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Introduction: Ischemic post-conditioning (I-post C) is a recognized therapeutic strategy for lung ischemia/reperfusion injury (LIRI). However, the specific mechanisms underlying the lung protection conferred by I-post C remain unclear. This study aimed to investigate the protective mechanisms and potential molecular regulatory networks of I-post C on lung tissue. Methods: Transcriptome analysis was performed on rat lung tissues obtained from Sham, ischemia-reperfusion (IR), and I-post C groups using RNA-seq to identify differentially expressed genes (DEGs). Subsequently, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and gene set enrichment analysis (GSEA) were conducted to elucidate significantly enriched pathways in the IR and I-post C groups. Additionally, protein-protein interaction (PPI) network analysis was carried out to examine associations among the DEGs. Pathological changes in lung tissues were assessed using hematoxylin-eosin (H&E) staining. The expression levels of CXCL1 and CXCL6 in the IR and I-post C groups were evaluated through immunofluorescence and Western blotting. Results: Our results showed that I-post C significantly attenuated both pulmonary edema and inflammatory cell infiltration. Transcriptome analysis identified 38 DEGs in the I-post C group compared to the IR group, comprising 21 upregulated and 17 downregulated genes. Among these, seven inflammation-related DEGs exhibited co-expression patterns with the Sham and IR groups, with notable downregulation of C xcl1 and C xcl6. GO analysis primarily linked these DEGs to neutrophil activation, chemotaxis, cytokine activity, and CCR chemokine receptor binding. KEGG analysis revealed enriched pathways, including the IL-17, TNF, and NF-κB signaling pathways. GSEA indicated downregulation of neutrophil chemotaxis and the IL-17 signaling pathway, correlating with reduced expression of C xcl1 and C xcl6. Validation of Cxcl1 and Cxcl6 mRNA expression via immunofluorescence and Western blotting supported the RNA-seq findings. Furthermore, a PPI network was constructed to elucidate interactions among the 29 DEGs. Conclusions: Through RNA-Seq analysis, we concluded that I-post C may reduce inflammation and suppress the IL-17 signaling pathway, thereby protecting against lung damage caused by LIRI, potentially involving neutrophil extracellular traps. [ABSTRACT FROM AUTHOR]

Introduction: Sexual dimorphism in Muscovy ducks results in substantial differences in muscle development potential between males and females, leading to significant variations in growth rates and body weights throughout their development. Methods: This study aimed to investigate the regulatory mechanisms underlying the differences in muscle development between genders in black Muscovy ducks, we analyzed the phenotypic characteristics and transcriptome profiles of breast muscles in male and female black Muscovy ducks at different developmental stages (postnatal days 28, 42, and 70). Results: In the analysis of tissue physical morphology, the results showed that females exhibit larger myofiber diameters and lower myofiber densities compared to males at postnatal day 42 (p < 0.05). The difference becomes more pronounced by day 70, however, no significant difference was observed at postnatal day 28. Transcriptome analysis identified a total of 1,118 unique differentially expressed genes (DEGs) across the various comparison groups. In different growth and development stages of black Muscovy ducks, the DEGs like MYLK4 , KIT , CD36 , ATP2A1 were significantly associated with myofiber hypertrophy, and key pathways such as AMPK signaling pathway, focal adhesion, and ECM-receptor interactions have been found to be closely associated with muscle size and hypertrophy. In the breast muscles of different sexes black Muscovy ducks, the DEGs such as TPM2 , HNRNPK , VCP , ATP2A2 , and ANKRD1 may be the reason for the difference in breast muscle size between male and female ducks. Furthermore, key pathways, including the cGMP-PKG signaling pathway, calcium signaling pathway, and hypertrophic cardiomyopathy are also involved in regulating the developmental potential differences in muscle between male and female ducks. Discussion: This study reveals the molecular mechanism regulating the muscle development in male and female black Muscovy ducks at different growth stages, and provides valuable insights into the specific genes responsible for muscle development, laying a theoretical foundation for enhancing the genetic quality of duck meat. [ABSTRACT FROM AUTHOR]

One of the fundamental aspects of genomic research is the identification of differentially expressed (DE) genes between two conditions. In the past decade, numerous DE analysis tools have been developed, employing various normalization methods and statistical modelling approaches. In this article, we introduce DElite , an R package that leverages the capabilities of four state-of-the-art DE tools: edgeR, limma, DESeq2, and dearseq. DElite returns the outputs of the four tools with a single command line, thus providing a simplified way for non-expert users to perform DE analysis. Furthermore, DElite provides a statistically combined output of the four tools, and in vitro validations support the improved performance of these combination approaches for the detection of DE genes in small datasets. Finally, DElite offers comprehensive and well-documented plots and tables at each stage of the analysis, thus facilitating result interpretation. Although DElite has been designed with the intention of being accessible to users without extensive expertise in bioinformatics or statistics, the underlying code is open source and structured in such a way that it can be customized by advanced users to meet their specific requirements. DElite is freely available for download from https://gitlab.com/soc-fogg-cro-aviano/DElite. [ABSTRACT FROM AUTHOR]

Trifoliate orange (Citrus trifoliata (L.) Raf.) is a cold-hardy citrus species that contributes to citrus production by frequently serving as a rootstock. Nevertheless, the molecular mechanisms underlying cold tolerance in citrus, particularly post-transcriptional regulation, remain largely unidentified. In this study, we constructed a transcriptome map of trifoliate orange subjected to cold stress by integrating full-length single-molecule sequencing and Illumina short-read sequencing. The hybrid sequencing approach yielded a more comprehensive set of full-length transcripts than was previously available from the reference genome. In particular, the high-quality transcripts enabled the detection of extensive alternative splicing (AS), with intron retention (IR) identified as the predominant AS event in trifoliate orange. Transcriptome analysis revealed that genes associated with starch and sucrose metabolism were significantly enriched among the cold-responsive genes. Consistent with these data, soluble sugar content was elevated by the cold treatments. Additionally, the expression of multiple genes encoding enzymes with antioxidant activity, including PODs and SODs, was induced, which plays a pivotal role in the mitigation of continuous ROS production. Furthermore, we observed that AS and transcriptional regulation modulate distinct pathways. We also found that the expression of genes encoding key transcription factors (TFs) was highly induced by cold stress and that some of the mRNAs encoding these key TFs were differentially spliced. This dataset provides comprehensive transcriptional and post-transcriptional profiles of the response to cold stress in trifoliate orange that may help to identify genes that contribute to cold tolerance in citrus. [ABSTRACT FROM AUTHOR]

Citrus is commercially propagated via grafting, which ensures trees have consistent fruit traits combined with favorable traits from the rootstock such as soil adaptability, vigor, and resistance to soil pathogens. Graft incompatibility can occur when the scion and rootstock are not able to form a permanent, healthy union. Understanding and preventing graft incompatibility is of great importance in the breeding of new fruit cultivars and in the choice of scion and rootstock by growers. The rootstock US-1283, a citrandarin generated from a cross of "Ninkat" mandarin (Citrus reticulata) and "Gotha Road" #6 trifoliate orange (Poncirus trifoliata), was released after years of field evaluation because of its superior productivity and good fruit quality on "Hamlin" sweet orange (C. sinensis) under Florida's growing conditions. Subsequently, it was observed that trees of "Bearss" lemon (C. limon) and "Valencia" sweet orange (C. sinensis) grafted onto US-1283 exhibited unhealthy growth near the graft union. The incompatibility manifested as stem grooving and necrosis underneath the bark on the rootstock side of the graft. Another citrandarin rootstock, US-812 (C. reticulata "Sunki" × P. trifoliata "Benecke"), is fully graft compatible with the same scions. Transcriptome analysis was performed on the vascular tissues above and below the graft union of US-812 and US-1283 graft combinations with "Bearss" and "Valencia" to identify expression networks associated with incompatibility and help understand the processes and potential causes of incompatibility. Transcriptional reprogramming was stronger in the incompatible rootstock than in the grafted scions. Differentially expressed genes (DEGs) in US-1283, but not the scions, were associated with oxidative stress and plant defense, among others, similar to a pathogen-induced immune response localized to the rootstock; however, no pathogen infection was detected. Therefore, it is hypothesized that this response could have been triggered by signaling miscommunications between rootstock and scion either through (1) unknown molecules from the scion that were perceived as danger signals by the rootstock, (2) missing signals from the scion or missing receptors in the rootstock necessary for the formation of a healthy graft union, (3) the overall perception of the scion by the rootstock as non-self, or (4) a combination of the above. [ABSTRACT FROM AUTHOR]

