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There are currently many clinical issues plaguing digestive oncologists, including the impact of dietary habits on the occurrence of early gastrointestinal cancer, the association between irritable bowel syndrome, ulcerative colitis, and early gastrointestinal cancer, the expected changes in gastrointestinal cancer after IBS, IBD, and susceptibility gene mutations, and the mechanisms by which susceptibility gene mutations in gastrointestinal cancer lead to different diseases. Meanwhile, as a carcinogen, betel nut is also prone to cancer and emotional disorders, and there are also many doctor-patient conflicts in the current clinical treatment of digestive tract tumors. To address the aforementioned issues, the research team analyzed dietary habits data using SOM clustering algorithm and isolated forest algorithm. Based on bioinformatics, new therapies have been developed for the pathogenesis and immune pathways of various cancers in the digestive system. Using network pharmacology methods, explore the toxicological mechanism of betel nut and its mechanism in mediating emotional disorders. Molecular docking is used to elucidate drug prediction. Based on four AI algorithms, the occurrence of gastrointestinal cancer was predicted through dietary habits. Using computer vision technology to address the deficiencies in early clinical reporting of cancer. This article provides clinical doctors with new treatment tools. [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical relevance of common myeloid progenitor (CMP) cells in breast tumor microenvironment (TME). Background: The role of rare cells in TME is less studied. In Silico transcriptomic analyses of real-world data enable us to detect and quantify rare cells, including CMP cells. Methods: A total of 5176 breast cancer (BC) patients from SCANB, METABRIC, and 5 single-cell sequence cohorts were analyzed using the xCell algorithm. The high group was defined as more than two-thirds of the CMP scores in each cohort. Results: CMP cells consist of 0.07% to 0.25% of bulk breast tumor cells, more in estrogen receptor-positive (ER+) compared with triple-negative (TN) subtype (0.1% to 0.75%, 0.18% to 0.33% of immune cells, respectively). CMP cells did not correlate with any of the myeloid lineages or stem cells in TME. CMP infiltration was higher in smaller tumors, with lower Nottingham grade, and in ER +/HER2- than in TNBC consistently in both SCAN-B and METABRIC cohorts. High CMP was significantly associated with a lower risk of brain metastasis and with better survival, particularly in ER+/HER2-. High CMP enriched epithelial-to-mesenchymal transition and angiogenesis pathways, and less cell proliferation and DNA repair gene sets. High CMP ER+/HER2- was associated with less immune cell infiltration and cytolytic activity (P<0.001). CMP infiltration correlated with neoadjuvant chemoimmunotherapy response for both ER+/HER2- and TNBC in the ISPY-2 cohort (AUC=0.69 and 0.74, respectively). Conclusions: CMP in BC is inversely associated with cell proliferation and brain metastasis, better response to immunotherapy, and survival. This is the first to report the clinical relevance of CMP infiltration in BC. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to explore the expression, clinical significance, and functional mechanism of FYN in lower-grade gliomas (LGG). Methods: The mRNA and protein expression of FYN in LGG tissues were detected using databases including OncoLnc, GEPIA, and Human protein atlas (HPA). The UCSC Xena browser, TIMER, STRING and Metascape databases were used to investigate Kaplan–Meier survival curves, correlations between FYN expression and various types of immune cell infiltration, protein interaction network and possible functional mechanism. Results: FYN expression in LGG, IDH mutation or 1p19q co-deletion subgroup was significantly higher than in corresponding control groups (p < 0.05). Patients with higher FYN expression had longer overall survival (p < 0.05). Male or no 1p19q co-deletion groups with higher FYN expression also had longer overall survival (p < 0.05). FYN expression had close correlation with infiltrating levels of cell purity, CD4+T cells, macrophages, and CD8+T cells (p < 0.05). Protein interaction network result showed correlation among FYN, SH2D1A, LCK, CAV1, SRC, CBL and PTK2. Functional enrichment analysis revealed that FYN and its related genes mainly participated in bacterial invasion of epithelial cells and natural killer cell mediated cytotoxicity. Peptidyl-tyrosine phosphorylation, negative regulation of anoikis, immune effector process, transmembrane receptor protein tyrosine kinase signaling pathway, epidermal growth factor receptor signaling pathway, and negative regulation of protein modification process may be the critical biological process. Conclusions: FYN is up-expressed in LGG and related to its good prognosis. It participated in tumor pathophysiological processes and may be a therapeutic target for LGG. [ABSTRACT FROM AUTHOR]

