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Fasting is a common phenomenon caused by environmental factors. Here, changes in growth, serum biochemical parameters, intestinal microbiota, and liver transcriptome were investigated of Pseudobagrus vachellii subjected to fasting and refeeding. Fasting resulted in a significant decrease in body weight, but a compensatory growth occurred after refeeding. Serum biochemical indices including triglycerides, glucose, urea nitrogen, aspartate transaminase, and alanine transaminase were strongly affected by fasting and refeeding. Large amounts of glucose and fat were utilised during fasting, and liver functions can be returned to normal in P. vachellii after refeeding. 16 S rDNA analysis showed that fasting altered intestinal microbiota homeostasis and decreased intestinal α-diversity. At the phylum level, the dominant phyla were Proteobacteria, Firmicutes, Fusobacteriota, and Bacteroidota. Additionally, fasting significantly increased the abundance of the genera Plesiomonas, Edwardsiella, and Barnesiellaceae, whereas Romboutsia abundance decreased, indicating an increase in opportunistic pathogen abundance. However, after 7 days of refeeding, the composition of the gut microbiota was partially recovered. Additionally, the transcriptome analysis of the liver tissues showed that most of the identified DEGs, such as ACACA, FASN, Akt3, SCDb, and FADS2, were related to energy- and metabolism-related pathways, including fatty acid metabolism, glucagon-signalling pathway, AMPK-signalling pathway, apoptosis, carbon metabolism, and oxidative phosphorylation. Many DEGs detected during fasting were restored to normal levels after refeeding. These findings provide an important theoretical basis for future investigation of the fish physiological and ecological mechanisms underlying adaptations to food restriction. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis is the causative agent of the disease, tuberculosis. The most researched clinical strain of Mycobacterium tuberculosis is H37Rv. To identify possible therapeutic targets, in-silico analyses of the Mycobacterium tuberculosis H37Rv genome were carried out. The genome sequence was downloaded from the website of NCBI (National Center for Biotechnology Information). The DEG (Database of Essential Genes) was consulted to identify essential genes. Additionally, homology searches with the human genome were conducted using BLASTX. Out of a total of 3924 genes, 594 were determined to be essential for Mycobacterium tuberculosis, of which 366 had no sequence similarity to the human genome. Out of 366 genes, 242 potential drug targets have been found after being screened for fictitious and unidentified genes. After functional analysis of these 242 possible targets using Uniprot, 181 of them were identified as potential drug targets. Among the 181 target genes, 42 were related to amino acid biosynthesis, 22 were related to cell wall biosynthesis, 19 to translation, 12 to transcription, 7 to lipid metabolism, 7 to carbohydrate metabolism, etc. [ABSTRACT FROM AUTHOR]

Atherosclerosis, a lipid‐driven chronic inflammatory disorder, is a significant global health concern associated with high rates of morbidity and mortality, imposing a substantial societal burden. The purpose of this study is to investigate the possible molecular mechanisms of atherosclerosis and identify potential therapeutic targets. We conducted an integrated bioinformatics analysis using data from peripheral blood mononuclear cell and TISSUE databases obtained from the Gene Expression Omnibus, to identify key genes associated with the progression of atherosclerosis. Here, IRF8 was found to be a key gene in atherosclerosis patients. Silencing IRF8 with small interfering RNA reduced inflammation in endothelial cells. This suggests IRF8 is a crucial biomarker for immune infiltration in atherosclerosis advance. [ABSTRACT FROM AUTHOR]

Background: Neutrophil extracellular traps (NETs) are related to the prognosis of cancer patients. Nevertheless, the potential prognostic values of NETs in skin cutaneous melanoma (SKCM) remains largely unknown. Materials and methods: The NET‐related gene signature was constructed by LASSO Cox regression analysis using the TCGA‐SKCM cohort. The overall survival (OS) and immune status in SKCM patients between the high‐ and low‐NET score (high‐score, low‐score) groups were explored. The scRNA‐seq dataset GSE115978 was used to understand the role of NET score in SKCM at single cell resolution. Results: A five NET genes‐based signature (TLR2, CLEC6A, PDE4B, SLC22A4 and CYP4F3) was constructed as the NET‐related prognostic model for SKCM. The OS of SKCM patients with low‐score was better than that in patients with high‐score. Additionally, NET score was negatively associated with infiltration of some immune cells (e.g. type I Macrophages, CD8‐T cells, CD4‐T cells). Moreover, patients with high‐score had low stromal, immune and ESTIMATE scores. Furthermore, drug sensitivity analysis results showed that Lapatinib, Trametinib and Erlotinib may have better therapeutic advantages in patients with high‐score. Conclusion: We established a NET‐related five gene signature in SKCM and found that the NET‐related signature may exhibit a good predictive ability for SKCM prognosis. The NET score may not only predict the survival outcome and drug sensitivity in SKCM, but also reflect the immune conditions of SKCM patients. [ABSTRACT FROM AUTHOR]

Background: The genes involved in cephalopod development and their association with hatching and survival during early life stages have been extensively studied. However, few studies have investigated the paralarvae transcriptome of the East Asian common octopus (Octopus sinen sis). Objective: This study aimed to identify the genes related to embryonic development and hatching in O. sinensis using RNA sequencing (RNA-seq) and verify the genes most relevant to different embryonic stages. Methods: RNA samples from hatched and 25 days post-hatching (dph) O. sinensis paralarvae were used to construct cDNA libraries. Clean reads from individual samples were aligned to the reference O. sinensis database to identify the differentially expressed genes (DEGs) between the 0- and 25-dph paralarvae libraries. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to supplement the RNA-seq data for embryogenic developmental stages. Results: A total of 12,597 transcripts were annotated and 5,468 DEGs were identified between the 0- and 25-dph O. sinensis paralarvae, including 2,715 upregulated and 2,753 downregulated transcripts in the 25-dph paralarvae. Several key DEGs were related to transmembrane transport, lipid biosynthesis, monooxygenase activity, lipid transport, neuropeptide signaling, transcription regulation, and protein-cysteine S-palmitoyltransferase activity during the post-hatching development of O. sinensis paralarvae. RT-qPCR analysis further revealed that SLC5A3A, ABCC12, and NPC1 transcripts in 20 and/or 30 days post-fertilization (dpf) embryos were significantly higher (p < 0.05) than those in 10-dpf embryos. Conclusion: Transcriptome profiles provide molecular targets to understand the embryonic development, hatching, and survival of O. sinensis paralarvae, and enhance octopus production. [ABSTRACT FROM AUTHOR]