Introduction: The placental vascular system plays an important role in the development of pregnancy hypertension in preeclampsia. The gene profiles of whole placental tissue (containing blood vessels and many other structural components) and pure vascular tissue should be very different. All previous reports using RNA-seq analysis in the placenta have tested its whole tissue or the villous part, and thus the gene profiles in the pure placental blood vessels are unknown. Methods: This study was the first to address this point with RNA-seq in human placenta at the transcript level. Isolated placental micro-vessels from normal and preeclamptic pregnancies were used for RNA-seq analysis, real-time quantitative polymerase chain reaction (RT-qPCR) verification, and vascular function tests. Furthermore, a vascular function-centric core network was constructed to show the gene-gene interactions and gene-function associations in the placental vessel system. Results: Differential expression analysis identified a total of 486 significantly changed transcripts. Bioinformatics analysis further confirmed that multiple genes were highly related to blood vessel and placental phenotypes. Several hub genes, including ELMO1 , YWHAE , and IL6ST , were significantly reduced in the placental vessels in preeclampsia. Vascular tension experiments showed that angiotensin II-mediated vasoconstriction and exogenous NO donor sodium nitroprusside-induced vasodilation were decreased, while phenylephrine-mediated vascular responses were unchanged in placental micro-vessels in preeclampsia. Discussion: The results provide important insights into the pathological process in the placental vasculature in preeclampsia and offer great potential for further investigation of these molecular targets in the human placental vascular system. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSC) are fibroblast-like non-hematopoietic cells with self-renewal and differentiation capacity, and thereby great potential in regeneration and wound healing. MSC populations are heterogeneous not only inherently, but also among different model species. In particular, porcine MSC serve as a frequently used resource for translational research, due to pigs' distinctive closeness to human anatomy and physiology. However, information on gene expression profiles from porcine MSC and its dynamics during differentiation is sparse, especially with regard to cell surface and inner cell markers. In this study, we investigated the transcriptome of bone marrow-derived MSC and its differentiated cell types in a minipig breed for experimental research, known as Mini-LEWE, using bulk mRNA sequencing. Our data highlighted Rap1 signaling and downstream pathways PI3K-Akt and MAPK signaling as potential players for the maintenance of stemness of BM-MSC. In addition, we were able to link the process of differentiation to changes in the regulation of actin cytoskeleton. A total of 18 "BM-MSC differentiation driver markers" were identified, potentially promoting the process of differentiation into adipocytes, chondrocytes as well as osteocytes. Our results offer a new perspective on the molecular phenotype of porcine BM-MSC and the transcriptional responses in new differentiated progeny. [ABSTRACT FROM AUTHOR]

Red alder (Alnus rubra) has highly desirable wood, dye pigment, and (traditional) medicinal properties which have been capitalized on for thousands of years, including by Pacific West Coast Native Americans. A rapidly growing tree species native to North American western coastal and riparian regions, it undergoes symbiosis with actinobacterium Frankia via their nitrogen-fixing root nodules. Red alder's desirable properties are, however, largely attributed to its bioactive plant phenol metabolites, including for plant defense, for its attractive wood and bark coloration, and various beneficial medicinal properties. Integrated transcriptome and metabolome data analyses were carried out using buds, leaves, stems, roots, and root nodules from greenhouse grown red alder saplings with samples collected during different time-points (Spring, Summer, and Fall) of the growing season. Pollen and catkins were collected from field grown mature trees. Overall plant phenol biochemical pathways operative in red alder were determined, with a particular emphasis on potentially identifying candidates for the long unknown gateway entry points to the proanthocyanidin (PA) and ellagitannin metabolic classes, as well as in gaining better understanding of the biochemical basis of diarylheptanoid formation, i.e. that help define red alder's varied medicinal uses, and its extensive wood and dye usage. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) stands as the third most widespread cancer globally with poor prognosis. Berberine (Ber), as one herbal phytochemical, showed promise in CRC therapy, but its exact mechanism is unclear. Small molecule traditional drugs face challenges in quick metabolism and low bio-availability after systemic administration. Nanodrug deliver system, with their unique properties, has the advantages of protecting drugs, improving drug bio-availability, and reducing toxic and side effects, which exhibited huge drug delivery potential. Herein, the PEG-PLGA nanocarrier was used for encapsulated Ber according to nanoprecipitation and obtained nanomedicine, denoted as NPBer. In vitro , the flow cytometry test and CCK8 assays indicated that NPBer was more easily taken up by HCT116 CRC cells, and had stronger inhibition on cell proliferation with the increase of drug concentration. In addition, RNA-Seq was employed to explore the alterations in the transcriptomes of cancer cells subsequent to treatment with Free Ber or NPBer.The sequencing results indicate that Free Ber could activate cellular aging mechanisms, intensified the iron death pathway, optimized oxidative phosphorylation efficiency, exacerbated apoptosis, accelerated programmed cell death, and negatively modulated key signaling pathways in CRC cells including Wnt, TGF-beta, Hippo, and mTOR signaling pathways. Based on PEG-PLGA nanocarriers, NPBer can improve the in vivo delivery efficiency of Ber, thereby enhancing its antitumor efficacy in vivo , enhancing apoptosis by enhancing the mitochondrial autophagy and autophagy activities of CRC cells, negatively regulating the inflammatory mediator to regulate TRP channels, and inhibiting the activation of Notch signaling pathway. In vivo , NPBer can significantly improve its accumulation and durable drug targeting in tumor site, resulting in induce maximum cell apoptosis and effectively inhibit the proliferation of HCT116 tumor. This strategy provided a promising antitumor therapeutic strategy using Ber-based drugs. [ABSTRACT FROM AUTHOR]

Liver cancer represents a complex and severe ailment that poses tough challenges to global healthcare. Transcriptome sequencing plays a crucial role in enhancing our understanding of cancer biology and accelerating the development of more effective methods for cancer diagnosis and treatment. In the course of our current investigation, we identified a total of 1,149 differentially expressed genes (DEGs), encompassing 499 upregulated and 650 downregulated genes, subsequent to prunetrin (PUR) treatment. Our methodology encompassed gene and pathway enrichment analysis, functional annotation, KEGG pathway assessments, and protein-protein interaction (PPI) analysis of the DEGs. The preeminent genes within the DEGs were found to be associated with apoptotic processes, cell cycle regulation, the PI3k/Akt pathway, the MAPK pathway, and the mTOR pathway. Furthermore, key apoptotic-related genes exhibited close interconnections and cluster analysis found three interacting hub genes namely, TP53 , TGFB1 and CASP8. Validation of these genes was achieved through GEPIA and western blotting. Collectively, our findings provide insights into the functional landscape of liver cancer-related genes, shedding light on the molecular mechanisms driving disease progression and highlighting potential targets for therapeutic intervention. [ABSTRACT FROM AUTHOR]

The terpene synthase (TPS) plays a pivotal roles in plant growth, development, and enhancing resilience against environmental stresses. Despite this, the bioinformatics analysis of the TPS family gene in soybean (Glycine max) is lacking. In this study, we investigated 36 GmTPS members in soybean, exhibiting a diverse range of protein lengths, spanning from 144 to 835 amino acids. A phylogenetic tree was constructed from these GmTPS genes revealed a classification into five distinct subgroups: Group1, Group2, Group3, Group4 and Group5. Notably, within each subgroup, we identified the motifs of GmTPS proteins were similar, although variations existed among different subfamilies. Gene duplication events analysis demonstrated that TPS genes expand differently in G. max , A. thaliana and O. sativa. Among, both tandem duplication and Whole genome duplication contributive to the expansion of TPS genes in G. max , and Whole genome duplication played a major role. Moreover, the cis-element analysis suggested that TPS is related to hormone signals, plant growth and development and environmental stress. Yeast two-hybrid (Y2H) assay results indicated TPS protein may form heterodimer to function, or may form complex with P450 proteins to function. RNA-seq results revealed a higher expression of most GmTPS genes in flowers, suggesting their potential contribution to flower development. Collectively, these findings offer a provide a holistic knowledge of the TPS gene family in soybean and will facilitate further characterization of TPSs effectively. [ABSTRACT FROM AUTHOR]

Introduction: The balanced fatty acid profile of olive oil not only enhances its stability but also contributes to its positive effects on health, making it a valuable dietary choice. Olive oil's high content of unsaturated fatty acids and low content of saturated fatty acids contribute to its beneficial effects on cardiovascular diseases and cancer. The quantities of these fatty acids in olive oil may fluctuate due to various factors, with genotype being a crucial determinant of the oil's quality. Methods: This study investigated the genetic basis of oil quality by comparing the transcriptome of two Iranian cultivars with contrasting oil profiles: Mari, known for its high oleic acid content, and Shengeh, characterized by high linoleic acid at Jaén index four. Results and discussion: Gas chromatography confirmed a significant difference in fatty acid composition between the two cultivars. Mari exhibited significantly higher oleic acid content (78.48%) compared to Shengeh (48.05%), while linoleic acid content was significantly lower in Mari (4.76%) than in Shengeh (26.69%). Using RNA sequencing at Jaén index four, we analyzed genes involved in fatty acid biosynthesis. Differential expression analysis identified 2775 genes showing statistically significant differences between the cultivars. Investigating these genes across nine fundamental pathways involved in oil quality led to the identification of 25 effective genes. Further analysis revealed 78 transcription factors and 95 transcription binding sites involved in oil quality, with BPC6 and RGA emerging as unique factors. This research provides a comprehensive understanding of the genetic and molecular mechanisms underlying oil quality in olive cultivars. The findings have practical implications for olive breeders and producers, potentially streamlining cultivar selection processes and contributing to the production of high-quality olive oil. [ABSTRACT FROM AUTHOR]

Saline-alkali soils limit rice growth and production. With an increasing global population, enhancing rice salt tolerance is crucial for improving yields in these areas. This study investigated the developmental characteristics of young panicles and pollen fertility in two rice varieties, 58M and 58L, under salt stress. Results showed that 58M had more substantial salt tolerance during panicle development. RNA sequencing of 18 samples from both varieties under high salt stress (0 h, 6 h, and 24 h) identified 469 common differentially expressed genes (DEGs) and 2,308 DEGs between the varieties. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment highlighted significant pathways such as phenylpropanoid biosynthesis, protein processing, and flavonoid biosynthesis. Six gene co-expression modules related to salt tolerance were identified, with six candidate genes (LOC_Os05g38530, LOC_Os04g07920, LOC_Os12g02105, LOC_Os01g06580, LOC_Os06g49250, and LOC_Os06g48300) potentially linked to salt tolerance. These findings provide insights into rice salt tolerance mechanisms and offer new genetic resources for breeding salt-tolerant rice. [ABSTRACT FROM AUTHOR]

