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The recently discovered SWEET (Sugar Will Eventually be Exported Transporter) proteins are involved in the selective transport of monosaccharides and disaccharides. The prokaryotic counterparts, semiSWEETs, form dimers with each monomer forming a triple‐helix transmembrane bundle (THB). The longer eukaryotic SWEETs have seven transmembrane helices with two THBs and a linker helix. Structures of semiSWEETs/SWEETs have been determined experimentally. Experimental studies revealed the role of plant SWEETs in vital physiological processes and identified residues responsible for substrate selectivity. However, SWEETs/semiSWEETs from metazoans and bacteria are not characterized. In this study, we used structure‐based sequence alignment and compared more than 2000 SWEET/semiSWEETs from four different taxonomic groups. Conservation of residue/chemical property was examined at all positions. Properties of clades/subclades of phylogenetic trees from each taxonomic group were analyzed. Conservation pattern of known residues in the selectivity‐filter was used to predict the substrate preference of plant SWEETs and some clusters of metazoans and bacteria. Some residues at the gating and substrate‐binding regions, pore‐facing positions and at the helix–helix interface are conserved across all taxonomic groups. Conservation of polar/charged residues at specific pore‐facing positions, helix–helix interface and in loops seems to be unique for plant SWEETs. Overall, the number of conserved residues is less in metazoan SWEETs. Plant and metazoan SWEETs exhibit high conservation of four and three proline residues respectively in "proline tetrad." Further experimental studies can validate the predicted substrate selectivity and significance of conserved polar/charged/aromatic residues at structurally and functionally important positions of SWEETs/semiSWEETs in plants, metazoans and bacteria. [ABSTRACT FROM AUTHOR]

Background and Aim Methods Results Conclusions Ulcerative colitis (UC) is a chronic inflammatory disease driven by immune dysregulation. PANoptosis, a novel form of programmed cell death, has been implicated in inflammatory diseases, but its specific role in UC remains unclear. This study aimed to identify PANoptosis‐related genes (PRGs) that may contribute to immune dysregulation in UC.Using bioinformatics analysis of the GEO databases, we identified seven hub PRGs. Based on these genes, we developed a predictive model to differentiate UC patients from healthy controls, and evaluated its diagnostic performance using ROC curve analysis. We further conducted functional enrichment, GSVA, and immune infiltration analyses. Immunohistochemistry (IHC) was used to validate the expression of hub genes in UC patients.The prediction model, based on the seven hub genes, exhibited diagnostic ability in discriminating UC patients from controls. Furthermore, these hub PRGs were found to be associated with immune cells, including dendritic cells, NK cells, macrophages, regulatory T cells (Tregs), and CD8+ T cells. They were also linked to key signaling pathways implicated in UC pathogenesis, such as IFNγ, TNFα, IL6‐and JAK‐STAT3, as well as hypoxia and apoptosis. Immunohistochemistry analysis validated the expression levels of hub PRGs in UC patients using paraffin sections of intestinal biopsy specimens.This study identified PANoptosis‐related genes with potential diagnostic value for UC and suggest that PANoptosis may contribute to the pathogenesis of UC by regulating specific immune cells and interacting with key signaling pathways. This highlights the potential importance of PANoptosis‐related genes as therapeutic targets in UC management. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to investigate the expression levels and biological significance of CKS2 in Burkitt cell lymphoma (BL) and diffuse large B‐cell lymphoma (DLBCL). Additionally, the potential synergistic anti‐tumor effects of CKS2 knockdown in combination with etoposide in BL and DLBCL were explored for the first time. Methods: Bioinformatics analysis was utilized to explore the transcriptional levels, prognostic value, and gene function enrichment of CKS2 in BL and DLBCL. Specific shRNA sequences were designed to target CKS2 for the purpose of constructing a lentiviral expression vector, and therapeutic effects were assessed through analyses of cell proliferation, cell cycle distribution, and cell apoptosis. Results: First, the study examined the increased transcriptional and protein levels of CKS2 in BL and DLBCL through analysis of various databases and immunohistochemistry tests. Elevated CKS2 expression was found to be correlated with a worse prognosis in BL and DLBCL patients, as evidenced by data from the TCGA and GEO databases. Enrichment analysis indicated that CKS2 functions were primarily linked to protein kinase regulatory activity, G1/S phase transition of the cell cycle, and the p53 signaling pathway, among others. Second, stable suppression of CKS2 gene expression in Raji and SUDHL6 cells using shRNA resulted in a significant inhibition of cell proliferation. Moreover, CKS2‐shRNA induced G0/G1 cell cycle arrest and apoptosis by activating the p53 signaling pathway in Raji and SUDHL6 cells. Third, the combined treatment of CKS2‐shRNA and etoposide exhibited a synergistic effect on the proliferation and apoptosis of Raji and SUDHL6 cells. Conclusions: Our findings suggest that CKS2 may play a critical role in the progression of BL and DLBCL and provide evidence for the potential therapeutic application of combining CKS2‐shRNA and etoposide agents in the treatment of BL and DLBCL. [ABSTRACT FROM AUTHOR]

Lysosomes are digestive organelles responsible for endocytosis and autophagy. Recently, the malignancy and invasiveness head and neck squamous cell carcinoma (HNSCC) has been increasingly studied with the role of lysosomes. A list of lysosome‐related genes were obtained from MSigDB. A Spearman correlation and univariate Cox regression analyses combined with differential expression analysis were conducted to detect differentially expressed lysosome‐related genes related to prognosis. The prediction of prognostic signature was evaluated by plotting survival curve, ROC, and by developing a nomogram. Immune subtypes, infiltration of immune cells, GSVA, TIDE, IC50 of common chemotherapy and targeted therapy, GO, and KEGG function enrichment analyses were carried out to explore the immune microenvironment of the signature. We constructed a lysosome‐related prognostic signature that could function as an independent prognostic indicator for patients with HNSCC. High‐risk patients were better suited to receive Doxorubicin, Mitomycin C, Pyrimethamine, anti‐PD‐L1 and anti‐CTLA‐4 immunotherapy, whereas low‐risk patients had sensitivity to Lapatinib. GO functional enrichment analysis showed that prognostic features were strongly associated with epidermis‐related functions (e.g., epidermal cell differentiation, epidermal development, and keratinization). In addition, a KEGG function enrichment analysis revealed a potential relationship between the risk assessment model and cardiomyopathy. We constructed a prognostic signature based on lysosome‐related genes and successfully predicted the survival outcome of HNSCC patients, which not only provides potential guidance for personalized treatment but also provides a new idea for precision treatment of HNSCC. [ABSTRACT FROM AUTHOR]

Bone cancer pain remains a significant clinical challenge, often refractory to conventional treatments. The upregulation of the P2X3 receptor in the dorsal root ganglia has been implicated in the pathogenesis of bone cancer pain. This study aimed to elucidate the role of the P2X3 receptor in this context and assess the therapeutic potential of receptor silencing. Utilizing a rat model with Walker 256 cells to simulate bone cancer pain, researchers conducted molecular analyses, including semi‐quantitative RT‐PCR and Western Blot, to investigate P2X3 receptor expression in the dorsal root ganglia. Results demonstrated a marked increase in P2X3 receptor levels in the dorsal root ganglia of the bone cancer pain model. Targeted silencing of the P2X3 receptor using specific shRNA delivered via lentiviral vectors significantly reduced pain sensitivity, underscoring the receptor's potential as a valuable therapeutic target. In addition, a comprehensive gene expression analysis leveraging the GEO data set GSE249443 was performed to explore the underlying biological pathways linked to bone cancer pain. This analysis provided insights into the intricate interplay between bone cancer pain and associated biological processes, offering a deeper understanding of the mechanisms involved in pain modulation and progression. In conclusion, this research identifies the P2X3 receptor as a critical molecular target for mitigating bone cancer pain. The selective silencing of the P2X3 receptor emerges as a promising and innovative therapeutic strategy, presenting novel avenues for managing bone cancer pain and potentially revolutionizing treatment approaches in this challenging domain. [ABSTRACT FROM AUTHOR]

Background: Laryngeal squamous cell carcinoma (LSCC) is a type of cancer of the respiratory tract that often presents with subtle symptoms at the early stage and is susceptible to recurrence and metastasis. Materials and Methods: To find out key regulatory genes involved in LSCC development, we downloaded LSCC‐related sequencing datasets for bioinformatics analysis. WGCNA was performed on GSE142083 and differential analysis was conducted on GSE51985 and TCGA‐HNSC. Intersection genes were taken from the above three datasets. To confirm the function of genes, we overexpressed and knocked down genes in cells and treated them with autophagy agonist Rapamycin and PI3K‐AKT pathway inhibitor. At the cellular level, the expression of CH25H, autophagy‐related proteins (LC3 I, LC3 II, p62, and Beclin 1), and PI3K‐AKT pathway‐related proteins (PI3K, AKT, and p‐AKT) were assessed via Western blot; the mRNA level of CH25H was evaluated through qRT‐PCR; the cell activity was examined by CCK8; the apoptosis was assessed through flow cytometry; and the cell migration and invasion were assessed through wound healing and Transwell assays. Results: Through bioinformatics analysis, we screened 7 genes (CH25H, NELL2, STC2, TMEM158, ZIC2, HOXD11, and HOXD10). Ultimately, CH25H was selected for follow‐up experiments. By detecting CH25H expression in human immortalized keratinocytes (HaCaT) and LSCC cells (Tu‐686, SNU899, and AMC‐HN‐8), it was found out that CH25H expression was higher in HaCaT cells than in LSCC cells. To elucidate the role of CH25H in LSCC development, we overexpressed CH25H in Tu‐686 cells and downregulated its expression in AMC‐HN‐8 cells. CH25H was revealed to reduce the proliferation, activity, invasion, and migration of LSCC cells while increasing their apoptosis levels. Significant changes were also observed in the expressions of autophagy‐ and PI3K‐AKT pathway‐related proteins. To further investigate the roles of autophagy and the PI3K‐AKT pathway in LSCC development, we respectively employed autophagy agonists and inhibitors targeting the PI3K‐AKT pathway to intervene the cells, and found that CH25H regulated the PI3K‐AKT pathway to promote autophagy, thus enhancing the apoptosis of LSCC cells. We further investigated CH25H's impact on tumor growth, autophagy, and the PI3K‐AKT pathway at the animal level and found that CH25H promoted autophagy of LSCC cells and inhibited the PI3K‐AKT pathway, and ultimately inhibiting the progression of LSCC. Conclusions: In summary, CH25H promotes autophagy and affects the malignant progression of LSCC through the PI3K‐AKT pathway. [ABSTRACT FROM AUTHOR]

