZT05 significantly affect the mycelium proteins of R. solani, including catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), selenium-dependent glutathione peroxidase (GSH-Px), soluble proteins, and malondialdehyde (MDA). Twenty genes associated with hyperparasitism, including extracellular proteases, oligopeptide transporters, G-protein coupled receptors (GPCRs), chitinases, glucanases, and proteases were found to be upregulated during the antagonistic process between T. virens ZT05 and R. solani. Thirty genes related to antibiosis function, including tetracycline resistance proteins, reductases, the heat shock response, the oxidative stress response, ATP-binding cassette (ABC) efflux transporters, and multidrug resistance transporters, were found to be upregulated during the side-by-side culture of T. virens ZT05 and R. solani. T. virens ZT05 has a significant inhibitory effect on R. solani, and its mechanism of action is associated with hyperparasitism and antibiosis.

Purpose: To explore the therapeutic mechanism of bone marrow mesenchymal stem cells derived exosomes (BMSC-Exos) for doxorubicin (DOX)-induced cardiotoxicity (DIC) and identify the long noncoding RNAs' (lncRNAs') anti-inflammation function derived by BMSC-Exos. Materials and Methods: High-throughput sequencing and transcriptome bioinformatics analysis of lncRNA were performed between DOX group and BEC (bone marrow mesenchymal stem cells derived exosomes coculture) group. Elevated lncRNA (ElncRNA) in the cardiomyocytes of BEC group compared with DOX group were confirmed. Based on the location and coexpression relationship between ElncRNA and its target genes, we predicted two target genes of ElncRNA, named cis_targets and trans_targets. The target genes were analyzed by enrichment analyses. Then, we identified the key cellular biological pathways regulating DIC. Experiments were performed to verify the therapeutic effects of exosomes and the origin of lncRNAs in vitro and in vivo. Results: Three hundred and one lncRNAs were differentially expressed between DOX and BEC groups (fold change >1.5 and p < 0.05), of which 169 lncRNAs were elevated in the BEC group compared with the DOX group. GO enrichment analysis of target genes of ElncRNAs showed that they were predominantly involved in inflammation-associated processes. KEGG analysis indicated that their regulatory pathways were mainly involved in oxidative stress-induced inflammation and proliferation of cardiomyocyte. The verification experiments in vitro showed that the oxidative stress and cell deaths were decreased in BEC groups. Moreover, from the top 10 ElncRNAs identified in the sequencing results, MSTRG.98097.4 and MSTRG.58791.2 were both decreased in the DOX group and elevated in BEC group. While in verification experiments in vivo, only the expression of MSTRG.58791.2 is consistent with the result in vitro. Conclusion: Our results show that ElncRNA, MSTRG.58791.2, is possibly secreted by the BMSC-Exos and able to alleviate DIC by suppressing inflammatory response and inflammation-related cell death. Keywords: doxorubicin-induced cardiotoxicity, exosomes, inflammation, transcriptome sequencing analysis

Boron (B) deficiency is detrimental to Glycine max (L.) Merr., which is one of the leading oil crops. In this study, physiological analysis of soybean seedlings under B deficiency and control after 12 h, 24 h, 72 h and 8 days was carried out, and the roots were subjected to transcriptome sequencing analysis. The results showed that under B deficiency, the plant height, SPAD and chlorophyll fluorescence value of soybean seedlings decreased significantly, indicating that B stress significantly inhibited plant growth and photosynthesis. RNA-seq revealed a total of 5126 DEGs (Differentially Expressed Genes), and nine DEGs co-existed at the four-time points, among which GLYMA_03G130600 regulates transcription factor ORG3, which is related to plant growth. GO analysis revealed a total of annotated 4018 DEGs, among which the terms plasma membrane, extracellular, enzyme activity, ion transport metabolic process and oxidoreductase activity were significantly enriched at the four time points, which might hinder the growth of soybean and accelerate senescence. KEGG analysis showed that at level 1, the DEGs were mainly enriched in photosynthesis-related, phenylpropanoid biosynthesis, nitrogen metabolism and plant hormone signal transduction. At level 2 of secondary metabolism, the DEGs were mainly enriched in energy metabolism and amino acid metabolism pathways, which indicates that B stresses mainly affect photosynthesis, hormone regulation and amino acid metabolism of soybean, thus affecting plant growth. The above results give deeper insight into the soybean response to B deficiency and lay the foundation for further studies of the molecular mechanism of soybean response to boron deficiency.