Background: Both bacterial and viral diseases are a major threat to farmed fish. As the antiviral immune mechanisms in lumpfish (Cyclopterus lumpus L.) are poorly understood, lumpfish leukocytes were stimulated with poly(I:C), a synthetic analog of double stranded RNA, which mimic viral infections, and RNA sequencing was performed. Methods: To address this gap, we stimulated lumpfish leukocytes with poly(I:C) for 6 and 24 hours and did RNA sequencing with three parallels per timepoint. Genome guided mapping was performed to define differentially expressed genes (DEGs). Results: Immune genes were identified, and transcriptome-wide analyses of early immune responses showed that 376 and 2372 transcripts were significantly differentially expressed 6 and 24 hours post exposure (hpe) to poly(I:C), respectively. The most enriched GO terms when time had been accounted for, were immune system processes (GO:0002376) and immune response (GO:0006955). Analysis of DEGs showed that among the most highly upregulated genes were TLRs and genes belonging to the RIG-I signaling pathway, including LGP2, STING and MX, as well as IRF3 and IL12A. RIG-I was not identified, but in silico analyses showed that genes encoding proteins involved in pathogen recognition, cell signaling, and cytokines of the TLR and RIG-I signaling pathway are mostly conserved in lumpfish when compared to mammals and other teleost species. Conclusions: Our analyses unravel the innate immune pathways playing a major role in antiviral defense in lumpfish. The information gathered can be used in comparative studies and lay the groundwork for future functional analyses of immune and pathogenicity mechanisms. Such knowledge is also necessary for the development of immunoprophylactic measures for lumpfish, which is extensively cultivated for use as cleaner fish in the aquaculture for removal of sea lice from Atlantic salmon (Salmo salar L.). [ABSTRACT FROM AUTHOR]

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The brain and liver of mandarin fish (Siniperca chuatsi) produce essential hormones for their growth and development. However, the mechanisms underlying the interplay of these hormones remain unclear. This study aimed to assess the slow – and fast-growing traits, including body weight and length of mandarin fish reared in a single pond. To compare the differentially expressed genes (DEGs) in slow – and fast-growing fishes, we performed RNA sequencing analysis. After assembling the clean reads, 192,280 transcripts and 100,416 unigenes were obtained. 344 and 845 DEGs in the brain and liver in the fast-and slow-growing group were annotated respectively. These DEGs were associated with signaling pathways involved in growth and development, such as AGE-RAGE, Transforming growth factor-β/Smad, Mitogen-activated protein kinase, Wingless/Integrated, and Insulin-like growth factor (IGF) 1. Furthermore, our fasting experiment revealed a concurrent decrease in body weight and the expression levels of genes related to the growth hormone (GH)/IGF system, alongside an increase in the insulin-like growth factor binding protein gene IGFBP3 expression. These findings suggest the GH/IGF system regulates body weight during fasting periods. The vast amount of transcriptome data generated in this study substantially expands the existing gene and genome resources for the growth traits of mandarin fish.

Modern concepts in irreversible thermodynamics are applied to system transformation and degradation analyses. Phenomenological entropy generation (PEG) theorem is combined with the Degradation-Entropy Generation (DEG) theorem for instantaneous multi-disciplinary, multi-scale, multi-component system characterization. A transformation-PEG theorem and space materialize with system and process defining elements and dimensions. The near-100% accurate, consistent results and features in recent publications demonstrating and applying the new TPEG methods to frictional wear, grease aging, electrochemical power system cycling—including lithium-ion battery thermal runaway—metal fatigue loading and pump flow are collated herein, demonstrating the practicality of the new and universal PEG theorem and the predictive power of models that combine and utilize both theorems. The methodology is useful for design, analysis, prognostics, diagnostics, maintenance and optimization. [ABSTRACT FROM AUTHOR]

Powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is one of the most destructive fungal diseases threatening global wheat production. Exploring powdery mildew resistance (Pm) gene(s) and dissecting the molecular mechanism of the host resistance are critical to effectively and reasonably control this disease. Durum wheat (Triticum turgidum L. var. durum Desf.) is an important gene donor for wheat improvement against powdery mildew. In this study, a resistant durum wheat accession W762 was used to investigate its potential resistance component(s) and profile its expression pattern in responding to Bgt invasion using bulked segregant RNA-Seq (BSR-Seq) and further qRT-PCR verification. Genetic analysis showed that the powdery mildew resistance in W762 did not meet monogenic inheritance and complex genetic model might exist within the population of W762 × Langdon (susceptible durum wheat). After BSR-Seq, 6,196 consistently different single nucleotide polymorphisms (SNPs) were called between resistant and susceptible parents and bulks, and among them, 763 SNPs were assigned to the chromosome arm 7B. Subsequently, 3,653 differentially expressed genes (DEGs) between resistant and susceptible parents and bulkswere annotated and analyzed by GeneOntology (GO), Cluster of Orthologous Groups (COG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. The potential regulated genes were selected and analyzed their temporal expression patterns following Bgt inoculation. As a result, nine disease-related genes showed distinctive expression profile after Bgt invasion and might serve as potential targets to regulate the resistance against powdery mildew in W762. Our study could lay a foundation for analysis of the molecular mechanism and also provide potential targets for the improvement of durable resistance against powdery mildew. [ABSTRACT FROM AUTHOR]

Abstract Pecan scab is a devastating disease that causes damage to pecan (Carya illinoinensis (Wangenh.) K. Koch) fruit and leaves. The disease is caused by the fungus Venturia effusa (G. Winter) and the main management practice for controlling the disease is by application of fungicides at 2-to-3-week intervals throughout the growing season. Besides disease-related yield loss, application of fungicides can result in considerable cost and increases the likelihood of fungicide resistance developing in the pathogen. Resistant cultivars are available for pecan growers; although, in several cases resistance has been overcome as the pathogen adapts to infect resistant hosts. Despite the importance of host resistance in scab management, there is little information regarding the molecular basis of genetic resistance to pecan scab. The purpose of this study was to elucidate mechanisms of natural pecan scab resistance by analyzing transcripts that are differentially expressed in pecan leaf samples from scab resistant and susceptible trees. The leaf samples were collected from trees in a provenance collection orchard that represents the natural range of pecan in the US and Mexico. Trees in the orchard have been exposed to natural scab infections since planting in 1989, and scab ratings were collected over three seasons. Based on this data, ten susceptible trees and ten resistant trees were selected for analysis. RNA-seq data was collected and analyzed for diseased and non-diseased parts of susceptible trees as well as for resistant trees. A total of 313 genes were found to be differentially expressed when comparing resistant and susceptible trees without disease. For susceptible samples showing scab symptoms, 1,454 genes were identified as differentially expressed compared to non-diseased susceptible samples. Many genes involved in pathogen recognition, defense responses, and signal transduction were up-regulated in diseased samples of susceptible trees, whereas differentially expressed genes in pecan scab resistant samples were generally down-regulated compared to non-diseased susceptible samples. Our results provide the first account of candidate genes involved in resistance/susceptibility to pecan scab under natural conditions in a pecan orchard. This information can be used to aid pecan breeding programs and development of biotechnology-based approaches for generating pecan cultivars with more durable scab resistance.