Anthropogenic activities in the environment affect the ecosystem and can play an important role in selecting and spreading antibiotic‐resistant bacteria (ARB) and genes (ARGs). The dairy farm environment may serve as a hotspot and reservoir for exchanging and spreading ARGs, but studies are scarce. Here, we investigated and characterized the extended‐spectrum β‐lactamase producing Escherichia coli strains recovered from the dairy farm environment co‐harboring blaOXA−1, catB3, and arr-3 genes. The isolates were identified and characterized by PCR, antimicrobial susceptibility testing, conjugation assay, whole genome sequencing (WGS), and multiple bioinformatics tools. Seven E. coli strains co‐harboring blaOXA−1, catB3, and arr-3 genes were identified which belonged to distinct sequence types (STs) and carried diverse plasmid replicon types. The conjugation assay revealed a successful transfer of blaOXA−1, catB3, and arr-3 genes into the recipient E. coli J53 with a co‐conjugation frequency ranging from (2.25 ± 0.3) × 10−4 to (3.85 ± 0.3) × 10−3. Bioinformatics analysis of WGS revealed the diversity of acquired ARGs, conferring resistance to aminoglycosides, beta‐lactams, quinolones, tetracyclines, macrolides, trimethoprim–sulfamethoxazole, phosphonic, phenicol, and rifamycin. The genetic environment analysis showed that aac(6′)‐Ib-cr-blaOXA−1‐catB3-arr-3-qacE1-sul1 was the common genetic backbone among the seven E. coli strains. Among the mobile genetic elements, insertion sequences were the predominant elements as compared to transposons. The phylogenetic analysis demonstrated a close relationship between the E. coli of this study and other strains of human–animal‐environment origin retrieved from the NCBI database. This study presented the whole genome‐based characterization of E. coli strains carrying the blaOXA−1‐catB3-arr-3 genes. It provided evidence that the dairy environment may harbor a variety of ARGs and act as a potential reservoir for their spread in the ecosystem. The results recommend the routine surveillance of ARGs carrying bacteria in dairy environments and the need for additional studies to understand the dissemination mechanism within One Health perspective to prevent their further spread. [ABSTRACT FROM AUTHOR]

Objective: Anterior disc displacement (ADD) is a common clinical issue and may cause osteoarthritis (OA). However, the research of protein changes in synovial fluid as disease development marker and potential treatment clue is still insufficient. Materials and Methods: We conducted the high‐resolution mass spectrometry (MS) of synovial fluid collected from 60 patients with normal disk position to ADD and ADD with osteoarthritis (OA). The proteins with significant changes among the 3 groups were analyzed by biological information and further validated by in primary rat condyle chondrocytes and OA animal model. Results: FGL2, THBS4, TNC, FN1, OMD etc. were significantly increased in ADD without OA (p < 0.05), which reflected the active extracellular matrix and collagen metabolism. FGFR1, FBLN2, GRB2 etc. were significantly increased in ADD with OA group (p < 0.05), which revealed an association with apoptosis and ferroptosis. Proteins such as P4HB, CBLN4, FHL1, VIM continuously increase in the whole disease progress (p < 0.05). Both the in vitro and in vivo results are consistent with protein changes detected in MS profile. Conclusion: This study firstly provides the expression changes of proteins from normal disc condyle relationship toward ADD with OA, which can be selected and studied further as disease progress marker and potential treatment targets. [ABSTRACT FROM AUTHOR]

Inflammations have been linked to tumours, suggesting a potential association between NLRP1 and cancer. Nevertheless, a systematic assessment of NLRP1's role across various cancer types currently absent. A comprehensive bioinformatic analysis was conducted to determine whether NLRP1 exhibits prognostic relevance linked to immune metabolism across various cancers. The study leveraged data from the TCGA and GTEx databases to explore the clinical significance, metabolic features, and immunological characteristics of NLRP1, employing various tools such as R, GEPIA, STRING and TISIDB. NLRP1 exhibited differential expression patterns across various cancers, with elevated expression correlating with a more favourable prognosis in lung adenocarcinoma (LUAD) and pancreatic adenocarcinoma (PAAD). Downregulation of NLRP1 reduced tumour metabolic activity in LUAD. Moreover, the mutational signature of NLRP1 was linked to a favourable prognosis. Interestingly, high NLRP1 expression inversely correlated with tumour stemness while positively correlating with tumour immune infiltration in various cancers including LUAD and PAAD. Through extensive big data analysis, we delved into the role of NLRP1 across various tumour types, constructing a comprehensive role map of its involvement in pan‐cancer scenarios. Our findings highlight the potential of NLRP1 as a promising therapeutic target specifically in LUAD and PAAD. [ABSTRACT FROM AUTHOR]

SQUAMOSA promoter‐binding protein‐like (SPL) gene family, a group of plant‐specific transcription factors, played crucial roles in regulating plant growth, development, signal transduction, and stress response. This study focuses on the SPL gene family in the fast‐growing Eucalyptus grandis, employing bioinformatics approaches to identify and analyze the gene physiochemical characteristics, conserved domains, structural composition, chromosomal distribution, phylogenetic relationships, cis‐acting elements, and their expression patterns in various tissues and stress treatments. Twenty‐three SPL genes were identified in E. grandis, which uneven distributed across seven chromosomes and classified into five groups. Prediction of cis‐acting elements revealed that these genes might be related to light, hormone, and stress responses. Furthermore, EgSPL9 and EgSPL23, mainly expressed in the stem apex and lateral branches, seem to be involved in hormone stress resistance. Our study provides insights into the potential functions of the EgSPL genes in plant growth, stress response, and hormone transduction, offering valuable perspectives for subsequent research into their biological roles. [ABSTRACT FROM AUTHOR]

Objective: The present study was performed to identify key biomarkers associated with immune cell infiltration in peri‐implantitis through bioinformatic analyses. Methods: Six peri‐implantitis soft tissue samples and six healthy gingiva samples were obtained from GSE106090, and were used to identify immune‐associated differentially expressed genes (DEGs) in peri‐implantitis. The candidate biomarkers associated with immune cell infiltration were examined by immunohistochemical staining. Results: We identified 2089 upregulated and 2173 downregulated genes. Upregulated DEGs were significantly associated with immune response. Ten key candidate biomarkers were identified in the PPI network, including IL1B, TLR2, TLR4, CCL4, CXCL8, IL10, IL6, CD4, CCL3, and PTPRC. The expression level of the 10 genes increased in peri‐implantitis soft tissue samples compared with healthy gingiva samples. The proportion of CD4+ T cells, iTreg, and Tfh in infiltration immune cells increased in peri‐implantitis soft tissue samples and were positively correlated with the expression level of candidate biomarkers TLR4, CCL3, CXCL8, and IL1B. Immunohistochemistry showed that there were more lymphocytes in peri‐implantitis soft tissue samples, with an increased expression level of TLR4, CCL3, CXCL8, and IL1B. Conclusion: Identification of four novel diagnostic biomarkers was helpful for revealing the molecular mechanisms and could serve as a risk predictor for the immune microenvironment in peri‐implantitis. [ABSTRACT FROM AUTHOR]

Although there are clear morphologic criteria for the diagnosis of papillary thyroid carcinoma (PTC), when the morphology is untypical or overlaps, accurate diagnostic indicators are necessary. Since few studies investigated the role of down‐regulated genes in PTC, this article aims to further explore the molecular markers associated with PTC. We conducted bioinformatics analysis of gene microarrays of PTC and normal adjacent tissues. Besides, quantitative real‐time quantitative polymerase chain reaction array and immunohistochemical staining were used to investigate the expression of the major down‐regulated genes. The results indicated that several important down‐regulated genes, including TLE1, BCL2, FHL1, GHR, KIT, and PPARGC1A were involved in the process of PTC. Compared to normal adjacent tissues, the mRNA expression of the major genes was down‐regulated in PTC (p＜0.05). Immunohistochemically, FHL1 shows negative or low expression in PTC tissues (p＜0.05). BCL2 did not show a significant difference between PTC and normal thyroid tissues (p > 0.05). TLE1, KIT, PPARGC1A and GHR showed negative expression in both tumor and normal tissues. These results suggested that FHL1 could serve as a novel tumor marker for precise diagnosis of PTC. [ABSTRACT FROM AUTHOR]

The Ebola virus poses a severe public health threat, yet understanding factors influencing disease outcomes remains incomplete. Our study aimed to identify critical pathways and hub genes associated with fatal and survivor Ebola disease outcomes. We analyzed differentially expressed hub genes (DEGs) between groups with fatal and survival outcomes, as well as a healthy control group. We conducted additional analysis to determine the functions and pathways associated with these DEGs. We found 13,198 DEGs in the fatal and 12,039 DEGs in the survival group compared to healthy controls, and 1873 DEGs in the acute fatal and survivor groups comparison. Upregulated DEGs in the comparison between the acute fatal and survivor groups were linked to ECM receptor interaction, complement and coagulation cascades, and PI3K‐Akt signaling. Upregulated hub genes identified from the acute fatal and survivor comparison (FGB, C1QA, SERPINF2, PLAT, C9, SERPINE1, F3, VWF) were enriched in complement and coagulation cascades; the downregulated hub genes (IL1B, 1L17RE, XCL1, CXCL6, CCL4, CD8A, CD8B, CD3D) were associated with immune cell processes. Hub genes CCL2 and F2 were unique to fatal outcomes, while CXCL1, HIST1H4F, and IL1A were upregulated hub genes unique to survival outcomes compared to healthy controls. Our results demonstrate for the first time the association of EVD outcomes to specific hub genes and their associated pathways and biological processes. The identified hub genes and pathways could help better elucidate Ebola disease pathogenesis and contribute to the development of targeted interventions and personalized treatment for distinct EVD outcomes. [ABSTRACT FROM AUTHOR]

