Annotation Enrichment Analysis Research Articles

Copper metabolism-related lncRNAs predict prognosis and immune landscape in liver cancer patients.

Characterized by its high mortality and easy recurrence, hepatocellular carcinoma (HCC) poses significant clinical challenges. The association between copper metabolism and development of cancer has been identified. However, the underlying mechanisms of copper metabolism-related long non-coding RNAs (CMRLs) in HCC remain elusive. To address the gap, our study analyzed the prognostic and immuno-therapeutic value of CMRLs in HCC. This research utilized The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) data (n=424) for analysis, applying the "limma" package in R software for differential gene analysis and construction of a prognostic signature. We validated the signature using training and validation groups stochastically divided at a ratio of 1:1 and assessed prognostic value via Kaplan-Meier, C-index, and receiver operating characteristic (ROC) curves. By multivariate Cox regression, independent prognostic indicators were identified, and a nomogram was formulated for survival forecasting. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses elucidated biological pathways, and the immune landscape was examined through multiple algorithms. Finally, drug sensitivity was determined from Genomics of Drug Sensitivity in Cancer (GDSC), with mutation analysis conducted via maftools. In this study, a predictive model based on four pivotal CMRLs (PRRT3-AS1, AC108752.1, AC092115.3, AL031985.3) significantly associated with HCC progression and prognosis was constructed and validated with the overall survival (OS) prediction area under the curve (AUC) values for 1, 3, and 5 years of 0.718, 0.688, and 0.669, respectively. The calibration curves and C-index values showed a solid prognostic ability of the nomogram. The high-risk group was notably higher than the low-risk group both in OS and tumor mutational burdens (TMBs). Moreover, functional annotation enrichment analysis of CMRLs revealed that the signature was mainly associated with mitotic function, chromosome, kinetochore, cell cycle, and oocyte meiosis. Furthermore, therapeutic drugs, including fluorouracil, afatinib, alpelisib, cedranib, crizotinib, erlotinib, gefitinib, and ipatasertib, were found to induce higher sensitivity in high-risk group. The prognostic signature consisting of four CMRLs displays an outstanding predictive performance and improves the precision of immuno-oncology.

Comparative transcriptomic and proteomic analyses of two salt-tolerant alfalfa (Medicago sativa L.) genotypes: investigation of the mechanisms underlying tolerance to salt.

Abiotic stressors such as salt stress restrict plant development and output, which lowers agricultural profitability. In this study, alfalfa (Medicago sativa L.) varieties with different levels of salt tolerance were examined using high-throughput RNA sequencing (RNA-Seq) and Tandem Mass Tags (TMT) technologies to study the reactions of the root systems to salt stress, from transcriptomics and proteomics perspectives. The varieties Atlantic (AT) and Zhongmu-1 (ZM-1) were selected and evaluated after 2 h and 6 h of treatment with 150 mM NaCl. The results showed that under salt stress for 2 h, 1810 differentially expressed genes (DEGs) and 160 differentially expressed proteins (DEPs) in AT were screened, while 9341 DEGs and 193 DEPs were screened in ZM-1. Under salt stress for 6 h, 7536 DEGs and 118 DEPs were screened in AT, while 11,754 DEGs and 190 DEPs were screened in ZM-1. Functional annotation and pathway enrichment analyses indicated that the DEGS and DEPs were mainly involved in the glutathione metabolism, biosynthesis of secondary metabolites, glycolysis/gluconeogenesis, carbon fixation in photosynthetic organisms, and photosynthesis pathways. A series of genes related to salt tolerance were also identified, including GSTL3 and GSTU3 of the GST gene family, PER5 and PER10, of the PER gene family, and proteins such as APR and COMT, which are involved in biosynthesis of secondary metabolites. This study provides insights into salt resistance mechanisms in plants, and the related genes and metabolic pathways identified may be helpful for alfalfa breeding in the future.

Proteomic Analysis of Follicular Fluid in Polycystic Ovary Syndrome: Insights into Protein Composition and Metabolic Pathway Alterations.