Cervical cancer (CC) is a frequent disease in women whose development is related with miRNA disorder. MiR-377-5p plays a negative role in the development of some tumors, while few studies have revealed its role in CC. In this study, the functions of miR-377-5p in CC were investigated by bioinformatics. Briefly, the expression and survival curve of miR-377-5p in CC was analyzed with the Cancer Genome Atlas (TCGA) database, and the abundance of miR-377-5p in clinical samples and CC cell lines were measured by qRT-PCR. Moreover, the MicroRNA Data Integration Portal (miRDIP) database was used to predict targets of miR-377-5p, and the Database for Annotation Visualization and Integrated Discovery (David) was used for enrichment analysis of the functions of the miR-377-5p. The Search Tool for the Retrieval of Interacting Genes (STRING) database was used to screen the hub targets of miR-377-5p. Moreover, the Gene Expression Profiling Interactive Analysis (GEPIA) database was used to analyze the abundance of the genes in CC. Results showed that decreased miR-377-5p was found in the CC tissues and cell lines, and low miR-377-5p was connected with poor prognosis of patients. Besides, the targets of miR-377-5p were enriched in the PI3K/AKT, MAPK and RAS signaling pathways. Moreover, CDC42, FLT1, TPM3 and CAV1 were screened as hub nodes in the targets of miR-377-5p, and increased CDC42, FLT1, TPM3 and CAV1 also indicated the poor survival rates of the patients in the long term. In conclusion, this study suggests that miR-377-5p downregulation is a biomarker event for CC progression. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to identify the optimal protein construction for designing a multiepitope vaccine with both prophylactic and therapeutic effects against cervical cancer, utilizing an immunoinformatics approach. The construction process involved using capsid epitopes L1 and L2, as well as oncoproteins E5, E6, and E7 from human papillomavirus (HPV) types 16 and 18. Methods: An experimental in silico analysis with an immunoinformatics approach was used to develop 2 multi-epitope vaccine constructs (A and B). Further analysis was then conducted to compare the constructs and select the one with the highest potential against cervical cancer. Results: This study produced 2 antigenic, non-allergenic, and nontoxic multi-epitope vaccine constructs (A and B), which exhibited the ideal physicochemical properties for a vaccine. Further analysis revealed that construct B effectively induced both cellular and humoral immune responses. Conclusion: The multi-epitope vaccine construct B for HPV 16 and 18, designed for both prophylactic and therapeutic purposes, met the development criteria for a cervical cancer vaccine. However, these findings need to be validated through in vitro and in vivo experiments. [ABSTRACT FROM AUTHOR]

As the dengue infection still impacts hundreds of millions of people globally, unprecedented efforts in dengue drug development have been more progressive in recent decades. Computational methods provide a fast, sustainable, and efficient screening of active compounds and newly created drug molecules, including those specifically targeting nonstructural proteins (NS) of dengue viruses. In this work, protein modeling for the NS proteins of DENV-2/16681 strain was performed using a template-based homology modeling for the NS3 protein and an Artificial Intelligence (AI)-based prediction via AlphaFold for the NS4B protein. Moreover, the protein-protein interaction between the two structures was predicted using the HADDOCK server, which employs information about active and passive residues of the interaction interface to guide the docking process. After the modeling and its respective refinement process, the predicted structures of NS3 and NS4B improved their steric clashing scoring from MolProbity assessment. The refined models were then docked, and the resulting docking pose was analyzed to extract the interacting residues based on the polar contacts within the interface of the two proteins. Our result presents a preliminary study to create a dataset related to in silico molecular interactions of the NS3-NS4B interaction of different DENV types. It is helpful for building a computational pipeline for elucidating protein-ligand problems in dengue drug screenings. [ABSTRACT FROM AUTHOR]

A wide variety of disciplines contribute to bioinformatics research, including computer science, biology, chemistry, mathematics, and physics. This study determines the number of research articles published on arXiv classified as bioinformatics topics and the most frequently used bioinformatics terms using topic modeling, Latent Dirichlet Allocation (LDA). An algorithm based on LDA is used to discover topics hidden within large collections of documents through the use of statistical analysis. Our research examined 226453 articles on arXiv between January 2023 and January 2024. As a result, there are more than 10521 articles categorized into bioinformatics topics. Most commonly, 6352 documents are in the "Mathematical Physics" category. The second most popular category is "Computer Science," with 2950 documents. Accordingly, the terms 'RNA,' 'sequence,' 'tree,' and 'homology' are the three most commonly used terms in bioinformatics. The study of RNA plays a vital role in molecular biology; thus, the study of RNA is prevalent in bioinformatics. Sequential data refer to the order in which nucleotides or amino acids can be found in a DNA molecule or a protein. [ABSTRACT FROM AUTHOR]

As one of the cancer types with the highest incidence rates, colorectal cancer (CRC) would benefit from treatments with fewer side effects and reduced treatment-resistant potential. One of the options is to harness the anti-CRC potential of natural products. Previous studies have shown that Calamus draco exudate, dragon's blood, has anticancer activity in liver cancer and acute myeloid leukemia, but its bioactivity has not been studied in CRC. Here we conduct a bioinformatics study based on network pharmacology to explore the anti-CRC potential and mechanism of C. draco -derived compounds. The bioinformatics pipeline is composed of compound and target collection, biological network evaluation, and enrichment analysis. We found that there are 43 bioactive compounds from C. draco targeting 91 CRC-related targets, of which most compounds target MEN1, PTGS2, and IDH1. Further analyses show that the targets of C. draco are involved in the cellular response to hypoxia. By inhibiting those targets, C. draco bioactive compounds can potentially hinder angiogenesis and increase treatment response efficacy. [ABSTRACT FROM AUTHOR]