The present study outlines the approach that was employed for cloning, expression, and characterization of the recombinant pullulanase enzyme from Bacillus cereus ATCC 14579 into Escherichia coli BL21(DE3) using pET‐25b (+) expression vector. The recombinant pullulanase enzyme was purified using ammonium sulfate precipitation and immobilized metal ion affinity chromatography (IMAC). The molecular mass of the purified pullulanase enzyme was measured using sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) as 95 kDa. The purified recombinant pullulanase enzyme demonstrated significant thermal stability, maintaining its structural integrity and functionality at temperatures as high as 90°C over a period of 4 h. The inclusion of divalent metal ions, specifically Ca2+ and Mg2+, had a positive effect on the activity of the pullulanase enzyme. Conversely, the presence of Co2+ and EDTA (Ethylene Diamine Tetra Acetic acid) resulted in suppression of the enzyme activity. The purified pullulanase enzyme demonstrated remarkable resistance when exposed to organic solvents. The enzyme activity was notably decreased in the presence of SDS (Sodium Dodecyl Sulfate) while β‐mercaptoethanol and tween‐60 did not substantially affect the enzyme activity and stability which suggest its potential applicability in the detergent sector. This discovery indicates a potential approach to improve the effectiveness of currently available detergents in the marketplace. [ABSTRACT FROM AUTHOR]

Background: Exportin 1 (XPO1) is a nuclear export protein that facilitates the transportation of various substances. XPO1 promotes tumor development as a poor prognostic factor in a variety of tumors and is a therapeutic target for screening inhibitors. However, the role of XPO1 in oral squamous cell carcinoma (OSCC) has yet to be determined. Methods: The expression patterns of XPO1 mRNA in OSCC were investigated using bioinformatics tools, and the expression levels of XPO1 protein in OSCC specimens were confirmed by immunohistochemical assays. Survival analysis was conducted to evaluate the impact of XPO1 on prognosis. GO and KEGG enrichment analyses were utilized to uncover the signaling pathways mediated by XPO1. Additionally, we examined the association between XPO1 and AKT/MAPK/TGFBR1 and immune infiltration. Results: XPO1 mRNA and protein expression levels were significantly enhanced in OSCC and associated with OSCC severity. Enhanced XPO1 expression was indicative of poor survival. Functional analysis showed that XPO1 mediated pathways associated with cell cycle and DNA replication and reduced immune infiltration in OSCC. Additionally, XPO1 mRNA and protein expression levels had significant positive relationships with AKT/MAPK/TGFBR1. Conclusions: XPO1, as a marker of poor prognosis in OSCC, can promote OSCC through AKT/MAPK/TGFBR1. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress (OS) plays a major role in the progress of hypoxic‐ischemic brain damage (HIBD). This study aimed to investigate OS‐related genes and their underlying molecular mechanisms in neonatal HIBD. Methods: Microarray data sets were acquired from the Gene Expression Omnibus (GEO) database to screen the differentially expressed genes (DEGs) between control samples and HIBD samples. OS‐related genes were drawn from GeneCards and OS‐DEGs in HIBD were obtained by intersecting with the DEGs. Subsequently, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were conducted to determine the underlying mechanisms and functions of OS‐DEGs in HIBD. Moreover, the hub genes were screened using the protein−protein interaction network and identified in the GSE144456 data set. CIBERSORT was then performed to evaluate the expression of immunocytes in each sample and perform a correlation analysis of the optimal OS‐DEGs and immunocytes. Finally, quantitative reverse transcription polymerase chain reaction (RT‐qPCR) and immunohistochemistry were performed to validate the expression levels of the optimal OS‐DEGs. Results: In total, 93 OS‐DEGs were identified. GO, KEGG, and GSEA enrichment analyses indicated that these genes were predominantly enriched in OS and inflammation. Four OS‐related biomarker genes (Jun, Fos, Tlr2, and Atf3) were identified and verified. CIBERSORT analysis revealed the dysregulation of six types of immune cells in the HIBD group. Moreover, 47 drugs that might target four OS‐related biomarker genes were screened. Eventually, RT‐qPCR and immunohistochemistry results for rat samples further validated the expression levels of Fos, Tlr2, and Atf3. Conclusions: Fos, Tlr2 and Atf3 are potential OS‐related biomarkers of HIBD progression. The mechanisms of OS are associated with those of neonatal HIBD. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic systemic inflammatory condition regarded as a major risk factor for colitis‐associated cancer. However, the underlying mechanisms of IBD remain unclear. First, five GSE data sets available in GEO were used to perform 'batch correction' and Robust Rank Aggregation (RRA) to identify differentially expressed genes (DEGs). Candidate molecules were identified using CytoHubba, and their diagnostic effectiveness was predicted. The CIBERSORT algorithm evaluated the immune cell infiltration in the intestinal epithelial tissues of patients with IBD and controls. Immune cell infiltration in the IBD and control groups was determined using the least absolute shrinkage selection operator algorithm and Cox regression analysis. Finally, a total of 51 DEGs were screened, and nine hub genes were identified using CytoHubba and Cytoscape. GSE87466 and GSE193677 were used as extra data set to validate the expression of the nine hub genes. CD4‐naïve T cells, gamma–delta T cells, M1 macrophages and resting dendritic cells (DCs) are the main immune cell infiltrates in patients with IBD. Signal transducer and activator of transcription 1, CCR5 and integrin subunit beta 2 (ITGB2) were significantly upregulated in the IBD mouse model, and suppression of ITGB2 expression alleviated IBD inflammation in mice. Additionally, the expression of ITGB2 was upregulated in IBD‐associated colorectal cancer (CRC). The silence of ITGB2 suppressed cell proliferation and tumour growth in vitro and in vivo. ITGB2 resting DCs may provide a therapeutic strategy for IBD, and ITGB2 may be a potential diagnostic marker for IBD‐associated CRC. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is a pregnancy‐related diabetic condition that may cause serious complications. However, its pathogenesis remains unclear. Placental damage due to GDM may lead to several health issues that cannot be ignored. Thus, we aimed to identify the mechanisms underlying GDM by screening differentially expressed genes (DEGs) related to vascular endothelial cells in the GDM databases and verify the expression of these DEGs in the placentas of women afflicted by GDM. Methods: We used GDM microarray datasets integrated from the Gene Expression Omnibus (GEO) database. Functional annotation and protein–protein interaction (PPI) analyses were used to screen DEGs. Placental tissues from 20 pregnant women with GDM and 20 healthy pregnant women were collected, and differential gene expression in the placental tissues was verified via qRT‐PCR, western blotting, and immunofluorescence. Results: Bioinformatics analysis revealed three significant DEGs: SNAIL2, PAPP-A, and TGFβ1. These genes were all predicted to be underexpressed in patients with GDM. The results of qRT‐PCR, western blot, and immunofluorescence analyses indicated that SNAIL2 and PAPP‐A in the placenta tissue of patients with GDM were significantly underexpressed. However, TGFβ1 in the placenta tissues of GDM was significantly overexpressed. Conclusion: SNAIL2, TGFβ1, and PAPP‐A may affect the placentas of pregnant women with GDM, warranting further investigation. [ABSTRACT FROM AUTHOR]

The pathogenesis of ankylosing spondylitis (AS) remains unclear, and while recent studies have implicated necroptosis in various autoimmune diseases, an investigation of its relationship with AS has not been reported. In this study, we utilized the Gene Expression Omnibus database to compare gene expressions between AS patients and healthy controls, identifying 18 differentially expressed necroptosis‐related genes (DENRGs), with 8 upregulated and 10 downregulated. Through the application of three machine learning algorithms—least absolute shrinkage and selection operation, support vector machine‐recursive feature elimination and random forest—two hub genes, FASLG and TARDBP, were pinpointed. These genes demonstrated high specificity and sensitivity for AS diagnosis, as evidenced by receiver operating characteristic curve analysis. These findings were further supported by external datasets and cellular experiments, which confirmed the downregulation of FASLG and upregulation of TARDBP in AS patients. Immune cell infiltration analysis suggested that CD4+ T cells, CD8+ T cells, NK cells and neutrophils may be associated with the development of AS. Notably, in the group with high FASLG expression, there was a significant infiltration of CD8+ T cells, memory‐activated CD4+ T cells and resting NK cells, with relatively less infiltration of memory‐resting CD4+ T cells and neutrophils. Conversely, in the group with high TARDBP expression, there was enhanced infiltration of naïve CD4+ T cells and M0 macrophages, with a reduced presence of memory‐resting CD4+ T cells. In summary, FASLG and TARDBP may contribute to AS pathogenesis by regulating the immune microenvironment and immune‐related signalling pathways. These findings offer new insights into the molecular mechanisms of AS and suggest potential new targets for therapeutic strategies. [ABSTRACT FROM AUTHOR]

The repurposing of therapeutic and preventive strategies against Alzheimer's disease (AD) is progressing rapidly. Pancratium aegyptiacum has been found to possess considerable anticholinesterase potential attributed to its alkaloid contents. In this study, the potential anti‐Alzheimer's activity of isolated flavonoids from P. aegyptiacum was investigated through computational analysis, focusing on the flavonoids rather than their well‐known alkaloids. Molecular docking was performed against three crucial targets involved in the development of AD, and the isolated phytoconstituents were analysed against these targets. Pathway enrichment analyses were also established, additionally, ADMETlab and PASS web servers predicted the pharmacological properties and potential biological functions of the isolated flavonoids. The phytochemical analysis of P. aegyptiacum aerial parts revealed the isolation and identification of eleven flavonoids. They were identified as derivatives of kaempferol (Km), quercetin (Qn) and isorhamnetin (Is). Our investigation revealed that these phytoconstituents potentially act against AD, with several phytochemicals showing superior binding affinity against essential AD targets. The Kyoto Encyclopaedia of Genes and Reactome pathway enrichment database revealed that isolated phytochemicals may have a role in regulating the immune pathway directly correlated to AD. Additionally, these phytochemicals exhibited lower toxicity with pleiotropic biological activities, including dementia treatment and neurotrophic factor enhancement. [ABSTRACT FROM AUTHOR]