This study explores the proteomic composition of follicular fluid (FF) from women undergoing oocyte retrieval for in vitro fertilisation (IVF), with a focus on the effects of polycystic ovary syndrome (PCOS). FF samples were collected from 74 patients, including 34 with PCOS and 40 oocyte donors. Proteomic profiling using machine learning identified significant differences in protein abundance between the PCOS and control groups. Of the 484 quantified proteins, 20 showed significantly altered levels in the PCOS group. Functional annotation and pathway enrichment analysis pointed to the involvement of protease inhibitors and immune-related proteins in the pathophysiology of PCOS, suggesting that inflammation and immune dysregulation may play a key role. Additionally, HDL assembly was identified as a significant pathway, with apolipoprotein-AI (APOA1) and alpha-2-macroglobulin (A2M) as the major proteins involved. Notably, myosin light polypeptide 6 was the most downregulated protein, showing the highest absolute fold change, and may serve as a novel independent biomarker for PCOS.

Exploring the Mechanism of Curcumin-mediated Photodynamic Therapy for Systemic Lupus Erythematosus Based on Network Pharmacology

ObjectiveTo explore the potential therapeutic targets, this study explored possible molecular mechanism of curcumin photodynamic therapy for systemic lupus erythematosus using network pharmacology. MethodsThe potential targets for systemic lupus erythematosus upon curcumin and photodynamic treatment were predicted using Venny2.1 online analysis platform, followed by GO functional annotation and KEGG enrichment analyses being performed to screen the possible underlying mechanisms. The core targets were then obtained through construction of protein-protein interaction (PPI) network maps using Cytoscape software. ResultsThe network pharmacology analyses showed that 73 common targets for curcumin, photodynamics, and systemic lupus erythematosus. The GO enrichment analysis and KEGG pathway enrichment analysis further highlighted the association between identified targets with 200 biological processes, 25 cellular components, 37 molecular functions and 125 pathways. The core targets including AKT1, ALB, TNF, EGFR, CASP3, HSP90AA1, STAT3, HRAS, SRC, and MMP9 were further predicted through PPI network analysis. ConclusionThis study provided a basis for the in-depth exploration of the mechanism of curcumin photodynamic therapy for systemic lupus erythematosus.

Cannabis use disorder increases risk of large-artery atherosclerotic stroke and migraine with aura through mendelian randomization study

Observational studies have shown some association between cannabis use disorder (CUD) and neurological disorders, but their causal relationship is unclear. In this study, we tested the potential causal relationship between CUD and three common neurological disorders using two-sample Mendelian randomization (TSMR) and multivariate MR (MVMR) methods. Thirty-two genetic loci were extracted as exposure factors from the largest genome-wide association study (GWAS) summary statistics for CUD to date. TSMR results showed that genetic prediction of CUD with all stroke, ischemic stroke, large-artery atherosclerotic stroke, migraine with aura, and Alzheimer’s disease (AD) had a positive causal relationship (P < 0.05), which was not found in several other diseases. The association between CUD and stroke, ischemic stroke, and AD in the MVMR study may have been influenced by confounding factors (P > 0.05). Subgroup analyses highlighted a causal relationship between genetically predicted CUD and large-artery atherosclerotic stroke (OR = 1.169; 95%CI 1.030–1.328; P = 0.016) and migraine with aura (OR = 1.142; 95% 1.021–1.278; P = 0.020). Our further functional mapping and annotation enrichment analyses using FUMA suggest that the brain-gut axis may serve as another layer of explanation for the existence of an association between CUD and neurological disorders.

Signaling Pathways in Clear Cell Renal Cell Carcinoma and Candidate Drugs Unveiled through Transcriptomic Network Analysis of Hub Genes

Clear cell renal cell carcinoma (ccRCC) is a type of kidney cancer. It advances quickly and often metastasizes, making the prognosis for patients challenging. This study used weighted gene co-expression network analysis (WGCNA) to study gene expression data of different stages of ccRCC obtained in the GEO database. The analysis identified three significant highly preserved gene modules across the datasets: GSE53757, GSE22541, GSE66272, and GSE73731. Functional annotation and pathway enrichment analysis using DAVID revealed inflammatory pathways (e.g., NF-kB, Hippo, and HIF-1 pathways) that may drive ccRCC development and progression. The study also introduced the involvement of viral infections associated with the disease in the metabolic reprogramming of ccRCC. A drug repurposing analysis was also conducted to identify potential drug candidates for ccRCC using the upregulated and downregulated hub genes. The top candidates are ziprasidone (dopamine and serotonin receptor antagonist) and fentiazac (cyclooxygenase inhibitor). Other drug candidates were also obtained, such as phosphodiesterase/DNA methyltransferase/ATM kinase inhibitors, acetylcholine antagonists, and NAD precursors. Overall, the study’s findings suggest that identifying several genes and signaling pathways related to ccRCC may uncover new targets, biomarkers, and even drugs that can be repurposed, which can help develop new and effective treatments for the disease.