Background: Frontal fibrosis alopecia (FFA) is a primary cicatricial alopecia and has received increasing attention in recent years. However, the pathogenesis of FFA has not been fully elucidated. Methods and results: Herein, we collected the transcriptome data of scalp lesions of seven patients with FFA and seven healthy controls. The differential expression analysis and weighted gene co‐expression network analysis were conducted and we identified 458 differentially expressed genes (DEGs) in two key modules. Later, we performed functional enrichment analysis and functional modules identification, revealing the participation of immune response and fatty acid metabolism. Based on the results, we processed further studies. On the one hand, we analyzed the infiltrating immune cells of FFA through CIBERSORT algorithm, indicating the activation of M1 macrophage and CD8+ T cell. On the other hand, considering lipid metabolism of FFA and oxidative stress of hair follicle cells in alopecia, we explored the potential ferroptosis of FFA. By intersection of DEGs and ferroptosis‐related genes from FerrDb database, 19 genes were identified and their expression was validated in an external dataset containing 36 FFA cases and 12 controls. Then, we used LASSO algorithms to construct a four‐gene diagnostic model, which achieved an AUC of 0.924 in validation dataset. Additionally, the immune cells were found to be related to ferroptosis in FFA. Conclusion: Taken together, this study contributed to reveal the molecular mechanisms of FFA and is expected to inspire future research on treatment. [ABSTRACT FROM AUTHOR]

The animal models used in biomedical research cover virtually every human disease. RatDEGdb, a knowledge base of the differentially expressed genes (DEGs) of the rat as a model object in biomedical research is a collection of published data on gene expression in rat strains simulating arterial hypertension, age-related diseases, psychopathological conditions and other human afflictions. The current release contains information on 25,101 DEGs representing 14,320 unique rat genes that change transcription levels in 21 tissues of 10 genetic rat strains used as models of 11 human diseases based on 45 original scientific papers. RatDEGdb is novel in that, unlike any other biomedical database, it offers the manually curated annotations of DEGs in model rats with the use of independent clinical data on equal changes in the expression of homologous genes revealed in people with pathologies. The rat DEGs put in RatDEGdb were annotated with equal changes in the expression of their human homologs in affected people. In its current release, RatDEGdb contains 94,873 such annotations for 321 human genes in 836 diseases based on 959 original scientific papers found in the current PubMed. RatDEGdb may be interesting first of all to human geneticists, molecular biologists, clinical physicians, genetic advisors as well as experts in biopharmaceutics, bioinformatics and personalized genomics. RatDEGdb is publicly available at https://www.sysbio.ru/RatDEGdb.

Abstract Differential analysis of bulk RNA-seq data often suffers from lack of good controls. Here, we present a generative model that replaces controls, trained solely on healthy tissues. The unsupervised model learns a low-dimensional representation and can identify the closest normal representation for a given disease sample. This enables control-free, single-sample differential expression analysis. In breast cancer, we demonstrate how our approach selects marker genes and outperforms a state-of-the-art method. Furthermore, significant genes identified by the model are enriched in driver genes across cancers. Our results show that the in silico closest normal provides a more favorable comparison than control samples.

Eukaryotes respond to secreted metabolites from the microbiome. However, little is known about the effects of exposure to volatiles emitted by microbes or in the environment that we are exposed to over longer durations. Using Drosophila melanogaster, we evaluated a yeast-emitted volatile, diacetyl, found at high levels around fermenting fruits where they spend long periods of time. Exposure to the diacetyl molecules in headspace alters gene expression in the antenna. In vitro experiments demonstrated that diacetyl and structurally related volatiles inhibited conserved histone deacetylases (HDACs), increased histone-H3K9 acetylation in human cells, and caused changes in gene expression in both Drosophila and mice. Diacetyl crosses the blood–brain barrier and exposure caused modulation of gene expression in the mouse brain, therefore showing potential as a neuro-therapeutic. Using two separate disease models previously known to be responsive to HDAC inhibitors, we evaluated the physiological effects of volatile exposure. Diacetyl exposure halted proliferation of a neuroblastoma cell line in culture. Exposure to diacetyl vapors slowed progression of neurodegeneration in a Drosophila model for Huntington’s disease. These changes strongly suggest that certain volatiles in the surroundings can have profound effects on histone acetylation, gene expression, and physiology in animals.

Purpose COVID-19 strangely kills some youth with no history of physical weakness, and in addition to the lungs, it may even directly harm other organs. Its complex mechanism has led to the loss of any significantly effective drug, and some patients with severe forms still die daily. Common methods for identifying disease mechanisms and drug design are often time-consuming or reductionist. Here, we use a novel holistic systems biology approach to predict its molecular mechanisms (in vitro), significant molecular relations with SARS, and repurpose drugs. Methods We have utilized its relative phylogenic similarity to SARS. Using the available omics data for SARS and the fewer data for COVID-19 to decode the mechanisms and their significant relations, We applied the Cytoscape analyzer, MCODE, STRING, and DAVID tools to predict the topographically crucial molecules, clusters, protein interaction mappings, and functional analysis. We also applied a novel approach to identify the significant relations between the two infections using the Fischer exact test for MCODE clusters. We then constructed and analyzed a drug-gene network using PharmGKB and DrugBank (retrieved using the dgidb). Results Some of the shared identified crucial molecules, BPs and pathways included Kaposi sarcoma-associated herpesvirus infection, Influenza A, and NOD-like receptor signaling pathways. Besides, our identified crucial molecules specific to host response against SARS-CoV-2 included FGA, BMP4, PRPF40A, and IFI16. Conclusion We also introduced seven new repurposed candidate drugs based on the drug-gene network analysis for the identified crucial molecules. Therefore, we suggest that our newly recommended repurposed drugs be further investigated in Vitro and in Vivo against COVID-19. [ABSTRACT FROM AUTHOR]

The widespread use of battery-powered electronic devices creates the need to develop methods to extend their maximum operating time. This can be achieved by using ambient energy, which would otherwise be dissipated. The conversion of energy, usually mechanical energy, into electric energy takes place in energy harvesters. Energy harvester systems based on a dielectric elastomer (DE) are a relatively new field that is being constantly developed. Due to their features, dielectric elastomer generators (DEGs) may complement the currently dominant piezoelectric harvesters. The major feature of employing a hyperelastic material is that it allows relatively large displacements to be utilised for generating energy, which is impossible in the case of piezoceramics. This article presents a DEG designed to operate under uniaxial tensile loads and which has a multilayer structure, describes the general operating principles of a DEG, explains the construction and assembly process of the investigated design and shows the electric circuit necessary to properly direct current flow during the DEG operation. The experimental part consists of two series of tests based on a central composite design (CCD). The objective of the first part was to map a capacitance response surface of the DEG in the selected range of the cyclic mechanical load. The second part concerned the amount of generated energy for the specific load case as a function of operating voltages. The result of the work is the formulation of regression models that allow the characteristics of the presented DEG design to be identified. [ABSTRACT FROM AUTHOR]