Copyright of China Journal of Oral & Maxillofacial Surgery is the property of Shanghai Jiao Tong University, College of Stomatology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Spinal muscular atrophy (SMA) with progressive myoclonic epilepsy (PME) affects the nervous system. Symptoms appear in early childhood and include muscle weakness, difficulty walking, seizures, and cognitive decline. Despite introducing various therapies to restore acid ceramidase function or reduce ceramide accumulation and gene therapy to correct genetic mutations, there are still unknown underlying molecular mechanisms related to this disorder. This article reports a novel variant c.118G>C in the ASAH1 gene. The patient presented with clinical manifestations such as progressive muscle weakness and myoclonic convulsions. Clinical features and electrophysiological investigations revealed a motor neuron disease and generalized epileptic discharge. A significant temporal interval was observed between the initial diagnosis of SMA and the subsequent manifestation of myoclonic seizures. The proband was genetically assessed through whole exome sequencing (WES) followed by variant confirmation and bioinformatics analysis. According to this article's findings and previous research, further diagnostic testing and management are needed to determine the severity and progression of the patient's condition. [ABSTRACT FROM AUTHOR]

Myotonic dystrophy type 1 (DM1) is the most common muscular dystrophy in adults, yet there are currently no disease-modifying treatments. Disrupted miRNA expressions may lead to dysregulation of target mRNAs and dysfunction involved in DM1 pathogenic mechanism. We used microarray platforms to examine the miRNA/mRNA expression profiles in skeletal muscle biopsies derived from DM1 patients and matched controls. Bioinformatics analysis and dual-luciferase reporter assay were conducted to provide insight into miRNA-mRNA regulatory networks altered in DM1. Twenty-three differentially expressed miRNAs and 135 differentially expressed genes were identified. qPCR confirmed that miR-3201, myogenic factor 5 (MYF5), myogenic differentiation 1 (MYOD1), CUGBP, Elav-like family member 1 (CELF1), and CELF2 were significantly up-regulated, while miR-196a, miR-200c, and miR-146a were significantly down-regulated. Enriched functions and pathways such as multicellular organismal development, RNA splicing, cell differentiation, and spliceosome are relevant to DM1. The miRNA-mRNA interaction network revealed that miR-182, miR-30c-2, and miR-200c were the critical nodes that potentially interacted with hub genes. Luciferase reporter assay confirmed the direct interaction between miR-196a and CELF2. Those results implied that the observed miRNA/mRNA dysregulation could contribute to specific functions and pathways related to DM1 pathogenesis, highlighting the dysfunction of miR-196a and CELF2. [ABSTRACT FROM AUTHOR]

Sialic acids are nine-carbon sugars that modify glycans on glycoconjugates and mediate important biological functions. While sialic acids have not been detected in insects (as it was considered that it is obtained from external sources), orthologs of sialic acid biosynthetic enzymes and insect ST6Gal sialyltransferases suggest ancestral sialylation pathways. Sialyltransferases contain conserved peptide regions called sialylmotifs (L, S, VS, III), participating in donor substrate binding and catalytic activity. We performed a computational analysis searching 27 insect proteomes for vertebrate sialylmotif sequences to identify putative novel insect sialyltransferases. Sialylmotif L sequences similar to mammalian ST3Gal IV and ST6GalNAc I were found in putative proteins from Galleria mellonella and Manduca sexta, respectively. Identifying sialyltransferase precursor genes in insects supports their evolutionary origin preceding vertebrate diversification. Despite the lack of sialic acid production, sialyltransferase genes in insects suggest an evolutionary perspective on conserved sialylation pathways. [ABSTRACT FROM AUTHOR]

[Display omitted] Novel biomarkers (BMs) are urgently needed for bronchial asthma (BA) with various phenotypes and endotypes. We sought to identify novel BMs reflecting tissue pathology from serum extracellular vesicles (EVs). We performed data-independent acquisition of serum EVs from 4 healthy controls, 4 noneosinophilic asthma (NEA) patients, and 4 eosinophilic asthma (EA) patients to identify novel BMs for BA. We confirmed EA-specific BMs via data-independent acquisition validation in 61 BA patients and 23 controls. To further validate these findings, we performed data-independent acquisition for 6 patients with chronic rhinosinusitis without nasal polyps and 7 patients with chronic rhinosinusitis with nasal polyps. We identified 3032 proteins, 23 of which exhibited differential expression in EA. Ingenuity pathway analysis revealed that protein signatures from each phenotype reflected disease characteristics. Validation revealed 5 EA-specific BMs, including galectin-10 (Gal10), eosinophil peroxidase, major basic protein, eosinophil-derived neurotoxin, and arachidonate 15-lipoxygenase. The potential of Gal10 in EVs was superior to that of eosinophils in terms of diagnostic capability and detection of airway obstruction. In rhinosinusitis patients, 1752 and 8413 proteins were identified from EVs and tissues, respectively. Among 11 BMs identified in EVs and tissues from patients with chronic rhinosinusitis with nasal polyps, 5 (including Gal10 and eosinophil peroxidase) showed significant correlations between EVs and tissues. Gal10 release from EVs was implicated in eosinophil extracellular trapped cell death in vitro and in vivo. Novel BMs such as Gal10 from serum EVs reflect disease pathophysiology in BA and may represent a new target for liquid biopsy approaches. [ABSTRACT FROM AUTHOR]