Background and Purpose: In major depressive disorder (MDD), exploration of biomarkers will be helpful in diagnosing the disorder as well as in choosing a treatment and predicting the treatment response. Currently, tRNA‐derived small ribonucleic acids (tsRNAs) have been established as promising non‐invasive biomarker candidates that may enable a more reliable diagnosis or monitoring of various diseases. Herein, we aimed to explore tsRNA expression together with functional activities in MDD development. Experimental Approach: Serum samples were obtained from patients with MDD and healthy controls, and small RNA sequencing (RNA‐Seq) was used to profile tsRNA expression. Dysregulated tsRNAs in MDD were validated by quantitative real‐time polymerase chain reaction (qRT‐PCR). The diagnostic utility of specific tsRNAs and the expression of these tsRNAs after antidepressant treatment were analysed. Key Results: In total, 38 tsRNAs were significantly differentially expressed in MDD samples relative to healthy individuals (34 up‐regulated and 4 down‐regulated). qRT‐PCR was used to validate the expression of six tsRNAs that were up‐regulated in MDD (tiRNA‐1:20‐chrM.Ser‐GCT, tiRNA‐1:33‐Gly‐GCC‐1, tRF‐1:22‐chrM.Ser‐GCT, tRF‐1:31‐Ala‐AGC‐4‐M6, tRF‐1:31‐Pro‐TGG‐2 and tRF‐1:32‐chrM.Gln‐TTG). Interestingly, serum tiRNA‐Gly‐GCC‐001 levels exhibited an area under the ROC curve of 0.844. Moreover, tiRNA‐Gly‐GCC‐001 is predicted to suppress brain‐derived neurotrophic factor (BDNF) expression. Furthermore, significant tiRNA‐Gly‐GCC‐001 down‐regulation was evident following an 8‐week treatment course and served as a promising baseline predictor of patient response to antidepressant therapy. Conclusion and Implications: Our current work reports for the first time that tiRNA‐Gly‐GCC‐001 is a promising MDD biomarker candidate that can predict patient responses to antidepressant therapy. [ABSTRACT FROM AUTHOR]

Background: Aberrant expression of adipocyte enhancer‐binding protein 1 (AEBP1) has been demonstrated to be involved in the tumorigenesis and progression of numerous cancers. This study was aimed to investigate the mechanism of AEBP1 in the development of cervical cancer. Methods: The expression of AEBP1 in cervical cancer was assessed by immunohistochemistry. The function of AEBP1 on cell proliferation, migration, and invasion was determined by methyl thiazolyl tetrazolium assay, colony formation, and transwell assay. The activation of related signaling pathway was determined by western blot. The bioinformatics analysis was performed by Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Results: Higher protein expression of AEBP1 was observed in patients with cervical cancer. Overexpressed AEBP1 promoted cell proliferation, migration, and invasion abilities in cervical cancer cells. Moreover, the research manifested that AEBP1 activated the phosphorylation of STAT3. GO and KEGG analysis showed that genes positively related to AEBP1 were highly enriched in functions like epithelial cell proliferation, muscle cell migration, myoblast migration, smooth muscle tissue development, ECM–receptor interaction, transcriptional misregulation in cancer, and proteoglycans in cancer. While genes negatively related to AEBP1 were associated with immunity, including inflammatory response, external‐stimulus response, neutrophil, granulocyte, and macrophage chemotaxis. Conclusions: This study suggested that AEBP1 acts as an oncogened and might be a potential therapeutic target for the treatment of cervical cancer. [ABSTRACT FROM AUTHOR]

RFC4 is required for DNA polymerase δ and DNA polymerase ε to initiate DNA template expansion. Downregulated RFC4 inhibits tumour proliferation by causing S‐phase arrest and inhibiting mitosis, resulting in the reduction of tumour cells. RFC4 has been implicated that it plays an important role in the initiation and progression of cancers, but a comprehensive analysis of the role of RFC4 in cancer has not been performed. We comprehensively analysed the expression, prognosis, methylation level, splicing level, relationship of RFC4 and immune infiltration, and pan‐cancer immunotherapy response used various databases (including TCGA, GTEx, UALCAN, Oncosplicing, TIDE, TISCH, HPA and CAMOIP), and experimented its biological function in HCC. Through pan‐cancer analysis, we found that RFC4 is significantly upregulated in most tumours. The tumour patients with high expression of RFC4 have poor prognosis. The methylation level and variable splicing level of RFC4 were abnormal in most tumours compared with the adjacent tissues. Furthermore, RFC4 was closely associated with immune cell infiltration in various cancers. RFC4 was significantly co‐expressed with immune checkpoints and other immune‐related genes. The expression of RFC4 could indicate the immunotherapy efficacy of some tumours. The RFC4 expression was associated with sensitivity to specific small molecule drugs. Cell experiments have shown that downregulated RFC4 can inhibit cell cycle and tumour cell proliferation. We conducted a systematic pan‐cancer analysis of RFC4, and the results showed that RFC4 can serve as a biomarker for cancer diagnosis and prognosis. These findings open new perspectives for precision medicine. [ABSTRACT FROM AUTHOR]

Background: Ultraviolet radiation causes skin photoaging by producing a variety of enzymes, which impact both skin health and hinder beauty. Currently, the early diagnosis and treatment of photoaging remain a challenge. Bioinformatics analysis has strong advantages in exploring core genes and the biological pathways of photoaging. Aims: To screen and validate key risk genes associated with plasminogen in photoaging and to identify potential target genes for photoaging. Methods: Two human transcriptome datasets were obtained by searching the Gene Expression Omnibus (GEO) database, and the mRNAs in the GSE131789 dataset were differentially analyzed, and then the weighted gene co‐expression network analysis (WGCNA) was performed to find out the strongest correlations. Template genes, interaction analysis of differentially expressed genes (DEGs), modular genes with the most WGCNA correlations, and genecard database genes related to plasminogen were performed, and further Kyoto genes and Genome Encyclopedia (KEGG) pathway analysis. Two different algorithms, least absolute shrinkage and selection operator (LASSO) and support vector machines‐recursive feature elimination (SVM‐RFE), were used to find key genes. Then the data set (GSE206495) was validated and analyzed. Real‐time PCR was performed to validate the expression of key genes through in vitro cellular experiments. Results: IFI6, IFI44L, HRSP12, and BMP4 were screened from datasets as key genes for photoaging and further analysis showed that these genes have significant diagnostic value for photoaging. Conclusion: IFI6, IFI44L, HRSP12, and BMP4 play a key role in the pathogenesis of photoaging, and serve as promising potential predictive biomarkers for photoaging. [ABSTRACT FROM AUTHOR]

Background: Dermatomyositis (DM) manifests as an autoimmune and inflammatory condition, clinically characterized by subacute progressive proximal muscle weakness, rashes or both along with extramuscular manifestations. Literature indicates that DM shares common risk factors with atherosclerosis (AS), and they often co‐occur, yet the etiology and pathogenesis remain to be fully elucidated. This investigation aims to utilize bioinformatics methods to clarify the crucial genes and pathways that influence the pathophysiology of both DM and AS. Method: Microarray datasets for DM (GSE128470, GSE1551, GSE143323) and AS (GSE100927, GSE28829, GSE43292) were retrieved from the Gene Expression Omnibus (GEO) database. The weighted gene co‐expression network analysis (WGCNA) was used to reveal their co‐expressed modules. Differentially expression genes (DEGs) were identified using the "limma" package in R software, and the functions of common DEGs were determined by functional enrichment analysis. A protein‐protein interaction (PPI) network was established using the STRING database, with central genes evaluated by the cytoHubba plugin, and validated through external datasets. Immune infiltration analysis of the hub genes was conducted using the CIBERSORT method, along with Gene Set Enrichment Analysis (GSEA). Finally, the NetworkAnalyst platform was employed to examine the transcription factors (TFs) responsible for regulating pivotal crosstalk genes. Results: Utilizing WGCNA analysis, a total of 271 overlapping genes were pinpointed. Subsequent DEG analysis revealed 34 genes that are commonly found in both DM and AS, including 31 upregulated genes and 3 downregulated genes. The Degree Centrality algorithm was applied separately to the WGCNA and DEG collections to select the 15 genes with the highest connectivity, and crossing the two gene sets yielded 3 hub genes (PTPRC, TYROBP, CXCR4). Validation with external datasets showed their diagnostic value for DM and AS. Analysis of immune infiltration indicates that lymphocytes and macrophages are significantly associated with the pathogenesis of DM and AS. Moreover, GSEA analysis suggested that the shared genes are enriched in various receptor interactions and multiple cytokines and receptor signaling pathways. We coupled the 3 hub genes with their respective predicted genes, identifying a potential key TF, CBFB, which interacts with all 3 hub genes. Conclusion: This research utilized comprehensive bioinformatics techniques to explore the shared pathogenesis of DM and AS. The three key genes, including PTPRC, TYROBP, and CXCR4, are related to the pathogenesis of DM and AS. The central genes and their correlations with immune cells may serve as potential diagnostic and therapeutic targets. [ABSTRACT FROM AUTHOR]

Behçet's disease (BD) is a complex autoimmune disorder impacting several organ systems. Although the involvement of abdominal aortic aneurysm (AAA) in BD is rare, it can be associated with severe consequences. In the present study, we identified diagnostic biomarkers in patients with BD having AAA. Mendelian randomization (MR) analysis was initially used to explore the potential causal association between BD and AAA. The Limma package, WGCNA, PPI and machine learning algorithms were employed to identify potential diagnostic genes. A receiver operating characteristic curve (ROC) for the nomogram was constructed to ascertain the diagnostic value of AAA in patients with BD. Finally, immune cell infiltration analyses and single‐sample gene set enrichment analysis (ssGSEA) were conducted. The MR analysis indicated a suggestive association between BD and the risk of AAA (odds ratio [OR]: 1.0384, 95% confidence interval [CI]: 1.0081–1.0696, p = 0.0126). Three hub genes (CD247, CD2 and CCR7) were identified using the integrated bioinformatics analyses, which were subsequently utilised to construct a nomogram (area under the curve [AUC]: 0.982, 95% CI: 0.944–1.000). Finally, the immune cell infiltration assay revealed that dysregulation immune cells were positively correlated with the three hub genes. Our MR analyses revealed a higher susceptibility of patients with BD to AAA. We used a systematic approach to identify three potential hub genes (CD247, CD2 and CCR7) and developed a nomogram to assist in the diagnosis of AAA among patients with BD. In addition, immune cell infiltration analysis indicated the dysregulation in immune cell proportions. [ABSTRACT FROM AUTHOR]