Background & aimsThe accumulation of neutral lipids within hepatocytes underlies non-alcoholic fatty liver disease (NAFLD), which affects a quarter of the world's population and is associated with hepatitis, cirrhosis, and hepatocellular carcinoma. Despite insights gained from both human and animal studies, our understanding of NAFLD pathogenesis remains limited. To better study the molecular changes driving the condition we aimed to generate a humanised NAFLD mouse model.MethodsWe generated TIRF (transgene-free Il2rg -/-/Rag2 -/-/Fah -/-) mice, populated their livers with human hepatocytes, and fed them a Western-type diet for 12 weeks.ResultsWithin the same chimeric liver, human hepatocytes developed pronounced steatosis whereas murine hepatocytes remained normal. Unbiased metabolomics and lipidomics revealed signatures of clinical NAFLD. Transcriptomic analyses showed that molecular responses diverged sharply between murine and human hepatocytes, demonstrating stark species differences in liver function. Regulatory network analysis indicated close agreement between our model and clinical NAFLD with respect to transcriptional control of cholesterol biosynthesis.ConclusionsThese NAFLD xenograft mice reveal an unexpected degree of evolutionary divergence in food metabolism and offer a physiologically relevant, experimentally tractable model for studying the pathogenic changes invoked by steatosis.Lay summaryFatty liver disease is an emerging health problem, and as there are no good experimental animal models, our understanding of the condition is poor. We here describe a novel humanised mouse system and compare it with clinical data. The results reveal that the human cells in the mouse liver develop fatty liver disease upon a Western-style fatty diet, whereas the mouse cells appear normal. The molecular signature (expression profiles) of the human cells are distinct from the mouse cells and metabolic analysis of the humanised livers mimic the ones observed in humans with fatty liver. This novel humanised mouse system can be used to study human fatty liver disease.

Abstract Introduction Aberrant gene expression is a key mechanism underlying pulmonary hypertension (PH) development. The alterations of genomic chromatin accessibility and their relationship with the aberrant gene expressions in PH are poorly understood. We used bulk Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing (RNA-seq) in pulmonary artery smooth muscle cells (PASMCs) of chronic hypoxia-exposed rats mimicking group 3 human PH. Methods Adult Sprague Dawley rats were commercially obtained from Hunan SJA (Hunan SJA Laboratory Animal Co., Changsha, China) and randomizedly allocated into four groups exposing to nomobaric hypoxia or normoxia for 1 or 28 days respectively. After the assessment of pulmonary hemodynamics, smooth muscle cells were isolated from intralobular arteries and simultaneously subjected to bulk Assay of ATAC-seq and RNA-seq. Results Hypoxic exposure for continuous 28-days, but not for 1-day, induced established PH phenotypes in rats. ATAC-seq revealed a major distribution of differential accessibility regions (DARs) annotated to the genome in out-of-promoter regions, following 1-day or 28-days hypoxia. 1188 DAR-associated genes and 378 differentially expressed genes (DEGs) were identified in rats after exposure to 1-day hypoxia, while 238 DAR-associated genes and 452 DEGs for 28-days hypoxia. Most of the DAR-associated genes or DEGs in 1-day did not overlap with that of 28-days hypoxia. A Pearson correlation analysis indicated no significant correlation between ATAC-seq and RNA-seq. Conclusions The alterations in genomic chromatin accessibility and genes expression of PASMCs in the initial stage of hypoxia are distinct from the established stage of hypoxia-induced PH. The genomic differential accessibility regions may not be the main mechanisms directly underlying the differentially expressed genes observed either in the initial or established stages of PH. Thus the time-course alterations of gene expression and their possible indirect link with genomic chromatin accessibility warrant more attention in mechanistic study of pulmonary hypertension.

ABSTRACT: Duck is an economically important poultry, and there is currently a major focus on improving its meat quality through breeding. There are wide variations in the growth regulation mechanisms of different duck breeds, that fundamental research on skeletal muscle growth is essential for understanding the regulation of unknown genes. The study aimed to broaden the understanding the duck skeletal muscle development and thereby to improve the performance of domestic ducks. In this study, RNA-seq data from skeletal muscles (breast muscle and leg muscle) of Pekin duck and Hanzhong Ma duck sampled at d 17, 21, and 27 of embryo (E17d, E21d, and E27d), as well as at 6-mo-old following birth (M6), to investigate and compare the mRNA temporal expression profiles and associated pathways that regulate skeletal myogenesis of different duck breeds. There were 331 to 1,440 annotated differentially expressed genes (DEGs) in breast muscle and 380 to 1,790 annotated DEGs in leg muscle from different databases between 2 duck breeds. Gene ontology (GO) enrichment in skeletal muscles indicated that these DEGs were mainly involved in biosynthetic process, developmental process, regulation of protein metabolic process and regulation of gene expression. KEGG analysis in skeletal muscles showed that a total of 41 DEGs were mapped to 7 KEGG pathways, including ECM-receptor interaction, focal adhesion, carbon metabolism, regulation of actin cytoskeleton, calcium signaling pathway, biosynthesis of amino acids and PPAR signaling pathway. The differential expression of 8 selected DEGs was verified by qRT-PCR, and the results were consistent with RNA-seq data. The identified DEGs, such as SDC, SPP1, PAK1, MYL9, PGK1, NOS1, PHGDH, TNNT2, FN1, and AQP4, were specially highlighted, indicating their associations with muscle development in the Pekin duck and Hanzhong Ma duck. This study provides a basis for revealing the differences in skeletal muscle development between Pekin duck and Hanzhong Ma duck.

Single cell RNA-sequencing (scRNA-seq) technology has significantly advanced the understanding of transcriptomic signatures. Although various statistical models have been used to describe the distribution of gene expression across cells, a comprehensive assessment of the different models is missing. Moreover, the growing number of features associated with scRNA-seq datasets creates new challenges for analytical accuracy and computing speed. Here, we developed a Python-based package (TensorZINB) to solve the zero-inflated negative binomial (ZINB) model using the TensorFlow deep learning framework. We used a sequential initialization method to solve the numerical stability issues associated with hurdle and zero-inflated models. A recursive feature selection protocol was used to optimize feature selections for data processing and downstream differentially expressed gene (DEG) analysis. We proposed a class of hybrid models combining nested models to further improve the model's performance. Additionally, we developed a new method to convert a continuous distribution to its equivalent discrete form, so that statistical models can be fairly compared. Finally, we showed that the proposed TensorFlow algorithm (TensorZINB) was numerically stable and that its computing speed and performance were superior to those of existing ZINB solvers. Moreover, we implemented seven hurdle and zero-inflated statistical models in Python and systematically assessed their performance using a real scRNA-seq dataset. We demonstrated that the ZINB model achieved the lowest Akaike information criterion compared with other models tested. Taken together, TensorZINB was accurate, efficient and scalable for the implementation of ZINB and for large-scale scRNA-seq data analysis with DEG identification. [ABSTRACT FROM AUTHOR]