Genetic disorders involved in skeleton system arise due to the disturbance in skeletal development, growth and homeostasis. Filamin B is an actin binding protein which is large dimeric protein which cross link actin cytoskeleton filaments into dynamic structure. A single nucleotide changes in the FLNB gene causes spondylocarpotarsal synostosis syndrome, a rare bone disorder due to which the fusion of carpels and tarsals synostosis occurred along with fused vertebrae. In the current study we investigated a family residing in north-western areas of Pakistan. The whole exome sequencing of proband was performed followed by Sanger sequencing of all family members of the subject to validate the variant segregation within the family. Bioinformatics tools were utilized to assess the pathogenicity of the variant. Whole Exome Sequencing revealed a novel variant (NM_001457: c.209C>T and p.Pro70Leu) in the FLNB gene which was homozygous missense mutation in the FLNB gene. The variant was further validated and visualized by Sanger sequencing and protein structure studies respectively as mentioned before. The findings have highlighted the importance of the molecular diagnosis in SCT (spondylocarpotarsal synostosis syndrome) for genetic risk counselling in consanguineous families. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The study aims to provide guidance on the identification of multiple-digit malformations as potential biomarkers and therapeutic targets. MATERIALS AND METHODS: Single-cell RNA sequencing (scRNA-seq) data of four multiple-finger malformation samples were downloaded from the GEO public database. Fibroblasts and keratinocytes were divided into cellular subpopulations and the transcription factors of different subpopulations were analyzed. The regulatory network of transcription factors and their target genes were constructed to analyze the functionality of regulons. RESULTS: Examination of the transcriptional profile data from 11,806 single cells uncovered significant associations between regulons and cell function in polydactyly. Specifically, the analysis highlighted the involvement of HOX family members and GLI2 transcription factors, including HOXD13, MSX2, LHX2, EMX2, LEF1, CREB3L2, and LHX2, in the polydactyly process within fibroblast cells. Furthermore, it sheds light on the roles of HES2 and GLIS1 in the formation and development of keratinocytes. CONCLUSIONS: Significant presence of transcription factors, especially HOXD13, MSX2, and LHX2, may be strongly related to the development of polydactyly. [ABSTRACT FROM AUTHOR]

Bioinformatics is a subject that analyzes and interprets the collection, processing, storage and dissemination of biological information, and explores biological problems by using information technology and related means. The outbreak of novel coronavirus pneumonia has been nearly three years. With the advancement of vaccine research and development in various countries, mass vaccination is bound to usher in a new turning point for epidemic control. China's policy of free vaccination for the new coronavirus vaccine will undoubtedly improve the vaccination rate, however, the vaccination rate still depends on people's will. This paper takes college students as the main research object. In the context of bioinformatics analysis, a questionnaire survey was conducted based on their knowledge, attitudes, and practice levels of COVID-19 vaccines. The results vividly illustrate five conclusions. Firstly, the reliability of information sources positively affected college students' cognitive level, degree of trust and inoculation intention of COVID-19 vaccination. Secondly, the professional degree of media positively affected college students' degree of trust and inoculation intention behavior of COVID-19 vaccine. Thirdly, the cognitive level and degree of trust about COVID-19 vaccine positively affected college students' intention behavior of COVID-19 vaccine vaccination. Fourthly, the positivity of information positively affected the willingness of college students to vaccinate against COVID-19 vaccine. Fifthly, there were significant differences in the willingness and behavior of college students with different genders in COVID-19 vaccination. Finally, three suggestions are given to improve college students' willingness to vaccinate against the coronavirus and to cope with similar incidents in the future. [ABSTRACT FROM AUTHOR]