Ailanthone suppresses cell proliferation of renal cell carcinoma partially via inhibition of EZH2

BackgroundAilanthone (Ail) extracted from medicinal plants has played an anticancer role in multiple cancers, while there is no research about Ail in renal cell carcinoma (RCC).MethodsIn the present study, we performed CCK-8 and flow cytometry to assess the effect of Ail on cell viability, apoptosis and cycle. We also performed tandem mass tags (TMT)-labeled quantitative proteomic technology and bioinformatic analysis to identify the functional pathway and proteins of Ail in RCC.ResultsThe results showed Ail could inhibit cell viability and induce cell apoptosis. Proteomic profiling identified 1732 differentially expressed proteins in cells treated with Ail, compared to the negative control group. Gene ontology function annotation and Gene Set Enrichment Analysis (GSEA) were performed to identified the involved biological processes, molecular function and pathway. Results of GSEA proved the enrichment of Deps in EZH2 targets. The comparison between Deps and EZH2 co-expressed genes revealed 44 overlapped genes and we identified 4 hub genes (CDC20, CEP55, TOP2A, and UBE2C) associated with RCC progression. The molecular docking study revealed a moderate to tight binding potential of Ail and EZH2, and western blotting showed EZH2 was suppressed after cells treated with Ail.ConclusionAltogether, we identified the anticancer role of Ail in RCC, including inhibition of cell proliferation and induction of apoptosis. The results also screened the key proteins mediate the function of Ail, which have laid a theoretical foundation for elucidating the applications of Ail in clinical research.

A PLATZ transcription factor PhePLATZ8 from Moso bamboo (Phyllostachys edulis) plays a positive role in regulating growth and abiotic stress tolerance

Moso bamboo is recognized as a rapid-growing plant with abundant lignocellulosic content, making it a crucial non-timber forest resource on a global scale. The growth of Moso bamboo is influenced by the rapid division and elongation of its internode meristem cells, but the molecular mechanism behind this process is still unclear. Here, by combining RNA-seq data from Moso bamboo internode samples with gene co-expression network and gene functional annotation enrichment analysis, a key candidate gene named PhePLATZ8, which regulates cell division in the internodes of Moso bamboo, has been screened out. PhePLATZ8 is localized to the nucleus and cytoplasm. The phenotype of transgenic Arabidopsis thaliana plants showed that PhePLATZ8 positively regulated the organ development of transgenic plants, including hypocotyl length, plant height, petiole length, blade shape, and seed size. Overexpression of PhePLATZ8 also significantly improved cell proliferation activities in the hypocotyl calluses of transgenic plants. qRT-PCR and luciferase assays showed that PhePLATZ8 was involved in the regulation of cell proliferation by activating the expression of several GRFs in A. thaliana and Moso bamboo. Futhermore, PhePLATZ8 was significantly induced by abiotic stress, and overexpression of PhePLATZ8 increased the tolerance of transgenic A. thaliana plants to drought and salt stress. Overall, our current study initially explored the role of PhePLATZ8 in the process of rapid growth and stress response of Moso bamboo, providing genetic resources for future molecular breeding of Moso bamboo.

Identification of plasma miR-4505, miR-4743-5p and miR-4750-3p as novel diagnostic biomarkers for coronary artery disease in patients with type 2 diabetes mellitus: a case-control study