Aim: Fetal growth restriction (FGR) can lead to short‐term and long‐term impairments in the fetus. The placenta functions as an exchanger for substance transport, playing a critical role in fetal growth. However, the mechanism from the placental standpoint is still not fully understood. In this study, we aimed to investigate the pathophysiological mechanisms in the placenta that mediated the development of FGR and sex differences. Methods: We analyzed the gene expression profiles of GSE100415 containing specific normotensive FGR placental samples and GSE114691 with canonical samples using three different methods, differentially expressed gene analysis, weighted gene co‐expression network analysis, and gene set enrichment analysis. Gene enrichment was performed, including the gene ontology and pathway from the Kyoto Encyclopedia of Genes and Genomes. The important process was then validated in pregnant Wistar rats subcutaneously administered dexamethasone (0.2 mg/kg/d) or saline from gestation Day 9 to 21. Results: Our results revealed little difference between the comparison of normal and normotensive FGR placental samples but confirmed the sex difference. Further analyses of the canonical samples identified the occurrence of vascular dysfunction, which was validated by the calculation of the vascular lumen area, showing that the vascular lumen in the FGR group was more than in the control. We also discovered 17 significantly expressed genes from the involved eigengenes. Conclusion: Our study provides an important theoretical and experimental basis to reevaluate the development of FGR from the placental standpoint and suggests a series of biomarkers for future clinical use. [ABSTRACT FROM AUTHOR]

Plants are often exposed to drought stress, and decreases in the soil water content can prevent plants from reaching their full genetic potential. Populus davidiana Dode belongs to the genus Populus, and it is a temperate deciduous tree that is cold and drought tolerant. To investigate the mechanism of P. davidiana response to drought stress, transcriptome analysis was performed on drought and control treatments of P. davidiana. We identified 10230 differentially expressed genes (DEGs). Most DEGs were enriched in pathways related to transcriptional regulation and hormone signal transduction, ROS metabolism, lignin synthesis, and the sugar metabolism process in two contrasting groups. Compared with the control condition, soluble sugars, proline, and POD activity were all increased under drought stress. In addition, Na+, K+, and Ca2+ were all higher under drought stress than in the control. These results not only revealed the mechanism of tolerance to drought stress in P. davidiana, but also promoted the development and application of drought-tolerant genetic resources in P. davidiana. [ABSTRACT FROM AUTHOR]

Purpose: The current outbreak of monkeypox (MPX) has created colossal concerns. However, immense research gaps have been noted in our understanding of the replication process, machinery, and genomic landscape during host cell infection. To fill this gap, differentially expressed genes (DEGs) were comprehensively analyzed during viral replication in host (MK2) cells. Methods: We used a microarray GEO dataset which was divided into three groups: control, MPXV-infected MK2 cells at 3 h, and MPXV-infected MK2 cells at 7 h. Using the dataset, DEG analysis, PPI network analysis, co-expression, and pathway analysis were conducted using bioinformatics, systems biology, and statistical approaches. Results: We identified 250 DEGs and 24 top-ranked genes. During the DEG analysis, we identified eight up-regulated genes (LOC695323, TMEM107, LOC695427, HIST1H2AD, LOC705469, PMAIP1, HIST1H2BJ, and HIST1H3D) and 16 down-regulated genes (HOXA9, BAMBI, LMO4, PAX6, AJUBA, CREBRF, CD24, JADE1, SLC7A11, EID2, SOX4, B4GALT5, PPARGC1A, BUB3, SOS2, and CDK19). We also developed PPI networks and performed co-expression analyses using the top-ranked genes. Furthermore, five genes were listed for co-expression pattern analysis. Conclusions: This study will help in better understanding the replication process, machinery, and genomic landscape of the virus. This will further aid the discovery and development of therapeutics against viruses.

Triple-negative breast cancer (TNBC) is more difficult to treat and has a higher mortality rate than other subtypes. Although hormone receptor-targeted therapy is an effective treatment to increase survival rate in breast cancer patients, it is not suitable for TNBC patients. To address the issues, differentially expressed genes (DEGs) in TNBC patients from the Gene Expression Omnibus (GEO) database were analyzed. A total of 170 genes were obtained from three Genomic Spatial Events (GSEs) using the intersection of each GSE dataset and 61 DEGs were identified after validation with the gene enrichment analysis. We combined this with the degree scores from the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and protein-protein interaction (PPI) network, of which 7 genes were correlated with survival rate. Finally, a proteomics database revealed that only the CHK1 protein level was differently expressed in basal-like compared with other subtypes. We demonstrated that CHK1 expression was higher in TNBC cell lines compared with non-TNBC cell lines, and CHK1 promotes epithelial to mesenchymal transition (EMT) as well as migration and invasion ability. Our study provides new insight into the TNBC subnetwork that may be useful in the prognosis and treatment of TNBC patients.

Background: Both bacterial and viral diseases are a major threat to farmed fish. As the antiviral immune mechanisms in lumpfish (Cyclopterus lumpus L.) are poorly understood, lumpfish leukocytes were stimulated with poly(I:C), a synthetic analog of double stranded RNA, which mimic viral infections, and RNA sequencing was performed. Methods: To address this gap, we stimulated lumpfish leukocytes with poly(I:C) for 6 and 24 hours and did RNA sequencing with three parallels per timepoint. Genome guided mapping was performed to define differentially expressed genes (DEGs). Results: Immune genes were identified, and transcriptome-wide analyses of early immune responses showed that 376 and 2372 transcripts were significantly differentially expressed 6 and 24 hours post exposure (hpe) to poly(I:C), respectively. The most enriched GO terms when time had been accounted for, were immune system processes (GO:0002376) and immune response (GO:0006955). Analysis of DEGs showed that among the most highly upregulated genes were TLRs and genes belonging to the RIG-I signaling pathway, including LGP2, STING and MX, as well as IRF3 and IL12A. RIG-I was not identified, but in silico analyses showed that genes encoding proteins involved in pathogen recognition, cell signaling, and cytokines of the TLR and RIG-I signaling pathway are mostly conserved in lumpfish when compared to mammals and other teleost species. Conclusions: Our analyses unravel the innate immune pathways playing a major role in antiviral defense in lumpfish. The information gathered can be used in comparative studies and lay the groundwork for future functional analyses of immune and pathogenicity mechanisms. Such knowledge is also necessary for the development of immunoprophylactic measures for lumpfish, which is extensively cultivated for use as cleaner fish in the aquaculture for removal of sea lice from Atlantic salmon (Salmo salar L.). [ABSTRACT FROM AUTHOR]

Early diagnosis and treatment of glaucoma are challenging. The discovery of glaucoma biomarkers based on gene expression data could potentially provide new insights for early diagnosis, monitoring, and treatment options of glaucoma. Non-negative Matrix Factorization (NMF) has been widely used in numerous transcriptome data analyses in order to identify subtypes and biomarkers of different diseases; however, its application in glaucoma biomarker discovery has not been previously reported. Our study applied NMF to extract latent representations of RNA-seq data from BXD mouse strains and sorted the genes based on a novel gene scoring method. The enrichment ratio of the glaucoma-reference genes, extracted from multiple relevant resources, was compared using both the classical differentially expressed gene (DEG) analysis and NMF methods. The complete pipeline was validated using an independent RNA-seq dataset. Findings showed our NMF method significantly improved the enrichment detection of glaucoma genes. The application of NMF with the scoring method showed great promise in the identification of marker genes for glaucoma. [ABSTRACT FROM AUTHOR]