Introduction: Low temperature inhibits the growth of most microorganisms. However, some microbes can grow well in a low temperature, even a freezing temperature. Methods: In this study, the mechanisms conferring cold resistance in the cryophylactic yeast Metschnikowia (M.) pulcherrima MS612, an isolate of the epidermis of ice grapes, were investigated based on comparative transcriptome analysis. Results: A total of 6018 genes and 374 differentially expressed genes (> 2-fold, p < 0.05) were identified using RNA-Seq. The differentially expressed genes were mainly involved in carbohydrate and energy metabolism, transport mechanisms, antifreeze protection, lipid synthesis, and signal transduction. M. pulcherrima MS612 maintained normal growth at low temperature (5°C) by enhancing energy metabolism, sterol synthesis, metal ion homeostasis, amino acid and MDR transport, while increased synthesis of glycerol and proline transport to improve its resistance to the freezing temperature (-5°C). Furthermore, cAMPPKA and ERAD signaling pathways contribute to resist the low temperature and the freezing temperature, respectively. Conclusion: This study provides new insights into cold resistance in cryophylactic microorganisms for maneuvering various metabolism to resist different cold environment. [ABSTRACT FROM AUTHOR]

The term "Long-COVID" (LC) is characterized by the aftereffects of COVID-19 infection. Various studies have suggested that Epstein-Barr virus (EBV) reactivation is among the significant reported causes of LC. However, there is a lack of in-depth research that could largely explore the pathogenic mechanism and pinpoint the key genes in the EBV and LC context. This study mainly aimed to predict the potential disease-associated common genes between EBV reactivation and LC condition using next-generation sequencing (NGS) data and reported naturally occurring biomolecules as inhibitors. We applied the bulk RNA-Seq from LC and EBV-infected peripheral blood mononuclear cells (PBMCs), identified the differentially expressed genes (DEGs) and the Protein-Protein interaction (PPI) network using the STRING database, identified hub genes using the cytoscape plugins CytoHubba and MCODE, and performed enrichment analysis using ClueGO. The interaction analysis of a hub gene was performed against naturally occurring bioflavonoid molecules using molecular docking and the molecular dynamics (MD) simulation method. Out of 357 common genes, 22 genes (CCL2, CCL20, CDCA2, CEP55, CHI3L1, CKAP2L, DEPDC1, DIAPH3, DLGAP5, E2F8, FGF1, NEK2, PBK, TOP2A, CCL3, CXCL8, DEPDC1, IL6, RETN, MMP2, LCN2, and OLR1) were classified as hub genes, and the remaining ones were classified as neighboring genes. Enrichment analysis showed the role of hub genes in various pathways such as immune-signaling pathways, including JAK-STAT signaling, interleukin signaling, protein kinase signaling, and toll-like receptor pathways associated with the symptoms reported in the LC condition. ZNF and MYBL TF-family were predicted as abundant TFs controlling hub genes' transcriptional machinery. Furthermore, OLR1 (PDB: 7XMP) showed stable interactions with the five shortlisted refined naturally occurring bioflavonoids, i.e., apigenin, amentoflavone, ilexgenin A, myricetin, and orientin compounds. The total binding energy pattern was observed, with amentoflavone being the top docked molecule (with a binding affinity of -8.3 kcal/mol) with the lowest total binding energy of -18.48 kcal/mol. In conclusion, our research has predicted the hub genes, their molecular pathways, and the potential inhibitors between EBV and LC potential pathogenic association. The in vivo or in vitro experimental methods could be utilized to functionally validate our findings, which would be helpful to cure LC or to prevent EBV reactivation. [ABSTRACT FROM AUTHOR]

Introduction: The advent of RNA sequencing (RNA-Seq) has significantly advanced our understanding of the transcriptomic landscape, revealing intricate gene expression patterns across biological states and conditions. However, the complexity and volume of RNA-Seq data pose challenges in identifying differentially expressed genes (DEGs), critical for understanding the molecular basis of diseases like cancer. Methods: We introduce a novel Machine Learning-Enhanced Genomic Data Analysis Pipeline (ML-GAP) that incorporates autoencoders and innovative data augmentation strategies, notably the MixUp method, to overcome these challenges. By creating synthetic training examples through a linear combination of input pairs and their labels, MixUp significantly enhances the model's ability to generalize from the training data to unseen examples. Results: Our results demonstrate the ML-GAP's superiority in accuracy, efficiency, and insights, particularly crediting the MixUp method for its substantial contribution to the pipeline's effectiveness, advancing greatly genomic data analysis and setting a new standard in the field. Discussion: This, in turn, suggests that ML-GAP has the potential to perform more accurate detection of DEGs but also offers new avenues for therapeutic intervention and research. By integrating explainable artificial intelligence (XAI) techniques, ML-GAP ensures a transparent and interpretable analysis, highlighting the significance of identified genetic markers. [ABSTRACT FROM AUTHOR]

Relapse remains a determinant of treatment failure and contributes significantly to mortality in acute myeloid leukemia (AML) patients. Despite efforts to understand AML progression and relapse mechanisms, findings on acquired gene mutations in relapse vary, suggesting inherent genetic heterogeneity and emphasizing the role of epigenetic modifications. We conducted a multi-omic analysis using Omni-C, ATAC-seq, and RNA-seq on longitudinal samples from two adult AML patients at diagnosis and relapse. Herein, we characterized genetic and epigenetic changes in AML progression to elucidate the underlying mechanisms of relapse. Differential interaction analysis showed significant 3D chromatin landscape reorganization between relapse and diagnosis samples. Comparing global open chromatin profiles revealed that relapse samples had significantly fewer accessible chromatin regions than diagnosis samples. In addition, we discovered that relapse-related upregulation was achieved either by forming new active enhancer contacts or by losing interactions with poised enhancers/potential silencers. Altogether, our study highlights the impact of genetic and epigenetic changes on AML progression, underlining the importance of multi-omic approaches in understanding disease relapse mechanisms and guiding potential therapeutic interventions. [ABSTRACT FROM AUTHOR]

Sahiwal cattle, known for their high milk yield, are propagated through artificial insemination (AI) using male germplasm, largely contingent on semen quality. Spermatozoa, produced in the testes, carry genetic information and molecular signals essential for successful fertilization. Seminal plasma, in addition to sperm, contains nano-sized lipid-bound extracellular vesicles (SP-EVs) that carry key biomolecules, including fertility-related miRNAs, which are essential for bull fertility. The current study focused on miRNA profiling of SP-EVs from high-fertile (HF) and low-fertile (LF) Sahiwal bulls. SP-EVs were isolated using size exclusion chromatography (SEC) and characterized by dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA). Western blotting detected the EV-specific protein markers TSG101 and CD63. The DLS analysis showed SP-EV sizes of 170-180 nm in HF and 130-140 nm in LF samples. The NTA revealed particle concentrations of 5.76 x 1010 to 5.86 x 1011 particles/mL in HF and 5.31 x 1010 to 2.70 x 1011 particles/mL in LF groups, with no significant differences in size and concentration between HF and LF. High-throughput miRNA sequencing identified 310 miRNAs in SP-EVs from both groups, with 61 upregulated and 119 downregulated in HF bull. Further analysis identified 41 miRNAs with significant fold changes and p-values, including bta-miR-1246, bta-miR-195, bta-miR-339b, and bta-miR-199b, which were analyzed for target gene prediction. Gene Ontology (GO) and KEGG pathway analyses indicated that these miRNAs target genes involved in transcription regulation, ubiquitin-dependent endoplasmic reticulum-associated degradation (ERAD) pathways, and signalling pathways. Functional exploration revealed that these genes play roles in spermatogenesis, motility, acrosome reactions, and inflammatory responses. qPCR analysis showed that bta-miR-195 had 80% higher expression in HF spermatozoa compared to LF, suggesting its association with fertility status (p < 0.05). In conclusion, this study elucidates the miRNA cargoes in SP-EVs as indicators of Sahiwal bull fertility, highlighting bta-miR-195 as a potential fertility factor among the various miRNAs identified. [ABSTRACT FROM AUTHOR]

Introduction: Hair cells (HCs) are the sensory receptors of the auditory and vestibular systems in the inner ears of vertebrates that selectively transduce mechanical stimuli into electrical activity. Although all HCs have the hallmark stereocilia bundle for mechanotransduction, HCs in non-mammals and mammals differ in their molecular specialization in the apical, basolateral, and synaptic membranes. HCs of non-mammals, such as zebrafish (zHCs), are electrically tuned to specific frequencies and possess an active process in the stereocilia bundle to amplify sound signals. Mammalian HCs, in contrast, are not electrically tuned and achieve amplification by somatic motility of outer HCs (OHCs). Methods: To understand the genetic mechanisms underlying differences between adult zebrafish and mammalian HCs, we compared their RNA-seq- characterized transcriptomes, focusing on protein-coding orthologous genes related to HC specialization. Results: There was considerable shared expression of gene orthologs among the HCs, including those genes associated with mechanotransduction, ion transport/channels, and synaptic signaling. However, there were some notable differences in expression among zHCs, OHCs, and inner HCs (IHCs), which likely underlie the distinctive physiological properties of each cell type. For example, OHCs highly express Slc26a5 which encodes the motor protein prestin that contributes toOHC electromotility. However, zHCs have only weak expression of slc26a5, and subsequently showed no voltage-dependent electromotility when measured. Notably, the zHCs expressed more paralogous genes including those associated with HC-specific functions and transcriptional activity, though it is unknown whether they have functions similar to their mammalian counterparts. There was overlap in the expressed genes associated with a known hearing phenotype. Discussion: Our analyses unveil substantial differences in gene expression patterns thatmay explain phenotypic specialization of zebrafish andmouse HCs. This dataset also includes several protein-coding genes to further the functional characterization of HCs and study of HC evolution from non-mammals to mammals. [ABSTRACT FROM AUTHOR]

