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BACKGROUND: Starch, dry matter content (DMC), proteins, and sugars are among the major influences on yam tuber quality. Genetic improvement programs need simple, rapid, and low‐cost tools to screen large populations. The objectives of this work were, using a quantitative trait loci mapping approach (QTL) on two diploid full‐sib segregating populations, (i) to acquire knowledge about the genetic control of these traits; (ii) to identify markers linked to the genomic regions controlling each trait, which are useful for marker‐assisted selection (MAS); (iii) to validate the QTLs on a diversity panel; and (iv) to identify candidate genes from the validated QTLs. RESULTS: Heritability for all traits was moderately high to high. Significant correlations were observed between traits. A total of 25 QTLs were identified, including six for DMC, six for sugars, six for proteins, and seven for starch. The phenotypic variance explained by individual QTLs ranged from 14.3% to 28.6%. The majority of QTLs were validated on a diversity panel, showing that they are not specific to the genetic background of the progenitors. The approximate physical location of validated QTLs allowed the identification of candidate genes for all studied traits. Those detected for starch content were mainly enzymes involved in starch and sucrose metabolism, whereas those detected for sugars were mainly involved in respiration and glycolysis. CONCLUSION: The validated QTLs will be useful for breeding programs using MAS to improve the quality of yam tubers. The putative genes should be useful in providing a better understanding of the physiological and molecular basis of these important tuber quality traits. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Objective: Interferon regulatory factor 1 (IRF1) is a transcriptional regulator conventionally associated with immunomodulation. Recent molecular analyses mapping DNA binding sites of IRF1 have suggested its potential function in DNA repair. However, the physiologic significance of this noncanonical function remains unexplored. Here, we investigated the role of IRF1 in osteoarthritis (OA), a condition marked by senescence and chronic joint inflammation. Methods: OA progression was examined in wild‐type and Irf1−/− mice using histologic assessments and microcomputed tomography analysis of whole‐joint OA manifestations and behavioral assessments of joint pain. An integrated analysis of assay for transposase‐accessible chromatin with sequencing and whole transcriptome data was conducted for the functional assessment of IRF1 in chondrocytes. The role of IRF1 in DNA repair and senescence was investigated by assaying γ‐H2AX foci and senescence‐associated beta‐galactosidase activity. Results: Our genome‐wide investigation of IRF1 footprinting in chondrocytes revealed its primary occupancies in the promoters of DNA repair genes without noticeable footprint patterns in those of interferon‐responsive genes. Chondrocytes lacking IRF1 accumulated irreversible DNA damage under oxidative stress, facilitating their entry into cellular senescence. IRF1 was down‐regulated in the cartilage of human and mouse OA. Although IRF1 overexpression did not elicit an inflammatory response in joints or affect OA development, genetic deletion of Irf1 caused enhanced chondrocyte senescence and exacerbated post‐traumatic OA in mice. Conclusion: IRF1 offers DNA damage surveillance in chondrocytes, protecting them from oxidative stress associated with OA risk factors. Our study provides a crucial and cautionary perspective that compromising IRF1 activity renders chondrocytes vulnerable to cellular senescence and promotes OA development. [ABSTRACT FROM AUTHOR]

Summary: Branch angle (BA) is a critical morphological trait that significantly influences planting density, light interception and ultimately yield in plants. Despite its importance, the regulatory mechanism governing BA in rapeseed remains poorly understood. In this study, we generated 109 transcriptome data sets for 37 rapeseed accessions with divergent BA phenotypes. Relative to adaxial branch segments, abaxial segments accumulated higher levels of auxin and exhibited lower expression of six TCP1 homologues and one GA20ox3. A co‐expression network analysis identified two modules highly correlated with BA. The modules contained homologues to known BA control genes, such as FUL, YUCCA6, TCP1 and SGR3. Notably, a homoeologous exchange (HE), occurring at the telomeres of A09, was prevalent in large BA accessions, while an A02‐C02 HE was common in small BA accessions. In their corresponding regions, these HEs explained the formation of hub gene hotspots in the two modules. QTL‐seq analysis confirmed that the presence of a large A07‐C06 HE (~8.1 Mb) was also associated with a small BA phenotype, and BnaA07.WRKY40.b within it was predicted as candidate gene. Overexpressing BnaA07.WRKY40.b in rapeseed increased BA by up to 20°, while RNAi‐ and CRISPR‐mediated mutants (BnaA07.WRKY40.b and BnaC06.WRKY40.b) exhibited decreased BA by up to 11.4°. BnaA07.WRKY40.b was exclusively localized to the nucleus and exhibited strong expression correlations with many genes related to gravitropism and plant architecture. Taken together, our study highlights the influence of HEs on rapeseed plant architecture and confirms the role of WRKY40 homologues as novel regulators of BA. [ABSTRACT FROM AUTHOR]

• Comprehensive analysis of prostate cancer samples and cell lines to explore telomeres and associated genes as prognostic biomarkers. • Despite few genetic alterations in localized disease, there is an increase in amplifications in the analyzed genes in metastatic disease. • Upregulation of shelterin and CST genes correlates with a more aggressive form of localized prostate cancer, despite limited genetic alterations. • Longer telomeres are observed in aggressive disease, indicating that increased expression of telomere-related genes could be an early biomarker for prostate cancer aggressiveness. Search for new clinical biomarkers targets in prostate cancer (PC) is urgent. Telomeres might be one of these targets. Telomeres are the extremities of linear chromosomes, essential for genome stability and control of cell divisions. Telomere homeostasis relies on the proper functioning of shelterin and CST complexes. Telomeric dysfunction and abnormal expression of its components are reported in most cancers and are associated with PC. Despite this, there are only a few studies about the expression of the main telomere complexes and their relationship with PC progression. We aimed to evaluate the role of shelterin (POT1, TRF2, TPP1, TIN2, and RAP1) and CST (CTC1, STN1, and TEN1) genes and telomere length in the progression of PC. We evaluated genetic alterations of shelterin and CST by bioinformatics in samples of localized (n = 499) and metastatic castration-resistant PC (n = 444). We also analyzed the expression of the genes using TCGA (localized PC n = 497 and control n = 152) and experimental approaches, with surgical specimens (localized PC n = 81 and BPH n = 10) and metastatic cell lines (LNCaP, DU145, PC3 and PNT2 as control) by real-time PCR. Real-time PCR also determined the telomere length in the same experimental samples. All acquired data were associated with clinical parameters. Genetic alterations are uncommon in PC, but POT1, TIN2, and TEN1 showed significantly more amplifications in the metastatic cancer. Except for CTC1 and TEN1, which are differentially expressed in localized PC samples, we did not detect an expression pattern relative to control and cell lines. Nevertheless, except for TEN1, the upregulation of all genes is associated with a worse prognosis in localized PC. We also found that increased telomere length is associated with disease aggressiveness in localized PC. The upregulation of shelterin and CST genes creates an environment that favors telomere elongation, giving selective advantages for localized PC cells to progress to more aggressive stages of the disease. [ABSTRACT FROM AUTHOR]

The order Agaricales was divided into eight suborders. However, the phylogenetic relationships among some suborders are largely unresolved, and the phylogenetic positions and delimitations of some taxa, such as Sarcomyxaceae and Tricholomopsis, remain unsettled. In this study, sequence data of 38 genomes were generated through genome skimming on an Illumina sequencing system. To anchor the systematic position of Sarcomyxaceae and Tricholomopsis, a phylogenetic analysis based on 555 single-copy orthologous genes from the aforementioned genomes and 126 publicly accessible genomes was performed. The results fully supported the clustering of Tricholomopsis with Phyllotopsis and Pleurocybella within Phyllotopsidaceae, which formed a divergent monophyletic major lineage together with Pterulaceae, Radulomycetaceae, and Macrotyphula in Agaricales. The analysis also revealed that Sarcomyxaceae formed a unique major clade. Therefore, two new suborders, Phyllotopsidineae and Sarcomyxineae, are proposed for the two major lineages. Analyses of 450 single-copy orthologous genes and four loci suggested that Tricholomopsis consisted of at least four clades. Tricholomopsis is subsequently subdivided into four distinct sections. Seventeen Tricholomopsis species in China, including six new species, are reported. Conoloma is established to accommodate T. mucronata. The substrate preference of Tricholomopsis species and the transitions of the pileate ornamentations among the species within the genus are discussed. [ABSTRACT FROM AUTHOR]

Introduction The number of smokers worldwide increased greatly during the past decades and reached 1.14 billion in 2019, becoming a leading risk factor for human health. Tobacco smoking has wide effects on human genetics, epigenetics, transcriptome, and gut microbiome. Although many studies have revealed effects of smoking on host transcriptome, research on the relationship between smoking, host gene expression, and the gut microbiome is limited. Aims and Methods We first explored transcriptome and metagenome profile differences between smokers and nonsmokers. To evaluate the relationship between host gene expression and gut microbiome, we then applied bidirectional mediation analysis to infer causal relationships between smoking, gene expression, and gut microbes. Results Metagenome and transcriptome analyses revealed 71 differential species and 324 differential expressed genes between smokers and nonsmokers. With smoking as an exposure variable, we identified 272 significant causal relationships between gene expression and gut microbes, among which there were 247 genes that mediate the effect of smoking on gut microbes. Pathway-based enrichment analysis showed that these genes were significantly enriched in heme metabolic pathway, which mainly mediated the changes of Bacteroides finegoldii and Lachnospiraceae bacterium 9_1_43BFAA. Additionally, by performing metabolome data analysis in the Integrated Human Microbiome Project (iHMP) database, we verified the correlation between the intermediate products of the heme metabolism pathway (porphobilinogen, bilirubin, and biliverdin) and gut microbiome. Conclusions By investigating the bidirectional interaction between smoking-related host gene expression and gut microbes, this study provided evidence for the mediation of smoking on gut microbes through co-involvement or interaction of heme metabolism. Implications By comparing the metagenome and transcriptome sequencing profiles between 34 smokers and 33 age- and gender-matched nonsmokers, we are the first to reveal causal relationships among tobacco smoking, host gene expression, and gut microbes. These findings offer insight into how smoking affects gut microbes through host gene expression and metabolism, which highlights the importance of heme metabolism in modulating the effects of smoking on gut microbiome. [ABSTRACT FROM AUTHOR]

