Search Results (2,662)

Male reproductive health is largely determined already in the early development of the testis. Although much work has been carried out to study the mechanisms of testicular development and spermatogenesis, there was previously no information on the differences in the protein composition of yak testicles during early development. In this study, the protein profiles in the testicles of 6- (M6), 18- (M18), and 30-month-old (M30) yaks were comparatively analyzed using TMT proteomics. A total of 5521 proteins were identified, with 13, 1295, and 1397 differentially expressed proteins (DEPs) in 30- vs. 18-, 18- vs. 6-, and 30- vs. 6-month-old testes, respectively. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that DEPs were mainly involved in signaling pathways related to testicular development and spermatogenesis, including the MAPK, PI3K–Akt, Wnt, mTOR, TGF-β, and AMPK signaling pathways. Furthermore, we also identified eight potential proteins (TEX101, PDCL2, SYCP2, SYCP3, COL1A1, COL1A2, ADAM10, and ATF1) that may be related to the testicular development and spermatogenesis of yaks. This study may provide new insights into the molecular mechanisms of the testicular development and spermatogenesis of yaks. Full article

With the rapid emergence and distribution of red crown rot (RCR) across countries, durable sources of resistance against Calonectria ilicicola in soybean [Glycine max (L.) Merrill] is required to control the disease. We employed two RIL populations for the experiment. We identified 15 and 14 QTLs associated with RCR resistance in ZM6 and MN populations, respectively, totaling 29 QTLs. Six and eight QTLs had phenotypic variation above 10% in ZM6 and MN populations, respectively. We identified six (6) “QTL hotspots” for resistance to RCR from the ZM6 and MN RIL populations on chromosomes 1, 7, 10, 11, 13, and 18. Gene annotations, gene ontology enhancement, and RNA sequencing assessment detected 23 genes located within six “QTL Hotspots” as potential candidate genes that could govern RCR resistance in soybeans. Our data will generally assist breeders in rapidly and effectively incorporating RCR resistance into high-yielding accession through marker-assisted selection. Full article

Acetolactate synthase (ALS) inhibitor herbicides are among widely marketed herbicide chemistries that act both against grass and broad-leaved weeds. Sorghum (Sorghum bicolor (L.) Moench) variants carrying resistance to ALS inhibitor herbicides were developed as a post-emergence weed control solution in sorghum. However, some ALS-resistant lines exhibit noticeable interveinal chlorosis at seedling stage, leading to reduced vigor. Although the plants eventually recover at an advanced growth stage, this may be a source of concern for growers and can undermine adoption of the technology. This study was initiated to identify mechanisms related to the manifestation of this phenotype. Two ALS-resistant genotypes, one displaying a yellow phenotype and the other a normal green phenotype, were cultivated, and tissue samples were collected at four time intervals, with the final sampling occurring after the genotypes had fully re-greened. RNA was extracted from the tissue samples and subjected to RNA-Seq analysis. Differential gene expression analysis was carried out using DESeq2, and a selected set of genes were confirmed via qRT-PCR. Gene Ontology enrichment and SorghumCyc pathway analysis uncovered notable regulatory changes in genes associated with chloroplasts, plant defense responses, and hormonal networks in the yellow genotypes. The pattern of gene expression strongly mimicked responses under abiotic stresses. In addition, the findings offer new insights into the potential for sorghum genotypes resistant to environmental stresses to also exhibit tolerance to a range of additional stresses. Full article

The objective of this study was to elucidate the mechanism of action of the active components of Coptidis rhizoma against porcine epidemic diarrhea and to provide a theoretical foundation for further development of novel anti-PED therapeutic agents based on Coptidis rhizoma. The potential targets of Coptidis rhizoma against PEDV were identified through a comprehensive literature review and analysis using the TCMSP pharmacological database, SwissDrugDesign database, GeneCards database, and UniProt database. Subsequently, the STRING database and Cytoscape 3.7.1 software were employed to construct a protein–protein interaction (PPI) network and screen key targets. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted on the identified targets. Molecular docking studies were performed using AutoDock 1.5.7 software to analyze the binding energy and modes of interaction between the active components of Coptidis rhizoma and the target proteins. The PyMOL 2.5.0a0 software was employed to visualize the docking results. Through comprehensive analysis, 74 specific targets of active components of Coptidis rhizoma against PEDV were identified. The core gene targets were screened, and an interaction network diagram was subsequently generated. Ultimately, 14 core targets were identified, with STAT3, ESR1, CASP3, and SRC exhibiting the most significant interactions. GO enrichment analysis revealed a total of 215 molecular items, including 48 biological function items, 139 biological process items, and 28 cellular component items. KEGG enrichment analysis identified 140 signaling pathways. Molecular docking analysis demonstrated that epiberberine and palmatine exhibited high binding affinity with STAT3 protein, worenine showed high binding affinity with ESR1 protein, obacunone exhibited high binding affinity with CASP3 protein, and epiberberine, obacunone, berberine, and berberruine exhibited high binding affinity with SRC protein. A network pharmacology and molecular docking technology approach was employed to screen six important active components of Coptidis rhizoma and four important potential targets against PEDV infection. The findings indicated that the active components of Coptidis rhizoma could serve as promising pharmaceutical agents for the prevention and control of PEDV, with significant potential for clinical application. Full article