Aims/Introduction: The molecular mechanisms of diabetic nephropathy (DN) are poorly identified. However, the advantage of an increasing amount on microarray data of diabetic nephropathy intrigued us to explore the mechanisms based on bioinformatics prediction for diabetic nephropathy. Materials and Methods: Bioinformatics analysis was conducted to screen the hub genes associated with diabetic nephropathy. The average human renal tubular epithelial cells were exposed to high glucose (HG) to generate an in vitro cell model. In addition, a mouse model of diabetic nephropathy was established using a high‐fat diet and streptozotocin injection. Finally, the shRNA targeting immunoglobulin heavy constant gamma 1 (IGHG1) was introduced in vitro and in vivo to illustrate its effect on downstream factors and on the development diabetic nephropathy. Results: Bioinformatics analysis revealed that IGHG1, TRIM11 (tripartite motif protein 11), and TonEBP are highly expressed in diabetic nephropathy. In vitro cell experiments demonstrated that IGHG1 positively regulates the expression of TRIM11 and TonEBP (tonicity‐responsive enhancer binding protein) in HK2 cells treated with high glucose. Furthermore, TRIM11 upregulates the expression of TonEBP through activation of the MEK/ERK (mitogen‐activated protein kinase/extracellular signal‐regulated kinase) signaling pathway in HK2 cells treated with high glucose. In vivo, animal experiments further confirmed that silencing IGHG1 could prevent the occurrence and development of diabetic nephropathy. Conclusion: The silencing of IGHG1 alleviated diabetic nephropathy by inhibiting the TRIM11/MEK/ERK axis and by downregulating TonEBP. [ABSTRACT FROM AUTHOR]

Background: This study aimed to type breast cancer in relation to reactive oxygen species (ROS), clinical indicators, single nucleotide variant (SNV) mutations, functional differences, immune infiltration, and predictive responses to immunotherapy or chemotherapy, and constructing a prognostic model. Methods: We used uniCox analysis, ConsensusClusterPlus, and the proportion of ambiguous clustering (PAC) to analyze The Cancer Genome Atlas (TCGA) data to determine optimal groupings and obtain differentially expressed ROS‐related genes. Clinical indicators were then combined with the classification results and the Chi‐square test was used to assess differences. We further examined SNV mutations, and functional differences using gene set enrichment analysis (GSEA) analysis, the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, immune cell infiltration, and response to immunotherapy and chemotherapy. A prognostic model for breast cancer was constructed using these differentially expressed genes, immunotherapy or chemotherapy responses, and survival curves. RT‐qPCR was used to detect the differences in the expression of LCE3D, CA1, PIRT and SMR3A in breast cancer cell lines and normal breast epithelial cell line. Results: We identified two distinct tumor types with significant differences in ROS‐related gene expression, clinical indicators, SNV mutations, functional pathways, and immune infiltration. The response to specific chemotherapy drugs and immunotherapy treatments also documented significant differences. The prognostic model constructed with 16 genes linked to survival could efficiently divide patients into high‐ and low‐risk groups. The high‐risk group showed a poorer prognosis, higher tumor purity, distinct immune microenvironment, and lower immunotherapy response. RT‐qPCR results showed that LCE3D, CA1, PIRT and SMR3A are highly expressed in breast cancer. Conclusion: Our methodical examination presented an enhanced insight into the molecular and immunological heterogeneity of breast cancer. It can contribute to the understanding of prognosis and offer valuable insights for personalized treatment strategies. Further, the prognostic model can potentially serve as a powerful tool for risk stratification and therapeutic decision‐making in clinical settings. [ABSTRACT FROM AUTHOR]

Objective: Several clinical studies have shown an association between polycystic ovary syndrome (PCOS) and asthma; however, the molecular link between these conditions remains unclear. In this study, we conducted a reanalysis and repurposing of existing databases in order to depict the common key genes, related signaling pathways, and similarity of the immune microenvironment between PCOS and asthma. Methods: PCOS and asthma data sets were downloaded, and common signal pathways were identified by using gene set enrichment analysis. Identified common susceptibility genes were explored by intersecting the weighted gene coexpression network analysis module genes for both diseases. Then, we performed protein–protein interaction, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes analyses of the common susceptibility genes. Finally, we analyzed the immune environment of PCOS and asthma. Results: We identified five hub genes, namely, MMP9, CDC42, CD44, CD19, and BCL2L1, and uncovered that these five hub genes showed a tendency to be upregulated in both PCOS and asthma and possessed good diagnostic ability. In addition, we revealed that both PCOS and asthma were significantly enriched in the FcεRI‐mediated signaling pathway. Moreover, we found that both PCOS and asthma exhibited infiltration of similar types of immune cells, such as monocytes, suggesting that the two diseases have similar pathological features. Conclusion: PCOS and asthma share common causative genes with a similar immune environment. Taken together, we uncovered previously unsuspected traits for comprehensive diagnosis and treatment of PCOS and asthma in the future. Synopsis: Polycystic ovary syndrome and asthma share common characteristic genes and related signaling pathways and have a similar immune microenvironment. [ABSTRACT FROM AUTHOR]

Background and Objectives: Periodontitis is an immuno‐inflammatory disease caused by dental plaque biofilms and inflammations. The regeneration of bone tissue in inflammatory environment is of great significance for the treatment of periodontal disease, but the specific molecular mechanism of bone formation in periodontitis still needs further exploration. The objective of this study was to identify key osteogenesis‐related genes (ORGs) in periodontitis. Methods: We used two datasets from the Gene Expression Omnibus (GEO) database to find differentially expressed mRNAs and miRNAs, further performed Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Then we predicted the downstream genes of the differentially expressed miRNAs (DEMs) by the TargetScan database and established a miRNA‐mRNA regulatory network. Finally, the osteogenic mechanism of periodontitis was explored through quantitative real‐time PCR (qRT‐PCR) by inducing inflammatory environment and osteogenic differentiation of hPDLSCs. Results: Through differential expression analysis and prediction of downstream target genes of DEMs, we created a miRNA‐mRNA regulatory network consisting of 29 DEMs and 11 differentially expressed osteogenesis‐related genes (DEORGs). In addition, the qRT‐PCR results demonstrated that BTBD3, PLAT, AKAP12, SGK1, and GLCE expression levels were significantly upregulated, while those of TIMP3, ZCCHC14, LIN7A, DNAH6, NNT, and ITGA6 were downregulated under the dual effects of inflammatory stimulation and osteogenic induction. Conclusion: DEORGs might be important factors in the osteogenic phase of periodontitis, and the miRNA‐mRNA network may shed light on the clarification of the role and mechanism of osteogenesis in periodontitis and contribute to the development of novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Background: Perinatal exposure to maternal obesity predisposes offspring to develop obesity later in life. Immune dysregulation in the hypothalamus, the brain center governing energy homeostasis, is pivotal in obesity development. This study aimed to identify key candidate genes associated with the risk of offspring obesity in maternal obesity. Methods: We obtained obesity‐related datasets from the Gene Expression Omnibus (GEO) database. GSE135830 comprises gene expression data from the hypothalamus of mouse offspring in a maternal obesity model induced by a high‐fat diet model (maternal high‐fat diet (mHFD) group and maternal chow (mChow) group), while GSE127056 consists of hypothalamus microarray data from young adult mice with obesity (high‐fat diet (HFD) and Chow groups). We identified differentially expressed genes (DEGs) and module genes using Limma and weighted gene co‐expression network analysis (WGCNA), conducted functional enrichment analysis, and employed a machine learning algorithm (least absolute shrinkage and selection operator (LASSO) regression) to pinpoint candidate hub genes for diagnosing obesity‐associated risk in offspring of maternal obesity. We constructed a nomogram receiver operating characteristic (ROC) curve to evaluate the diagnostic value. Additionally, we analyzed immune cell infiltration to investigate immune cell dysregulation in maternal obesity. Furthermore, we verified the expression of the candidate hub genes both in vivo and in vitro. Results: The GSE135830 dataset revealed 2868 DEGs between the mHFD offspring and the mChow group and 2627 WGCNA module genes related to maternal obesity. The overlap of DEGs and module genes in the offspring with maternal obesity in GSE135830 primarily enriched in neurodevelopment and immune regulation. In the GSE127056 dataset, 133 DEGs were identified in the hypothalamus of HFD‐induced adult obese individuals. A total of 13 genes intersected between the GSE127056 adult obesity DEGs and the GSE135830 maternal obesity module genes that were primarily enriched in neurodevelopment and the immune response. Following machine learning, two candidate hub genes were chosen for nomogram construction. Diagnostic value evaluation by ROC analysis determined Sytl4 and Kncn2 as hub genes for maternal obesity in the offspring. A gene regulatory network with transcription factor–miRNA interactions was established. Dysregulated immune cells were observed in the hypothalamus of offspring with maternal obesity. Expression of Sytl4 and Kncn2 was validated in a mouse model of hypothalamic inflammation and a palmitic acid‐stimulated microglial inflammation model. Conclusion: Two candidate hub genes (Sytl4 and Kcnc2) were identified and a nomogram was developed to predict obesity risk in offspring with maternal obesity. These findings offer potential diagnostic candidate genes for identifying obesity‐associated risks in the offspring of obese mothers. [ABSTRACT FROM AUTHOR]

Objective: To analysis the relationship between periodontitis (PD) and oral squamous cell carcinoma (OSCC) by bioinformatic analysis. Materials and Methods: We analyzed the gene expression profiles of PD (GSE16134) from the Gene Expression Omnibus (GEO) database and OSCC samples from TCGA‐HNSC (head and neck squamous cell carcinoma) and identified common differentially expressed genes (DEGs) in PD and OSCC. Then, functional annotation and signaling pathway enrichment, protein interaction network construction, and hub gene identification were performed. Subsequently, the function and signaling pathway enrichment of hub genes, miRNA interaction, and transcription factor interaction analyses were carried out. We analyzed GSE10334 and GSE30784 as validation datasets, and performed qRT‐PCR experiments simultaneously for validation, and obtained 4 hub genes. Finally, immune infiltration analysis and clinical correlation analysis of 4 hub genes and related miRNAs were performed. Results: We identified 31 DEGs (16 up‐regulated and 15 down‐regulated). Four hub genes were obtained by qRT‐PCR and validation dataset analysis, including IL‐1β, CXCL8, MMP12, and MMP13. The expression levels of them were all significantly upregulated in both diseases. The functions of these genes focus on three areas: neutrophil chemotaxis, migration, and CXCR chemokine receptor binding. Key pathways include IL‐17 signaling pathway, chemokine signaling pathway, and cytokine–cytokine receptor interactions pathway. Immune infiltration analysis showed that the expressions of 4 hub genes were closely related to a variety of immune cells. ROC curve analysis indicated that AUCs of 4 hub genes are all greater than 0.7, among which MMP12 and MMP13 were greater than 0.9. Kaplan–Meier survival analysis indicated that worse OS was strongly correlated with CXCL8 and MMP13 high‐expression groups. MMP12 low‐expression group was strongly associated with worse OS. The results of multivariate Cox regression analysis showed that age, N stage, CXCL8, MMP12, and MMP13 were independent prognostic factors for OS. We also identified 3 miRNAs, including hsa‐miR‐19b‐3p, hsa‐miR‐181b‐2‐3p, and hsa‐miR‐495‐3p, that were closely related to 4 hub genes. Hsa‐miR‐495‐3p is closely related to the diagnosis and prognosis of OSCC. Conclusions: We identified 4 hub genes between PD and OSCC, including IL‐1β, CXCL8, MMP12, and MMP13. These genes may mediate the co‐morbid process of PD and OSCC through inflammation‐related pathways such as the IL‐17 signaling pathway. It is worth noting that CXCL8, MMP12, and MMP13 have great significance in the diagnosis and prognosis of OSCC. [ABSTRACT FROM AUTHOR]