• gEFS is extremely rare phenomenon among IVF patients. • The pathogenesis of gEFS remain largely elusive. • Pathogenic variants in genes related to HA, folliculogenesis and ovarian function may be considered as a genetic etiology of gEFS. Empty follicle syndrome (EFS) is a condition in which no oocytes are retrieved in an IVF cycle despite apparently normal follicular development and meticulous follicular aspiration following ovulation induction. The EFS is called genuine (gEFS) when the trigger administration is correct. The existence of gEFS is a subject of controversy, and it is quite rare with an undetermined etiology. Genetic defects in specific genes have been demonstrated to be responsible for this condition in some patients. Our objective was to identify novel genetic variants associated with gEFS. We conducted a prospective observational study including 1,689 egg donors from July 2017 to February 2023. WES were performed in patients suffering gEFS. Only 7 patients (0.41 %) exhibited gEFS after two ovarian stimulation cycles and we subsequently performed whole exome sequencing (WES) on these patients. Following stringent filtering, we identified 6 variants in 5 affected patients as pathogenic in new candidate genes which have not been previously associated with gEFS before, but which are involved in important biological processes related to folliculogenesis. These genetic variants included c.603_618del in HMMR , c.1025_1028del in LMNB1 , c.1091-1G > A in TDG , c.607C > T in HABP2 , c.100 + 2 T > C in HAPLN1 and c.3592_3593del in JAG2. As a conclusion, we identified new candidate genes related to gEFS that expand the mutational spectrum of genes related to gEFS.This study show that WES might be an efficient tool to identify the genetic etiology of gEFS and provide further understanding of the pathogenic mechanism of gEFS. [ABSTRACT FROM AUTHOR]

Background: Antipsychotics, including risperidone (RIS), are frequently indicated for various autism spectrum disorder (ASD) manifestations; however, "actionable" PGx testing in psychiatry regarding antipsychotic dosing and selection has limited applications in routine clinical practice because of the lack of standard guidelines, mostly due to the inconsistency and scarcity of genetic variant data. The current study is aimed at examining the association of RIS effectiveness, according to ABC-CV and CGI indexes, with relevant pharmacokinetics (PK) and pharmacodynamics (PD) genes. Methods: Eighty-nine ASD children who received a consistent RIS-based regimen for at least 8 weeks were included. The Axiom PharmacoFocus Array technique was employed to generate accurate star allele-predicted phenotypes of 3 PK genes (CYP3A4, CYP3A5, and CYP2D6). Genotype calls for 5 candidate PD receptor genes (DRD1, DRD2, DRD3, HTR2C, and HTR2A) were obtained and reported as wild type, heterozygous, or homozygous for 11 variants. Results: Based on the ABC total score, 42 (47.2%) children were classified as responders, while 47 (52.8%) were classified as nonresponders. Multivariate logistic regression analyses, adjusted for nongenetic factors, suggested nonsignificant impacts of the star allele-predicted phenotypes of all 3 PK genes on improvement in ASD symptoms or CGI scores. However, significant positive or negative associations of certain PD variants involved in dopaminergic and serotonergic pathways were observed with specific ASD core and noncore symptom subdomains. Our significant polymorphism findings, mainly those in DRD2 (rs1800497, rs1799978, and rs2734841), HTR2C (rs3813929), and HTR2A (rs6311), were largely consistent with earlier findings (predictors of RIS effectiveness in adult schizophrenia patients), confirming their validity for identifying ASD children with a greater likelihood of core symptom improvement compared to noncarriers/wild types. Other novel findings of this study, such as significant improvements in DRD3 rs167771 carriers, particularly in ABC total and lethargy/social withdrawal scores, and DRD1 rs1875964 homozygotes and DRD2 rs1079598 wild types in stereotypic behavior, warrant further verification in biochemical and clinical studies to confirm their feasibility for inclusion in a PGx panel. Conclusion: In conclusion, we provide evidence of potential genetic markers involved in clinical response variability to RIS therapy in ASD children. However, replication in prospective samples with greater ethnic diversity and sample sizes is necessary. [ABSTRACT FROM AUTHOR]

Objective: Pancreatic beta cell destruction is a hallmark of type 1 diabetes (T1D), a heterogeneous disorder with a wide range of potential causes. T cell activation molecules have been shown to play an important role in the development of T1D, according to the majority of studies. Some autoimmune diseases have been linked to SNPs in the 4q27 region, specifically in the KIAA1109-interleukin 2 (IL2)-IL21 block. The purpose of this research was to look into how certain polymorphic variants in the 4q27 region are linked to T1D. Methods: We investigated whether variants in the 4q27 region could be a causal factor in T1D susceptibility. Polymorphisms of ten single-nucleotide polymorphisms (SNPs) belonging to the KIAA1109/IL21/IL2 block were studied in 255 individuals from 59 families using the Sequenom MassARRAY platform. Results: The IL21/IL2 region was found to have a significant association with T1D in Tunisian cohorts. We found that the T allele of the rs2221903 marker is disproportionately passed down from parents to their children. In addition, haplotype analyses encompassing all of the SNPs under consideration show that the GACAGGA and the shortly TT haplotypes were significantly over-transmitted from parents to their children, suggesting they may be a T1D genetic susceptibility factor in our population. Conclusion: Several autoimmune disorders (ADs) have been linked to the IL2/IL21 genes, suggesting that there is a shared genetic background that confers a common genetic predisposition across ADs. More research into the genetic and functional aspects of the 4q27 region is needed to better explain the role it plays in the risk of ADs. [ABSTRACT FROM AUTHOR]

Urinary cancer is synonymous with clear cell renal cell carcinoma (ccRCC). Unfortunately, existing treatments for this illness are ineffective and unpromising. Finding novel ccRCC biomarkers is crucial to creating successful treatments. The Cancer Genome Atlas provided clear cell renal cell carcinoma transcriptome data. Functional enrichment analysis was performed on ccRCC and control samples' differentially expressed N6‐methyladenosine RNA methylation and ferroptosis‐related genes (DEMFRGs). Machine learning was used to find and model ccRCC patients' predicted genes. A nomogram was created for clear cell renal cell carcinoma patients. Prognostic genes were enriched. We examined patients' immune profiles by risk score. Our prognostic genes predicted ccRCC treatment drugs. We found 37 DEMFRGs by comparing 1913 differentially expressed ccRCC genes to 202 m6A RNA methylation FRGs. Functional enrichment analysis showed that hypoxia‐induced cell death and metabolism pathways were the most differentially expressed methylation functional regulating genes. Five prognostic genes were found by machine learning: TRIB3, CHAC1, NNMT, EGFR, and SLC1A4. An advanced renal cell carcinoma nomogram with age and risk score accurately predicted the outcome. These five prognostic genes were linked to various cancers. Immunological cell number and checkpoint expression differed between high‐ and low‐risk groups. The risk model successfully predicted immunotherapy outcome, showing high‐risk individuals had poor results. NIACIN, TAE‐684, ROCILETINIB, and others treat ccRCC. We found ccRCC prognostic genes that work. This discovery may lead to new ccRCC treatments. [ABSTRACT FROM AUTHOR]

Background: The way in which socioeconomic status (SES) moderates the etiology of reading attainment has been explored many times, with past work often finding that genetic influences are suppressed under conditions of socioeconomic deprivation and more fully realized under conditions of socioeconomic advantage: a gene–SES interaction. Additionally, past work has pointed toward the presence of gene–location interactions, with the relative influence of genes and environment varying across geographic regions of the same country/state. Method: This study investigates the extent to which SES and geographical location interact to moderate the genetic and environmental components of reading attainment. Utilizing data from 2,135 twin pairs in Florida (mean age 13.82 years, range 10.71–17.77), the study operationalized reading attainment as reading comprehension scores from a statewide test and SES as household income. We applied a spatial twin analysis procedure to investigate how twin genetic and environmental estimates vary by geographic location. We then expanded this analysis to explore how the moderating role of SES on said genetic and environmental influences also varied by geographic location. Results: A gene–SES interaction was found, with heritability of reading being suppressed in lower‐ (23%) versus higher‐SES homes (78%). The magnitude of the moderating parameters were not consistent by location, however, and ranged from −0.10 to 0.10 for the moderating effect on genetic influences, and from −0.30 to 0.05 for the moderating effect on environmental influences. For smaller areas and those with less socioeconomic variability, the magnitude of the genetic moderating parameter was high, giving rise to more fully realized genetic influences on reading there. Conclusions: SES significantly influences reading variability. However, a child's home location matters in both the overall etiology and how strongly SES moderates said etiologies. These results point toward the presence of multiple significant environmental factors that simultaneously, and inseparably, influence the underlying etiology of reading attainment. [ABSTRACT FROM AUTHOR]