Although morbidity has decreased in developed regions, cervical cancer (CC) continues to have the highest incidence of all gynecological malignancies. The burden of morbidity and mortality in developing regions is also rising quickly, especially for advanced CC. Along with apoptosis, iron death, and other forms of programmed cell death, pyroptosis is a significant inflammatory process. Its connection to the malignancy mechanism has been verified. The expression of genes linked to pyroptosis in CC tissue and its relationship to prognosis, however, remain poorly understood. Using The Cancer Genome Atlas, we first discovered 13 differentially expressed pyroptosis-related genes (DE-PRGs) in the study (TCGA). Based on DE-PRGs, CC patients were divided into four subtypes. The 4 parts' times showed large variations according to the K-M curve. Then, using the least absolute shrinkage and selection operator (LASSO) Cox regression method, we created a mod el for predicting CC based on pyroptosis-associated genes. There were significant differences in overall survival (OS) times involving the high-risk and low-risk groups for all CC patients in the TCGA group, who were divided into lowrisk and high-risk groups (p equals 0.0441). The risk score status as an independent prognostic factor for CC was confirmed by independent prognostic predictor validation. The analyses of single-sample gene set and enrichment analysis (ssGSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO) all revealed significant differences in immune cells and immune pathways involving high- and lowrisk groups (p less than 0.001), indicating a weakened immune status in high-risk groups. In conclusion, pyroptosis-associated genes are involved in tumor immunity and can help determine a patient's prognosis for CC. As a result, we have created and validated a signature that is related to pyroptosis and predicts CC prognosis, which may aid in early diagnosis, prognostic analysis, and immunotherapy. [ABSTRACT FROM AUTHOR]

Background and objective Bone is a common site for metastasis in lung adenocarcinoma, but the mechanism behind lung adenocarcinoma bone metastasis is still unclear. And currently, there is a lack of easily traceable and stable lung adenocarcinoma bone metastasis cell models, which limits the research on the mechanism of lung adenocarcinoma bone metastasis. The establishment of human lung adenocarcinoma cell line that are highly metastatic to bone, labeled with green fluorescent proteins (GFP) and fireflies luciferase (LUC), along with transcriptomic characterization, would be beneficial for research on lung adenocarcinoma bone metastasis and provide new experimental methods. Methods The human lung adenocarcinoma cell line A549-GFP-LUC was injected into nude mice via the left ventricle to construct a bone metastasis model, and was domesticated in vivo for three consecutive times to obtain the human high bone metastasis lung adenocarcinoma cell line A549-GFP-LUC-BM3; cell counting kit-8 (CCK-8), colony formation assay, scratch wound assays, Transwell assay and Western blot were used to compare the proliferation and invasion abilities of A549-GFP-LUC-BM3 with the parental cells. A549-GFP-LUC-BM3 cells and parental cells were further analyzed by transcriptomic sequencing. Results Human high-bone metastatic lung adenocarcinoma cells A549-GFP-LUC-BM3 was successfully established. Compared to parental cells, this cells exhibited a significantly higher incidence of bone metastasis and enhanced in vitro proliferation, migration, and invasion abilities. Transcriptomic sequencing results revealed that the A549-GFP-LUC-BM3 cell line had 2954 differentially expressed genes compared to the parental cells, with 1021 genes up-regulated and 1933 genes down-regulated. Gene Ontology (GO) functional enrichment analysis indicated that the differentially expressed genes were primarily localized in cellular components such as the cell periphery. The molecular functions identified as significantly enriched included signaling receptor activity, calcium ion binding, and extracellular matrix structural constituent. Additionally, the biological processes found to be enriched were cell adhesion and biological adhesion. The enrichment analysis conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that the differentially expressed genes were primarily involved in the metabolism of xenobiotics by cytochrome P450, retinol metabolism, drug metabolism-cytochrome P450, cell adhesion molecules, steroid hormone biosynthesis, and the nuclear factor kappa B (NF-B) signaling pathway. Conclusion The highly bone-metastatic human lung adenocarcinoma cell line with GFP and luciferase double labeling was successfully established. The biological behavior and transcriptome sequencing of the cell line suggest that it has a high bone-metastatic potential. [ABSTRACT FROM AUTHOR]

Copyright of Acta Agronomica Sinica is the property of Crop Science Society of China and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Acta Agronomica Sinica is the property of Crop Science Society of China and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

[Display omitted] Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by dry, pruritic skin. Several studies have described nocturnal increases in itching behavior, suggesting a role for the circadian rhythm in modulating symptom severity. However, the circadian rhythm of metabolites in the skin and serum of patients with AD is yet to be described. We sought to assess circadian patterns of skin and serum metabolism in patients with AD. Twelve patients with moderate to severe AD and 5 healthy volunteers were monitored for 28 hours in a controlled environment. Serum was collected every 2 hours and tape strips every 4 hours from both lesional and nonlesional skin in participants with AD and location-, sex-, and age-matched healthy skin of controls. We then performed an untargeted metabolomics analysis, examining the circadian peaks of metabolism in patients with AD. Distinct metabolic profiles were observed in AD versus control samples. When accounting for time of collection, the greatest differences in serum metabolic pathways were observed in arachidonic acid, steroid biosynthesis, and terpenoid backbone biosynthesis. We identified 42 circadian peaks in AD or control serum and 17 in the skin. Pathway enrichment and serum-skin metabolite correlation varied throughout the day. Differences were most evident in the late morning and immediately after sleep onset. Although limited by a small sample size and observational design, our findings suggest that accounting for sample collection time could improve biomarker detection studies in AD and highlight that metabolic changes may be associated with nocturnal differences in symptom severity. [ABSTRACT FROM AUTHOR]