BackgroundType 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) are commonly coexisting clinical entities with still growing incidence worldwide. Recently, circulating microRNAs (miRNAs) have emerged as novel molecular players in cardiometabolic diseases. This study aimed to identify a specific miRNA signature as a candidate biomarker for CAD in T2DM and to delineate potential miRNA-dependent mechanisms contributing to diabetic atherosclerosis.MethodsA total of 38 plasma samples from T2DM patients with and without CAD, CAD patients and healthy controls were collected for expression profiling of 2,578 miRNAs using microarrays. To investigate the regulatory role of differentially expressed (DE)-miRNA target genes, functional annotation and pathway enrichment analyses were performed utilizing multiple bioinformatics tools. Then, protein-protein interaction networks were established leveraging the STRING database in Cytoscape software, followed by cluster analysis and hub gene identification. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was carried out for microarray data validation in the larger replication cohort of 94 participants. Receiver operating characteristic analysis was applied to evaluate the diagnostic values of miRNAs. Multivariate logistic regression analysis was used to develop miRNA-based diagnostic models.ResultsIn the discovery stage, overexpression of hsa-miR-4505, hsa-miR-4743-5p, hsa-miR-6846-5p, and down-regulation of hsa-miR-3613-3p, hsa-miR-4668-5p, hsa-miR-4706, hsa-miR-6511b-5p, hsa-miR-6750-5p, hsa-miR-4750-3p, hsa-miR-320e, hsa-miR-4717-3p, hsa-miR-7850-5p were detected in T2DM-CAD patients. The DE-miRNA target genes were significantly enriched in calcium ion binding, regulation of actin cytoskeleton, and gene expression. hsa-miR-4505, hsa-miR-4743-5p, and hsa-miR-4750-3p were found to be involved in fatty acid metabolism, leukocyte transendothelial migration, and neurotrophin signaling pathway. Dysregulation of hsa-miR-4505, hsa-miR-4743-5p, and hsa-miR-4750-3p in T2DM-CAD patients compared with T2DM subjects and controls (all p < 0.001) was further confirmed by RT-qPCR. All validated miRNAs demonstrated good discriminatory values for T2DM-CAD (AUC = 0.833–0.876). The best performance in detecting CAD in T2DM was achieved for a combination of three miRNAs (AUC = 0.959, 100% sensitivity, 86.67% specificity).ConclusionsOur study revealed a unique profile of plasma-derived miRNAs in T2DM patients with CAD. Potential miRNA-regulated pathways were also identified, exploring the underlying pathogenesis of CAD in T2DM. We developed a specific three-miRNA panel of hsa-miR-4505, hsa-miR-4743-5p and hsa-miR-4750-3p, that could serve as a novel non-invasive biomarker for CAD in patients with T2DM.

Integrative bioinformatics analysis for the identification of hub genes and Virtual screening of phytochemicals to inhibit AURKA in HepatoCellular carcinoma

HepatoCellular Carcinoma (HCC) is one of the most deadly and prevalent neoplasia, accounting for nearly 830,180 mortalities and 905,677 fresh occurrences worldwide annually. Aggressive malignancy with multifaceted etiologies increases in occurrence due to inadequate early diagnosis and ineffective treatment outcomes. Hence the present study aims to identify novel HCC associated biomarkers and inhibit the plausible genes through phytocompounds. Herein, we have implemented the meta-analysis of GSE36376, GSE57957 and GSE84598 micro-array profiles by utilizing GEO2R which resulted in identification of 1683 aberrantly expressed genes. The predicted DEGs were further subjected to Functional annotation and pathway enrichment analysis by using Blast2GO and ExpressAnalyst respectively. Successively, Protein-Protein Interaction analysis was performed by Cytoscape software, and the top 11 most significant hub nodes were identified. The most frequently occurring hub gene Aurora Kinase A (AURKA) was considered as plausible target for subsequent identification of inhibitors. The plant-derived small molecules retrieved from NPACT database were subjected to molecular docking, Molecular dynamic simulations and MMGBSA analysis against AURKA. Conclusively, findings from our study postulates Garcinone C and Silymarin targeting elevated AURKA levels which may contribute as potential inhibitors for HCC patients. However, these outcomes provide only computational insights for targeted HCC-therapeutics but for clinical application of Garcinone C and Silymarin in vitro and in vivo molecular validations are still warranted.

Role of blood metabolites in mediating the effect of gut microbiome on the mutated-RAS/BRAF metastatic colorectal cancer-specific survival

BackgroundRecent studies have linked alterations in the gut microbiome and metabolic disruptions to the invasive behavior and metastasis of colorectal cancer (CRC), thus affecting patient prognosis. However, the specific relationship among gut microbiome, metabolite profiles, and mutated-RAS/BRAF metastatic colorectal cancer (M-mCRC) remains unclear. Furthermore, the potential mechanisms and prognostic implications of metabolic changes induced by gut microbiome alterations in patients with M-mCRC still need to be better understood.MethodsWe conducted Mendelian randomization (MR) to evaluate the causal relationship of genetically predicted 196 gut microbiome features and 1400 plasma metabolites/metabolite ratios on M-mCRC-specific survival. Additionally, we identified significant gut microbiome-metabolites/metabolite ratio associations based on M-mCRC. Metabolite information was annotated, and functional annotation and pathway enrichment analyses were performed on shared proteins corresponding to significant metabolite ratios, aiming to reveal potential mechanisms by which gut microbiome influences M-mCRC prognosis via modulation of human metabolism.ResultsWe identified 11 gut microbiome features and 49 known metabolites/metabolite ratios correlated with M-mCRC-specific survival. Furthermore, we identified 17 gut microbiome-metabolite/metabolite ratio associations specific to M-mCRC, involving eight lipid metabolites and three bilirubin degradation products. The shared proteins corresponding to significant metabolite ratios were predominantly localized within the integral component of the membrane and exhibited enzymatic activities such as glucuronosyltransferase and UDP-glucuronosyltransferase, crucial in processes such as glucuronidation, bile secretion, and lipid metabolism. Moreover, these proteins were significantly enriched in pathways related to ascorbate and aldarate metabolism, pentose and glucuronate interconversions, steroid hormone biosynthesis, and bile secretion.ConclusionOur study offers novel insights into the potential mechanisms underlying the impact of the gut microbiome on the prognosis of M-mCRC. These findings serve as a meaningful reference for exploring potential therapeutic targets and strategies in the future.