Rice serves as the main food source in many regions of the world. However, rice production is impacted by abiotic stress including drought, salt, temperature shifts, submersion, etc. Some rice accessions have a genetic potential to withstand in such stress conditions. Thus, identification and characterization of genes that are responsible to endure abiotic stress conditions are critical for developing new rice varieties with improved characteristics. In this respect, we studied the protein–protein interaction (PPI) network in abiotic stress-tolerant genes of rice cultivars. We explored various rice genome databases to retrieve abiotic stress-tolerant genes for this purpose. In total, 7984 genes were collected from different databases; out of these, 1408 were successfully mapped in PPI network of STRING. Subsequently, the network topology, hub protein identification, sub-network generation and functional enrichment analysis were performed using different plug-ins implemented in Cytoscape 3.9.0. We identified 17 key genes (MPK5, WRKY24, WRKY28, P5CS, DREB2A, MYB2, CLPB1, HSP81-2, HSP90, MCM2, NHX2, APX1, NYC1, CDKB1-1, CDKB2-1, ORR5 and HK4) after analysis of network using cytoHubba and MCODE tools. These identified key genes were effectively classified across diverse biological processes, encompassing hydrogen peroxide detoxification, cellular components like transport systems and molecular functions such as transcriptional activation and repression. Further, among identified key genes DREB2A, APX1 and NHX2, and MYB2, WRKY28 and WRKY24 were found to be upregulated and downregulated, respectively, in rice cultivars for different stress conditions (cold, salt and drought) in publicly available expression datasets. This information enables researchers and breeders for the development of novel abiotic stress-tolerant rice varieties. [ABSTRACT FROM AUTHOR]

Summary: Elucidating the mechanisms regulating nitrogen (N) deficiency responses in plants is of great agricultural importance. Previous studies revealed that decreased expression of NITRATE‐INDUCIBLE GARP‐TYPE TRANSCRIPTIONAL REPRESSOR1 (NIGT1) transcriptional repressor genes upon N deficiency is involved in N deficiency‐inducible gene expression in Arabidopsis thaliana. However, our knowledge of the mechanisms controlling N deficiency‐induced changes in gene expression is still limited.Through the identification of Dof1.7 as a direct target of NIGT1 repressors and a novel N deficiency response‐related transcriptional activator gene, we here show that NIGT1 and Dof1.7 transcription factors (TFs) differentially regulate N deficiency‐inducible expression of three high‐affinity nitrate transporter genes, NRT2.1, NRT2.4, and NRT2.5, which are responsible for most of the soil nitrate uptake activity of Arabidopsis plants under N‐deficient conditions.Unlike NIGT1 repressors, which directly suppress NRT2.1, NRT2.4, and NRT2.5 under N‐sufficient conditions, Dof1.7 directly activated only NRT2.5 but indirectly and moderately activated NRT2.1 and NRT2.4 under N‐deficient conditions, probably by indirectly decreasing NIGT1 expression. Thus, Dof1.7 converted passive transcriptional activation into active and potent transcriptional activation, further differentially enhancing the expression of NRT2 genes.These findings clarify the mechanism underlying different expression patterns of NRT2 genes upon N deficiency, suggesting that time‐dependent multilayered transcriptional regulation generates complicated expression patterns of N deficiency‐inducible genes. [ABSTRACT FROM AUTHOR]

This article explores the recruitment of arbuscular mycorrhizal (AM) conserved genes for ectomycorrhizal (ECM) symbiosis. ECM symbiosis, which is a more recent form of symbiosis than AM symbiosis, involves the formation of a mantle around the root and an intercellular Hartig net. The study found that ECM host species from the Fagales order maintained the majority of AM-conserved genes, unlike other non-AM hosts. Transcriptome analysis revealed that several of these maintained genes were induced in ECM symbiosis, suggesting that ECM formation recruits AM-derived mechanisms. The study focuses on ECM-only hosts, which are plant species that exclusively engage in ECM symbiosis and have lost the ability to form AM symbiosis. The researchers discovered that ECM-only hosts maintain 64% of the AM-conserved orthologous groups (OGs), highlighting the importance of these genes in ECM symbiosis. They also identified specific genes, such as RAM2, involved in lipid biosynthesis and arbuscule formation in ECM roots. The study suggests that the preservation of AM-conserved genes in ECM-only hosts supports their role in ECM symbiosis. [Extracted from the article]

Objective: To evaluate gene expression associated with vaginal bleeding in the 52‐mg hormonal intrauterine device (IUD) users. Materials and Methods: We conducted a prospective study involving 100 women seeking to use the 52‐mg hormonal IUD for contraception. We excluded women with a history or current condition of abnormal uterine bleeding and who were unable to attend a 1‐year follow up. Women who expelled the device, removed it for reasons unrelated to vaginal bleeding, or were lost to follow up were discontinued. We collected endometrial biopsies immediately before IUD placement and assessed 20 selected genes using reverse transcription quantitative polymerase chain reaction. Users maintained a uterine bleeding diary for 12 months following IUD insertion. For statistical analysis, participants were categorized into groups with or without vaginal bleeding at 3 and 12 months. Results: Women with elevated CXCL9 expression had an 8.15‐fold higher likelihood of experiencing vaginal bleeding at 3 months (odds ratio [OR] 8.15, 95% confidence interval [CI] 2.24–29.61, P = 0.001). At 12 months of follow up, women with increased TIMP1 expression had a 2.74‐fold higher chance of experiencing vaginal bleeding (OR 2.74, 95% CI 1.08–6.95, P = 0.033). CXCL9 ≥ 1.5 and IL17A ≥ 0.68 were associated with a higher probability of vaginal bleeding at 3 months, while TIMP1 levels ≥0.943 were linked to an increased risk of bleeding at 12 months. Conclusion: Users of the 52‐mg hormonal IUD with elevated relative CXCL9 expression face an increased risk of vaginal bleeding at 3‐month follow up, whereas those with heightened TIMP1 expression are more likely to experience vaginal bleeding at 12 months. Synopsis: Users of hormonal intrauterine devices with higher expression of CXCL9 and TIMP1 have greater chance of unpredictable bleeding. These results are useful for pre‐use guidance. [ABSTRACT FROM AUTHOR]

Peroxiredoxins are antioxidant proteins that detoxify peroxynitrite, hydrogen peroxide, and organic hydroperoxides, impacting various physiological processes such as immune responses, apoptosis, cellular homeostasis, and so on. In the present study, we identified and characterized peroxiredoxin 1 from Antheraea pernyi (thereafter designated as ApPrx-1) that encodes a predicted 195 amino acid residue protein with a 21.8 kDa molecular weight. Quantitative real-time PCR analysis revealed that the mRNA level of ApPrx-1 was highest in the hemocyte, fat body, and midgut. Immune-challenged larval fat bodies and hemocytes showed increased ApPrx-1 transcript. Moreover, ApPrx-1 expression was induced in hemocytes and the whole body of A. pernyi following exogenous H 2 O 2 administration. A DNA cleavage assay performed using recombinant ApPrx-1 protein showed that rApPrx-1 protein manifests the ability to protect supercoiled DNA damage from oxidative stress. To test the rApPrx-1 protein antioxidant activity, the ability of the rApPrx-1 protein to remove H 2 O 2 was assessed in vitro using rApPrx-1 protein and DTT, while BSA + DDT served as a control group. The results revealed that ApPrx-1 can efficiently remove H 2 O 2 in vitro. In the loss of function analysis, we found that ApPrx-1 significantly increased the levels of H 2 O 2 in ApPrx-1 -depleted larvae compared to the control group. We also found a significantly lower survival rate in the larvae in which ApPrx-1 was knocked down. Interestingly, the antibacterial activity was significantly higher in the ApPrx-1 depleted larvae, compared to the control. Collectively, evidence strongly suggests that ApPrx-1 may regulate physiological activities and provides a reference for further studies to validate the utility of the key genes involved in reliving oxidative stress conditions and regulating the immune responses of insects. • Prx-1 gene was identified from the Chinese oak silkworm, A. pernyi. • Microbial challenges modulate the expression patterns of ApPrx-1 in immune tissues. • Recombinant ApPrx-1 protein protects supercoiled DNA damage from oxidative stress. • Silencing of ApPrx-1 strongly affected the H 2 O 2 and bacterial clearance in A. pernyi. [ABSTRACT FROM AUTHOR]

Bacteria with streamlined genomes, that harbor full functional genes for essential metabolic networks, are able to synthesize the desired products more effectively and thus have advantages as production platforms in industrial applications. To obtain streamlined chassis genomes, a large amount of effort has been made to reduce existing bacterial genomes. This work falls into two categories: rational and random reduction. The identification of essential gene sets and the emergence of various genome-deletion techniques have greatly promoted genome reduction in many bacteria over the past few decades. Some of the constructed genomes possessed desirable properties for industrial applications, such as: increased genome stability, transformation capacity, cell growth, and biomaterial productivity. The decreased growth and perturbations in physiological phenotype of some genome-reduced strains may limit their applications as optimized cell factories. This review presents an assessment of the advancements made to date in bacterial genome reduction to construct optimal chassis for synthetic biology, including: the identification of essential gene sets, the genome-deletion techniques, the properties and industrial applications of artificially streamlined genomes, the obstacles encountered in constructing reduced genomes, and the future perspectives. [ABSTRACT FROM AUTHOR]

