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Keloid formation is a pathological consequence resulting from cutaneous irritation and injury, primarily attributed to excessive collagen matrix deposition and fibrous tissue proliferation. Chronic inflammation, left uncontrolled over an extended period, also stands as a substantial contributing factor. The precise mechanisms underlying keloid formation remain unclear. Therefore, this study aimed to identify key genes for diagnostic purposes. To achieve this, we used two Gene Expression Omnibus (GEO) data sets to identify differentially expressed genes. We identified one particular gene, homeobox C9 (HOXC9), using a thorough strategy involving two algorithms (least absolute shrinkage and selection operator and support vector machine-recursive feature elimination) and weighted gene co-expression network analysis. We then assessed its expression in normal and keloid tissues. In addition, we explored its temporal expression patterns via Mfuzz time clustering analysis. In our comprehensive analysis, we observed that immune infiltration, as well as cell proliferation, are crucial to keloid formation. Thus, we investigated immune cell infiltration in the keloid and normal groups, as well as the correlation between HOXC9 and these immune cells. It was found that HOXC9 was closely associated with the immune microenvironment of keloids. This shows that HOXC9 can serve as a potential biomarker and therapeutic target for keloids. [ABSTRACT FROM AUTHOR]

Background: ST6GALNAC family members function as sialyltransferases and have been implicated in cancer progression. However, their aberrant expression levels, prognostic values and specific roles in metastatic prostate cancer (PCa) remain largely unclear. Methods: Two independent public datasets (TCGA-PRAD and GSE21032), containing 648 PCa samples in total, were employed to comprehensively examine the mRNA expression changes of ST6GALNAC family members in PCa, as well as their associations with clinicopathological parameters and prognosis. The dysregulation of ST6GALNAC5 was further validated in a mouse PCa model and human PCa samples from our cohort (n = 64) by immunohistochemistry (IHC). Gene Set Enrichment Analysis, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and drug sensitivity analyses were performed to enrich the biological processes most related to ST6GALNAC5. Sulforhodamine B, transwell, luciferase reporter and chromatin immunoprecipitation (ChIP) assays were used to examine the PCa cell proliferation, invasion and transcriptional regulation, respectively. Results: Systematical investigation of six ST6GALNAC family members in public datasets revealed that ST6GALNAC5 was the only gene consistently and significantly upregulated in metastatic PCa, and ST6GALNAC5 overexpression was also positively associated with Gleason score and predicted poor prognosis in PCa patients. IHC results showed that (1) ST6GALNAC5 protein expression was increased in prostatic intraepithelial neoplasia and further elevated in PCa from a PbCre;PtenF/F mouse model; (2) overexpressed ST6GALNAC5 protein was confirmed in human PCa samples comparing with benign prostatic hyperplasia samples from our cohort (p < 0.001); (3) ST6GALNAC5 overexpression was significantly correlated with perineural invasion of PCa. Moreover, we first found transcription factor GATA2 positively and directly regulated ST6GALNAC5 expression at transcriptional level. ST6GALNAC5 overexpression could partially reverse GATA2-depletion-induced inhibition of PCa cell invasion. The GATA2-ST6GALNAC5 signature exhibited better prediction on the poor prognosis in PCa patients than GATA2 or ST6GALNAC5 alone. Conclusions: Our results indicated that GATA2-upregulated ST6GALNAC5 might serve as an adverse prognostic biomarker promoting prostate cancer cell invasion. [ABSTRACT FROM AUTHOR]

Background: The receptor-like kinase (RLK) gene families in plants contains a large number of members. They are membrane proteins with an extracellular receptor domain and participate in biotic and abiotic stress responses. Results: In this study, we identified RLKs in 15 representative plant genomes, including wheat, and classified them into 64 subfamilies by using four types of phylogenetic trees and HMM models. Conserved exon‒intron structures with conserved exon phases in the kinase domain were found in many RLK subfamilies from Physcomitrella patens to Triticum aestivum. Domain distributions of RLKs were also diagrammed. Collinearity events and tandem gene clusters suggested that polyploidization and tandem duplication events contributed to the member expansions of T. aestivum RLKs. Global expression pattern analysis was performed by using public transcriptome data. These analyses were involved in T. aestivum, Aegilops tauschii and Brachypodium distachyon RLKs under biotic and abiotic stresses. We also selected 9 RLKs to validate the transcriptome prediction by using qRT‒PCR under drought treatment and with Fusarium graminearum infection. The expression trends of these 9 wheat RLKs from public transcriptome data were consistent with the results of qRT‒PCR, indicating that they might be stress response genes under drought or F. graminearum treatments. Conclusion: In this study, we identified, classified, evolved, and expressed RLKs in wheat and related plants. Thus, our results will provide insights into the evolutionary history and molecular mechanisms of wheat RLKs. [ABSTRACT FROM AUTHOR]