Two hub genes of bipolar disorder, a bioinformatics study based on the GEO database

Bipolar disorder is a mood illness that affects many people. It has a high recurrence frequency and will cause significant damage to the patient's social function. At present, the pathogenesis of BD is not clear. The National Center for Biotechnology Information (NCBI) established and maintained the Gene Expression Omnibus (GEO) database, a gene expression database. For bioinformatics analysis, researchers can obtain expression data from the internet. At present, the samples of the dataset used in the research of BD are mostly from brain tissue, and the data containing blood samples are rarely used. GEO databases (GSE46416, GSE5388, and GSE5389) were used to retrieve public data, and utilizing the online tool GEO2R, differentially expressed genes (DEGs) were retrieved. The common DEGs between the samples of patients with BD and the samples of the normal population were screened by Venn diagrams. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used to perform functional annotation and pathway enrichment analysis of DEGs. A protein-protein interaction network (PPI) was built to investigate hub genes on this basis. There were 117 up-regulated DEGs and 38 down-regulated DEGs discovered, with two hub genes [SRC, CDKN1A] among the up-regulated DEGs. These two hub genes were also highly enriched in the oxytocin signaling pathway, proteoglycans in cancer and bladder cancer, according to KEGG analysis. The results of the receiver operating characteristic curve (ROC) of SRC and CDKN1A in the three datasets strongly suggested that SRC and CDKN1A were potential diagnostic markers of BD. The results strongly suggest that SRC and CDKN1A are related to the pathogenesis of BD.

Early changes of microRNAs in blood one month after bariatric surgery

BackgroundChanges in microRNAs (miRNAs) are relevant to bariatric surgery and its comorbidities. The characteristics of changes in miRNAs of the early postoperative period following both bariatric procedures, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), as well as the factors that related to the effectiveness of early weight loss remain unclear.MethodsWe recruited 18 patients who performed SG and 15 patients who performed RYGB. Their preoperative and 1-month postoperative clinical data and fasting serum samples were collected, and the latter were analyzed by RNA-sequencing. Differential expression analysis of miRNAs was performed by the R-tool. Functional classification annotation and pathway enrichment analysis of targeted genes were analyzed by KOBAS software. The change profiles of miRNAs for both surgeries and their correlation with clinical characteristics and weight loss effectiveness were further analyzed.ResultsA total of 85 differentially expressed miRNAs were identified before and after SG, while a total of 76 were found before and after RYGB. The target genes of these miRNAs were similar in the Gene Ontology enrichment analysis in SG and RYGB, and the enrichment analysis in the Kyoto Encyclopedia of Genes and Genomes was mainly related to metabolic pathways. Hsa-miR-493-5p, hsa-miR-184, and hsa-miR-3199 exhibited similar changes in SG and RYGB, and the former two were correlated with clinical characteristics. Hsa-miR-6729-5p, hsa-miR-4659b-5p, and hsa-miR-2277-5p were correlated with the weight loss effectiveness of SG, while hsa-miR-4662a-5p was correlated with the weight loss effectiveness of RYGB.ConclusionsShort-term metabolic improvement and weight loss occurring after SG and RYGB surgery might be related to changes in miRNAs, which act on multiple biological pathways by regulating genes. In addition, some clinical characteristics and miRNAs were related to the effectiveness of early weight loss after SG and RYGB surgery.Clinical Trial RegistrationChiCTR2200058333.