Breast cancer is a major health concern affecting women and men globally. Early detection and accurate classification of breast cancer are vital for effective treatment and survival of patients. This study addresses the challenge of accurately classifying breast tumors using machine learning classifiers such as MLP, AdaBoostM1, logit Boost, Bayes Net, and the J48 decision tree. The research uses a dataset available publicly on GitHub to assess the classifiers' performance and differentiate between the occurrence and non-occurrence of breast cancer. The study compares the 10-fold and 5-fold cross-validation effectiveness, showing that 10- fold cross-validation provides superior results. Also, it examines the impact of varying split percentages, with a 66% split yielding the best performance. This shows the importance of selecting appropriate validation techniques for machine learning-based breast tumor classification. The results also indicate that the J48 decision tree method is the most accurate classifier, providing valuable insights for developing predictive models for cancer diagnosis and advancing computational medical research. [ABSTRACT FROM AUTHOR]

Background and objective Lung squamous cell carcinoma (LUSC) is a subtypes of non-small cell lung cancer (NSCLC). It has been reported that members of the protocadherin γ family can regulate tumor cell growth by inhibiting the Wnt signaling pathway. Protocadherin-gamma subfamily B4 (PCDHGB4) as a family member in LUSC was rarely reported. The aim of this study was to investigate the role and potential prognostic value of PCDHGB4 in the development of LUSC using bioinformatics methods. Methods The Cancer Genome Atlas (TCGA), cBioPortal and UALCAN databases were used to analyze the expression, prognosis, clinicopathological features, immune cell infiltration, immune regulatory genes, immune checkpoint inhibitors (ICIs), and methyltransferases of PCDHGB4 in LUSC. At the single cell level, we analyzed the clustering results of cell subtypes and the expression of PCDHGB4 in different immune cell subpopulations. In addition, we compared the promoter methylation levels of PCDHGB4 in LUSC tissues and normal tissues and performed protein-protein interaction and mutation analysis. Finally, enrichment analysis was performed based on the differentially expressed genes. Results Bioinformatics analysis results showed that the expression level of PCDHGB4 in LUSC tissues was lower than that in normal tissues. Survival analysis showed that increased PCDHGB4 expression was associated with poor prognosis. Single-cell sequencing analysis showed that PCDHGB4 was expressed in T cells, monocytes or macrophages, and dendritic cells. It was further found that PCDHGB4 played an important role in tumor immunity and confirmed that PCDHGB4 was associated with immune checkpoints, immune regulatory genes, and methyltransferases. Besides, enrichment analysis revealed that PCDHGB4 was involved in multiple cancer-related pathways. Conclusion The expression of PCDHGB4 was low in LUSC. PCDHGB4 was related to the poor prognosis of patients, and PCDHGB4 was closely related to the infiltration and pathway of tumor immune cells. PCDHGB4 may be a potential prognostic marker and a new target for immunotherapy in LUSC. [ABSTRACT FROM AUTHOR]

Copyright of Acta Agronomica Sinica is the property of Crop Science Society of China and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

OBJECTIVE: In this study, we investigated the internal relationship between the pathogenesis of diabetic kidney disease (DKD) and abnormal glucose and lipid metabolism to identify potential biomarkers for diagnosis and treatment and investigated the role of the immune microenvironment of glucose and lipid metabolism disorders in the occurrence and progression of DKD. MATERIALS AND METHODS: The chip datasets GSE104948 and GSE96804 from the Gene Expression Common Database (GEO) were merged using the "lima" and "sva" software packages in R Software (4.2.3), and the merged dataset was used as the validation set. The intersection between the differential genes of DKD and the glucose and lipid metabolism genes in the MSigDB database was identified, and a nomogram of the incidence risk of DKD was built using three machine learning methods, namely LASSO regression, support vector machine (SVM), and random forest (RF), to validate the accuracy of the prediction model. Immune scores were conducted using the unsupervised clustering method, and patients were divided into two subgroups. The two subgroups were screened for differential genes for enrichment analysis. The differential genes of patients diagnosed with DKD were clustered into two gene subgroups for co-expression analysis. In this study, we utilized the Cytoscape software to construct a network of interactions among key genes. RESULTS: Using machine learning, a diagnostic model was developed with G6PC and HSD17B14 as key factors. Enrichment analysis and immune scoring demonstrated that the development of DKD was related to the imbalance in the microenvironment brought about by glucose lipid metabolism disorders. CONCLUSIONS: G6PC and HSD17B14 may be potential biomarkers for DKD, and the established predictive model is more helpful in predicting the incidence of DKD. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Both non-alcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC) are prevalent diseases worldwide. This study aimed to explore the underlying mechanisms of NAFLD and HCC and identify new therapeutic targets for human cancers. MATERIALS AND METHODS: NAFLD and HCC gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) were utilized to identify co-expressed genes associated with NAFLD and HCC. Public databases were consulted to find common targets of NAFLD and HCC. Enrichment analysis and CIBERSORT techniques were employed to analyze the pathways enriched with DEGs and the attributes of infiltrating immune cells. Furthermore, the expression data of UROC1 and clinical information of patients were acquired from The Cancer Genome Atlas (TCGA) database. Finally, the expression of the UROC1 was validated by immunohistochemistry (IHC). RESULTS: Through a comprehensive bioinformatics analysis, eight hub genes (CCL2, CCR2, IL6, CSF3R, ATL2, SESN3, UROC1, FIGNL1) were identified. Enrichment analysis indicated that in- flammatory and immune response may be common features between NAFLD and HCC. CIBERSORT analysis revealed an imbalance of plasma cells and macrophages in NAFLD and HCC. Pan-cancer analysis demonstrated that UROC1 expression was related to clinical outcomes and tumor immunity in various cancers. Moreover, a strong correlation was exhibited between UROC1 expression and crucial elements, including tumor mutation burden (TMB), microsatellite instability (MSI), multiple immune checkpoints (ICP), and tumor microenvironment (TME). Importantly, an adverse clinical prognosis of HCC was linked to decreased UROC1 expression, which was consistent with IHC results. CONCLUSIONS: We identified eight hub genes (CCL2, CCR2, IL6, CSF3R, ATL2, SESN3, UROC1, FIGNL1), which may become early diagnostic and therapeutic targets for NAFLD and HCC. The pan-cancer analysis of UROC1 provides new evidence for its broad application prospects in the field of HCC and other cancers. [ABSTRACT FROM AUTHOR]