Background: Resveratrol is a potent phytochemical known for its potential in treating cardiometabolic multimorbidity. However, its underlying mechanisms remain unclear. Our study systematically investigates the effects of resveratrol on cardiometabolic multimorbidity and elucidates its mechanisms using network pharmacology and molecular docking techniques. Methods: We screened cardiometabolic multimorbidity-related targets using the OMIM, GeneCards, and DisGeNET databases, and utilized the DSigDB drug characterization database to predict resveratrol’s effects on cardiometabolic multimorbidity. Target identification for resveratrol was conducted using the TCMSP, SymMap, DrugBank, Swiss Target Prediction, CTD, and UniProt databases. SwissADME and ADMETlab 2.0 simulations were used to predict drug similarity and toxicity profiles of resveratrol. Protein–protein interaction (PPI) networks were constructed using Cytoscape 3.9.1 software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were performed via the DAVID online platform, and target-pathway networks were established. Molecular docking validated interactions between core targets and resveratrol, followed by molecular dynamics simulations on the optimal core proteins identified through docking. Differential analysis using the GEO dataset validated resveratrol as a core target in cardiometabolic multimorbidity. Results: A total of 585 cardiometabolic multimorbidity target genes were identified, and the predicted results indicated that the phytochemical resveratrol could be a major therapeutic agent for cardiometabolic multimorbidity. SwissADME simulations showed that resveratrol has potential drug-like activity with minimal toxicity. Additionally, 6703 targets of resveratrol were screened. GO and KEGG analyses revealed that the main biological processes involved included positive regulation of cell proliferation, positive regulation of gene expression, and response to estradiol. Significant pathways related to MAPK and PI3K-Akt signaling pathways were also identified. Molecular docking and molecular dynamics simulations demonstrated strong interactions between resveratrol and core targets such as MAPK and EGFR. Conclusions: This study predicts potential targets and pathways of resveratrol in treating cardiometabolic multimorbidity, offering a new research direction for understanding its molecular mechanisms. Additionally, it establishes a theoretical foundation for the clinical application of resveratrol. Full article

Endoglin (ENG) mutation causes type 1 hereditary hemorrhagic telangiectasia (HHT1). HHT1 patients have arteriovenous malformations (AVMs) in multiple organs, including the brain. In mice, Eng deletion induced by R26RCreER or SM22αCre leads to AVM development in the brain and other organs. We hypothesized that an increase in Eng- negative ECs will enhance AVM severity. To increase EC Eng deletion, we used a codon-improved cre (icre), which is more potent in recombination of the floxed alleles than the wild-type (WT) cre. R26RCreER;Eng^f/f mice that have a Rosa promoter driving and tamoxifen (TM)-inducible WT cre expression globally, and PdgfbiCreER;Eng^f/f mice that have a Pdgfb promoter driving and TM-inducible icre expression in ECs were treated with three intra-peritoneal injections of TM (2.5 mg/25 g of body weight) to delete Eng globally or in the ECs. AAV-VEGF was stereotactically injected into the brain to induce brain focal angiogenesis and brain AVM. We found that icre caused more Eng deletion in the brain, indicated by a lower level of Eng proteins (p < 0.001) and fewer Eng-positive ECs (p = 0.01) than mice with WT cre. Mice with icre-mediated Eng deletion have more abnormal vessels (p = 0.02), CD68⁺ macrophages (p = 0.002), and hemorrhage (p = 0.04) and less vascular pericyte and smooth muscle coverage than mice with WT cre. In addition, arteriovenous shunts were detected in the intestines of icre mice, a phenotype that has not been detected in WT cre mice before. RNA-seq analysis showed that 8 out of the 10 top upregulated pathways identified by gene ontology (GO) analysis are related to inflammation. Therefore, the increase in Eng deletion in ECs exacerbates AVM severity, which is associated with enhanced inflammation. Strategies that can reduce Eng-negative ECs could be used to develop new therapies to reduce AVM severity for HHT1 patients. Full article