Osteonecrosis of the femoral head (ONFH) is a condition caused by a disruption or damage to the femoral head's blood supply, which causes the death of bone cells and bone marrow components and prevents future regeneration. Ferroptosis, a type of controlled cell death, is caused by iron‐dependent lipid peroxidation. Here, we identified ferroptosis‐related genes and infiltrating immune cells involved in ONFH and predicted the underlying molecular mechanisms. The GSE123568 dataset was subjected to differential expression analysis to identify genes related to ferroptosis. Subsequently, GO and KEGG pathway enrichment analyses, as well as protein–protein interaction (PPI) network analysis, were conducted. Hub genes involved in ferroptosis were identified using machine learning and other techniques. Additionally, immune infiltration analysis and lncRNA–miRNA‐mRNA network prediction analysis were performed. Finally, we determined whether ferroptosis occurred by measuring iron content. The hub genes were validated by ROC curve analysis and qRT–PCR. Four ferroptosis‐related hub genes (MAPK3, PTGS2, STK11, and SLC2A1) were identified. Additionally, immune infiltration analysis revealed a strong correlation among ONFH, hub genes, and various immune cells. Finally, we predicted the network relationship between differentially expressed lncRNAs and hub genes in the lncRNA–miRNA–mRNA network. MAPK3, PTGS2, STK11, and SLC2A1 have been identified as potential ferroptosis‐related biomarkers and drug targets for the diagnosis and prognosis of ONFH, while some immune cells, as well as the interaction between lncRNA, miRNA, and mRNA, have also been identified as potential pathogenesis markers and therapeutic targets. [ABSTRACT FROM AUTHOR]

This study aims to investigate the role of anoikis‐related genes in diabetic foot (DF) by utilizing bioinformatics analysis to identify key genes associated with anoikis in DF. We selected the GEO datasets GSE7014, GSE80178 and GSE68183 for the extraction and analysis of differentially expressed anoikis‐related genes (DE‐ARGs). GO analysis and KEGG analysis indicated that DE‐ARGs in DF were primarily enriched in apoptosis, positive regulation of MAPK cascade, anoikis, focal adhesion and the PI3K‐Akt signalling pathway. Based on the LASSO and SVM‐RFE algorithms, we identified six characteristic genes. ROC curve analysis revealed that these six characteristic genes had an area under the curve (AUC) greater than 0.7, indicating good diagnostic efficacy. Expression analysis in the validation set revealed downregulation of CALR in DF, consistent with the training set results. GSEA results demonstrated that CALR was mainly enriched in blood vessel morphogenesis, endothelial cell migration, ECM‐receptor interaction and focal adhesion. The HPA database revealed that CALR was moderately enriched in endothelial cells, and CALR was found to interact with 63 protein‐coding genes. Functional analysis with DAVID suggested that CALR and associated genes were enriched in the phagosome component. CALR shows promise as a potential marker for the development and treatment of DF. [ABSTRACT FROM AUTHOR]

Background: Low back pain (LBP) is the main factor of global disease burden. Intervertebral disc degeneration (IVDD) has long been known as the leading reason of LBP. Increasing studies have verified that circular RNAs (circRNAs)‐microRNAs (miRNAs)‐mRNAs network is widely involved in the pathological processes of IVDD. However, no study was made to demonstrate the circRNAs‐mediated ferroptosis, oxidative stress, extracellular matrix metabolism, and immune response in IVDD. Methods: We collected 3 normal and 3 degenerative nucleus pulposus tissues to conduct RNA‐sequencing to identify the key circRNAs and miRNAs in IVDD. Bioinformatics analysis was then conducted to construct circRNAs‐miRNAs‐mRNAs interaction network associated with ferroptosis, oxidative stress, extracellular matrix metabolism, and immune response. We also performed animal experiments to validate the therapeutic effects of key circRNAs in IVDD. Results: We found that circ_0015435 was most obviously upregulated and circ_0071922 was most obviously downregulated in IVDD using RNA‐sequencing. Then we observed that hsa‐miR‐15a‐5p was the key downstream of circ_0071922, and hsa‐miR‐15a‐5p was the top upregulated miRNA in IVDD. Bioinformatics analysis was conducted to predict that 56 immunity‐related genes, 29 ferroptosis‐related genes, 23 oxidative stress‐related genes and 8 ECM‐related genes are the targets mRNAs of hsa‐miR‐15a‐5p. Then we constructed a ceRNA network encompassing 24 circRNAs, 6 miRNAs, and 101 mRNAs. Additionally, we demonstrated that overexpression of circ_0071922 can alleviate IVDD progression in a rat model. Conclusions: The findings of this study suggested that circ_0071922‐miR‐15a‐5p‐mRNA signaling network might affect IVDD by modulating the nucleus pulposus cells ferroptosis, oxidative stress, ECM metabolism, and immune response, which is an effective therapeutic targets of IVDD. [ABSTRACT FROM AUTHOR]

Aging is acknowledged as the most significant risk factor for cardiovascular disease (CVD). This study sought to identify and validate potential aging‐related genes associated with CVD by using bioinformatics. The confluence of the limma test, weighted correlation network analysis (WGCNA), and 2129 aging and senescence‐associated genes led to the identification of aging‐related differential expression genes (ARDEGs). By using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), potential biological roles and pathways of ARDEGs were identified. To find the significantly different functions between CVD and non‐cardiovascular disease (nCVD) and to reckon the processes score, enrichment analysis of all genes was carried out using gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA). By using GO and KEGG, potential biological roles and pathways of ARDEGs were identified. To evaluate the immune cell composition of the immune microenvironment, we performed an immune infiltration analysis on the dataset from the training group. We were able to acquire four ARDEGs (PTGS2, MMP9, HBEGF, and FN1). Aging, cellular senescence, and nitric oxide signal transduction were selected for biological function analysis. The diagnostic value of the four ARDEGs in distinguishing CVD from nCVD samples was deemed to be favorable. This research identified four ARDEGs that are associated with CVD. This study provides insight into prospective novel biomarkers for aging‐related CVD diagnosis and progression monitoring. [ABSTRACT FROM AUTHOR]

Background: Isoleucinyl‐tRNA synthetase (IARS) is encoded by the IARS1 gene and catalyzes the binding of isoleucine to specific tRNA. Objective: This study aims to investigate the pathogenicity of novel IARS1 variants and the genotype–phenotype association, in order to expand the spectrum of pathogenic variants and phenotypes of IARS1‐related disease and provide new evidence for the phenotypic spectrum of IARS1 variants. Methods: Clinical data of the proband were collected, and trio whole‐exome sequencing (WES) was performed on the proband and the parents. Candidate variants were validated using Sanger sequencing. Bioinformatics software was utilized to analyze the functional consequences of identified variants and predict their potential deleteriousness. Results: A 17‐month‐old female patient presented with microcephaly, left external ear malformation, decreased muscle strength and tone in all limbs, epileptic seizures, global developmental delay, and developmental regression. Trio WES identified compound heterozygous variants in the IARS1 gene, c.120‐1G>A and c.2164C>A, which were novel pathogenic and likely pathogenic variants, respectively. The phenotype of developmental regression has not been reported before. Only one patient with IARS1 compound heterozygous variants has been reported in the world to have an epileptic phenotype, and this is the second patient with an epileptic phenotype. Bioinformatics analysis revealed that the splicing variant disrupted the canonical splice donor site, while the missense variant altered the local electrostatics of the IARS1 protein surface, potentially leading to functional abnormalities. Conclusion: This study identified novel IARS1 variants and the phenotype of developmental regression, expanding the spectrum of pathogenic variants and phenotypes of IARS1‐related diseases and providing new evidence for the rare phenotype of epileptic seizures caused by IARS1 variants. [ABSTRACT FROM AUTHOR]

Background: The role of genes associated with the cuproptosis cell signaling pathway in prognosis and immunotherapy in ovarian cancer (OC) has been extensively investigated. In this study, we aimed to explore these mechanisms and establish a prognostic model for patients with OC using bioinformatics techniques. Methods: We obtained the single cell sequencing data of ovarian cancer from the Gene Expression Omnibus (GEO) database and preprocessed the data. We analyzed a variety of factors including cuproptosis cell signal score, transcription factors, tumorigenesis and progression signals, gene set variation analysis (GSVA) and intercellular communication. Differential gene analysis was performed between groups with high and low cuproptosis cell signal scores, as well as Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Using bulk RNA sequencing data from The Cancer Genome Atlas, we used the least absolute shrinkage and selection operator (LASSO)‐Cox algorithm to develop cuproptosis cell signaling pathword‐related gene signatures and validated them with GEO ovarian cancer datasets. In addition, we analyzed the inherent rules of the genes involved in building the model using a variety of bioinformatics methods, including immune‐related analyses and single nucleotide polymorphisms. Molecular docking is used to screen potential therapeutic drugs. To confirm the analysis results, we performed various wet experiments such as western blot, cell counting kit 8 (CCK8) and clonogenesis tests to verify the role of the Von Willebrand Factor (VWF) gene in two ovarian cancer cell lines. Results: Based on single‐cell data analysis, we found that endothelial cells and fibroblasts showed active substance synthesis and signaling pathway activation in OC, which further promoted immune cell suppression, cancer cell proliferation and metastasis. Ovarian cancer has a high tendency to metastasize, and cancer cells cooperate with other cells to promote disease progression. We developed a signature consisting of eight cuproptosis‐related genes (CRGs) (MAGEF1, DNPH1, RARRES1, NBL1, IFI27, VWF, OLFML3 and IGFBP4) that predicted overall survival in patients with ovarian cancer. The validity of this model is verified in an external GEO validation set. We observed active infiltrating states of immune cells in both the high‐ and low‐risk groups, although the specific cells, genes and pathways of activation differed. Gene mutation analysis revealed that TP53 is the most frequently mutated gene in ovarian cancer. We also predict small molecule drugs associated with CRGs and identify several potential candidates. VWF was identified as an oncogene in ovarian cancer, and the protein was expressed at significantly higher levels in tumor samples than in normal samples. The high‐score model of the cuproptosis cell signaling pathway was associated with the sensitivity of OC patients to immunotherapy. Conclusions: Our study provides greater insight into the mechanisms of action of genes associated with the cuproptosis cell signaling pathway in ovarian cancer, highlighting potential targets for future therapeutic interventions. [ABSTRACT FROM AUTHOR]