Background: This study employed RNA-seq technology and meta-analysis to unveil the molecular mechanisms of neuropsychiatric systemic lupus erythematosus (NPSLE) within the central nervous system. Methods: Downloaded transcriptomic data on systemic lupus erythematosus (SLE) from the Gene Expression Omnibus (GEO) and analyzed differential genes in peripheral blood samples of NPSLE patients and healthy individuals. Employed WGCNA to identify key genes related to cognitive impairment and validated findings via RNA-seq. Conducted GO, KEGG, and GSEA analyses, and integrated PPI networks to explore gene regulatory mechanisms. Assessed gene impacts on dendritic cells and blood-brain barrier using RT-qPCR, ELISA, and in vitro models. Results: Public databases and RNA-seq data have revealed a significant upregulation of CCL2 (C-C motif chemokine ligand 2) in the peripheral blood of both SLE and NPSLE patients, primarily secreted by mature dendritic cells. Furthermore, the secretion of CCL2 by mature dendritic cells may act through the RSAD2-ISG15 axis and is associated with the activation of the NLRs (Nod Like Receptor Signaling Pathway) signaling pathway in vascular endothelial cells. Subsequent in vitro cell experiments confirmed the high expression of CCL2 in peripheral blood dendritic cells of NPSLE patients, with its secretion being regulated by the RSAD2-ISG15 axis and inducing vascular endothelial cell pyroptosis through the activation of the NLRs signaling pathway. Clinical trial results ultimately confirmed that NPSLE patients exhibiting elevated CCL2 expression also experienced cognitive decline. Conclusions: The secretion of CCL2 by dendritic cells induces pyroptosis in vascular endothelial cells, thereby promoting blood-brain barrier damage and triggering cognitive impairment in patients with systemic lupus erythematosus. [ABSTRACT FROM AUTHOR]

Introduction: Tobacco vein mottling virus (TVMV) is a member of the family Potyviridae. The 3' untranslated region (3'UTR) of viral genomic RNA has been reported to significantly impact viral infection. Nevertheless, the role of the TVMV 3'UTR during viral infection remains unknown. Methods: Here, a 3'UTR-GFP expression vector was transiently expressed in Nicotiana benthamiana, in which the 3'UTR of TVMV was introduced upstream of the green fluorescent protein (GFP) gene. Transcriptome sequencing was performed to analyze the genes associated with plant resistance. The effect of the TVMV 3'UTR on GFP expression was studied using an Agrobacteriummediated transient expression assay, revealing that the TVMV 3'UTR significantly inhibited GFP expression. Transcriptome analysis of differentially expressed genes in 3'UTR-GFP in N. benthamiana was performed to elucidate the why the TVMV 3'UTR inhibited GFP expression. Results: Eighty genes related to plant disease resistance were differentially expressed, including 29 upregulated and 51 downregulated genes. Significantly upregulated genes included those encoding the calcium-binding protein CML24, leucine-rich repeat receptor-like tyrosine-protein kinase, and respiratory burst oxidase homolog protein E. The significantly downregulated genes included calcium-binding protein 7, ethylene-responsive transcription factor 10, endoglucanase 5, and receptor-like protein kinase. Discussion: These findings indicate that the 3'UTR of TVMV may inhibit the expression of GFP gene by inducing the expression of plant resistance genes. This study provides a theoretical basis for further research on the function and mechanism of the TVMV 3'UTR. [ABSTRACT FROM AUTHOR]

Maize is one of the most successful crops in utilizing heterosis which significantly improves maize stresses resistance and yield. Drought is a destructive abiotic stress that significantly reduces crop yield, particularly in maize. Drought stress and rewatering frequently occur during the growth and development of maize; however, themolecular mechanisms of heterosis under drought stress and re-watering have rarely been systematically investigated. Zhengdan7137 and Zhengdan7153 are two maize hybrid varieties with robust heterosis, and separately belongs to the SS×NSS and Reid×Tangsipingtou heterotic groups. 54 transcriptomes of these two hybrids and their parental inbred lines were analyzed under well-watering (WW), waterdeficit (WD), and re-watering (RW) conditions using RNA-Seq. In this study, we identified 3,411 conserved drought response genes (CDRGs) and 3,133 conserved re-watering response genes (CRRGs) between Zhengdan7137 and Zhengdan7153. When comparing CDRGs and CRRGs to overdominance and underdominance genes, we identified 303 and 252 conservative drought response overdominance genes (DODGs) and underdominance genes (DUDGs), respectively, and 165 and 267 conservative re-watering response overdominance genes (RODGs) and underdominance genes (RUDGs), respectively. DODGs are involved in stress response-related processes, such as L-phenylalanine metabolism, carbohydrate metabolism, and heat response, whereas DUDGs are associated with glucose metabolism, pentose-phosphate shunt, and starch metabolism. RODGs and RUDGs contribute to the recovery of hybrids from drought stress by upregulating cell propagation and photosynthesis processes, and repressing stress response processes, respectively. It indicated overdominant and underdominant genes conservatively contributed to hybrid heterosis under drought stress. These results deepen our understanding of the molecular mechanisms of drought resistance, uncover conservative molecular mechanisms of heterosis under drought stress and re-watering, and provide potential targets for improving drought resistance in maize. [ABSTRACT FROM AUTHOR]

The terpene synthase (TPS) plays a pivotal roles in plant growth, development, and enhancing resilience against environmental stresses. Despite this, the bioinformatics analysis of the TPS family gene in soybean (Glycine max) is lacking. In this study, we investigated 36 GmTPS members in soybean, exhibiting a diverse range of protein lengths, spanning from 144 to 835 amino acids. A phylogenetic treewas constructed from these GmTPS genes revealed a classification into five distinct subgroups: Group1, Group2, Group3, Group4 and Group5. Notably, within each subgroup, we identified the motifs of GmTPS proteins were similar, although variations existed among different subfamilies. Gene duplication events analysis demonstrated that TPS genes expand differently in G. max, A. thaliana and O. sativa. Among, both tandem duplication and Whole genome duplication contributive to the expansion of TPS genes in G. max, and Whole genome duplication played amajor role. Moreover, the cis-element analysis suggested that TPS is related to hormone signals, plant growth and development and environmental stress. Yeast two-hybrid (Y2H) assay results indicated TPS protein may form heterodimer to function, or may form complex with P450 proteins to function. RNA-seq results revealed a higher expression of most GmTPS genes in flowers, suggesting their potential contribution to flower development. Collectively, these findings offer a provide a holistic knowledge of the TPS gene family in soybean and will facilitate further characterization of TPSs effectively. [ABSTRACT FROM AUTHOR]

Background: This study employed RNA-seq technology and meta-analysis to unveil the molecular mechanisms of neuropsychiatric systemic lupus erythematosus (NPSLE) within the central nervous system. Methods: Downloaded transcriptomic data on systemic lupus erythematosus (SLE) from the Gene Expression Omnibus (GEO) and analyzed differential genes in peripheral blood samples of NPSLE patients and healthy individuals. Employed WGCNA to identify key genes related to cognitive impairment and validated findings via RNA-seq. Conducted GO, KEGG, and GSEA analyses, and integrated PPI networks to explore gene regulatory mechanisms. Assessed gene impacts on dendritic cells and blood-brain barrier using RT-qPCR, ELISA, and in vitro models. Results: Public databases and RNA-seq data have revealed a significant upregulation of CCL2 (C-C motif chemokine ligand 2) in the peripheral blood of both SLE and NPSLE patients, primarily secreted by mature dendritic cells. Furthermore, the secretion of CCL2 by mature dendritic cells may act through the RSAD2-ISG15 axis and is associated with the activation of the NLRs (Nod Like Receptor Signaling Pathway) signaling pathway in vascular endothelial cells. Subsequent in vitro cell experiments confirmed the high expression of CCL2 in peripheral blood dendritic cells of NPSLE patients, with its secretion being regulated by the RSAD2-ISG15 axis and inducing vascular endothelial cell pyroptosis through the activation of the NLRs signaling pathway. Clinical trial results ultimately confirmed that NPSLE patients exhibiting elevated CCL2 expression also experienced cognitive decline. Conclusions: The secretion of CCL2 by dendritic cells induces pyroptosis in vascular endothelial cells, thereby promoting blood-brain barrier damage and triggering cognitive impairment in patients with systemic lupus erythematosus. [ABSTRACT FROM AUTHOR]

Intestinal organoids are valuable tools for investigating intestinal physiology and pathology ex vivo. In previous studies, intestinal organoids of commercial pigs have been developed. Here, we established intestinal organoids derived from Wuzhishan miniature pigs (WZS pigs), a unique kind of pig in the Hainan province of China. Three-dimensional (3D) intestinal organoids and organoid monolayers were developed and assessed. Furthermore, the susceptibility of organoid monolayers of WZS pigs to transmissible gastroenteritis virus (TGEV) was demonstrated. An RNA-seq analysis revealed that the TGEV infection stimulated antiviral and inflammatory immune responses in organoid monolayer models. The study implied the transmission risk of swine enteric coronavirus on WZS pigs and provided useful tools for further research on WZS pigs as laboratory miniature pig models. [ABSTRACT FROM AUTHOR]