Background: Among the major transcription factors, SPL plays a crucial role in plant growth, development, and stress response. Foxtail millet (Setaria italica), as a C4 crop, is rich in nutrients and is beneficial to human health. However, research on the foxtail millet SPL (SQUAMOSA PROMOTER BINDING-LIKE) gene family is limited. Results: In this study, a total of 18 SPL genes were identified for the comprehensive analysis of the whole genome of foxtail millet. These SiSPL genes were divided into seven subfamilies (I, II, III, V, VI, VII, and VIII) according to the classification of the Arabidopsis thaliana SPL gene family. Structural analysis of the SiSPL genes showed that the number of introns in subfamilies I and II were much larger than others, and the promoter regions of SiSPL genes were rich in different cis-acting elements. Among the 18 SiSPL genes, nine genes had putative binding sites with foxtail millet miR156. No tandem duplication events were found between the SiSPL genes, but four pairs of segmental duplications were detected. The SiSPL genes expression were detected in different tissues, which was generally highly expressed in seeds development process, especially SiSPL6 and SiSPL16, which deserve further study. The results of the expression levels of SiSPL genes under eight types of abiotic stresses showed that many stress responsive genes, especially SiSPL9, SiSPL10, and SiSPL16, were highly expressed under multiple stresses, which deserves further attention. Conclusions: In this research, 18 SPL genes were identified in foxtail millet, and their phylogenetic relationships, gene structural features, duplication events, gene expression and potential roles in foxtail millet development were studied. The findings provide a new perspective for the mining of the excellent SiSPL gene and the molecular breeding of foxtail millet. [ABSTRACT FROM AUTHOR]

Background: Parenteral nutrition (PN) may serve as a nutritional supportive therapy accompanied by oral medication, but the effect of PN on intestinal expression of drug metabolism-related genes remains unknown. Methods: Twelve Bama piglets receiving PN for 14 days were used as in vivo model. Changes in intestinal drug metabolism-related genes were examined by proteomic analysis. Serum levels of fibroblast growth factor 19 (FGF19) were determined by ELISA, and the effect of FGF19 on the expression of drug metabolism-related genes was examined using murine ileum organoids. Results: A total of 1063 differentially expressed proteins were identified in PN group. Of note, two drug transporters (Abcb1 and Abcc2) were significantly decreased in PN group, along with two glutathione-related drug-metabolizing enzymes, glutathione peroxidase (Gpx2) and glutathione S-transferase (Gsta1). Serum FGF19 levels were dramatically reduced in PN group. Treatment with recombinant FGF19 in vitro dose-dependently up-regulated the expression of Abcb1, Abcc2, Gpx2 and Gsta1 in organoids. Conclusion: Our data indicated that intestinal drug metabolism-related genes were significantly dysregulated under PN, and some of the changed genes were attributed to gut-derived FGF19. [ABSTRACT FROM AUTHOR]