This work aimed to identify markers and candidate genes underlying porcine digestive traits. In total, 331 pigs were genotyped by 80 K Chip data or 50 K Chip data. For apparent neutral detergent fiber digestibility, a total of 19 and 21 candidate single nucleotide polymorphisms (SNP) were respectively identified using a genome‐wide efficient mixed‐model association algorithm and linkage‐disequilibrium adjusted kinship. Among them, three quantitative trait locus (QTL) regions were identified. For apparent acid detergent fiber digestibility, a total of 16 and 17 SNPs were identified by these two methods, respectively. Of these, three QTL regions were also identified. Moreover, two candidate genes (MST1 and LATS1), which are functionally related to intestinal homeostasis and health, were detected near these significant SNPs. Taken together, our results could provide a basis for deeper research on digestive traits in pigs. [ABSTRACT FROM AUTHOR]

Genetic research for the assessment of mastitis and milk production traits simultaneously has a long history. The main issue that arises in this context is the known existence of a positive correlation between the risk of mastitis and lactation performance due to selection. The transcriptome‐wide association study (TWAS) approach endeavors to combine the expression quantitative trait loci and genome‐wide association study summary statistics to decode complex traits or diseases. Accordingly, we used the farmgtex project results as a complete bovine database for mastitis and milk production. The results of colocalization and TWAS approaches were used for the detection of functional associated candidate genes with milk production and mastitis traits on multiple tissue‐based transcriptome records. Also, we used the david database for gene ontology to identify significant terms and associated genes. For the identification of interaction networks, the genemania and string databases were used. Also, the available z‐scores in TWAS results were used for the calculation of the correlation between tissues. Therefore, the present results confirm that LYNX1, DGAT1, C14H8orf33, and LY6E were identified as significant genes associated with milk production in eight, six, five, and five tissues, respectively. Also, FBXL6 was detected as a significant gene associated with mastitis trait. CLN3 and ZNF34 genes emerged via both the colocalization and TWAS approaches as significant genes for milk production trait. It is expected that TWAS and colocalization can improve our perception of the potential health status control mechanism in high‐yielding dairy cows. [ABSTRACT FROM AUTHOR]

Qingyuan partridge chicken is a renowned indigenous yellow broiler breed in China. Egg production traits are important economic traits for chickens. With the decreasing cost of whole genome resequencing, identifying candidate genes with more precision has become possible. In order to identify molecular markers and candidate genes associated with egg production traits, we conducted genome‐wide association studies based on the resequencing data of 287 female Qingyuan partridge chickens. For each hen, age at first egg and egg laying rate were recorded and calculated, respectively. With a univariate linear mixed model, we detected one genome‐wide significant single nucleotide polymorphism (SNP) and three chromosome‐wide significant SNPs associated with egg laying rate. MTA2 is highly likely to be a functional gene for egg laying rate. Our study identifies MTA2 as the first time to be associated with egg laying rate. Findings in our study will advance our understanding of the genetic basis of egg production and have the potential to improve the efficiency of genomic selection in chickens. [ABSTRACT FROM AUTHOR]

Crispr/CAS9‐enabled homologous recombination to insert a tag in frame with an endogenous gene can circumvent difficulties such as context‐dependent promoter activity that complicate analysis of gene expression and protein accumulation patterns. However, there have been few reports examining whether such gene targeting/gene tagging (GT) can alter expression of the target gene. The enzyme encoded by Δ1‐pyrroline‐5‐carboxylate synthetase 1 (P5CS1) is key for stress‐induced proline synthesis and drought resistance, yet its expression pattern and protein localisation have been difficult to assay. We used GT to insert YFP in frame with the 5′ or 3′ ends of the endogenous P5CS1 and At14a‐Like 1 (AFL1) coding regions. Insertion at the 3′ end of either gene generated homozygous lines with expression of the gene‐YFP fusion indistinguishable from the wild type allele. However, for P5CS1 this occurred only after selfing and advancement to the T5 generation allowed initial homozygous lethality of the insertion to be overcome. Once this was done, the GT‐generated P5CS1‐YFP plants revealed new information about P5CS1 localisation and tissue‐specific expression. In contrast, insertion of YFP at the 5′ end of either gene blocked expression. The results demonstrate that GT can be useful for functional analyses of genes that are problematic to properly express by other means but also show that, in some cases, GT can disrupt expression of the target gene. Summary statement: Gene tagging (GT) of Arabidopsis thaliana P5CS1 and AFL1 shows the potential of GT for functional analysis of stress‐related genes, but also provides examples of how GT can dramatically disrupt expression of the target gene. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress indicators affect chronic orofacial pain (COFP), but how to reduce these effects is uncertain. Objectives: 11 oxidative stress biomarkers were collected as exposures, while four forms of COFP were chosen as outcomes for Mendelian randomization (MR) study. Methods: The effect estimates between oxidative stress and COFP were calculated using inverse variance‐weighted MR (IVW‐MR). Then, functional mapping and annotation (FUMA) was utilized in order to carry out SNP‐based functional enrichment analyses. In addition, the IVW‐MR method was applied to combine effect estimates when using genetic variants associated with oxidative stress biomarkers as an instrument for exploring potential druggable targets. Results: The results indicated that oxidative stress biomarkers (causal OR of uric acid (UA), 0.998 for myofascial pain, 95% CI 0.996–1.000, p <.05; and OR of glutathione transferase (GST), 1.002 for dentoalveolar pain, 95% CI 1.000–1.003, p <.05) were significantly linked with the probability of COFP. Functional analysis also demonstrated that UA and myofascial pain genes were prominent in nitrogen and uracil metabolism, while GST and dentoalveolar pain genes were enriched in glutathione metabolism. Also, the study provided evidence that solute carrier family 2 member 9 (SLC2A9) and glutathione S‐transferase alpha 2 (GSTA2) cause discomfort in the myofascial pain (OR = 1.003, 95% CI 1.000–1.006; p <.05) and dentoalveolar region (OR = 1.001, 95% CI 1.000–1.002; p <.05), respectively. Conclusions: In conclusion, this MR study indicates that genetically predicted myofascial pain was significantly associated with decreased UA and dentoalveolar pain was significantly associated with increased GST level. SLC2A9 inhibitor and GSTA2 inhibitor were novel chronic orofacial pain therapies and biomarkers, but clinical trials are called to examine if these oxidative biomarkers have the protective effect against orofacial pain, and further research are needed to explore the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Objective: This study was conducted to investigate the differential expression of the major histocompatibility complex (MHC) gene region in Eimeria-infected broiler. Methods: We profiled gene expression of Eimeria-infected and uninfected ceca of broilers sampled at 4, 7, and 21 days post-infection (dpi) using RNA sequencing. Differentially expressed genes (DEGs) between two sample groups were identified at each time point. DEGs located on chicken chromosome 16 were used for further analysis. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis was conducted for the functional annotation of DEGs. Results: Fourteen significant (false discovery rate <0.1) DEGs were identified at 4 and 7 dpi and categorized into three groups: MHC-Y class I genes, MHC-B region genes, and non-MHC genes. In Eimeria-infected broilers, MHC-Y class I genes were upregulated at 4 dpi but downregulated at 7 dpi. This result implies that MHC-Y class I genes initially activated an immune response, which was then suppressed by Eimeria. Of the MHC-B region genes, the DMB1 gene was upregulated, and TAP-related genes significantly implemented antigen processing for MHC class I at 4 dpi, which was supported by KEGG pathway analysis. Conclusion: This study is the first to investigate MHC gene responses to coccidia infection in chickens using RNA sequencing. MHC-B and MHC-Y genes showed their immune responses in reaction to Eimeria infection. These findings are valuable for understanding chicken MHC gene function. [ABSTRACT FROM AUTHOR]

Focal segmental glomerulosclerosis (FSGS) is a complex disease which describes different kinds of kidney defects, not exclusively linked with podocyte defects. Since nephrin mutation was first described in association with early-onset nephrotic syndrome (NS), many advancements have been made in understanding genetic patterns associated with FSGS. New genetic causes of FSGS have been discovered, displaying unexpected genotypes, and recognizing possible site of damage. Many recent large-scale sequencing analyses on patients affected by idiopathic chronic kidney disease (CKD), kidney failure (KF) of unknown origin, or classified as FSGS, have revealed collagen alpha IV genes, as one of the most frequent sites of pathogenic mutations. Also, recent interest in complex and systemic lysosomal storage diseases, such as Fabry disease, has highlighted GLA mutations as possible causes of FSGS. Tubulointerstitial disease, recently classified by KDIGO based on genetic subtypes, when associated with UMOD variants, may phenotypically gain FSGS features, as well as ciliopathy genes or others, otherwise leading to completely different phenotypes, but found carrying pathogenic variants with associated FSGS phenotype. Thus, glomerulosclerosis may conceal different heterogeneous conditions. When a kidney biopsy is performed, the principal objective is to provide an accurate diagnosis. The broad spectrum of phenotypic expression and genetic complexity is demonstrating that a combined path of management needs to be applied. Genetic investigation should not be reserved only to selected cases, but rather part of medical management, integrating with clinical and renal pathology records. FSGS heterogeneity should be interpreted as an interesting opportunity to discover new pathways of CKD, requiring prompt genotype–phenotype correlation. In this review, we aim to highlight how FSGS represents a peculiar kidney condition, demanding multidisciplinary management, and in which genetic analysis may solve some otherwise unrevealed idiopathic cases. Unfortunately there is not a uniform correlation between specific mutations and FSGS morphological classes, as the same variants may be identified in familial cases or sporadic FSGS/NS or manifest a variable spectrum of the same disease. These non-specific features make diagnosis challenging. The complexity of FSGS genotypes requires new directions. Old morphological classification does not provide much information about the responsible cause of disease and misdiagnoses may expose patients to immunosuppressive therapy side effects, mistaken genetic counseling, and misguided kidney transplant programs. [ABSTRACT FROM AUTHOR]

The article presents a case study of an 18-year-old female diagnosed with chronic myeloid leukemia (CML) who rapidly progressed to the blast phase despite treatment with tyrosine kinase inhibitors (TKIs). Topics discussed include the identification of recurrent fusion genes in CML-blast phase, their potential role in disease progression and drug resistance, and the need for further research to understand their prevalence and clinical implications.