Background: Peripheral inflammation is often associated with depressive disorders, and immunological biomarkers of depression remain a focus of investigation. Methods: We performed RNA-seq analysis of RNA transcripts of human peripheral blood mononuclear cells from a case-control study including subjects with self-reported depression in the pre-symptomatic state of major depressive disorder and analyzed differentially expressed genes (DEGs) and the frequency of intron retention (IR) using rMATS. Results: Among the statistically significant DEGs identified, the 651 upregulated DEGs were particularly enriched in the term "bacterial infection and phagocytosis", whereas the 820 downregulated DEGs were enriched in the terms "antigen presentation" and "T-cell proliferation and maturation". We also analyzed 158 genes for which the IR was increased (IncIR) and 211 genes for which the IR was decreased (DecIR) in the depressed subjects. Although the Gene Ontology terms associated with IncIR and DecIR were very similar to those of the up- and downregulated genes, respectively, IR genes appeared to be particularly enriched in genes with sensor functions, with a preponderance of the term "ciliary assembly and function". The observation that IR genes specifically interact with innate immunity genes suggests that immune-related genes, as well as cilia-related genes, may be excellent markers of depression. Re-analysis of previously published RNA-seq data from patients with MDD showed that common IR genes, particularly our predicted immune- and cilia-related genes, are commonly detected in populations with different levels of depression, providing validity for using IR to detect depression. Conclusion: Depression was found to be associated with activation of the innate immune response and relative inactivation of T-cell signaling. The DEGs we identified reflect physiological demands that are controlled at the transcriptional level, whereas the IR results reflect a more direct mechanism for monitoring protein homeostasis. Accordingly, an alteration in IR, namely IncIR or DecIR, is a stress response, and intron-retained transcripts are sensors of the physiological state of the cytoplasm. The results demonstrate the potential of relative IR as a biomarker for the immunological stratification of depressed patients and the utility of IR for the discovery of novel pathways involved in recovery from depression. [ABSTRACT FROM AUTHOR]

Introduction: The severity of Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often dictated by a range of comorbidities. A considerable literature suggests iron deficiency and iron overload may contribute to increased infection, inflammation and disease severity, although direct causal relationships have been difficult to establish. Methods: Here we generate iron deficient and iron loaded C57BL/6 J mice by feeding standard low and high iron diets, with mice on a normal iron diet representing controls. All mice were infected with a primary SARS-CoV-2 omicron XBB isolate and lung inflammatory responses were analyzed by histology, immunohistochemistry and RNA-Seq. Results: Compared with controls, iron deficient mice showed no significant changes in lung viral loads or histopathology, whereas, iron loaded mice showed slightly, but significantly, reduced lung viral loads and histopathology. Transcriptional changes were modest, but illustrated widespread dysregulation of inflammation signatures for both iron deficient vs. controls, and iron loaded vs. controls. Some of these changes could be associated with detrimental outcomes, whereas others would be viewed as beneficial. Discussion: Diet-associated iron deficiency or overload thus induced modest modulations of inflammatory signatures, but no significant histopathologically detectable disease exacerbations. [ABSTRACT FROM AUTHOR]

Various species of rhizobium establish compatible symbiotic relationships with soybean (Glycinemax) leading to the formation of nitrogen-fixing nodules in roots. The formation of functional nodules is mediated through complex developmental and transcriptional reprogramming that involves the activity of thousands of plant genes. However, host transcriptome that differentiate between functional or nonfunctional nodules remain largely unexplored. In this study, we investigated differential compatibilities between rhizobium strains (Bradyrhizobium diazoefficiens USDA110 Bradyrhizobium sp. strain LVM105) and cultivated and wild soybeans. The nodulation assays revealed that both USDA110 and LVM105 strains effectively nodulate G. soja but only USDA110 can form symbiotic relationships with Williams 82. LVM105 formed pseudonodules on Williams 82 that consist of a central nodule-like mass that are devoid of any rhizobia. RNA-seq data revealed that USDA110 and LVM105 induce distinct transcriptome programing in functional mature nodules formed on G. soja roots, where genes involved in nucleosome assembly, DNA replication, regulation of cell cycle, and defense responses play key roles. Transcriptome comparison also suggested that activation of genes associated with cell wall biogenesis and organization and defense responses together with downregulation of genes involved in the biosynthesis of isoprenoids and antioxidant stress are associated with the formation of non-functional nodules on Williams 82 roots. Moreover, our analysis implies that increased activity of genes involved in oxygen binding, amino acid transport, and nitrate transport differentiates between fully-developed nodules in cultivated versus wild soybeans. [ABSTRACT FROM AUTHOR]

Introduction: Reactive oxygen species (ROS) generation is a common disease defense mechanism in plants. However, it is unclear whether Citrus host activates defense response against Diaporthe citri causing citrus melanose disease by producing ROS, and the underlying molecular mechanisms are unknown. Methods: DAB staining and RNA-Seq technology were used to compare the active oxygen burst and differential gene expression, respectively, in uninfected and infected Citrus sinensis leaves at different time points during D. citri infection in vivo. The functions of CsRBOH (a significant DEG) were confirmed in N. benthamiana through the Agrobacterium-mediated transient expression system. Results: DAB staining indicated that C. sinensis initiated defense against D. citri infection within 24 h by generating ROS. Illumina sequencing revealed 25,557 expressed genes of C. sinensis. The most upregulated DEGs (n = 1,570) were identified 72 h after fungal inoculation (sample denoted as CD72). In the CD72 vs. Cs (samples at 0 h after fungal inoculation) comparison, the KEGG pathway category with the highest number of genes (n = 62) and most significant enrichment was Protein processing in endoplasmic reticulum, followed by Glutathione metabolism and MAPK signaling pathway-plant. GO analysis revealed that the DEGs of CD72 vs. Cs related to active oxygen burst and chitin recognition were significantly grouped into the regulation of biological processes and molecular functions, with GO terms including response to ROS, response to fungus, and oxidoreductase activity. Remarkably, CsRBOH was significantly enriched in the GO and KEGG analyses, and its expression pattern in qRT-PCR and DAB staining results were consistent. Among the 63 ROS-related DEGs, HSP genes and genes associated with the peroxidase family were highly significant as revealed by protein–protein interaction networks. Furthermore, ROS accumulation, cell death, and upregulation of defense-related genes were observed in N. benthamiana leaves with CsRBOH expressed through the Agrobacterium-mediated transient expression system. Conclusion: Our findings suggested that C. sinensis activates CsRBOH and ROSrelated genes, leading to ROS accumulation to resist the invasion by D. citri. This study laid the foundation for future research on molecular mechanisms and breeding of C. sinensis cultivars resistant to citrus melanose. [ABSTRACT FROM AUTHOR]

The tomato-potato psyllid, Bactericera cockerelli (Šulc), belonging to the Hemiptera order, is an insect pest of solanaceous crops and vectors a fastidious bacterium, Candidatus Liberibacter solanacearum (CLso), the presumptive causal agent of zebra chip and vein greening diseases in potatoes and tomatoes, respectively. The genome of B. cockerelli has been sequenced recently, providing new avenues to elucidate mechanistic insights into pathogenesis in vegetable crops. In this study, we performed RNA-sequencing of the critical psyllid organs (salivary glands and ovaries) involved in CLso pathology and transmission to host plants. Transcriptome analysis revealed differentially expressed genes and organ-specific enrichment of gene ontology (GO) terms related to metabolic processes, response to stress/stimulus, phagocytosis, proteolysis, endocytosis, and provided candidate genes encoding transcription factors (TFs). To examine gene regulatory networks across the psyllid organs under CLso(-) and CLso(+) conditions, we performed weighted gene co-expression network analysis (WGCNA), and unique modules differentiating the psyllid organs were identified. A comparative GO analysis of the unique gene modules revealed functional terms enriched in response to stress, gene regulation, and cell division processes in the ovaries. In contrast, respiration, transport, and neuronal transmission-related GO terms were enriched in the salivary glands. Altogether, this study reveals new insights into tissue-specific expression of the psyllid organs in the absence or presence of CLso bacterium. This knowledge can be leveraged to develop new pest and disease management strategies by delineating the regulatory networks involved in the psyllid-CLso interaction. [ABSTRACT FROM AUTHOR]

Introduction: Influenza A virus (IAV) infection is a global respiratory disease, which annually leads to 3-5 million cases of severe illness, resulting in 290,000-650,000 deaths. Additionally, during the past century, four global IAV pandemics have claimed millions of human lives. The epithelial lining of the trachea plays a vital role during IAV infection, both as point of viral entry and replication as well as in the antiviral immune response. Tracheal tissue is generally inaccessible from human patients, which makes animal models crucial for the study of the tracheal host immune response. Method: In this study, pigs were inoculated with swine- or human-adapted H1N1 IAV to gain insight into how host adaptation of IAV shapes the innate immune response during infection. In-depth multi-omics analysis (global proteomics and RNA sequencing) of the host response in upper and lower tracheal tissue was conducted, and results were validated by microfluidic qPCR. Additionally, a subset of samples was selected for histopathological examination. Results: A classical innate antiviral immune response was induced in both upper and lower trachea after infection with either swine- or human-adapted IAV with upregulation of genes and higher abundance of proteins associated with viral infection and recognition, accompanied by a significant induction of interferon stimulated genes with corresponding higher proteins concentrations. Infection with the swine-adapted virus induced a much stronger immune response compared to infection with a human-adapted IAV strain in the lower trachea, which could be a consequence of a higher viral load and a higher degree of inflammation. Discussion: Central components of the JAK-STAT pathway, apoptosis, pyrimidine metabolism, and the cytoskeleton were significantly altered depending on infection with swine- or human-adapted virus and might be relevant mechanisms in relation to antiviral immunity against putative zoonotic IAV. Based on our findings, we hypothesize that during host adaptation, IAV evolve to modulate important host cell elements to favor viral infectivity and replication. [ABSTRACT FROM AUTHOR]