DHA dietary intervention caused different hippocampal lipid and protein profile in ApoE-/- and C57BL/6J mice

BackgroundChanges in protein and lipid levels may occur in the Alzheimer’s disease brain, and DHA can have beneficial effects on it. To investigate the impact of DHA dietary intervention on brain protein and lipid profile in ApoE-/- mice and C57 mice. MethodThree-month-old ApoE-/- mice and C57 mice were randomly divided into two groups respectively, and fed with control diet and DHA-fortified diet for five months. Cortical TC, HDL-C and LDL-C levels and cholesterol metabolism-related protein expression were measured by ELISA or immunohistochemistry methods. Hippocampus were collected for proteomic and lipidomics analysis by LC-MS/MS and differential proteins and lipid metabolites were screened and further analyzed by GO functional annotation and KEGG pathway enrichment analysis. ResultsDHA intervention decreased cortical TC level in both C57 and ApoE-/- mice (P < 0.05), but caused different change of cortical HDL-C, LDL-C level and LDL-C/HDL-C ratio in C57 and ApoE-/- mice (P < 0.05). Discrepant cortical and hippocampal LDLR, ABCG1, Lox1 and SORT1 protein expression was found between C57 and ApoE-/- mice (P < 0.05), and DHA treatment caused different changes of these proteins in C57 and ApoE-/- mice (P < 0.05). Differential hippocampal proteins and lipids profile were found in C57 and ApoE-/- mice before and after DHA treatment, which were mainly involved in vesicular transport and phospholipid metabolic pathways. ConclusionApoE genetic defect caused abnormal cholesterol metabolism, and affected protein and lipid profile, as well as discrepant response of hippocampal protein and lipids profile in the brain of mice given DHA fortified diet intervention.

Genome-wide association study for cashmere traits in Inner Mongolia cashmere goat population reveals new candidate genes and haplotypes

BackgroundThe cashmere goat industry is one of the main pillars of animal husbandry in Inner Mongolia Autonomous Region, and plays an irreplaceable role in local economic development. With the change in feeding methods and environment, the cashmere produced by Inner Mongolia cashmere goats shows a tendency of coarser, and the cashmere yield can not meet the consumption demand of people. However, the genetic basis behind these changes is not fully understood. We measured cashmere traits, including cashmere yield (CY), cashmere diameter (CD), cashmere thickness (CT), and fleece length (FL) traits for four consecutive years, and utilized Genome-wide association study of four cashmere traits in Inner Mongolia cashmere goats was carried out using new genomics tools to infer genomic regions and functional loci associated with cashmere traits and to construct haplotypes that significantly affect cashmere traits.ResultsWe estimated the genetic parameters of cashmere traits in Inner Mongolia cashmere goats. The heritability of cashmere yield, cashmere diameter, and fleece length traits of Inner Mongolia cashmere goats were 0.229, 0.359, and 0.250, which belonged to the medium heritability traits (0.2 ~ 0.4). The cashmere thickness trait has a low heritability of 0.053. We detected 151 genome-wide significantly associated SNPs with four cashmere traits on different chromosomes, which were very close to the chromosomes of 392 genes (located within the gene or within ± 500 kb). Notch3, BMPR1B, and CCNA2 have direct functional associations with fibroblasts and follicle stem cells, which play important roles in hair follicle growth and development. Based on GO functional annotation and KEGG enrichment analysis, potential candidate genes were associated with pathways of hair follicle genesis and development (Notch, P13K-Akt, TGF-beta, Cell cycle, Wnt, MAPK). We calculated the effective allele number of the Inner Mongolia cashmere goat population to be 1.109–1.998, the dominant genotypes of most SNPs were wild-type, the polymorphic information content of 57 SNPs were low polymorphism (0 < PIC < 0.25), and the polymorphic information content of 79 SNPs were moderate polymorphism (0.25 < PIC < 0.50). We analyzed the association of SNPs with phenotypes and found that the homozygous mutant type of SNP1 and SNP3 was associated with the highest cashmere yield, the heterozygous mutant type of SNP30 was associated with the lowest cashmere thickness, the wild type of SNP76, SNP77, SNP78, SNP80, and SNP81 was associated with the highest cashmere thickness, and the wild type type of SNP137 was associated with the highest fleece length. 21 haplotype blocks and 68 haplotype combinations were constructed. Haplotypes A2A2, B2B2, C2C2, and D4D4 were associated with increased cashmere yield, haplotypes E2E2, F1F1, G5G5, and G1G5 were associated with decreased cashmere fineness, haplotypes H2H2 was associated with increased cashmere thickness, haplotypes I1I1, I1I2, J1J4, L5L3, N3N2, N3N3, O2O1, P2P2, and Q3Q3 were associated with increased cashmere length. We verified the polymorphism of 8 SNPs by KASP, and found that chr7_g.102631194A > G, chr10_g.82715068 T > C, chr1_g.124483769C > T, chr24_g.12811352C > T, chr6_g.114111249A > G, and chr6_g.115606026 T > C were significantly genotyped in verified populations (P < 0.05).ConclusionsIn conclusion, the genetic effect of single SNP on phenotypes is small, and SNPs are more inclined to be inherited as a whole. By constructing haplotypes from SNPs that are significantly associated with cashmere traits, it will help to reveal the complex and potential causal variations in cashmere traits of Inner Mongolia cashmere goats. This will be a valuable resource for genomics and breeding of the cashmere goat.