The floral color phenotypes of Osmanthus fragrans cultivars range from light yellow to orange yellow, with ‘Yanzhi Hong’ being the only reported cultivar with a red color. However, the underlying reason for this unique floral coloration remains unclear. The study conducted targeted metabolomics and transcriptomics analyses on the petals of ‘Yanzhi Hong’ at both initial and peak flowering stages. Candidate gene expression was validated, and expression levels of the petals of three cultivars were compared using RT-qPCR. The results revealed the presence of 27 components in the petals of ‘Yanzhi Hong’, including 5 carotenoids, 8 xanthophylls, and 14 xanthophyll esters. Notably, lycopene was detected in abundance for the first time in O. fragrans cultivars. Carotenes accounted for 78.82 ± 3.17% and 91.19 ± 1.69% of the total carotenoid content in petals during the initial and peak flowering stages, respectively, with all carotene contents increasing during the peak flowering period. β-carotene, lycopene, and γ-carotene were identified as the top three carotene components in petals during both initial and full flowering stages. The unique blush red color of ‘Yanzhi Hong’ petals could be attributed to the low content of α-carotene and the rich accumulation of lycopene. Furthermore, a total of 1550 differentially expressed genes (DEGs) were identified in petals at the peak flowering stage relative to the initial flowering stage, with 1003 genes being downregulated and 547 genes being upregulated during the full flowering stage. There are 926 differentially expressed genes (DEGs) annotated in the Gene Ontology (GO) database. Among these DEGs, those that were downregulated and upregulated during the peak flowering period showed significant enrichment in carbohydrate metabolism and oxidation–reduction processes, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified 14 structural genes associated with phenylpropanoid biosynthesis and 7 structural genes linked to carotenoid biosynthesis. Expression levels of candidate genes involved in carotenoid biosynthesis were examined in the petals of three cultivars (‘Yanzhi Hong’, ‘Liuye Jingui’, and ‘Gecheng Dangui’) at both the initial and peak flowering stages. The results indicated that the decreased expression of LYG009054 (LYCE) and LYG018651 (LYCB) in ‘Yanzhi Hong’ resulted in higher lycopene accumulation and lower α-carotene content in the petals. This study offers valuable insights into the mechanisms underlying the unique flower color phenotype of O. fragrans, proving a basis for further research on carotenoid metabolism pathways and the breeding of new cultivars with a variety of flower colors in O. fragrans. Full article

Fermentation with Bacillus subtilis significantly enhances the physiological activity and bioavailability of soymilk, but the resulting characteristic flavor seriously affects its industrial promotion. The objective of this study was to identify key proteins associated with characteristic flavors in B. subtilis BSNK-5-fermented soymilk using tandem mass tag (TMT) proteomics. The results showed that a total of 765 differentially expressed proteins were identified. Seventy differentially expressed proteins related to characteristic flavor were screened through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. After integrating metabolomics data, fifteen key proteases of characteristic flavor components in BSNK-5-fermented soymilk were further identified, and free ammonia was added. In addition, there were five main formation mechanisms, including the decomposition of urea to produce ammonia; the degradation of glutamate by glutamate dehydrogenase to produce ammonia; the degradation of threonine and non-enzymatic changes to form the derivative 2,5-dimethylpyrazine; the degradation of valine, leucine, and isoleucine to synthesize isovalerate and 2-methylbutyrate; and the metabolism of pyruvate and lactate to synthesize acetate. These results provide a theoretical foundation for the improvement of undesirable flavor in B. subtilis BSNK-5-fermented soy foods. Full article

The untranslated regions (UTRs) within plant mRNAs play crucial roles in regulating gene expression and the functionality of post-translationally modified proteins by various mechanisms. These regions are vital for plants’ ability to sense to multiple developmental and environmental stimuli. In this study, we conducted a genome-wide analysis of UTRs and UTR-containing genes in maize (Zea mays). Using the ZmLAZ1 family as a case study, we demonstrated that the length of 5′ UTRs could influence gene expression levels by employing GUS reporter gene assays. Although maize and arabidopsis (Arabidopsis thaliana), as well as rice (Oryza sativa), have distinct functional categories of UTR-containing genes, we observed a similar lengthwise distribution of UTRs and a recurring appearance of certain gene ontology (GO) terms between maize and rice. These suggest a potentially conserved mechanism within the Poaceae species. Furthermore, the analysis of cis-acting elements in these 5′ UTRs of the ZmLAZ1 gene family further supports the hypothesis that UTRs confer functional specificity to genes in a length-dependent manner. Our findings offer novel insights into the role of UTRs in maize, contributing to the broader understanding of gene expression regulation in plants. Full article