Background: Altered T‐cell repertoire with an aberrant T‐cell activation and imbalance of the Th17/Treg cells has been reported in acquired aplastic anemia (aAA). miRNAs are well known to orchestrate T‐cell activation and differentiation, however, their role in aAA is poorly characterized. The study aimed at identifying the profile of miRNAs likely to be involved in T‐cell activation and the Th17/Treg‐cell imbalance in aAA, to explore newer therapeutic targets. Methods: Five milliliters peripheral blood samples from 30 patients of aAA and 15 healthy controls were subjected to flow cytometry for evaluating Th17‐ and Treg‐cell subsets. The differential expression of 7 selected miRNAs viz; hsa‐miR‐126‐3p, miR‐146b‐5p, miR‐155‐5p, miR‐16, miR‐17, miR‐326, and miR‐181c was evaluated in the PB‐MNCs. Expression analysis of the miRNAs was performed using qRT‐PCR and fold change was calculated by 2−ΔΔCt method. The alterations in the target genes of deregulated miRNAs were assessed by qRT‐PCR. The targets studied included various transcription factors, cytokines, and downstream proteins. Results: The absolute CD3+ lymphocytes were significantly elevated in the PB of aAA patients when compared with healthy controls (p < 0.0035), however, the CD4:CD8 ratio was unperturbed. Th17: Treg‐cell ratio was altered in aAA patients (9.1 vs. 3.7%, p value <0.05), which correlated positively with disease severity and the PNH positive aAA. Across all severities of aAA, altered expression of the 07 miRNAs was noted in comparison to controls; upregulation of miR‐155 (FC—2.174, p‐value‐0.0001), miR‐146 (FC—2.006, p‐value‐0.0001), and miR‐17 (FC—3.1, p‐value‐0.0001), and downregulation of miR‐126 (FC—0.329, p‐value‐0.0001), miR‐181c (FC—0.317, p‐value‐0.0001), miR‐16 (FC—0.348, p‐value‐0.0001), and miR‐326 (FC—0.334, p‐value‐0.0001). Target study for these miRNAs revealed an increased expression of transcription factors responsible for Th1 and Th17 differentiation (T‐bet, RORϒt, IL‐17, IL‐6, and IFN‐ϒ), T‐cell activation (NFκB, MYC, and PIK3R2), downregulation of FOX‐P3, and other regulatory downstream molecules like SHIP‐1, ETS‐1, IRAK‐1, TRAF‐6, and PTEN. Conclusion: The study for the first time highlights the plausible role of different miRNAs in deregulating the Th17/Treg‐cell imbalance in aAA, and comprehensively suggest the role of altered NF‐kB and mTOR pathways in aAA. The axis may be actively explored for development of newer therapeutic targets in aAA. [ABSTRACT FROM AUTHOR]

Birth weight is a robust predictor of valued life course outcomes, emphasizing the importance of prenatal development. But does birth weight act as a proxy for environmental conditions in utero, or do biological processes surrounding birth weight themselves play a role in healthy development? To answer this question, we leverage variation in birth weight that is, within families, orthogonal to prenatal environmental conditions: one's genes. We construct polygenic scores in two longitudinal studies (Born in Bradford, N  = 2008; Wisconsin Longitudinal Study, N  = 8488) to empirically explore the molecular genetic correlates of birth weight. A 1 standard deviation increase in the polygenic score is associated with an ~100-grams increase in birth weight and a 1.4 pp (22 percent) decrease in low birth weight probability. Sibling comparisons illustrate that this association largely represents a causal effect. The polygenic score–birth weight association is increased for children who spend longer in the womb and whose mothers have higher body mass index, though we find no differences across maternal socioeconomic status. Finally, the polygenic score affects social and cognitive outcomes, suggesting that birth weight is itself related to healthy prenatal development. [ABSTRACT FROM AUTHOR]

The Shiga toxin producing Escherichia coli (STEC) are considered to be one of the most important groups of emerging public health pathogens with cattle being the main reservoir. The objective of this study was to isolate and characterise Escherichia coli Shiga toxins in dairy cattle farms. A total of 252 faeces samples were collected from healthy cows belonging to 37 farms. PCR screening of samples for the common sequences of stx1/stx2 genes and stx1 and stx2 genes resulted in a STEC faecal excretion prevalence of 59.5% at the farm level and 26.6% at the individual level. Among positive animals, 85.1% carried STEC with a single stx1 gene and 14.9% with the stx1 and stx2 genes. Immunomagnetic separation was performed on 40 PCR-positive samples (10/10 positive for the stx1 and stx2 genes and 30/57 positive only for stx1). Biochemical identification revealed the presence of 66 E. coli strains (27.5%). The search for virulence genes on these strains by PCR showed that only twenty-two (33.33%) were STEC. The presence of the stx1, stx2, ehx and eae genes was characterised in 30.3%, 4.54%, 13.63% and 1.51% of the strains, respectively, indicating that the virulotype with stx alone was dominant. Serological identification showed the absence of O157 sero-groups and the presence of O1(2), O2, O18(2), O128 sero-groups. The susceptibility testing of STEC showed 68.18% resistance to chloramphenicol, 63.64% to neomycin, 59.1% to ampicillin, 22.73% to trimethoprim + sulfamethoxazole and 9.1% to amoxicillin + clavulanic acid and nalidixic acid. Four strains showed multi-resistance. Bovine carriage of STEC constitutes a public health risk by contamination of milk and meat. To protect human health, it is necessary to limit the bovine STEC shedding. [ABSTRACT FROM AUTHOR]

The evolutionary forces underlying the rapid evolution in sequences and functions of new genes remain a mystery. Adaptation by natural selection explains the evolution of some new genes. However, many new genes perform sex-biased functions that have rapidly evolved over short evolutionary time scales, suggesting that new gene evolution may often be driven by conflicting selective pressures on males and females. It is well established that such sexual conflict (SC) plays a central role in maintaining phenotypic and genetic variation within populations, but the role of SC in driving new gene evolution remains essentially unknown. This review explores the connections between SC and new gene evolution through discussions of the concept of SC, the phenotypic and genetic signatures of SC in evolving populations, and the molecular mechanisms by which SC could drive the evolution of new genes. We synthesize recent work in this area with a discussion of the case of Apollo and Artemis , two extremely young genes (<200,000 years) in Drosophila melanogaster , which offered the first empirical insights into the evolutionary process by which SC could drive the evolution of new genes. These new duplicate genes exhibit the hallmarks of sexually antagonistic selection: rapid DNA and protein sequence evolution, essential sex-specific functions in gametogenesis, and complementary sex-biased expression patterns. Importantly, Apollo is essential for male fitness but detrimental to female fitness, while Artemis is essential for female fitness but detrimental to male fitness. These sexually antagonistic fitness effects and complementary changes to expression, sequence, and function suggest that these duplicates were selected for mitigating SC, but that SC has not been fully resolved. Finally, we propose Sexual Conflict Drive as a self-driven model to interpret the rapid evolution of new genes, explain the potential for SC and sexually antagonistic selection to contribute to long-term evolution, and suggest its utility for understanding the rapid evolution of new genes in gametogenesis. [ABSTRACT FROM AUTHOR]

Background: Pulmonary arterial hypertension (PAH) is a complex and progressive illness that has a multifaceted origin, significant fatality rates, and profound effects on health. The pathogenesis of PAH is poorly defined due to the insufficient understanding of the combined impact of endoplasmic reticulum (ER) stress and immune infiltration, both of which play vital roles in PAH development. This study aims to identify potential ER stress-related biomarkers in PAH and investigate their involvement in immune infiltration. Methods: The GEO database was used to download gene expression profiles. Genes associated with ER stress were obtained from the MSigDB database. Weighted gene co-expression network analysis (WGCNA), GO, KEGG, and protein-protein interaction (PPI) were utilized to conduct screening of hub genes and explore potential molecular mechanisms. Furthermore, the investigation also delved into the presence of immune cells in PAH tissues and the correlation between hub genes and the immune system. Finally, we validated the diagnostic value and expression levels of the hub genes in PAH using subject-workup characterization curves and real-time quantitative PCR. Results: In the PAH and control groups, a total of 31 genes related to ER stress were found to be differentially expressed. The enrichment analysis revealed that these genes were primarily enriched in reacting to stress in the endoplasmic reticulum, dealing with unfolded proteins, transporting proteins, and processing proteins within the endoplasmic reticulum. EIF2S1, NPLOC4, SEC61B, SYVN1, and DERL1 were identified as the top 5 hub genes in the PPI network. Immune infiltration analysis revealed that these hub genes were closely related to immune cells. The receiver operating characteristic (ROC) curves revealed that the hub genes exhibited excellent diagnostic efficacy for PAH. The levels of SEC61B, NPLOC4, and EIF2S1 expression were in agreement with the findings of bioinformatics analysis in the PAH group. Conclusions: Potential biomarkers that could be utilized are SEC61B, NPLOC4, and EIF2S1, as identified in this study. The infiltration of immune cells was crucial to the development and advancement of PAH. This study provided new potential therapeutic targets for PAH. [ABSTRACT FROM AUTHOR]