The recent re-emergence of the monkeypox (mpox) epidemic in nonendemic regions has raised concerns regarding a potential global outbreak. The mpox virus (MPV) is a smallpox-like virus belonging to the genus Orthopoxvirus (family: Poxviridae). Although studies suggest that MPV infection suppresses the Toll-like receptor-3- and tumor necrosis factor-α-related signaling pathways, whether MPV regulates other immune-related pathways remains unclear. In this study, two distinct temporal patterns were used for establishing an MPV-infected human immortal epithelial cancer cell line (HeLa). These two durations 2 and 12 h of incubation were selected to identify the coregulated genes and pathways affected by MPV infection. The use of the Gene Ontology framework, Kyoto Encyclopedia of Genes and Genome database, and MetaCore software yielded valuable insights. Specifically, various pathways were found to be enriched in HeLa cells infected with MPV for 2 and 12 h. These pathways included Notch, CD40, CD95, hypoxia-inducible factor-1-α, interleukin (IL)− 1, IL-6, phosphoinositide 3-kinase, nuclear factor-κB, mitogen-activated protein kinase, and oxidative stress–induced signalling pathways. Clusters and pathways of metabolism and viral replication cycles were significantly associated with the 2-hour infection group. This association was identified based on the regulation of genes such as HSPG2, RHPN2, MYL1, ASPHD2, CA9, VIPR1, SNX12, MGC2752, SLC25A1, PEX19, and AREG. Furthermore, clusters and pathways related to immunity and cell movement were found to be associated with the 12-hour infection group. This association was identified based on the regulation of genes such as C1orf21, C19orf48, HRK, IL8, GULP1, SCAND2, ATP5C1, FEZ1, SGSH, TACC2, CYP4X1, MMP1, CPB1, P2RY13, WDR27, PRPF4, and ENDOD1. This study can improve our understanding of the mechanisms underlying the pathophysiology and post-infection sequelae of mpox. Our findings provide valuable insights into the various modes of MPV infection. [ABSTRACT FROM AUTHOR]

Neuropathic pain is caused by injury or disease of the somatosensory system, and its course is usually chronic. Several studies have been dedicated to investigating neuropathic pain-related targets; however, little attention has been paid to the persistent alterations that these targets, some of which may be crucial to the pathophysiology of neuropathic pain. The present study aimed to identify potential targets that may play a crucial role in neuropathic pain and validate their long-term impact. Through bioinformatics analysis of RNA sequencing results, we identified Slc9a1 and validated the reduced expression of sodium-hydrogen exchanger 1 (NHE1), the protein that Slc9a1 encodes, in the spinal nerve ligation (SNL) model. Colocalization analysis revealed that NHE1 is primarily co-localized with vesicular glutamate transporter 2-positive neurons. In vitro experiments confirmed that poly(lactic-co-glycolic acid) nanoparticles loaded with siRNA successfully inhibited NHE1 in SH-SY5Y cells, lowered intracellular pH, and increased intracellular calcium concentrations. In vivo experiments showed that sustained suppression of spinal NHE1 expression by siRNA-loaded nanoparticles resulted in delayed hyperalgesia in naïve and SNL model rats, whereas amiloride-induced transient suppression of NHE1 expression yielded no significant changes in pain sensitivity. We identified Slc9a1 , which encodes NHE1, as a key gene in neuropathic pain. Utilizing the sustained release properties of nanoparticles enabled us to elucidate the chronic role of decreased NHE1 expression, establishing its significance in the mechanisms of neuropathic pain. [ABSTRACT FROM AUTHOR]