Sometimes, for medical reasons, when a frozen tissue has already thawed, an operation by re-transplantation may be cancelled, and ovarian tissues should be re-frozen for transplantation next time. Research about the repeated cryopreservation of ovarian cells is rarely reported. It has been published that there is no difference in the follicle densities, proportions of proliferation of early preantral follicles, appearance of atretic follicles, or ultrastructural quality of frozen-thawed and re-frozen-rethawed tissue. However, the molecular mechanisms of a repeated cryopreservation effect on the developmental potential of ovarian cells are unknown. The aim of our experiments was to investigate the effect of re-freezing and re-thawing ovarian tissue on gene expression, gene function annotation, and protein–protein interactions. The morphological and biological activity of primordial, primary, and secondary follicles, aimed at using these follicles for the formation of artificial ovaries, was also detected. Second-generation mRNA sequencing technology with a high throughput and accuracy was adopted to determine the different transcriptome profiles in the cells of four groups: one-time cryopreserved (frozen and thawed) cells (Group 1), two-time cryopreserved (re-frozen and re-thawed after first cryopreservation) cells (Group 2), one-time cryopreserved (frozen and thawed) and in vitro cultured cells (Group 3), and two times cryopreserved (re-frozen and re-thawed after first cryopreservation) and in vitro cultured cells (Group 4). Some minor changes in the primordial, primary, and secondary follicles in terms of the morphology and biological activity were detected, and finally, the availability of these follicles for the formation of artificial ovaries was explored. It was established that during cryopreservation, the CEBPB/CYP19A1 pathway may be involved in regulating estrogen activity and CD44 is crucial for the development of ovarian cells. An analysis of gene expression in cryopreserved ovarian cells indicates that two-time (repeated) cryopreservation does not significantly affect the developmental potential of these cells. For medical reasons, when ovarian tissue is thawed but cannot be transplanted, it can be immediately re-frozen again. [ABSTRACT FROM AUTHOR]

Introduction: Aberrant gene expression is a key mechanism underlying pulmonary hypertension (PH) development. The alterations of genomic chromatin accessibility and their relationship with the aberrant gene expressions in PH are poorly understood. We used bulk Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing (RNA-seq) in pulmonary artery smooth muscle cells (PASMCs) of chronic hypoxia-exposed rats mimicking group 3 human PH. Methods: Adult Sprague Dawley rats were commercially obtained from Hunan SJA (Hunan SJA Laboratory Animal Co., Changsha, China) and randomizedly allocated into four groups exposing to nomobaric hypoxia or normoxia for 1 or 28 days respectively. After the assessment of pulmonary hemodynamics, smooth muscle cells were isolated from intralobular arteries and simultaneously subjected to bulk Assay of ATAC-seq and RNA-seq. Results: Hypoxic exposure for continuous 28-days, but not for 1-day, induced established PH phenotypes in rats. ATAC-seq revealed a major distribution of differential accessibility regions (DARs) annotated to the genome in out-of-promoter regions, following 1-day or 28-days hypoxia. 1188 DAR-associated genes and 378 differentially expressed genes (DEGs) were identified in rats after exposure to 1-day hypoxia, while 238 DAR-associated genes and 452 DEGs for 28-days hypoxia. Most of the DAR-associated genes or DEGs in 1-day did not overlap with that of 28-days hypoxia. A Pearson correlation analysis indicated no significant correlation between ATAC-seq and RNA-seq. Conclusions: The alterations in genomic chromatin accessibility and genes expression of PASMCs in the initial stage of hypoxia are distinct from the established stage of hypoxia-induced PH. The genomic differential accessibility regions may not be the main mechanisms directly underlying the differentially expressed genes observed either in the initial or established stages of PH. Thus the time-course alterations of gene expression and their possible indirect link with genomic chromatin accessibility warrant more attention in mechanistic study of pulmonary hypertension. [ABSTRACT FROM AUTHOR]

This document is a corrigendum published in the journal Frontiers in Immunology. It corrects an error in the acknowledgment section of a previously published article titled "Transcriptome-wide analyses of early immune responses in lumpfish leukocytes upon stimulation with poly(I:C)." The correction provides additional information about the funding received for the project and acknowledges the organizations that provided support. The authors apologize for the error and state that it does not affect the scientific conclusions of the article. The corrigendum is open access and was approved by the Frontiers Editorial Office. [Extracted from the article]

BackgroundBoth bacterial and viral diseases are a major threat to farmed fish. As the antiviral immune mechanisms in lumpfish (Cyclopterus lumpus L.) are poorly understood, lumpfish leukocytes were stimulated with poly(I:C), a synthetic analog of double stranded RNA, which mimic viral infections, and RNA sequencing was performed.MethodsTo address this gap, we stimulated lumpfish leukocytes with poly(I:C) for 6 and 24 hours and did RNA sequencing with three parallels per timepoint. Genome guided mapping was performed to define differentially expressed genes (DEGs).ResultsImmune genes were identified, and transcriptome-wide analyses of early immune responses showed that 376 and 2372 transcripts were significantly differentially expressed 6 and 24 hours post exposure (hpe) to poly(I:C), respectively. The most enriched GO terms when time had been accounted for, were immune system processes (GO:0002376) and immune response (GO:0006955). Analysis of DEGs showed that among the most highly upregulated genes were TLRs and genes belonging to the RIG-I signaling pathway, including LGP2, STING and MX, as well as IRF3 and IL12A. RIG-I was not identified, but in silico analyses showed that genes encoding proteins involved in pathogen recognition, cell signaling, and cytokines of the TLR and RIG-I signaling pathway are mostly conserved in lumpfish when compared to mammals and other teleost species.ConclusionsOur analyses unravel the innate immune pathways playing a major role in antiviral defense in lumpfish. The information gathered can be used in comparative studies and lay the groundwork for future functional analyses of immune and pathogenicity mechanisms. Such knowledge is also necessary for the development of immunoprophylactic measures for lumpfish, which is extensively cultivated for use as cleaner fish in the aquaculture for removal of sea lice from Atlantic salmon (Salmo salar L.).