Research Focusing on How Qinge Pill Functions in Managing Stress Urinary Incontinence, Utilizing Network Pharmacology

Objective: Investigating how Qing-e pill aids in managing stress urinary incontinence through network pharmacology. Methods: Utilizing the TCM system's pharmacological database and analytical framework (TCMSP), along with literature exploration, the active components and their respective targets for Qing-e pill were identified, leading to the creation of a network of compound TCM - active ingredients - targets. The focus of SUI was identified using the GeneCards and OMIM databases. The active ingredient SUI-target network model was developed and examined using the Cytoscape 3.10.1 software. The protein interaction network (PPI) was created using the STRING database, incorporating gene ontology functional annotation (GO) and Tokyo Genome Encyclopedia (KEGG) pathway enrichment analysis on key targets through DAVID online, with molecular docking performed using Surflex software. Results: Screening yielded 86 active components, 461 possible targets, 2551 SUI targets, and 187 typical targets for Qing-e pill and SUI. The outcomes of network analysis revealed Qing-e pill's primary targets for SUI treatment were AKT1, IL6, JUN, TNF, HSP90AA1, ESR1, CTNNB1, EGFR, among others. The primary biological mechanisms encompassed reactions to lipopolysaccharide, molecules originating from bacteria, metal ions, growth of epithelial cells, and the control of membrane potential, among others. KEGG enrichment primarily aims to utilize the AGE-RAGE signaling pathway in treating a range of conditions, including diabetes complications, prostate cancer, fluid shear stress, atherosclerosis, lipid and atherosclerosis, IL-17 signaling pathway, and more. Conclusion: Initially, network pharmacology shed light on the foundational materials and operational methods of Qing-e pill in treating SUI, offering a theoretical foundation for their clinical use.

Network pharmacological prediction of the mechanism of action of Shen-Zhu-Lian-Bai Decoction in the treatment of ulcerative colitis

The incidence of ulcerative colitis (UC) is on the rise globally. Shen-Zhu-Lian-Bai decoction (SZLBD) can relieve the clinical symptoms of UC. This study aimed to investigate the underlying molecular mechanism of SZLBD in the treatment of UC. The key treatment targets of SZLBD for UC were obtained based on the online database, and combined with the STRING database and Cytoscape 3.7.2 software, PPI network was constructed and visualized. The GEO database was utilized to validate the expression levels of core targets in UC. Metascape database GO functional annotation and KEGG pathway enrichment analysis. Molecular docking technology was used to verify the docking of core compounds with key targets. RT-qPCR and Western Blot were used to detect the expression of key targets in HCoEpiC cells for verification. After screening, 67 targets shared by SZLBD and UC were obtained. It is predicted that IL-6, IL-1B, and AKT1 might be the key targets of SZLBD in the treatment of UC. Quercetin was the main active ingredient. GEO results showed that the expression levels of IL-6, IL-1B and AKT1 were higher in the UC group compared to the control group. GO and KEGG analyses showed that these targets were related to apoptosis and inflammation. The results of molecular docking demonstrated that the AKT1 gene, a key target of quercetin, had the highest affinity of -9.2 kcal/mol. Cell experiments found that quercetin could affect the expression of IL-6, IL-1B, and AKT1. This study preliminarily explored and verified the mechanism of action of SZLBD in the treatment of UC, which provides a theoretical basis for subsequent in vivo mechanism studies.

Interfamily Grafted Hybrids Vitis vinifera/Schisandra chinensis Resulted in Transcriptomic, Phenotypic, and Metabolic Changes.