Th17 cells which are crucial for host immunity have been demonstrated to increase HBV infection. However, the mechanism of the Th17 cell increase is unknown. Hence, the mechanism of Th17 cell enhancement is important to provide a theoretical foundation for chronic hepatitis B immunotherapy. This study included 15 instances in the healthy control (HC) and 15 cohorts in the chronic hepatitis B (CHB). Their CD4+T cells were isolated from their peripheral blood and then subjected to RNA transcriptome sequencing. Then, to identify target genes linked to Th17‐cell differentiation, DEGs associated with CHB were convergent with the Th17‐cell‐associated genes from the KEGG database. Hub genes of DEG and target genes linked to Th17 cells were analysed for correlation. The AhR‐related genes were located using the GeneMANIA database. To analyse the function of the genes, GO and KEGG pathways were employed. Protein–protein interaction network analysis employed the Metascape, STRING and Cytoscape databases. Finally, Western blotting and RT‐qPCR were used to validate AhR. A total of 348 differential genes were identified in CHB patients. CytoHubba was used for screening five hub genes associated with CHB: CXCL10, RACGAP1, TPX2, FN1 and GZMA. This study aimed to determine the mechanism of elevated Th17 cells in CHB. As a result, further investigation using the convergence of DGEs and Th17 cell‐related genes identified three target genes: AhR, HLA‐DQA1 and HLA‐DQB1, all of which were elevated in CHB. The three genes were primarily involved in immune response‐related processes, according to the GO enrichment analysis. Correlation analysis of CXCL10, RACGAP1, TPX2, FN1 and GZMA genes with AhR, HLA‐DQA1 and HLA‐DQB1 revealed that AhR was positively associated with CXCL10 and GZMA genes, which best respond to the severity of CHB disease. Combined with the role of AhR in Th17 cell differentiation, the genes AhR was chosen for confirmation by RT‐qPCR and WB in this study. The results showed that the CHB group had higher expression levels of AhR at both RT‐qPCR and WB levels. Furthermore, this study's findings revealed that AhR may contribute to the development of CHB by affecting the differentiation of Th17 cells. [ABSTRACT FROM AUTHOR]

Ellagic acid (EA) is a natural polyphenolic compound. Recent studies have shown that EA has potential anticancer properties against gastric cancer (GC). This study aims to reveal the potential targets and mechanisms of EA against GC. This study adopted methods of bioinformatics analysis and network pharmacology, including the weighted gene co‐expression network analysis (WGCNA), construction of protein–protein interaction (PPI) network, receiver operating characteristic (ROC) and Kaplan–Meier (KM) survival curve analysis, Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, molecular docking and molecular dynamics simulations (MDS). A total of 540 EA targets were obtained. Through WGCNA, we obtained a total of 2914 GC clinical module genes, combined with the disease database for screening, a total of 606 GC‐related targets and 79 intersection targets of EA and GC were obtained by constructing Venn diagram. PPI network was constructed to identify 14 core candidate targets; TP53, JUN, CASP3, HSP90AA1, VEGFA, HRAS, CDH1, MAPK3, CDKN1A, SRC, CYCS, BCL2L1 and CDK4 were identified as the key targets of EA regulation of GC by ROC and KM curve analysis. The enrichment analysis of GO and KEGG pathways of key targets was performed, and they were mainly enriched in p53 signalling pathway, PI3K‐Akt signalling pathway. The results of molecular docking and MDS showed that EA could effectively bind to 13 key targets to form stable protein–ligand complexes. This study revealed the key targets and molecular mechanisms of EA against GC and provided a theoretical basis for further study of the pharmacological mechanism of EA against GC. [ABSTRACT FROM AUTHOR]

The SARS‐CoV‐2 outbreak resulted in significant challenges and loss of life. The Nipah virus, known for its high infectivity and severity, was designated an emergency concern by the World Health Organization. To understand its mutations, the Nipah virus proteins were analyzed extensively, with a focus on the essential G and F proteins responsible for viral entry into host cells. Our bioinformatics analysis unveiled multiple mutations, including simultaneous mutations within a single sequence. Notably, the G273S mutation in the F protein was identified as a potential cause of structural damage, which carries significant implications for vaccine development. Comparing the docking scores of G and F proteins with the Ephrin B2 receptor, it was found that the Y228H mutation in the G protein and the D252G mutation in the F protein likely affect virus entry into host cells. Moreover, our investigation into stability and deformability highlighted the impact of the Y228H mutation in the G protein complex. Molecular dynamics simulations revealed increased flexibility and conformational changes in the G protein complex with the Y228H mutation compared with the known complex. Furthermore, evaluating the root mean square deviation variation demonstrated greater dynamic behavior in the G protein complex and the Ephrin B2 receptor complex. This comprehensive study provides valuable insights into Nipah virus mutations, their significance for vaccine development, and the importance of understanding protein complex behavior in drug discovery. The identified mutations, especially G273S and Y228H, hold crucial implications for future research and potential interventions against the Nipah virus. [ABSTRACT FROM AUTHOR]

The article focuses on revealing the regulatory potency of CKAP5 in Human Papillomavirus positive Head and Neck Squamous Cell Carcinoma (HPV+ HNSCC) through Competing Endogenous RNA (ceRNA) analysis. It is discussed that Utilizing high-throughput sequencing technology, the study identifies differential gene expression and constructs a ceRNA network, highlighting CKAP5 as a potential therapeutic target in HPV+ HNSCC, emphasizing its significance in disease progression and prognosis.

Prenatal tobacco exposure (PTE) correlates significantly with a surge in adverse pregnancy outcomes, yet its pathological mechanisms remain partially unexplored. This study aims to meticulously examine the repercussions of PTE on placental immune landscapes, employing a coordinated research methodology encompassing bioinformatics, machine learning and animal studies. Concurrently, it aims to screen biomarkers and potential compounds that could sensitively indicate and mitigate placental immune disorders. In the course of this research, two gene expression omnibus (GEO) microarrays, namely GSE27272 and GSE7434, were included. Gene set enrichment analysis (GSEA) and immune enrichment investigations on differentially expressed genes (DEGs) indicated that PTE might perturb numerous innate or adaptive immune‐related biological processes. A cohort of 52 immune‐associated DEGs was acquired by cross‐referencing the DEGs with gene sets derived from the ImmPort database. A protein–protein interaction (PPI) network was subsequently established, from which 10 hub genes were extracted using the maximal clique centrality (MCC) algorithm (JUN, NPY, SST, FLT4, FGF13, HBEGF, NR0B2, AREG, NR1I2, SEMA5B). Moreover, we substantiated the elevated affinity of tobacco reproductive toxicants, specifically nicotine and nitrosamine, with hub genes through molecular docking (JUN, FGF13 and NR1I2). This suggested that these genes could potentially serve as crucial loci for tobacco's influence on the placental immune microenvironment. To further elucidate the immune microenvironment landscape, consistent clustering analysis was conducted, yielding three subtypes, where the abundance of follicular helper T cells (p < 0.05) in subtype A, M2 macrophages (p < 0.01), neutrophils (p < 0.05) in subtype B and CD8+ T cells (p < 0.05), resting NK cells (p < 0.05), M2 macrophages (p < 0.05) in subtype C were significantly different from the control group. Additionally, three pivotal modules, designated as red, blue and green, were identified, each bearing a close association with differentially infiltrated immunocytes, as discerned by the weighted gene co‐expression network analysis (WGCNA). Functional enrichment analysis was subsequently conducted on these modules. To further probe into the mechanisms by which immune‐associated DEGs are implicated in intercellular communication, 20 genes serving as ligands or receptors and connected to differentially infiltrating immunocytes were isolated. Employing a variety of machine learning techniques, including one‐way logistic regression, LASSO regression, random forest and artificial neural networks, we screened 11 signature genes from the intersection of immune‐associated DEGs and secretory protein‐encoding genes derived from the Human Protein Atlas. Notably, CCL18 and IFNA4 emerged as prospective peripheral blood markers capable of identifying PTE‐induced immune disorders. These markers demonstrated impressive predictive power, as indicated by the area under the curve (AUC) of 0.713 (0.548–0.857) and 0.780 (0.618–0.914), respectively. Furthermore, we predicted 34 potential compounds, including cyclosporine, oestrogen and so on, which may engage with hub genes and attenuate immune disorders instigated by PTE. The diagnostic performance of these biomarkers, alongside the interventional effect of cyclosporine, was further corroborated in animal studies via ELISA, Western blot and immunofluorescence assays. In summary, this study identifies a disturbance in the placental immune landscape, a secondary effect of PTE, which may underlie multiple pregnancy complications. Importantly, our research contributes to the noninvasive and timely detection of PTE‐induced placental immune disorders, while also offering innovative therapeutic strategies for their treatment. [ABSTRACT FROM AUTHOR]

Alterations in DNA methylation in malignant diseases have been heralded as promising targets for diagnostic, prognostic, and predictive values. This study was based on epigenetic alterations and immune cell infiltration analysis to investigate the mechanism of CD3D methylation in uveal melanoma (UM). Bioinformatics analysis was performed on transcriptome data, 450 K methylation data, and clinical information of UM patients from the TCGA database. Stromal and immune cell infiltration was evaluated by calculating the StromalScore and ImmuneScore of UM samples. UM samples were divided into high and low StromalScore and ImmuneScore groups, followed by differential and enrichment analyses. PPI network construction and correlation analysis was used to identify the core prognosis‐related genes. The bioinformatics analysis results were confirmed in UM cell experiments. StromalScore and ImmuneScore were significantly associated with the prognosis of UM patients. CD3D, IRF1, CCL3, and FN1 were identified as core genes driven by methylation that affected the prognosis of UM patients. CD3D expression showed the highest correlation with its methylation and was closely related to the four key immune cells in UM development. CD3D was hypomethylated and abundantly expressed in UM cells, while silencing of CD3D inhibited the proliferation, migration, and invasion of UM cells in vitro. In summary, this study identifies hypomethylation of CD3D promoter in UM, which was associated with immune cell infiltration of UM. [ABSTRACT FROM AUTHOR]