The antiparasitic drug halofuginone is important for controlling apicomplexan parasites. However, the occurrence of halofuginone resistance is a major obstacle for it to the treatment of apicomplexan parasites. Current studies have identified the molecular marker and drug resistance mechanisms of halofuginone in Plasmodium falciparum. In this study, we tried to use transcriptomic data to explore resistance mechanisms of halofuginone in apicomplexan parasites of the genus Eimeria (Apicomplexa: Eimeriidae). After halofuginone treatment of E. tenella parasites, transcriptome analysis was performed using samples derived from both resistant and sensitive strains. In the sensitive group, DEGs associated with enzymes were significantly downregulated, whereas the DNA damaging process was upregulated after halofuginone treatment, revealing the mechanism of halofuginone-induced parasite death. In addition, 1,325 differentially expressed genes (DEGs) were detected between halofuginone resistant and sensitive strains, and the DEGs related to translation were significantly downregulated after halofuginone induction. Overall, our results provide a gene expression profile for further studies on the mechanism of halofuginone resistance in E. tenella. [ABSTRACT FROM AUTHOR]

The current outbreak of monkeypox (MPX) has created colossal concerns. However, immense research gaps have been noted in our understanding of the replication process, machinery, and genomic landscape during host cell infection. To fill this gap, differentially expressed genes (DEGs) were comprehensively analyzed during viral replication in host (MK2) cells. We used a microarray GEO dataset which was divided into three groups: control, MPXV-infected MK2 cells at 3 h, and MPXV-infected MK2 cells at 7 h. Using the dataset, DEG analysis, PPI network analysis, co-expression, and pathway analysis were conducted using bioinformatics, systems biology, and statistical approaches. We identified 250 DEGs and 24 top-ranked genes. During the DEG analysis, we identified eight up-regulated genes (LOC695323 , TMEM107 , LOC695427 , HIST1H2AD , LOC705469 , PMAIP1 , HIST1H2BJ , and HIST1H3D) and 16 down-regulated genes (HOXA9 , BAMBI , LMO4 , PAX6 , AJUBA , CREBRF , CD24 , JADE1 , SLC7A11 , EID2 , SOX4 , B4GALT5 , PPARGC1A , BUB3 , SOS2 , and CDK19). We also developed PPI networks and performed co-expression analyses using the top-ranked genes. Furthermore, five genes were listed for co-expression pattern analysis. This study will help in better understanding the replication process, machinery, and genomic landscape of the virus. This will further aid the discovery and development of therapeutics against viruses. [ABSTRACT FROM AUTHOR]

Nucleocytoplasmic transport receptors play key roles in the nuclear translocation of disease resistance proteins, but the associated mechanisms remain unclear. The Arabidopsis thaliana gene SAD2 encodes an importin β-like protein. A transgenic Arabidopsis line overexpressing SAD2 (OESAD2/Col-0) showed obvious resistance to Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) compared to the wild type (Col-0), but the knockout mutant sad2-5 was susceptible. Transcriptomic analysis was then performed on Col-0, OESAD2/Col-0, and sad2-5 leaves at 0, 1, 2, and 3 days post-inoculation with Pst DC3000. A total of 1825 differentially expressed genes (DEGs) were identified as putative biotic stress defense genes regulated by SAD2, 45 of which overlapped between the SAD2 knockout and overexpression datasets. Gene Ontology (GO) analysis indicated that the DEGs were broadly involved in single-organism cellular metabolic processes and in response to stimulatory stress. Kyoto Encyclopedia of Genes and Genomes (KEGG) biochemical pathway analysis revealed that many of the DEGs were associated with the biosynthesis of flavonoids and other specialized metabolites. Transcription factor analysis showed that a large number of ERF/AP2, MYB, and bHLH transcription factors were involved in SAD2-mediated plant disease resistance. These results provide a basis for future exploration of the molecular mechanisms associated with SAD2-mediated disease resistance and establish a set of key candidate disease resistance genes. [ABSTRACT FROM AUTHOR]

Patients with preexisting metabolic disorders such as diabetes are at a higher risk of developing severe coronavirus disease 2019 (COVID-19). Mitochondrion, the very organelle that controls cellular metabolism, holds the key to understanding disease progression at the cellular level. Our current study aimed to understand how cellular metabolism contributes to COVID-19 outcomes. Metacore pathway enrichment analyses on differentially expressed genes (encoded by both mitochondrial and nuclear deoxyribonucleic acid (DNA)) involved in cellular metabolism, regulation of mitochondrial respiration and organization, and apoptosis, was performed on RNA sequencing (RNASeq) data from blood samples collected from healthy controls and patients with mild/moderate or severe COVID-19. Genes from the enriched pathways were analyzed by network analysis to uncover interactions among them and up- or downstream genes within each pathway. Compared to the mild/moderate COVID-19, the upregulation of a myriad of growth factor and cell cycle signaling pathways, with concomitant downregulation of interferon signaling pathways, were observed in the severe group. Matrix metallopeptidase 9 (MMP9) was found in five of the top 10 upregulated pathways, indicating its potential as therapeutic target against COVID-19. In summary, our data demonstrates aberrant activation of endocrine signaling in severe COVID-19, and its implication in immune and metabolic dysfunction. [ABSTRACT FROM AUTHOR]

Cold damage is one of the most important environmental factors influencing crop growth, development, and production. In this study, we generated a pair of near-isogenic lines (NILs), Towada and ZL31, and Towada showed more cold sensitivity than ZL31 in the rice seedling stage. To explore the transcriptional regulation mechanism and the reason for phenotypic divergence of the two lines in response to cold stress, an in-depth comparative transcriptome study under cold stress was carried out. Our analysis uncovered that rapid and high-amplitude transcriptional reprogramming occurred in the early stage of cold treatment. GO enrichment and KEGG pathway analysis indicated that genes of the response to stress, environmental adaptation, signal transduction, metabolism, photosynthesis, and the MAPK signaling pathway might form the main part of the engine for transcriptional reprogramming in response to cold stress. Furthermore, we identified four core genes, OsWRKY24, OsCAT2, OsJAZ9, and OsRR6, that were potential candidates affecting the cold sensitivity of Towada and ZL31. Genome re-sequencing analysis between the two lines revealed that only OsWRKY24 contained sequence variations which may change its transcript abundance. Our study not only provides novel insights into the cold-related transcriptional reprogramming process, but also highlights the potential candidates involved in cold stress. [ABSTRACT FROM AUTHOR]

The effect of PARP1 knockout in HEK293 cells on the gene expression of DNA base excision repair (BER) proteins was studied. It was shown that the expression of all differentially expressed genes (DEGs) of BER was reduced by knockout. The expression of the DNA glycosylase gene NEIL1, which is considered to be one of the common "hubs" for binding BER proteins, has changed the most. The expression of genes of auxiliary subunits of DNA polymerases δ and ε is also significantly reduced. The PARP1 gene knockout cell line obtained is an adequate cell model for studying the activity of the BER process in the absence of PARP1 and testing drugs aimed at inhibiting repair processes. It has been found for the first time that knockout of the PARP1 gene results in a significant change in the level of expression of proteins responsible for ribosome biogenesis and the functioning of the proteasome. [ABSTRACT FROM AUTHOR]

Aim: Head and Neck squamous cell carcinoma (HNSCC) is the second most prevalent cancer in Pakistan. Methods: Gene expression data from TCGA and GETx for normal genes to analyze Differentially Expressed Genes (DEGs). Data was further investigated using the Enrichr tool to perform Gene Ontology (GO). Results: Our analysis identified most significantly differentially expressed genes and explored their established cellular functions as well as their potential involvement in tumor development. We found that the highly expressed Keratin family and S100A9 genes. The under-expressed genes KRT4 and KRT13 provide instructions for the production of keratin proteins. Conclusion: Our study suggests that factors such as poor oral hygiene and smokeless tobacco can result in oral stress and cellular damage and cause cancer.