Background: Cervical cancer (CC) is the fourth aggressive tumor affecting women worldwide. Circular RNA (circRNA) is enrolled in CC process. This study aims to unveil the profiles of circ_101119 (circCDK17) in cell proliferation, migration, invasion, apoptosis and glycolysis in CC. Methods: The expression levels of circCDK17, microRNA-1294 (miR-1294) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) mRNA were detected by quantitative real time polymerase chain reaction (qRT-PCR). The protein expression levels of YWHAZ, recombinant glucose transporter 1 (GLUT1) and hexokinase 2 (HK2) were determined by western blot. Cell proliferation, migratory and invasive abilities and apoptosis were illustrated by cell counting kit-8 (CCK-8) assay, transwell assay and flow cytometry analysis, respectively. Cell lactate production, glucose uptake and adenosine 5'-triphosphate (ATP) level were severally elucidated by lactate assay kit, glucose assay kit and ATP detection kit. Results: CircCDK17 expression and the mRNA and protein expression levels of YWHAZ were dramatically upregulated, while miR-1294 expression was obviously downregulated in CC tissues or cells compared with control groups. CircCDK17 silencing suppressed cell proliferation, migration, invasion and glycolysis, and induced cell apoptosis in CC; however, miR-1294 inhibitor restrained these effects. Additionally, circCDK17 was a sponge of miR-1294 and miR-1294 bound to YWHAZ. Furthermore, circCDK17 knockdown inhibited tumor formation in vivo. Conclusion: CircCDK17 knockdown repressed cell proliferation, migration, invasion and glycolysis, and promoted cell apoptosis via miR-1294/YWHAZ axis in CC. This finding provides a theoretical basis in studying circRNA-mediated therapy in CC. [ABSTRACT FROM AUTHOR]

Background: Carrot which contains lots of nutrients has a large demand around the world. The soluble sugar content in fleshy root of carrot directly influences its taste and quality. Sucrose, as an important member of soluble sugar, is the main product of photosynthesis in higher plants and it plays pivotal roles in physiological processes including energy supply, signal transduction, transcriptional regulation, starch and cellulose synthesis, and stress tolerance. Sucrose synthase is a key enzyme involved in sucrose metabolism and is closely related to sucrose content. However, the molecular mechanism involved in sucrose metabolism in carrot has lagged behind. Results: Here, carrot roots of five developmental stages from four carrot cultivars were collected, and the contents of soluble sugar and sucrose in different stages and cultivars were surveyed. Three DcSus genes (DcSus1, DcSus2, and DcSus3), with lengths of 2427 bp, 2454 bp and 2628 bp, respectively, were identified and cloned in carrot. Phylogenetic analysis from the deduced amino acid sequences suggested that three DcSus were clustered into three distinct groups (SUSI, II and III). Results of enzymatic profiles demonstrated that the DcSus activities showed decrease trends during taproot development. Correlation analysis indicated that the DcSus activity showed negative correlation with soluble sugar content and strong negative correlation with sucrose concentration. Quantitative real-time PCR analysis showed that the expression profiles of the DcSus genes are significantly different in carrot tissues (root, leaf blade, and petiole), and the expression levels of the DcSus genes in the leaf blade were much higher than that in the root and petiole. The expression profiles of DcSus genes showed strong negative correlation with both sucrose content and soluble sugar content. Conclusions: During carrot root development, the soluble sugar content and sucrose content showed increasing trends, while DcSus activities had persisting declinations, which may be due to the decreasing expression levels of genes encoding sucrose synthase. Our data demonstrate that synthesis of sucrose in carrot tissue is closely related with DcSus genes. The results from our study would not only provide effective insights of sucrose metabolism in carrot, but also are beneficial for biologists to improve carrot quality. [ABSTRACT FROM AUTHOR]

Background: Circadian rhythms are oscillating physiological and behavioral changes governed by an internal molecular clock, and dysfunctions in circadian rhythms have been associated with ageing and various neurodegenerative diseases. However, the evidence directly connecting the neurodegeneration-associated proteins to circadian control at the molecular level remains sparse. Methods: Using meta-analysis, synchronized animals and cell lines, cells and tissues from FUS R521C knock-in rats, we examined the role of FUS in circadian gene expression regulation. Results: We found that FUS, an oscillating expressed nuclear protein implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), exerted a novel feedback route to regulate circadian gene expression. Nr1d1-encoded core circadian protein REV-ERBα bound the Fus promoter and regulated the expression of Fus. Meanwhile, FUS was in the same complex as PER/CRY, and repressed the expression of E box-containing core circadian genes, such as Per2, by mediating the promoter occupancy of PSF-HDAC1. Remarkably, a common pathogenic mutant FUS (R521C) showed increased binding to PSF, and caused decreased expression of Per2. Conclusions: Therefore, we have demonstrated FUS as a modulator of circadian gene expression, and provided novel mechanistic insights into the mutual influence between circadian control and neurodegeneration-associated proteins. [ABSTRACT FROM AUTHOR]