Domestic animals have multiple phenotypes of skin and coat color, which arise from different genes and their products, such as proteins and metabolites responsible with melanin deposition. However, the complex regulatory network of melanin synthesis remains to be fully unraveled. Here, the skin and tongue tissues of Liangshan black sheep (black group) and Liangshan semi-fine-wool sheep (pink group) were collected, stained with hematoxylin–eosin (HE) and Masson–Fontana, and the transcriptomic and metabolomic data were further analyzed. We found a large deposit of melanin granules in the epidermis of the black skin and tongue. Transcriptome and metabolome analysis identified 744 differentially expressed genes (DEGs) and 443 differentially expressed metabolites (DEMs) between the pink and black groups. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses revealed the DEGs and DEMs were mainly enriched in the pathways of secondary metabolic processes, melanin biosynthesis processes, melanin metabolism processes, melanosome membranes, pigment granule membranes, melanosome, tyrosine metabolism, and melanogenesis. Notably, we revealed the gene ENSARG00020006042 may be a family member of YWHAs and involved in regulating melanin deposition. Furthermore, several essential genes (TYR, TYRP1, DCT, PMEL, MLANA, SLC45A2) were significantly associated with metabolite prostaglandins and compounds involved in sheep pigmentation. These findings provide new evidence of the strong correlation between prostaglandins and related compounds and key genes that regulate sheep melanin synthesis, furthering our understanding of the regulatory mechanisms and molecular breeding of pigmentation in sheep. Full article

Glaucoma is a leading cause of permanent blindness, affecting 80 million people worldwide. Recent studies have emphasized the importance of neuroinflammation in the early stages of glaucoma, involving immune and glial cells. To investigate this further, we used the GSE27276 dataset from the GEO (Gene Expression Omnibus) database and neuroinflammation genes from the GeneCards database to identify differentially expressed neuroinflammation-related genes associated with primary open-angle glaucoma (POAG). Subsequently, these genes were submitted to Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes for pathway enrichment analyses. Hub genes were picked out through protein-protein interaction networks and further validated using the external datasets (GSE13534 and GSE9944) and real-time PCR analysis. The gene–miRNA regulatory network, receiver operating characteristic (ROC) curve, genome-wide association study (GWAS), and regional expression analysis were performed to further validate the involvement of hub genes in glaucoma. A total of 179 differentially expressed genes were identified, comprising 60 upregulated and 119 downregulated genes. Among them, 18 differentially expressed neuroinflammation–related genes were found to overlap between the differentially expressed genes and neuroinflammation–related genes, with six genes (SERPINA3, LCN2, MMP3, S100A9, IL1RN, and HP) identified as potential hub genes. These genes were related to the IL-17 signaling pathway and tyrosine metabolism. The gene–miRNA regulatory network showed that these hub genes were regulated by 118 miRNAs. Notably, GWAS data analysis successfully identified significant single nucleotide polymorphisms (SNPs) corresponding to these six hub genes. ROC curve analysis indicated that our genes showed significant accuracy in POAG. The expression of these genes was further confirmed in microglia, Müller cells, astrocytes, and retinal ganglion cells in the Spectacle database. Moreover, three hub genes, SERPINA3, IL1R1, and LCN2, were validated as potential diagnostic biomarkers for high-risk glaucoma patients, showing increased expression in the OGD/R-induced glaucoma model. This study suggests that the identified hub genes may influence the development of POAG by regulation of neuroinflammation, and it may offer novel insights into the management of POAG. Full article

Carcinogenesis is closely related to the expression, maintenance, and stability of DNA. These processes are regulated by one-carbon metabolism (1CM), which involves several vitamins of the complex B (folate, B2, B6, and B12), whereas alcohol disrupts the cycle due to the inhibition of folate activity. The relationship between nutrients related to 1CM (all aforementioned vitamins and alcohol) in breast cancer has been reviewed. The interplay of genes related to 1CM was also analyzed. Single nucleotide polymorphisms located in those genes were selected by considering the minor allele frequency in the Caucasian population and the linkage disequilibrium. These genes were used to perform several in silico functional analyses (considering corrected p-values < 0.05 as statistically significant) using various tools (FUMA, ShinyGO, and REVIGO) and databases such as the Kyoto Encyclopedia of Genes and Genomes (KEGG) and GeneOntology (GO). The results of this study showed that intake of 1CM-related B-complex vitamins is key to preventing breast cancer development and survival. Also, the genes involved in 1CM are overexpressed in mammary breast tissue and participate in a wide variety of biological phenomena related to cancer. Moreover, these genes are involved in alterations that give rise to several types of neoplasms, including breast cancer. Thus, this study supports the role of one-carbon metabolism B-complex vitamins and genes in breast cancer; the interaction between both should be addressed in future studies. Full article