Background: Osteoporosis (OP), the "silent epidemic" of our century, poses a significant challenge to public health, predominantly affecting postmenopausal women and the elderly. It evolves from mild symptoms to pronounced severity, stabilizing eventually. Unique among OP's characteristics is the altered metabolic profile of affected cells, particularly in pyrimidine metabolism (PyM), a crucial pathway for nucleotide turnover and pyrimidine decomposition. While metabolic adaptation is acknowledged as a therapeutic target in various diseases, the specific role of PyM genes (PyMGs) in OP's molecular response remains to be clarified. Methods: In pursuit of elucidating and authenticating PyMGs relevant to OP, we embarked on a comprehensive bioinformatics exploration. This entailed the integration of Weighted Gene Co-expression Network Analysis (WGCNA) with a curated list of 37 candidate PyMGs, followed by the examination of their biological functions and pathways via Gene Set Variation Analysis (GSVA). The Least Absolute Shrinkage and Selection Operator (LASSO) technique was harnessed to identify crucial hub genes. We evaluated the diagnostic prowess of five PyMGs in OP detection and explored their correlation with OP's clinical traits, further validating their expression profiles through independent datasets (GSE2208, GSE7158, GSE56815, and GSE35956). Results: Our analytical rigor unveiled five PyMGs—IGKC, TMEM187, RPS11, IGLL3P, and GOLGA8N—with significant ties to OP. A deeper dive into their biological functions highlighted their roles in estrogen response modulation, cytosolic calcium ion concentration regulation, and GABAergic synaptic transmission. Remarkably, these PyMGs emerged as potent diagnostic biomarkers for OP, distinguishing affected individuals with substantial accuracy. Conclusions: This investigation brings to light five PyMGs intricately associated with OP, heralding new avenues for biomarker discovery and providing insights into its pathophysiological underpinnings. These findings not only deepen our comprehension of OP's complexity but also herald the advent of more refined diagnostic and therapeutic modalities. [ABSTRACT FROM AUTHOR]

Background: Unlike Transposable Elements (TEs) and gene/genome duplication, the role of the so-called nuclear plastid DNA sequences (NUPTs) in shaping the evolution of genome architecture and function remains poorly studied. We investigate here the functional and evolutionary fate of NUPTs in the orphan crop Moringa oleifera (moringa), featured by the highest fraction of plastid DNA found so far in any plant genome, focusing on (i) any potential biases in their distribution in relation to specific nuclear genomic features, (ii) their contribution to the emergence of new genes and gene regions, and (iii) their impact on the expression of target nuclear genes. Results: In agreement with their potential mutagenic effect, NUPTs are underrepresented among structural genes, although their overall transcription levels and broadness were only lower when involved exonic regions; the occurrence of plastid DNA generally did not result in a broader expression, except among those affected in introns by older NUPTs. In contrast, we found a strong enrichment of NUPTs among specific superfamilies of retrotransposons and several classes of RNA genes, including those participating in the protein biosynthetic machinery (i.e., rRNA and tRNA genes) and a specific class of regulatory RNAs. A significant fraction of NUPT RNA genes was found to be functionally expressed, thus potentially contributing to the nuclear pool. Conclusions: Our results complete our view of the molecular factors driving the evolution of nuclear genome architecture and function, and support plastid DNA in moringa as a major source of (i) genome complexity and (ii) the nuclear pool of RNA genes. [ABSTRACT FROM AUTHOR]

Background: E2F/DP (Eukaryotic 2 transcription factor/dimerization partner) family proteins play an essential function in the cell cycle development of higher organisms. E2F/DP family genes have been reported only in a few plant species. However, comprehensive genome-wide characterization analysis of the E2F/DP gene family of Solanum lycopersicum has not been reported so far. Results: This study identified eight nonredundant SlE2F/DP genes that were classified into seven groups in the phylogenetic analysis. All eight genes had a single E2F-TDP domain and few genes had additional domains. Two segmental duplication gene pairs were observed within tomato, in addition to cis-regulatory elements, miRNA target sites and phosphorylation sites which play an important role in plant development and stress response in tomato. To explore the three-dimensional (3D) models and gene ontology (GO) annotations of SlE2F/DP proteins, we pointed to their putative transporter activity and their interaction with several putative ligands. The localization of SlE2F/DP-GFP fused proteins in the nucleus and endoplasmic reticulum suggested that they may act in other biological functions. Expression studies revealed the differential expression pattern of most of the SlE2F/DP genes in various organs. Moreover, the expression of E2F/DP genes against abiotic stress, particularly SlE2F/DP2 and/or SlE2F/DP7, was upregulated in response to heat, salt, cold and ABA treatment. Furthermore, the co-expression analysis of SlE2F/DP genes with multiple metabolic pathways was co-expressed with defence genes, transcription factors and so on, suggested their crucial role in various biological processes. Conclusions: Overall, our findings provide a way to understand the structure and function of SlE2F/DP genes; it might be helpful to improve fruit development and tolerance against abiotic stress through marker-assisted selection or transgenic approaches. [ABSTRACT FROM AUTHOR]

Background: Freezing stress is one of the major abiotic stresses that causes extensive damage to plants. LEA (Late embryogenesis abundant) proteins play a crucial role in plant growth, development, and abiotic stress. However, there is limited research on the function of LEA genes in low-temperature stress in Brassica napus (rapeseed). Results: Total 306 potential LEA genes were identified in B. rapa (79), B. oleracea (79) and B. napus (148) and divided into eight subgroups. LEA genes of the same subgroup had similar gene structures and predicted subcellular locations. Cis-regulatory elements analysis showed that the promoters of BnaLEA genes rich in cis-regulatory elements related to various abiotic stresses. Additionally, RNA-seq and real-time PCR results indicated that the majority of BnaLEA family members were highly expressed in senescent tissues of rapeseed, especially during late stages of seed maturation, and most BnaLEA genes can be induced by salt and osmotic stress. Interestingly, the BnaA.LEA6.a and BnaC.LEA6.a genes were highly expressed across different vegetative and reproductive organs during different development stages, and showed strong responses to salt, osmotic, and cold stress, particularly freezing stress. Further analysis showed that overexpression of BnaA.LEA6.a increased the freezing tolerance in rapeseed, as evidenced by lower relative electrical leakage and higher survival rates compared to the wild-type (WT) under freezing treatment. Conclusion: This study is of great significance for understanding the functions of BnaLEA genes in freezing tolerance in rapeseed and offers an ideal candidate gene (BnaA.LEA6.a) for molecular breeding of freezing-tolerant rapeseed cultivars. [ABSTRACT FROM AUTHOR]

Background: Data about the prevalence of plasmid-mediated quinolone resistance (PMQR) and extended-spectrum beta-lactamase (ESBL) production in P. aeruginosa compared to the Enterobacteriaceae family is limited. The availability of limited therapeutic options raises alarming concerns about the treatment of multidrug-resistant P. aeruginosa. This study aimed to assess the presence of PMQR and ESBL genes among P. aeruginosa strains. Methods: Fifty-six P. aeruginosa strains were isolated from 330 patients with different clinical infections. Phenotypically fluoroquinolone-resistant isolates were tested by PCR for the presence of six PMQR genes. Then, blaTEM, blaSHV, and blaCTX-M type ESBL genes were screened to study the co-existence of different resistance determinants. Results: Overall, 22/56 (39.3%) of the studied P. aeruginosa isolates were phenotypically resistant to fluoroquinolones. PMQR-producing P. aeruginosa isolates were identified in 20 isolates (90.9%). The acc(6')-Ib-cr was the most prevalent PMQR gene (77.3%). The qnr genes occurred in 72.7%, with the predominance of the qnrA gene at 54.5%, followed by the qnrS gene at 27.3%, then qnrB and qnrC at 22.7%. The qepA was not detected in any isolate. The acc(6')-Ib-cr was associated with qnr genes in 65% of positive PMQR isolates. Significant differences between the fluoroquinolone-resistant and fluoroquinolone-susceptible isolates in terms of the antibiotic resistance rates of amikacin, imipenem, and cefepime (P value < 0.0001) were found. The ESBL genes were detected in 52% of cephalosporin-resistant P. aeruginosa isolates. The most frequent ESBL gene was blaCTX-M (76.9%), followed by blaTEM (46.2%). No isolates carried the blaSHV gene. The acc(6')-Ib-cr gene showed the highest association with ESBL genes, followed by the qnrA gene. The correlation matrix of the detected PMQR and ESBL genes indicated overall positive correlations. The strongest and most highly significant correlation was between qnrA and acc(6')-Ib-cr (r = 0.602) and between qnrA and blaCTX-M (r = 0.519). Conclusion: A high prevalence of PMQR genes among the phenotypic fluoroquinolone-resistant P. aeruginosa isolates was detected, with the co-carriage of different PMQR genes. The most frequent PMQR was the acc(6')-Ib-cr gene. Co-existence between PMQR and ESBL genes was found, with 75% of PMQR-positive isolates carrying at least one ESBL gene. A high and significant correlation between the ESBL and PMQR genes was detected. [ABSTRACT FROM AUTHOR]