Background: Metaplastic breast carcinoma (MBC) is a rare breast cancer subtype; most cases are triple‐negative breast cancers (TNBCs) and are poorly responsive to conventional systemic therapy. Few potential diagnostic and prognostic markers for distinguishing between metaplastic TNBC and nonmetaplastic TNBC have been discovered. We performed bioinformatic analysis to explore the underlying mechanism by which metaplastic TNBC differs from nonmetaplastic TNBC and provides potential pathogenic genes of metaplastic TNBC. Methods: Differentially expressed genes (DEGs) in metaplastic tumors and nonmetaplastic tumors from TNBC patients were screened using GSE165407. The GSE76275 data set and The Cancer Genome Atlas (TCGA) database were used to screen DEGs in TNBC and non‐TNBC. Metascape and DAVID were used for the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and Gene Ontology (GO) analysis of DEGs. Online databases, including UALCAN, GEPIA, HPA, Breast Cancer Gene‐Expression Miner, and quantitative PCR and western blot, were used to examine KLK5 messenger RNA and protein expression in breast cancer. Analysis of KLK5‑associated genes was performed with TCGA data, and the LinkedOmics database was used to detect the genes co‐expressed with KLK5. STRING (Search Tool for the Retrieval of Interacting Genes) and Cytoscape were used to screen for hub genes. Kaplan‑Meier plotter was used for survival analysis. Results: KLK5 was identified among the DEGs in nonmetaplastic TNBC and metaplastic TNBC. The KLK5 gene was overexpressed in nonmetaplastic TNBC but downregulated in metaplastic TNBC. KEGG and GO analyses revealed that epithelial‐to‐mesenchymal transition was a pathogenic mechanism in metaplastic TNBC and an important pathway by which KLK5 and its associated genes DSG1 and DSG3 influence metaplastic TNBC progression. Prognosis analysis showed that only low expression of KLK5 in metaplastic TNBC had clinical significance. Conclusion: Our research indicated that KLK5 may be a pivotal molecule with a key role in the mechanism of tumorigenesis in metaplastic TNBC. [ABSTRACT FROM AUTHOR]

Ferroptosis is a novel form of cell death that plays a key role in several diseases, including inflammation and tumours; however, the role of ferroptosis‐related genes in diabetic foot remains unclear. Herein, diabetic foot‐related genes were downloaded from the Gene Expression Omnibus and the ferroptosis database (FerrDb). The least absolute shrinkage and selection operator regression algorithm was used to construct a related risk model, and differentially expressed genes were analysed through immune infiltration. Finally, we identified relevant core genes through a protein–protein interaction network, subsequently verified using immunohistochemistry. Comprehensive analysis showed 198 genes that were differentially expressed during ferroptosis. Based on functional enrichment analysis, these genes were primarily involved in cell response, chemical stimulation, and autophagy. Using the CIBERSORT algorithm, we calculated the immune infiltration of 22 different types of immune cells in diabetic foot and normal tissues. The protein–protein interaction network identified the hub gene TP53, and according to immunohistochemistry, the expression of TP53 was high in diabetic foot tissues but low in normal tissues. Accordingly, we identified the ferroptosis‐related gene TP53 in the diabetic foot, which may play a key role in the pathogenesis of diabetic foot and could be used as a potential biomarker. [ABSTRACT FROM AUTHOR]

The aim of this study was twofold: (1) evaluate the effect of benzo[a]pyrene (BaP) on expression levels of AQP3 and Notch1 genes in HaCaT cells exposed "in vitro" and (2) investigate the possible biological role of assessed genes by bioinformatics methods. Cells were exposed to increasing concentrations of BaP (0.0–4.0 μM) for 1–4 days. After treatments, cell viability and expression levels of AhR, CYP1A1, AQP3, and Notch1 genes were evaluated. The possible biological role of assessed genes was evaluated using bioinformatics tools. Low cytotoxicity in HaCaT cells dosed with BaP was detected. A significant overexpression (p <.05) of CYP1A1, AQP3, and Notch1 was found in exposed HaCaT cells. The gene expression upregulation was dependent on AhR activation. The bioinformatics analysis showed that these genes were enriched in related cancer signaling pathways. The findings suggest that AQP3 and Notch1 are upregulated by AhR activation in HaCaT cells exposed to BaP. [ABSTRACT FROM AUTHOR]

Background: Lung adenocarcinoma (LUAD) is a highly aggressive cancer in advanced stages and has the highest cancer‐related death across the world. Anoikis has emerged as a specific form of apoptotic cell death that may play a vital role in the formation and development of tumors. Methods: Based on The Cancer Genome Atlas dataset, we developed a novel anoikis‐related genes (ARGs) signature in LUAD and evaluated the differences between low and high‐risk groups in clinical characteristics, expression patterns, immune cell infiltration, and drug sensitivity, etc. According to multivariate Cox regression analysis, the risk score was identified as a significant independent prognostic factor. The possible biological pathways of ARGs' were assessed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The immune infiltration landscape and risk score of ARGs were analyzed by ESTIMATE and CIBERSORT analysis. A nomogram grounded on six key ARGs and clinicopathological features was provided. Moreover, experiment validation of the expression patterns of six hub ARGs in lung cancer cell lines was conducted. Results: We identified 53 survival‐related LUAD anoikis‐related differentially expressed genes and finally six hub anoikis genes (LDHA, SLC2A1, SERPINB5, ITGB4, BRCA2, and PIK3R1) were selected to construct an ARG model. The risk model could efficiently cluster the patients into low‐ and high‐risk groups which could accurately predict clinical outcomes for LUAD patients. There is evidence that the prognostic risk score is a remarkable prognostic factor in determining overall survival. Different immune statuses and drug sensitivity between low‐ and high‐risk groups were explored according to functional analysis. On the basis of risk scores and LUAD clinicopathological features, a novel nomogram was developed. Ultimately, all six key genes except for PIK3R1 were proved to be upregulated in LUAD tissues and cell lines by bioinformatics analysis and experimental validation. Conclusions: The result of the present study suggest that ARGs could be carcinogenic to LUAD and could be used as an effective stratification factor to customize therapies and forecast the survival rate in LUAD patients. [ABSTRACT FROM AUTHOR]

Background: Palatogenesis requires a precise spatiotemporal regulation of gene expression. Recent studies indicate that microRNAs (miRNAs) are key factors in normal palatogenesis. The present study aimed to explain the regulatory mechanisms of miRNAs during palate development. Methods: Pregnant ICR mice were choose at embryonic day 10.5 (E10.5). Hemotoxylin and eosin (H&E) staining was used to observe the morphological changes during the development of palatal process at embryonic day (E)13.5, E14.0, E14.5, E15.0 and E15.5. The fetal palatal tissues were collected at E13.5, E14.0, E14.5 and E15.0 to explore miRNA expression and function by high throughput sequencing and bioinformatic analysis. Mfuzz cluster analysis was used to look for miRNAs related to the fetal mice palate formation. The target genes of miRNAs were predicted by miRWalk. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed base on target genes. The mesenchymal cell proliferation and apoptosis related miRNAs‐genes networks were predicted and constructed using miRWalk and Cytoscape software. The expression of mesenchymal cell proliferation and apoptosis related miRNAs at the E13.5, E14.0, E14.5, and E15.0 was detected by a quantitative real‐time PCR (RT‐qPCR) assay. Results: H&E staining found that the palatal process grows vertically along the sides of the tongue at E13.5, the position of the tongue begins to descend and the bilateral palatal processes rise above the tongue at E14.0, the palatal process grows horizontally at E14.5, there is palatal contact fusion at E15.0, and the palatal suture disappeared at E15.5. Nine clusters of miRNA expression changes were identified in the fetal mice palate formation progression, including two reducing trends, two rising trends and five disordered trends. Next, the heatmap showed the miRNA expression from Clusters 4, 6, 9, 12 in the E13.5, E14.0, E14.5 and E15.0 groups. GO functional and KEGG pathway enrichment analysis found target genes of miRNAs in clusters involved in regulation of mesenchymal phenotype and the mitogen‐activated protein kinase (MAPK) signaling pathway. Next, mesenchymal phenotype related miRNA‐genes networks were constructed. The heatmap showing that the mesenchymal phenotype related miRNA expression of Clusters 4, 6, 9 and 12 at E13.5, E14.0, E14.5 and E15.0. Furthermore, the mesenchymal cell proliferation and apoptosis related miRNA‐gene networks were identified in Clusters 6 and 12, including mmu‐miR‐504‐3p‐Hnf1b, etc. The expression level of mesenchymal cell proliferation and apoptosis related miRNAs at the E13.5, E14.0, E14.5, and E15.0 was verified by a RT‐qPCR assay. Conclusions: For the first time, we identified that clear dynamic miRNA expression during palate development. Furthermore, we demonstrated that mesenchymal cell proliferation and apoptosis related miRNAs, genes and the MAPK signaling pathway are important during fetal mice palate development. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is a multidrug‐resistant coccobacillus responsible for severe nosocomial infectious diseases. This study mainly focuses on investigating the antimicrobial resistance features of a clinically isolated strain (A. baumannii CYZ) using the PacBio Sequel II sequencing platform. The chromosomal size of A. baumannii CYZ is 3,960,760 bp, which contains a total of 3803 genes with a G + C content of 39.06%. Functional analysis performed using the Clusters of Orthologous Groups of Proteins (COGs), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, as well as the Comprehensive Antibiotic Resistance Database (CARD) revealed a complicated set of antimicrobial resistance determinants in the genome of A. baumannii CYZ, which were mainly classified into multidrug efflux pumps and transport systems, β‐lactamase relative and penicillin‐binding proteins, aminoglycoside modification enzymes, alternation of antibiotic target sites, lipopolysaccharide relative, and other mechanisms. A total of 35 antibiotics were tested for the antimicrobial susceptibility of A. baumannii CYZ, and the organism exhibited a stronger antimicrobial resistance ability. The phylogenetic relationship indicated that A. baumannii CYZ has high homology with A. baumannii ATCC 17978; however, the former also exhibited its specific genome characteristics. Our research results give insight into the genetic antimicrobial‐resistant features of A. baumannii CYZ as well as provide a genetic basis for the further study of the phenotype. [ABSTRACT FROM AUTHOR]