Cell immortalization, a hallmark of cancer development, is a process that cells can undergo on their path to carcinogenesis. Spontaneously immortalized mouse embryonic fibroblasts (MEFs) have been used for decades; however, changes in the global transcriptome during this process have been poorly described. In our research, we characterized the poly-A RNA transcriptome changes after spontaneous immortalization. To this end, differentially expressed genes (DEGs) were screened using DESeq2 and characterized by gene ontology enrichment analysis and protein–protein interaction (PPI) network analysis to identify the potential hub genes. In our study, we identified changes in the expression of genes involved in proliferation regulation, cell adhesion, immune response and transcriptional regulation in immortalized MEFs. In addition, we performed a comparative analysis with previously reported MEF immortalization data, where we propose a predicted gene regulatory network model in immortalized MEFs based on the altered expression of Mapk11, Cdh1, Chl1, Zic1, Hoxd10 and the novel hub genes Il6 and Itgb2. Full article

Background: Colorectal cancer (CRC) ranks among the most prevalent malignancies affecting the gastrointestinal tract. The infiltration of CD8⁺ T cells significantly influences the prognosis and progression of tumor patients. Methods: This study establishes a CRC immune risk model based on CD8⁺ T cell-related genes. CD8⁺ T cell-related genes were identified through Weighted Gene Co-expression Network Analysis (WGCNA), and the enriched gene sets were annotated via Gene Ontology (GO) and Reactome pathway analysis. Employing machine learning methods, including the Least Absolute Shrinkage and Selection Operator (LASSO) algorithm and Random Forest (RF), we identified nine genes associated with CD8⁺ T-cell infiltration. The infiltration levels of immune cells in CRC tissues were assessed using the ssGSEA algorithm. Results: These genes provide a foundation for constructing a prognostic model. The TCGA-CRC sample model’s prediction scores were categorized, and the prediction models were validated through Cox regression analysis and Kaplan–Meier curve analysis. Notably, although CRC tissues with higher risk scores exhibited elevated levels of CD8⁺ T-cell infiltration, they also demonstrated heightened expression of immune checkpoint genes. Furthermore, comparison of microsatellite instability (MSI) and gene mutations across the immune subgroups revealed notable gene variations, particularly with APC, TP53, and TNNT1 showing higher mutation frequencies. Finally, the predictive model’s efficacy was corroborated through the use of Tumor Immune Dysfunction and Exclusion (TIDE), Immune Profiling Score (IPS), and immune escape-related molecular markers. The predictive model was validated through an external cohort of CRC and the Bladder Cancer Immunotherapy Cohort. CLRN3 expression levels in tumor and adjacent normal tissues were assessed using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Subsequent in vitro and in vivo experiments demonstrated that CLRN3 knockdown significantly attenuated the malignant biological behavior of CRC cells, while overexpression had the opposite effect. Conclusions: This study presents a novel prognostic model for CRC, providing a framework for enhancing the survival rates of CRC patients by targeting CD8⁺ T-cell infiltration. Full article

Pakchoi is a kind of nonheading Chinese cabbage being widely cultivated not only in China but also all over Asia. High temperature is a major limiting factor influencing the yield and quality of pakchoi, while the mechanism of pakchoi dealing with high-temperature challenges remains largely elusive. In the present study, we conducted a comparative transcriptomic analysis, which was also validated by qPCR, of the heat-tolerant Xinxiaqing (XXQ) variant and Suzhouqing (SZQ) variant, which are heat-sensitive under high-temperature treatment. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses suggest that high-temperature-induced phytohormones signal transduction, especially auxin signal transduction, regulates the heat responses of pakchoi. Our further investigations imply that high-temperature-activated auxin signal plays a positive role in helping pakchoi deal with high-temperature challenge; IAA-pretreated pakchoi plants exhibited greater resistance to the high-temperature treatment, probably due to the induction of antioxidant activity. In addition, our study also identified six heat shock proteins/factors (HSPs/HSFs) whose up-regulation correlates with the elevated heat tolerance of pakchoi. Notably, among these high-temperature-induced heat-responsive factors, HSP20 and HSP26.5 are under the regulation of auxin signal, and this signal cascade contributes to enhancing the thermostability of pakchoi. In the present study, we identified crucial high-temperature-responsive factors and signaling pathways in pakchoi, which help in understanding the mechanism of pakchoi coping with high-temperature challenge. Full article