Brassica vegetables exhibit pronounced heterosis; nevertheless, investigations on fertility-related genes are scarce. The present study scrutinized a recessive genic male-sterile line, 7-3A, capable of generating a completely sterile population, holding significant promise for flowering Chinese cabbage breeding. By whole-genome resequencing of sterile and fertile plants, the male-sterile gene was confined to approximately 185 kb on chromosome A07, situated between markers C719 and NP10 in Brassica rapa var. Chiifu-401. Notably, substantial structural variation was identified within this region across diverse Brassica rapa reference genomes. Despite discernible expression level disparities of a homologous gene, Bnams4b, between male sterile and fertile plants, no sequence divergence was detected. Further elucidation is required to pinpoint a novel sterile gene within the candidate interval. This investigation contributes to the advancement of both the molecular-assisted breeding scheme for flowering Chinese cabbage and the comprehension of male sterility mechanisms. [ABSTRACT FROM AUTHOR]

Increasing yield is an important goal of barley breeding. In this study, 54 papers published from 2001–2022 on QTL mapping for yield and yield-related traits in barley were collected, which contained 1080 QTLs mapped to the barley high-density consensus map for QTL meta-analysis. These initial QTLs were integrated into 85 meta-QTLs (MQTL) with a mean confidence interval (CI) of 2.76 cM, which was 7.86-fold narrower than the CI of the initial QTL. Among these 85 MQTLs, 68 MQTLs were validated in GWAS studies, and 25 breeder's MQTLs were screened from them. Seventeen barley orthologs of yield-related genes in rice and maize were identified within the hcMQTL region based on comparative genomics strategy and were presumed to be reliable candidates for controlling yield-related traits. The results of this study provide useful information for molecular marker-assisted breeding and candidate gene mining of yield-related traits in barley. [ABSTRACT FROM AUTHOR]

Objective: Duchenne muscular dystrophy (DMD) is a devastating X-linked neuromuscular disorder caused by various defects in the dystrophin gene and still no universal therapy. This study aims to identify the hub genes unrelated to excessive immune response but responsible for DMD progression and explore therapeutic siRNAs, thereby providing a novel treatment. Methods: Top ten hub genes for DMD were identified from GSE38417 dataset by using GEO2R and PPI networks based on Cytoscape analysis. The hub genes unrelated to excessive immune response were identified by GeneCards, and their expression was further verified in mdx and C57 mice at 2 and 4 months (M) by (RT-q) PCR and western blotting. Therapeutic siRNAs were deemed as those that could normalize the expression of the validated hub genes in transfected C2C12 cells. Results: 855 up-regulated and 324 down-regulated DEGs were screened from GSE38417 dataset. Five of the top 10 hub genes were considered as the candidate genes unrelated to excessive immune response, and three of these candidates were consistently and significantly up-regulated in mdx mice at 2 M and 4 M when compared with age-matched C57 mice, including Col1a2, Fbn1 and Fn1. Furthermore, the three validated up-regulated candidate genes can be significantly down-regulated by three rational designed siRNA (p < 0.0001), respectively. Conclusion: COL1A2, FBN1 and FN1 may be novel biomarkers for DMD, and the siRNAs designed in our study were help to develop adjunctive therapy for Duchenne muscular dystrophy. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course Background: Fulminant type 1 diabetes is characterized by a low prevalence of autoantibodies, and was originally described as a nonautoimmune subtype of type 1 diabetes. Herein, we report a case in which we observed the process of extremely rapid onset of diabetes and early decline in anti-glutamic acid decarboxylase (GAD) antibody titers during the inpatient stay. Case Report: A 61-year-old man was brought to our hospital with marked hyperglycemia (1327 mg/dL), ketonemia (3-hydroxybutyrate: 14 012 µmol/L), and moderately elevated HbA1c (7.2%) and glycoalbumin (22.3%). C-peptide levels were undetectable. He had suffered from thirst, polyuria, and fatigue for 2 days. Abrupt onset was proven by the clinical data when he visited the hospital with respiratory symptoms 6 days before his admission; plasma glucose, glycoalbumin, C-peptide, and insulin levels were 117 mg/dL, 13.0%, 5.07 ng/mL, and 24.4 µIU/mL, respectively. The anti-GAD antibody titer measured by enzyme-linked immunosorbent assay was 111 U/mL at admission, 22.8 U/mL 2 weeks after admission, and negative 1 year later. He had a susceptible haplotype DRB1*09: 01-DQB1*03: 03, which is significantly more common in anti-GAD antibody-positive patients with fulminant type 1 diabetes. Conclusions: The early decline of anti-GAD antibody titer likely reflected rapid and complete beta cell loss. The sequential metabolic and immunological observation in this case may provide insight into the pathogenesis of fulminant type 1 diabetes. [ABSTRACT FROM AUTHOR]

Pathway enrichment analysis is a ubiquitous computational biology method to interpret a list of genes (typically derived from the association of large-scale omics data with phenotypes of interest) in terms of higher-level, predefined gene sets that share biological function, chromosomal location, or other common features. Among many tools developed so far, Gene Set Enrichment Analysis (GSEA) stands out as one of the pioneering and most widely used methods. Although originally developed for microarray data, GSEA is nowadays extensively utilized for RNA-seq data analysis. Here, we quantitatively assessed the performance of a variety of GSEA modalities and provide guidance in the practical use of GSEA in RNA-seq experiments. We leveraged harmonized RNA-seq datasets available from The Cancer Genome Atlas (TCGA) in combination with large, curated pathway collections from the Molecular Signatures Database to obtain cancer-type-specific target pathway lists across multiple cancer types. We carried out a detailed analysis of GSEA performance using both gene-set and phenotype permutations combined with four different choices for the Kolmogorov-Smirnov enrichment statistic. Based on our benchmarks, we conclude that the classic/unweighted gene-set permutation approach offered comparable or better sensitivity-vs-specificity tradeoffs across cancer types compared with other, more complex and computationally intensive permutation methods. Finally, we analyzed other large cohorts for thyroid cancer and hepatocellular carcinoma. We utilized a new consensus metric, the Enrichment Evidence Score (EES), which showed a remarkable agreement between pathways identified in TCGA and those from other sources, despite differences in cancer etiology. This finding suggests an EES-based strategy to identify a core set of pathways that may be complemented by an expanded set of pathways for downstream exploratory analysis. This work fills the existing gap in current guidelines and benchmarks for the use of GSEA with RNA-seq data and provides a framework to enable detailed benchmarking of other RNA-seq-based pathway analysis tools. [ABSTRACT FROM AUTHOR]

The Presenilin (Psn) gene is closely related to aging, but it is still unclear the role of Psn genes in skeletal muscle. Here, the Psn-UAS/Mhc-GAL4 system in Drosophila was used to regulate muscle Psn overexpression(MPO) and muscle Psn knockdown(MPK). Drosophila were subjected to endurance exercise from 4 weeks to 5 weeks old. The results showed that MPO and exercise significantly increased climbing speed, climbing endurance, lifespan, muscle SOD activity, Psn expression, Sirt1 expression, PGC-1α expression, and armadillo (arm) expression in aged Drosophila, and they significantly decreased muscle malondialdehyde levels. Interestingly, when the Psn gene is knockdown by 0.78 times, the PGC-1α expression and arm expression were also down-regulated, but the exercise capacity and lifespan were increased. Furthermore, exercise combined with MPO further improved the exercise capacity and lifespan. MPK combined with exercise further improves the exercise capacity and lifespan. Thus, current results confirmed that the muscle Psn gene was a vital gene that contributed to the healthy aging of skeletal muscle since whether it was overexpressed or knocked down, the aging progress of skeletal muscle structure and function was slowed down by regulating the activity homeostasis of Sirt1/PGC-1α pathway and Psn/arm pathway. Exercise enhanced the function of the Psn gene to delay skeletal muscle aging by up regulating the activity of the Sirt1/PGC-1α pathway and Psn/arm pathway. [ABSTRACT FROM AUTHOR]