This document is a data report on gene expression after hepatic portal vein ligation (PVL) in rats. It discusses the increasing incidence of primary liver cancer and the surgical interventions available. The report focuses on the technique of portal vein ligation in rats and its comparison to portal vein embolization. It also discusses the role of non-coding RNAs, particularly microRNAs, in liver biology and the potential for therapeutic targeting in liver diseases and surgical interventions. The document provides sequencing statistics for small RNA samples obtained from a study on hepatic perfusion and function in healthy and venous-ligated livers. The dataset is valuable for understanding the relationship between hepatic perfusion and gene expression, particularly for non-coding RNAs. The animal study was conducted ethically and the research was funded by the DFG within the Research Unit Programme FOR 5151 QuaLiPerF. The authors declare no conflicts of interest, except for one author who was employed by Oncgnostics GmbH. The claims expressed in the article are solely those of the authors and do not necessarily represent their affiliated organizations or the publisher. [Extracted from the article]

Asparagus (Asparagus officinalis L.) is an important vegetable crop in southern Ontario, Canada, where winter air and soil temperatures below 0°C are common. Consequently, cultivars growing in this area must possess winterhardiness and freezing tolerance for survival. Asparagus acquires freezing tolerance in the fall through cold acclimation and loses freezing tolerance in the spring through deacclimation. To understand the molecular bases of these processes, transcriptomic analysis (RNA-Seq) was conducted on two cultivars, one adapted, 'Guelph Millennium' (GM), and one unadapted, 'UC157' (UC), to the winter conditions of southern Ontario. RNA extracted from bud and rhizome tissues, sampled on three dates during early spring and late fall, was subjected to sequencing. In the fall, the numbers of differentially expressed (DE) genes at the second and third harvests increased, relative to the first harvest, in dormant buds and rhizomes as freezing tolerance of cultivars increased, and the majority of DE genes were downregulated. In spring, freezing tolerance decreased as plants deacclimated and most genes DE at second and third harvests were upregulated in both cultivars. GM had lower LT50 (lethal temperature at which 50% of plants die) values and hence higher freezing tolerance than UC on specific sampling dates during both spring and fall, and expression patterns of specific genes were correlated with LT50 differences. Functional analysis revealed that these genes were involved in carbohydrate metabolic process, plant hormone signal transduction (auxin and gibberellin), proline metabolism, biosynthesis of secondary metabolites, circadian rhythm, and late embryogenesis abundant proteins and could be associated with cold acclimation and deacclimation processes. These findings will help researchers understand the molecular mechanisms of freezing tolerance in asparagus, leading to breeding and genetic strategies to improve the trait. [ABSTRACT FROM AUTHOR]

Postherpetic neuralgia (PHN) is a common, severe, and hard-to-treat chronic pain condition in clinics. Although PHN is developed from herpes zoster (HZ), the developing mechanism is unknown. A previous study investigated blood metabolomic and proteomic profiling in patients with PHN and HZ. The current study aims to explore the blood transcriptomic signature of PHN compared to HZ patients. Whole blood from eight PHN and 15 HZ patients was used for RNA-Seq analysis. There were 82 and 1,788 genes detected specifically in the PHN and HZ groups, respectively. PHN-specific genes are involved in viral infection, lipid and carbohydrate metabolism, and immune response. For genes coexpressed in PHN and HZ patients, there were 407 differential expression genes (DEGs), including 205 upregulated (UP DEGs) and 202 downregulated (DOWN DEGs) in PHN compared to HZ groups. DEGs are involved in viral infection, type I interferon (IFN), and hemoglobin and oxygen carrier activity. UP DEGs are associated with regulatory T cells (Tregs), activated NK cells, and neutrophils, while DOWN DEGs are associated with Tregs, resting NK cells, and monocytes. The results suggest that the metabolism of lipid, glycan, and nucleotides, type I IFN signaling, and altered neutrophil activation are associated with and might contribute to the development of PHN in HZ. It is also suggested that persistent or altered activation of nonspecific immunity may contribute to the development of PHN from HZ. [ABSTRACT FROM AUTHOR]

Cd (cadmium) is a highly toxic heavy metal pollutant often present in soil and detrimentally impacting the production and quality of horticultural crops. Cd affects various physiological and biochemical processes in plants, including chlorophyll synthesis, photosynthesis, mineral uptake and accumulation, and hormonal imbalance, leading to cell death. The MYB family of transcription factors plays a significant role in plant response to environmental influences. However, the role of MYB116 in abiotic stress tolerance remains unclear. In this study, we reported that Chinese cabbage transcription factor BrMYB116 enhanced Cd stress tolerance in yeast. The expression level of BrMYB116 was increased by Cd stress in Chinese cabbage. Additionally, yeast cells overexpressing BrMYB116 showed improved Cd stress tolerance and reduced Cd accumulation. Moreover, we found that BrMYB116 interacted with facilitator of iron transport (FIT3) to enhance Cd stress tolerance. ChIP-qPCR results showed that ScFIT3 was activated through specific binding to its promoter. Additionally, the overexpression of ScFIT3 induced Cd stress tolerance and reduced Cd accumulation in yeast and Chinese cabbage. These results suggest new avenues for plant genomic modification to mitigate Cd toxicity and enhance the safety of vegetable production. [ABSTRACT FROM AUTHOR]

Camellia drupifera, a significant woody oil crop in southern China, produces oil from its fruit seeds. Understanding sugar metabolism enzyme regulation is crucial for sugar accumulation and oil synthesis in fruit organs. This study examines the dynamic changes in sugar metabolism across four developmental stages of C. drupifera fruits, from rapid fruit enlargement to oil conversion. We analyzed sugar content, enzyme activity, and transcriptomic data to identify key periods and mechanisms involved in sugar metabolism. Our findings indicate that photosynthetic products are rapidly transported from leaves to fruit organs after synthesis, with transport efficiency decreasing significantly after 48 hours. September was identified as a critical period for oil conversion, during which the highest sucrose levels and SuSy-II enzyme activity were detected in the kernels. A positive correlation was found between high expression of ten genes related to sugar metabolism enzymes and sugar transport proteins and sucrose content. Notably, the expression levels of c158337.graph_c0 (SPS), c166323.graph_c0 (SuSy), c159295.graph_c0 (SUC2-like), and c156402.graph_c0 (SUC2-like) significantly increased during the oil conversion phase.These findings provide a crucial theoretical foundation for elucidating the molecular mechanisms of sugar metabolism in C. drupifera fruits, offering insights that could enhance its economic yield. [ABSTRACT FROM AUTHOR]

Introduction: Chronic inflammation of the gastrointestinal tissues underlies gastrointestinal inflammatory disorders, leading to tissue damage and a constellation of painful and debilitating symptoms. These disorders include inflammatory bowel diseases (Crohn's disease and ulcerative colitis), and eosinophilic disorders (eosinophilic esophagitis and eosinophilic duodenitis). Gastrointestinal inflammatory disorders can often present with overlapping symptoms necessitating the use of invasive procedures to give an accurate diagnosis. Methods: This study used peripheral blood mononuclear cells from individuals with Crohn's disease, ulcerative colitis, eosinophilic esophagitis, and eosinophilic duodenitis to better understand the alterations to the transcriptome of individuals with these diseases and identify potentialmarkers of active inflammation within the peripheral blood of patients that may be useful in diagnosis. Single-cell RNAsequencing was performed on peripheral blood mononuclear cells isolated from the blood samples of pediatric patients diagnosed with gastrointestinal disorders, including Crohn's disease, ulcerative colitis, eosinophilic esophagitis, eosinophilic duodenitis, and controls with histologically healthy gastrointestinal tracts. Results: We identified 730 (FDR < 0.05) differentially expressed genes between individuals with gastrointestinal disorders and controls across eight immune cell types. Discussion: There were common patterns among GI disorders, such as the widespread upregulation of MTRNR2L8 across cell types, and many differentially expressed genes showed distinct patterns of dysregulation among the different gastrointestinal diseases compared to controls, including upregulation of XIST across cell types among individuals with ulcerative colitis and upregulation of Th2-associated genes in eosinophilic disorders. These findings indicate both overlapping and distinct alterations to the transcriptome of individuals with gastrointestinal disorders compared to controls, which provide insight as to which genes may be useful as markers for disease in the peripheral blood of patients. [ABSTRACT FROM AUTHOR]

Introduction: Fusarium wilt (FW) caused by Fusarium oxysporum f. sp. cucumerinum (Foc) is a destructive soil-borne disease in cucumber (Cucumis sativus. L). However, there remains limited knowledge on the molecular mechanisms underlying FW resistance-mediated defense responses in cucumber. Methods: In this study, metabolome and transcriptome profiling were carried out for two FW resistant (NR) and susceptible (NS), near isogenic lines (NILs) before and after Foc inoculation. NILs have shown consistent and stable resistance in multiple resistance tests conducted in the greenhouse and in the laboratory. A widely targeted metabolomic analysis identified differentially accumulated metabolites (DAMs) with significantly greater NR accumulation in response to Foc infection, including many phenolic acid and flavonoid compounds from the flavonoid biosynthesis pathway. Results: Transcriptome analysis identified differentially expressed genes (DEGs) between the NILs upon Foc inoculation including genes for secondary metabolite biosynthesis and transcription factor genes regulating the flavonoid biosynthesis pathway. Joint analysis of the metabolomic and transcriptomic data identified DAMs and DEGs closely associated with the biosynthesis of phenolic acid and flavonoid DAMs. The association of these compounds with NRconferred FW resistance was exemplified by in vivo assays. These assays found two phenolic acid compounds, bis (2-ethylhexyl) phthalate and diisooctyl phthalate, as well as the flavonoid compound gallocatechin 3-O-gallate to have significant inhibitory effects on Foc growth. The antifungal effects of these three compounds represent a novel finding. Discussion: Therefore, phenolic acids and flavonoids play important roles in NR mediated FW resistance breeding in cucumber. [ABSTRACT FROM AUTHOR]