Dysferlin (DYSF) has drawn much attention due to its involvement in dysferlinopathy and was reported to affect monocyte functions in recent studies. However, the role of DYSF in the pathogenesis of atherosclerotic cardiovascular diseases (ASCVD) and the regulation mechanism of DYSF expression have not been fully studied. In this study, Gene Expression Omnibus (GEO) database and epigenome-wide association study (EWAS) literatures were searched to find the DNA methylation-driven genes (including DYSF) of ASCVD. The hub genes related to DYSF were also identified through weighted correlation network analysis (WGCNA). Regulation of DYSF expression through its promoter methylation status was verified using peripheral blood leucocytes (PBLs) from ASCVD patients and normal controls, and experiments on THP1 cells and Apoe-/- mice. Similarly, the expressions of DYSF related hub genes, mainly contained SELL, STAT3 and TMX1, were also validated. DYSF functions were then evaluated by phagocytosis, transwell and adhesion assays in DYSF knock-down and overexpressed THP1 cells. The results showed that DYSF promoter hypermethylation up-regulated its expression in clinical samples, THP1 cells and Apoe-/- mice, confirming DYSF as a DNA methylation-driven gene. The combination of DYSF expression and methylation status in PBLs had a considerable prediction value for ASCVD. Besides, DYSF could enhance the phagocytosis, migration and adhesion ability of THP1 cells. Among DYSF related hub genes, SELL was proven to be the downstream target of DYSF by wet experiments. In conclusion, DYSF promoter hypermethylation upregulated its expression and promoted monocytes activation, which further participated in the pathogenesis of ASCVD. [ABSTRACT FROM AUTHOR]

Banana is one of the major food crops and its production is subject to many pests and diseases. Banana breeding exploits wild relatives and progenitor species for the introgression of resistant genes (R) into cultivated varieties to overcome these hurdles. With advances in sequencing technologies, whole-genome sequences are available for many Musa spp. and many of them are potential donors of disease resistance genes. Considering their potential role, R genes from these species were explored to develop an user-friendly open-access database that will be useful for studying and implementing disease resistance in bananas. MusaRgene database is complemented with complete details of 3598 R genes identified from eight Musa spp. and rice, Arabidopsis, sorghum along with its classification and separate modules on its expression under various stresses in resistant and susceptible cultivars and corresponding SSRs are also provided. This database can be regarded as the primary resource of information on R genes from bananas and their relatives. R genes from other allele mining studies are also incorporated which will enable the identification of its homolog in related Musa spp. MusaRgene database will aid in the identification of genes and markers associated, cloning of full-length R genes, and genetic transformation or gene editing of the R genes in susceptible cultivars. Multiple R genes can also be identified for pyramiding the genes to increase the level of resistance and durability. Overall, this database will facilitate the understanding of defense mechanisms in bananas against biotic or abiotic stresses leading to the development of promising disease-resistant varieties. [ABSTRACT FROM AUTHOR]

RNA-sequencing (RNA-seq) is a versatile, high-throughput technology that is being widely employed for screening differentially expressed genes (DEGs) in various diseases. Echinococcosis, a globally distributed zoonosis, has been reported to impose a heavy disease burden in pastoral areas of China. Herein we aimed to explore the molecular mechanisms underlying echinococcosis. In this study, peripheral blood samples were collected from six patients with alveolar echinococcosis (AE), six patients with cystic echinococcosis (CE), and six healthy controls. RNA-Seq (mRNA) was performed to detect gene transcript and expression levels, and DEGs were subjected to bioinformatic analyses. In comparison with healthy controls, 492 DEGs (270 upregulated, 222 downregulated) were found in the AE group and 424 DEGs (170 upregulated, 254 downregulated) were found in the CE group (|log2 (fold change)| > 1 and P < 0.05). Further, 60 genes were upregulated and 39 were downregulated in both the AE and CE groups. Gene ontology enrichment analysis indicated that DEGs were mainly involved in molecular functions, including extracellular space, extracellular region, organ and system development, and anatomical structure development. Protein–protein interaction (PPI) networks were constructed to depict the complex relationship between DEGs and interacting proteins. [ABSTRACT FROM AUTHOR]

Panicle degeneration, sometimes known as abortion, causes heavy losses in grain yield. However, the mechanism of naturally occurring panicle abortion is still elusive. In a previous study, we characterized a mutant, apical panicle abortion1331 (apa1331), exhibiting abortion in apical spikelets starting from the 6 cm stage of panicle development. In this study, we have quantified the five phytohormones, gibberellins (GA), auxins (IAA), abscisic acid (ABA), cytokinins (CTK), and brassinosteroids (BR), in the lower, middle, and upper parts of apa1331 and compared these with those exhibited in its wild type (WT). In apa331, the lower and middle parts of the panicle showed contrasting concentrations of all studied phytohormones, but highly significant changes in IAA and ABA, compared to the upper part of the panicle. A comparative transcriptome of apa1331 and WT apical spikelets was performed to explore genes causing the physiological basis of spikelet abortion. The differential expression analysis revealed a significant downregulation and upregulation of 1587 and 978 genes, respectively. Hierarchical clustering of differentially expressed genes (DEGs) revealed the correlation of gene ontology (GO) terms associated with antioxidant activity, peroxidase activity, and oxidoreductase activity. KEGG pathway analysis using parametric gene set enrichment analysis (PGSEA) revealed the downregulation of the biological processes, including cell wall polysaccharides and fatty acids derivatives, in apa1331 compared to its WT. Based on fold change (FC) value and high variation in expression during late inflorescence, early inflorescence, and antherdevelopment, we predicted a list of novel genes, which presumably can be the potential targets of inflorescence development. Our study not only provides novel insights into the role of the physiological dynamics involved in panicle abortion, but also highlights the potential targets involved in reproductive development. [ABSTRACT FROM AUTHOR]

Abstract Introduction A vaccine for malaria is urgently required but no vaccine has yet shown satisfactory protective efficacy especially for Plasmodium falciparum. P. falciparum infection can progress to cerebral malaria (CM), a neurological syndrome with exceedingly high mortality. Designing effective P. falciparum vaccines require more understanding of the protective immune response while the host immune response to CM and the mechanisms are still elusive. Here, we aim to identify host gene responses to CM and host gene networks associated with CM pathogenesis. Methods An innovative genomic analysis strategy, the weighted gene coexpression network analysis (WGCNA) combined with differential gene expression analysis, was used in this study. Data for analysis contain 93 whole blood samples, derived from two previous public transcriptome datasets. Results This approach led to the identification of numerous differentially expressed human transcripts and dozens of coexpression gene modules. We further identified nine key genes, including MBP, SAMSN1, PSMF1, SLC39A8, EIF3B, SMPDL3A, FABP5, SPSB3, and SHARPIN, of which the last four genes were first identified to be related to CM in the present study. Conclusion The results provided a comprehensive characterization of host gene expression profiles in CM and offered some new insight into malaria vaccine design. These identified key genes could be potential targets or immune modulators for novel therapeutic interventions of CM.