In the protozoan parasite Leishmania, most genes encoding for ribosomal proteins (RPs) are present as two or more copies in the genome. However, their untranslated regions (UTRs) are predominantly divergent and might be associated with a distinct regulation of the expression of paralogous genes. Herein, we investigated the expression profiles of two RPs (S16 and L13a) encoded by duplicated genes in Leishmania major. The genes encoding for the S16 protein possess identical coding sequences (CDSs) and divergent UTRs, whereas the CDSs of L13a diverge by two amino acids and by their UTRs. Using CRISPR/Cas9 genome editing, we generated knockout (Δ) and endogenously tagged transfectants for each paralog of L13a and S16 genes. Combining tagged and Δ cell lines we found evidence of differential expression of both RPS16 and RPL13a isoforms throughout parasite development, with one isoform consistently more abundant than its respective copy. In addition, compensatory expression was observed for each paralog upon deletion of the corresponding isoform, suggesting functional conservation between these proteins. This differential expression pattern relates to post-translational processes, given compensation occurs at the level of the protein, with no alterations detected at transcript level. Ribosomal profiles for RPL13a indicate a standard behavior for these paralogues suggestive of interaction with heavy RNA-protein complexes, as already reported for other RPs in trypanosomatids. We identified paralog-specific bound to their 3'UTRs which may be influential in regulating paralog expression. In support, we identified conserved cis-elements within the 3'UTRs of RPS16 and RPL13a; cis-elements exclusive to the UTR of the more abundant paralog or to the less abundant ones were identified. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to identify and analyze the mitochondrial genes associated with sepsis patients in order to elucidate the underlying mechanism of sepsis immunity and provide new ideas for the clinical treatment of sepsis. Methods: The hospitalized cases of sepsis (n = 20) and systemic inflammatory response syndrome (SIRS) (n = 12) admitted to the Emergency Intensive Care Unit (EICU) of the Affiliated Hospital of Southwest Medical University from January 2019 to December 2019 were collected consecutively. RNA-seq was used to sequence the RNA (mRNA) of peripheral blood cells. Bioinformatics techniques were used to screen and identify differentially expressed RNAs, with an absolute value of fold change (FC) greater than or equal to 1.2 and a false discovery rate (FDR) less than 0.05. At the same time, mitochondrial genes were obtained from the MitoCarta 3.0 database. Differential genes were then intersected with mitochondrial genes. The resulting crossover genes were subjected to GO, KEGG, and PPI analysis. Subsequently, the GSE65682 dataset was downloaded from the GEO database for survival analysis to assess the prognostic value of core genes, and GSE67652 was downloaded for ROC curve analysis to validate the diagnostic value of core genes. Finally, the localization of core genes was clarified through 10X single-cell sequencing. Results: The crossing of 314 sepsis differential genes and 1136 mitochondrial genes yielded 28 genes. GO and KEGG analysis showed that the crossover genes were mainly involved in the mitochondrion, mitochondrial matrix, and mitochondrial inner membrane. Survival analysis screened four genes that were significantly negatively associated with the prognosis of sepsis, namely FIS1, FKBP8, GLRX5, and GUK1. A comparison of peripheral blood RNA-seq results between the sepsis group and the SIRS group showed that the expression levels of these four genes were significantly decreased in the sepsis group compared to the SIRS group. ROC curve analysis based on GSE67652 indicates these four genes' high sensitivity and specificity for sepsis detection. Additionally, single-cell RNA sequencing found that the core genes were mainly expressed in macrophages, T cells, and B cells. Conclusions: Mitochondria-related genes (FIS1, FKBP8, GLRX5, GUK1) were underexpressed in the sepsis group, negatively correlated with survival, and mainly distributed in immune cells. This finding may guide studying the immune-related mechanisms of sepsis. This study protocol was reviewed by the Ethics Committee of the Affiliated Hospital of Southwest Medical University (ethics number: KY2018029), the clinical trial registration number is ChiCTR1900021261, and the registration date is February 4, 2019. [ABSTRACT FROM AUTHOR]

Background: Late-onset Alzheimer's disease (LOAD) is the most common type of dementia, but its pathogenesis remains unclear, and there is a lack of simple and convenient early diagnostic markers to predict the occurrence. Objective: Our study aimed to identify diagnostic candidate genes to predict LOAD by machine learning methods. Methods: Three publicly available datasets from the Gene Expression Omnibus (GEO) database containing peripheral blood gene expression data for LOAD, mild cognitive impairment (MCI), and controls (CN) were downloaded. Differential expression analysis, the least absolute shrinkage and selection operator (LASSO), and support vector machine recursive feature elimination (SVM-RFE) were used to identify LOAD diagnostic candidate genes. These candidate genes were then validated in the validation group and clinical samples, and a LOAD prediction model was established. Results: LASSO and SVM-RFE analyses identified 3 mitochondria-related genes (MRGs) as candidate genes, including NDUFA1, NDUFS5, and NDUFB3. In the verification of 3 MRGs, the AUC values showed that NDUFA1, NDUFS5 had better predictability. We also verified the candidate MRGs in MCI groups, the AUC values showed good performance. We then used NDUFA1, NDUFS5 and age to build a LOAD diagnostic model and AUC was 0.723. Results of qRT-PCR experiments with clinical blood samples showed that the three candidate genes were expressed significantly lower in the LOAD and MCI groups when compared to CN. Conclusion: Two mitochondrial-related candidate genes, NDUFA1 and NDUFS5, were identified as diagnostic markers for LOAD and MCI. Combining these two candidate genes with age, a LOAD diagnostic prediction model was successfully constructed. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the most common form of dementia in the elderly marked by central nervous system (CNS) neuronal loss and amyloid plaques. FAM222A, encoding an amyloid plaque core protein, is an AD brain atrophy susceptibility gene that mediates amyloid-β aggregation. However, the expression interplay between FAM222A and other AD-related pathway genes is unclear. Objective: Our goal was to study FAM222A's whole-genome co-expression profile in multiple tissues and investigate its interplay with other AD-related genes. Methods: We analyzed gene expression correlations in Genotype-Tissue Expression (GTEx) tissues to identify FAM222A co-expressed genes and performed functional enrichment analysis on identified genes in CNS system. Results: Genome-wide gene expression profiling identified 673 genes significantly correlated with FAM222A (p < 2.5×10–6) in 48 human tissues, including 298 from 13 CNS tissues. Functional enrichment analysis revealed that FAM222A co-expressed CNS genes were enriched in multiple AD-related pathways. Gene co-expression network analysis for identified genes in each brain region predicted other disease associated genes with similar biological function. Furthermore, co-expression of 25 out of 31 AD-related pathways genes with FAM222A was replicated in brain samples from 107 aged subjects from the Aging, Dementia and TBI Study. Conclusion: This gene co-expression study identified multiple AD-related genes that are associated with FAM222A, indicating that FAM222A and AD-associated genes can be active simultaneously in similar biological processes, providing evidence that supports the association of FAM222A with AD. [ABSTRACT FROM AUTHOR]

Simple Summary: Shitou geese are the exclusive representative of a large-sized goose breed in China, typically exhibiting gray feathers but also possessing a recessive white plumage. However, the precise mechanism underlying the formation of this white plumage coloration in Shitou geese remains unclear. Here, a transcriptome sequencing analysis was conducted to identify candidate genes and microRNAs (miRNAs) that may be associated with the white plumage color in Shitou geese. A number of pigmentation genes and miRNAs were identified as candidates that may regulate white plumage color formation in Shitou geese. This result may be important for understanding the genetic mechanism underlying the formation of white plumage color in Shitou geese. The Shitou goose, a highly recognized indigenous breed with gray plumage originating from Chaozhou Raoping in Guangdong Province, China, is renowned for being the largest goose species in the country. Notably, during the pure breeding process of Shitou geese, approximately 2% of the offspring in each generation unexpectedly exhibited white plumage. To better understand the mechanisms underlying white plumage color formation in Shitou geese, we conducted a comparative transcriptome analysis between white and gray feather follicles, aiming to identify key genes and microRNAs that potentially regulate white plumage coloration in this unique goose breed. Our results revealed a number of pigmentation genes, encompassing TYR, TYRP1, EDNRB2, MLANA, SOX10, SLC45A2, GPR143, TRPM1, OCA2, ASIP, KIT, and SLC24A5, which were significantly down-regulated in the white feather follicles of Shitou geese. Among these genes, EDNRB2 and KIT emerged as the most promising candidate genes for white plumage coloration in Shitou geese. Additionally, our analysis also uncovered 46 differentially expressed miRNAs. Of these, miR-144-y may play crucial roles in the regulation of feather pigmentation. Furthermore, the expression of novel-m0086-5p, miR-489-y, miR-223-x, miR-7565-z, and miR-3535-z exhibits a significant negative correlation with the expression of pigmentation genes including TYRP1, EDNRB2, MLANA, SOX10, TRPM1, and KIT, suggesting these miRNAs may indirectly regulate the expression of these genes, thereby influencing feather color. Our findings provide valuable insights into the genetic mechanisms underlying white plumage coloration in Shitou geese and contribute to the broader understanding of avian genetics and coloration research. [ABSTRACT FROM AUTHOR]

Simple Summary: The reproduction of goats is a highly complex and dynamic process of life regulation, which is synergistically regulated by various aspects such as central nervous system regulation, reproductive system development, oocyte maturation, and fertilized egg development. In goats, there is still an urgent need to explore marker genes related to reproductive performance. This study identified the RPL4 gene as a key marker gene related to reproductive capacity in goat oocytes through various bioinformatics analysis methods including WGCNA, PPI network analysis, and differential gene expression analysis. The results reveal that the RPL4 gene in oocytes has the potential to serve as a biological marker for determining the reproductive rate of goats, deepening our understanding of the regulatory mechanisms of goat reproductive performance. Reproduction in goats is a highly complex and dynamic process of life regulation, involving coordinated regulation from various aspects such as central nervous system regulation, reproductive system development, oocyte maturation, and fertilized egg development. In recent years, researchers have identified numerous genes associated with goat reproductive performance through high-throughput sequencing, single-cell sequencing, gene knockout, and other techniques. However, there is still an urgent need to explore marker genes related to goat reproductive performance. In this study, a single-cell RNA sequencing dataset of oocytes (GSE136005) was obtained from the Gene Expression Omnibus (GEO) database. Weighted Gene Co-expression Network Analysis (WGCNA) was utilized to identify modules highly correlated with goat litter size. Through gene function enrichment analysis, it was found that genes within the modules were mainly enriched in adhesive junctions, cell cycle, and other signaling pathways. Additionally, the top 30 hub genes with the highest connectivity in WGCNA were identified. Subsequently, using Protein–Protein Interaction (PPI) network analysis, the top 30 genes with the highest connectivity within the modules were identified. The intersection of hub genes, key genes in the PPI network, and differentially expressed genes (DEGs) led to the identification of the RPL4 gene as a key marker gene associated with reproductive capacity in goat oocytes. Overall, our study reveals that the RPL4 gene in oocytes holds promise as a biological marker for assessing goat litter size, deepening our understanding of the regulatory mechanisms underlying goat reproductive performance. [ABSTRACT FROM AUTHOR]