Huntington's disease (HD) is a rare genetic neurodegenerative disorder caused by an expansion of CAG repeats in the Huntingtin (HTT) gene. One hypothesis suggests that the mutant HTT gene contributes to HD neuropathology through transcriptional dysregulation involving microRNAs (miRNAs). In particular, the miR-132/212 cluster is strongly diminished in the HD brain. This study explores the effects of miR-132/212 deficiency specifically in adult HD zQ175 mice. The absence of miR-132/212 did not impact body weight, body temperature, or survival rates. Surprisingly, miR-132/212 loss seemed to alleviate, in part, the effects on endogenous Htt expression, HTT inclusions, and neuronal integrity in HD zQ175 mice. Additionally, miR-132/212 depletion led to age-dependent improvements in certain motor functions. Transcriptomic analysis revealed alterations in HD-related networks in WT- and HD zQ175-miR-132/212-deficient mice, including significant overlap in BDNF and Creb1 signaling pathways. Interestingly, however, a higher number of miR-132/212 gene targets was observed in HD zQ175 mice lacking the miR-132/212 cluster, especially in the striatum. These findings suggest a nuanced interplay between miR-132/212 expression and HD pathogenesis, providing potential insights into therapeutic interventions. Further investigation is needed to fully understand the underlying mechanisms and therapeutic potential of modulating miR-132/212 expression during HD progression. [ABSTRACT FROM AUTHOR]

Plant height (PH) is a crucial trait for strengthening lodging resistance and boosting yield in foxtail millet. To identify quantitative trait loci (QTL) and candidate genes associated with PH, we first developed a genetic map using a recombinant inbred line (RIL) population derived from a cross between Aininghuang and Jingu 21. Then, PH phenotyping data and four variations of best linear unbiased prediction (BLUP) were collected from nine environments and three development stages. Next, QTL mapping was conducted using both unconditional and conditional QTL methods. Subsequently, candidate genes were predicted via transcriptome analysis of parental samples at three developmental stages. The results revealed that the genetic map, based on re-sequencing, consisted of 4,360 bin markers spanning 1,016.06 cM with an average genetic distance of 0.23 cM. A total of 19 unconditional QTL, accounting for 5.23%–35.36% of the phenotypic variation explained (PVE), which included 7 major and 4 stable QTL, were identified. Meanwhile, 13 conditional QTL, explaining 5.88%–40.35% of PVE, including 5 major and 3 stable QTL, were discovered. Furthermore, four consistent and stable QTL were identified. Finally, eight candidate genes were predicted through RNA-seq and weighted gene co-expression network analysis (WGCNA). Those findings provide a crucial foundation for understanding the genetic mechanisms underlying PH development and facilitate molecular marker-assisted breeding of ideal plant types in foxtail millet. [ABSTRACT FROM AUTHOR]

Introduction: The deregulation of lncRNAs expression has been associated with neuronal damage in Alzheimer's disease (AD), but how or whether they can influence its onset is still unknown. We investigated 2 RNA-seq datasets consisting, respectively, of the hippocampal and fusiform gyrus transcriptomic profile of AD patients, matched with non-demented controls. Methods: We performed a differential expression analysis, a gene correlation network analysis (WGCNA) and a pathway enrichment analysis of two RNA-seq datasets. Results: We found deregulated lncRNAs in common between hippocampus and fusiform gyrus and deregulated gene groups associated to functional pathways related to neurotransmission and memory consolidation. lncRNAs, co-expressed with known AD-related coding genes, were identified from the prioritized modules of both brain regions. Discussion: We found common deregulated lncRNAs in the AD hippocampus and fusiform gyrus, that could be considered common signatures of AD pathogenesis, providing an important source of information for understanding the molecular changes of AD. [ABSTRACT FROM AUTHOR]

Background: An accumulating body of research indicates that the pons is related to the occurrence of depression. Si-Ni-San (SNS) is a well-known Chinese herbal formula that is used to treat depression. Chinese herbal formulae have multiple therapeutic characteristics. Although it has been proven that SNS can exert antidepressant effects by improving changes in the limbic system, it is currently unclear whether SNS has therapeutic targets in the pons. This study aimed to explore the therapeutic targets of SNS in the pons for depression treatment. Materials and methods: Two experiments were conducted. In Experiment 1, 32 rats were divided into four groups: (1) a Control (C) group that received distilled water as a vehicle; (2) a Model (M) group that received the chronic unpredictable mild stress (CUMS) procedure and was administered distilled water; (3) a Stress + SNS (MS) group that received the CUMS procedure and was administered SNS dissolved in distilled water; and (4) a Stress + Fluoxetine (MF) group that received the CUMS procedure and was administered fluoxetine dissolved in distilled water. The open field test (OFT), the sucrose preference test (SPT), and the novel object recognition test (NOR) were performed to test the antidepressant effects of SNS. High-throughput mRNA sequencing (RNA-seq) was used to explore possible gene targets of SNS in the pons, and quantitative real-time PCR was performed to verify the results. High-performance liquid chromatography was used to detect neurotransmitters. Finally, correlation analyses were conducted between behaviors, genes expression, and neurotransmitters. In Experiment 2, 18 rats were divided into the same three groups as in Experiment 1: (1) C, (2) M, and (3) MS. fMRI was used to confirm whether SNS altered the pons in a rat model of depression. Results: SNS significantly improved sucrose preference in the SPT and TN-TO in the NOR compared to the M group (P < 0.05). RNA-seq filtered 49 differentially expressed genes(DEGs) that SNS could reverse in the pons of the CUMS depression model. Real-time PCR detected six genes, including Complexin2 (Cplx2), Serpinf1, Neuregulin1 (Nrg1), Annexin A1 (Anxa1), β-arrestin 1 (Arrb1) and presenilin 1 (Psen1). SNS significantly reversed changes in the expression of Anxa1, Nrg1, and Psen1 caused by CUMS (P < 0.05), which is consistent with the DEGs results. Additionally, SNS significantly reversed norepinephrine (NE) changes in the pons. There were 18 noteworthy correlations between behavior, genes, and neurotransmitters (P < 0.05). fMRI showed that SNS can decrease the amplitude of low-frequency fluctuations (ALFF) in the pons of living depressed rats. Conclusion: The pons is an important target brain region for SNS to exert its antidepressant effects. SNS may improve pontine NE levels by regulating the Anxa1, Nrg1, and Psen1 genes, thereby exerting antidepressant effects and improving cognitive function. [ABSTRACT FROM AUTHOR]

Aluminum hydroxide has long been employed as a vaccine adjuvant for its safety profile, although its precise mechanism of action remains elusive. In this study, we investigated the transcriptomic responses in sheep spleen following repetitive vaccination with aluminum adjuvanted vaccines and aluminum hydroxide alone. Notably, this work represents the first exploration of the sheep spleen transcriptome in such conditions. Animals were splitted in 3 treatment groups: vaccine group, adjuvant alone group and control group. A total of 18 high-depth RNA-seq libraries were sequenced, resulting in a rich dataset which also allowed isoform-level analysis. The comparisons between vaccine-treated and control groups (V vs C) as well as between vaccine-treated and adjuvant-alone groups (V vs A) revealed significant alterations in gene expression profiles, including protein coding genes and long non-coding RNAs. Among the differentially expressed genes, many were associated with processes such as endoplasmic reticulum (ER) stress, immune response and cell cycle. The analysis of co-expression modules further indicated a correlation between vaccine treatment and genes related to ER stress and unfolded protein response. Surprisingly, adjuvant-alone treatment had little impact on the spleen transcriptome. Additionally, the role of alternative splicing in the immune response was explored. We identified isoform switches in genes associated with immune regulation and inflammation, potentially influencing protein function. In conclusion, this study provides valuable insights into the transcriptomic changes in sheep spleen following vaccination with aluminum adjuvanted vaccines and aluminum hydroxide alone. These findings shed light on the molecular mechanisms underlying vaccine-induced immune responses and emphasize the significance of antigenic components in aluminum adjuvant mechanism of action. Furthermore, the analysis of alternative splicing revealed an additional layer of complexity in the immune response to vaccination in a livestock species. [ABSTRACT FROM AUTHOR]