Long-distance transfer of genetic material and metabolites between rootstock and scions is well documented in homo-grafted hybrids but has rarely been reported in genetically-distant grafts where the rootstock and scion belong to different families. In this study, we grafted Vitis vinifera scions onto Schisandra chinensis stocks and obtained 20 vegetative hybrids, Vitis vinifera/Schisandra chinensis (Vs). After 25 years of growth, we found that the phenotypes of the leaves, internodes, and fruits of the Vs hybrids above the graft union resembled an intermediate phenotype between V. vinifera and S. chinensis, and the new traits were stable when propagated vegetatively. We further analyzed genetic differences between Vv plants and Vs hybrids using high-throughput sequencing, while metabolomes were analyzed by liquid chromatography-mass spectrometry (LC-MS). We found a total of 2113 differentially expressed genes (DEGs). GO annotation and KEGG pathway enrichment analysis showed that these DEGs enriched mainly in oxidation-reduction and metabolic processes. Seventy-nine differentially expressed miRNAs (DEMs) containing 27 known miRNAs and 52 novel miRNAs were identified. A degradation analysis detected 840 target genes corresponding to 252 miRNAs, of which 12 DEMs and their corresponding target gene expression levels were mostly negatively correlated. Furthermore, 1188 differential metabolic compounds were identified. In particular, in Vs hybrids, the abundance of the metabolites schizandrin and gomisin as the main medicinal ingredients in S. chinensis were down-regulated and up-regulated, respectively. Our data demonstrated the effects of interfamily grafts on the phenotype, transcript profile and metabolites of the scion, and also provided new insight into the genetic, phenotypic, and metabolic plasticity associated with genetically distant grafted hybrids.

Fine Mapping of QTLs for Alkaline Tolerance in Crucian Carp (Carassius auratus) Using Genome-Wide SNP Markers.

Crucian carp (Carassius auratus) is widely distributed in the world and has become an economically freshwater fish. The population in Lake Dali Nur can tolerate the extreme alkaline environment with alkalinity over 50 mmol/L (pH 9.6), thus providing a special model for exploring alkali-tolerant molecular markers in an extremely alkaline environment. In this study, we constructed a high-density and high-resolution linkage map with 16,224 SNP markers based on genotyping-by-sequencing (GBS) consisting of 152 progenies and conducted QTL studies for alkali-tolerant traits. The total length of the linkage map was 3918.893 cM, with an average distance of 0.241 cM. Two QTLs for the ammonia-N-tolerant trait were detected on LG27 and LG45. A QTL for the urea-N-tolerant trait was detected on LG27. Interestingly, mapping the two QTLs on LG27 revealed that the mapped genes were both located in the intron of CDC42. GO functional annotation and KEGG enrichment analysis results indicated that the biological functions might be involved in the cell cycle, cellular senescence, MAPK, and Ras signaling pathways. These findings suggest that CDC42 may play an important role in the process of dealing with extremely alkaline environments.

Advances in Inflammatory Bowel Disease Diagnostics: Machine Learning and Genomic Profiling Reveal Key Biomarkers for Early Detection.

This study, utilizing high-throughput technologies and Machine Learning (ML), has identified gene biomarkers and molecular signatures in Inflammatory Bowel Disease (IBD). We could identify significant upregulated or downregulated genes in IBD patients by comparing gene expression levels in colonic specimens from 172 IBD patients and 22 healthy individuals using the GSE75214 microarray dataset. Our ML techniques and feature selection methods revealed six Differentially Expressed Gene (DEG) biomarkers (VWF, IL1RL1, DENND2B, MMP14, NAAA, and PANK1) with strong diagnostic potential for IBD. The Random Forest (RF) model demonstrated exceptional performance, with accuracy, F1-score, and AUC values exceeding 0.98. Our findings were rigorously validated with independent datasets (GSE36807 and GSE10616), further bolstering their credibility and showing favorable performance metrics (accuracy: 0.841, F1-score: 0.734, AUC: 0.887). Our functional annotation and pathway enrichment analysis provided insights into crucial pathways associated with these dysregulated genes. DENND2B and PANK1 were identified as novel IBD biomarkers, advancing our understanding of the disease. The validation in independent cohorts enhances the reliability of these findings and underscores their potential for early detection and personalized treatment of IBD. Further exploration of these genes is necessary to fully comprehend their roles in IBD pathogenesis and develop improved diagnostic tools and therapies. This study significantly contributes to IBD research with valuable insights, potentially greatly enhancing patient care.