Introduction: Glycyrrhiza uralensis Fisch, a traditional Chinese medicinal herb known for its diverse pharmacological effects including heat-clearing, detoxification, phlegm dissolving, and cough relief, has experienced an exponential increase in demand due to its expanding clinical use and development prospects. Currently, large-scale cell culture stands out as one of the most promising biotechnological approaches for producing bioactive compounds from medicinal plants. However, the problem of cell browning represents a significant bottleneck in industrial applications of cell culture. Methods: This study focuses on the Glycyrrhiza uralensis Fisch cells from the Ordos plateau, aiming to elucidate the enzymatic browning process during plant cell culture. Key substrates and genes involved in enzymatic browning were identified by metabolome and transcriptome analysis of normal and browning cells. Results: Metabolome analysis reveals significant changes in the levels of chalcone, isoflavone, imidazole-pyrimidine, purine nucleosides, organic oxides, carboxylic acids and their derivatives, benzene and its derivatives, flavonoids, 2-arylated benzofuran flavonoids, diazanaphthalenes and fatty acyls within browning cells. In particular, chalcones, isoflavones, and flavones compounds account for a higher proportion of these changes. Furthermore, these compounds collectively show enrichment in four metabolic pathways: Isoflavone biosynthesis pathway; Cutin suberine and wax biosynthesis pathway; Aminoacyl-tRNA biosynthesis pathway; Isoquinoline alkaloid biosynthesis pathway; Transcriptome analysis revealed that the MYB transcription factor is a key regulator of flavonoid synthesis during the browning process in cells. In addition, 223 differentially expressed genes were identified, including phenylpropane, shikimic acid, glycolysis, and pentose phosphate pathways. Among these genes, 23 are directly involved in flavonoid biosynthesis; qPCR validation showed that eight genes (GlPK, GlPAL, Gl24CL, Gl1PDT, Gl3CHI, GlC4H, Gl2F3'H, and Gl2CCR) were up-regulated in browning cells compared to normal cells. These findings corroborate the sequencing results and underscore the critical role of these genes in cellular browning. Discussion: Consequently, modulation of their expression offers promising strategies for effective control of cellular browning issues. [ABSTRACT FROM AUTHOR]

Introduction: The advancement of high-throughput, high-quality, flexible, and cost-effective genotyping platforms is crucial for the progress of dairy breeding in Bactrian camels. This study focuses on developing and evaluating a 1K functional liquid single nucleotide polymorphism (SNP) array specifically designed for milk performance in Bactrian camels. Methods: We utilized RNA sequencing data from 125 lactating camels to identify and select 1,002 loci associated with milk production traits for inclusion in the SNP array. The array's performance was then assessed using 24 randomly selected camels. Additionally, the array was employed to genotype 398 individuals, which allowed for population validation to assess the polymorphism of SNP sites. Results: The SNP array demonstrated high overall SNP call rates (> 99%) and a remarkable 100% consistency in genotyping. Population validation results indicate that camels from six breeding areas in Northwest China share a similar genetic background regarding lactation functionality. Discussion: This study highlights the potential of the SNP array to accelerate the breeding process of lactating Bactrian camels and provides a robust technical foundation for improving lactation performance. [ABSTRACT FROM AUTHOR]

This study investigated how gene expression is affected by dietary fatty acids (FA) by using pigs as a reliable model for studying human diseases that involve lipid metabolism. This includes changes in FA composition in the liver, blood serum parameters and overall metabolic pathways. RNA-Seq data from 32 pigs were analyzed using Weighted Gene Co-expression Network Analysis (WGCNA). Our aim was to identify changes in blood serum parameters and gene expression between diets containing 3% soybean oil (SOY3.0) and a standard pig production diet containing 1.5% soybean oil (SOY1.5). Significantly, both the SOY1.5 and SOY3.0 groups showed significant modules, with a higher number of coexpressed modules identified in the SOY3.0 group. Correlated modules and specific features were identified, including enriched terms and pathways such as the histone acetyltransferase complex, type I diabetes mellitus pathway, cholesterol metabolism, and metabolic pathways in SOY1.5, and pathways related to neurodegeneration and Alzheimer's disease in SOY3.0. The variation in co-expression observed for HDL in the groups analyzed suggests different regulatory patterns in response to the higher concentration of soybean oil. Key genes co-expressed with metabolic processes indicative of diseases such as Alzheimer's was also identified, as well as genes related to lipid transport and energy metabolism, including CCL5, PNISR, DEGS1. These findings are important for understanding the genetic and metabolic responses to dietary variation and contribute to the development of more precise nutritional strategies. [ABSTRACT FROM AUTHOR]

Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome (PUUVHFRS) is characterized by strong neutrophil activation. Neutrophils are the most abundant immune cell type in the circulation and are specially equipped to rapidly respond to infections. They are more heterogenous than previously appreciated, with specific neutrophil subsets recently implicated in inflammation and immunosuppression. Furthermore, neutrophils can be divided based on their density to either low-density granulocytes (LDGs) or "normal density" polymorphonuclear cell (PMN) fractions. In the current study we aimed to identify and characterize the different neutrophil subsets in the circulation of PUUV-HFRS patients. PMNs exhibited an activation of antiviral pathways, while circulating LDGs were increased in frequency following acute PUUV-HFRS. Furthermore, cell surface marker expression analysis revealed that PUUV-associated LDGs are primarily immature and most likely reflect an increased neutrophil production from the bone marrow. Interestingly, both the frequency of LDGs and the presence of a "left shift" in blood associated with the extent of thrombocytopenia, one of the hallmarks of severe HFRS, suggesting that maturing neutrophils could play a role in disease pathogenesis. These results imply that elevated circulating LDGs might be a general finding in acute viral infections. However, in contrast to the COVID-19 associated LDGs described previously, the secretome of PUUV LDGs did not show significant immunosuppressive ability, which suggests inherent biological differences in the LDG responses that can be dependent on the causative virus or differing infection kinetics. [ABSTRACT FROM AUTHOR]

Background: A high-fat diet (HFD) contributes to various metabolic disorders and obesity, which are major contributors to cardiovascular disease. As an essential regulator for heart homeostasis, cardiac resident macrophages may go awry and contribute to cardiac pathophysiology upon HFD. Thus, to better understand how HFD induced cardiac dysfunction, this study intends to explore the transcriptional and functional changes in cardiac resident macrophages of HFD mice. Methods: C57BL/6J female mice that were 6 weeks old were fed with HFD or normal chow diet (NCD) for 16 weeks. After an evaluation of cardiac functions by echocardiography, mouse hearts were harvested and cardiac resident CCR2- macrophages were sorted, followed by Smart sequencing. Bioinformatics analysis including GO, KEGG, and GSEA analyses were employed to elucidate transcriptional and functional changes. Results: Hyperlipidemia and obesity were observed easily upon HFD. The mouse hearts also displayed more severe fibrosis and diastolic dysfunction in HFD mice. Smart sequencing and functional analysis revealed metabolic dysfunctions, especially lipid-related genes and pathways. Besides this, antigenpresentation-related gene such as Ctsf and inflammation, particularly for NFkB signaling and complement cascades, underwent drastic changes in cardiac resident macrophages. GO cellular compartment analysis was also performed and showed specific organelle enrichment trends of the involved genes. Conclusion: Dysregulated metabolism intertwines with inflammation in cardiac resident macrophages upon HFD feeding in mice, and further research on crosstalk among organelles could shed more light on potential mechanisms. [ABSTRACT FROM AUTHOR]

Senecavirus A (SVA) is an emerging virus that causes the vesicular disease in pigs, clinically indistinguishable from other high consequence vesicular diseases. This virus belongs to the genus Senecavirus in the family Picornaviridae. Its genome is a positive-sense, single-stranded RNA, approximately 7,300 nt in length, with a 3' poly(A) tail but without 5'-end capped structure. SVA can efficiently propagate in different cells, including some non-pig-derived cell lines. A wildtype SVA was previously rescued from its cDNA clone using reverse genetics in our laboratory. In the present study, the BSR-T7/5 cell line was inoculated with the passage-5 SVA. At 12 h post-inoculation, SVA-infected and noninfected cells were independently collected for the analysis on comparative transcriptomics. The results totally showed 628 differentially expressed genes, including 565 upregulated and 63 downregulated ones, suggesting that SVA infection significantly stimulated the transcription initiation in cells. GO and KEGG enrichment analyses demonstrated that SVA exerted multiple effects on immunity-related pathways in cells. Furthermore, the RNA sequencing data were subjected to other in-depth analyses, such as the single-nucleotide polymorphism, transcription factors, and protein-protein interactions. The present study, along with our previous proteomics and metabolomics researches, provides a multi-omics insight into the interaction between SVA and its hosts. [ABSTRACT FROM AUTHOR]

Introduction: Plumbagin is an important phytochemical and has been reported to exhibit potent larvicidal activity against several insect pests, However, the insecticidal mechanism of plumbagin against pests is still poorly understood. This study aimed to investigate the insecticidal activities of plumbagin and the underlying molecular mechanisms against a devastating agricultural pest, the fall armyworm Spodoptera frugiperda. Methods: The effects of plumbagin on S. frugiperda larval development and the activities of two detoxification enzymes were initially examined. Next, transcriptomic changes in S. frugiperda after plumbagin treatment were investigated. Furthermore, RNA-seq results were validated by qPCR. Results: Plumbagin exhibited a high larvicidal activity against the second and third instar larvae of S. frugiperda with 72 h LC50 of 0.573 and 2.676 mg/g, respectively. The activities of the two detoxification enzymes carboxylesterase and P450 were significantly increased after 1.5 mg/g plumbagin treatment. Furthermore, RNA-seq analysis provided a comprehensive overview of complex transcriptomic changes in S. frugiperda larvae in response to 1.5 mg/g plumbagin exposure, and revealed that plumbagin treatment led to aberrant expression of a large number of genes related to nutrient and energy metabolism, humoral immune response, insect cuticle protein, chitin-binding proteins, chitin synthesis and degradation, insect hormone, and xenobiotic detoxification. The qPCR results further validated the reproducibility and reliability of the transcriptomic data. Discussion: Our findings provide a valuable insight into understanding the insecticidal mechanism of the phytochemical plumbagin. [ABSTRACT FROM AUTHOR]