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The onset of obstetric antiphospholipid syndrome (APS) occurs when antiphospholipid antibodies act upon the placenta. During pregnancy, APS exhibits traits such as vascular thrombosis, inflammation, and hindered trophoblast implantation. The involvement of microRNA expression has been proposed as a genetic factor contributing to the syndrome's development. MicroRNAs play a role in regulating gene expression in various cellular processes, including the formation of placental tissue. Therefore, additional research is needed to explore the control of placental miRNA in APS. In this study, we aimed to profile miRNA expressions from placenta tissue of patients with APS. Differentially expressed miRNAs were determined for its targeted genes and pathways. Agilent microarray platform was used to measure placental microRNA expressions between normal placental tissue and those obtained from patients with APS. Differentially expressed miRNAs were detected using GeneSpring GX software 14.2 and sequences were mapped using TargetScan software to generate the predicted target genes. Pathway analysis for the genes was then performed on PANTHER and REACTOME software. Selected miRNAs and their associated genes of interest were validated using qPCR. Microarray findings revealed, 9 downregulated and 21 upregulated miRNAs expressed in placenta of patients with APS. Quantitative expressions of 3 selected miRNAs were in agreement with the microarray findings, however only miR-525-5p expression was statistically significant. Pathway analysis revealed that the targeted genes of differentially expressed miRNAs were involved in several hypothesised signalling pathways such as the vascular endothelial (VE) growth factor (VEGF) and inflammatory pathways. VE-cadherin, ras homolog member A (RHOA) and tyrosine kinase receptor (KIT) showed significant downregulation while Retinoblastoma gene (RET), Dual specificity protein phosphatase 10 (DUSP10) and B-lymphocyte kinase (BLK) genes were significantly upregulated. These preliminary findings suggest the involvement of miRNAs and identified novel associated genes involvement in the mechanism of obstetric APS, particularly through the alteration of vascular-associated regulators and the inflammatory signalling cascade. [ABSTRACT FROM AUTHOR]

We previously reported that dickkopf WNT signaling pathway inhibitor 3 (DKK3) expression is correlated with poorer prognosis in head and neck squamous cell carcinoma (HNSCC). Here we investigated DKK3 expression by using The Cancer Genome Atlas (TCGA) public database and bioinformatic analyses. We used the RNA sequence data and divided the tumor samples into " DKK3 -high" and " DKK3 -low" groups according to median DKK3 expression. The correlations between DKK3 expression and the clinical data were investigated. Differentially expressed genes (DEGs) were detected using DESEq2 and analyzed by ShinyGO 0.77. A gene set enrichment analysis (GSEA) was also performed using GSEA software. The DEGs were also analyzed with TargetMine to establish the protein–protein interaction (PPI) network. DKK3 expression was significantly increased in cancer samples, and a high DKK3 expression was significantly associated with shorter overall survival. We identified 854 DEGs, including 284 up-regulated and 570 down-regulated. Functional enrichment analyses revealed several Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with extracellular matrix remodeling. The PPI network identified COL8A1 , AGTR1 , FN1 , P4HA3 , PDGFRB, and CEP126 as the key genes. These results suggested the cancer-promoting ability of DKK3 , the expression of which is a promising prognostic marker and therapeutic target for HNSCC. [ABSTRACT FROM AUTHOR]

This study aimed to identify the molecular mechanism of curcumin on periodontitis based on a pharmacological network strategy. The potential therapeutic targets of curcumin and differentially expressed genes in periodontitis were identified. Subsequently, we extracted the molecules in common and analyzed them. A metabolic pathway enrichment and gene ontology analysis were performed and the protein–protein interaction network was inferred. These analyses allowed the identification of key proteins. Finally, a molecular docking of the main key proteins was performed with curcumin. Our results showed that 55 genes are differentially expressed in periodontitis and are potential targets of curcumin. In addition, we observed that these genes participate in cell motility and immune response and are related to chemokine receptors (CXCRs) and enzymatic activity, such as arachidonate 5-lipoxygenase (ALOX5). We identified six key proteins, IL1B, CXCL8, CD44, MMP2, EGFR, and ITGAM; molecular docking revealed that these six proteins spontaneously bind to curcumin. The results of this study helps us understand the molecular mechanism of curcumin in periodontitis. We propose that curcumin affects proinflammatory cytokines, ALOX5, and cell migration through chemokine receptors and acts on the cell membrane. Additionally, we identified six key proteins that are essential in this mechanism, all of which spontaneously bind to curcumin. [Display omitted] [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study aimed to investigate the therapeutic effects and underlying mechanisms of Sankudiwan (SKDW) on myocardial ischemia-reperfusion injury (MIRI) in a rat model. MATERIALS AND METHODS: Rats were subjected to MIRI and treated with varying doses of SKDW. The myocardial infarct size, cardiac function, histological changes, apoptosis, and inflammation were assessed using TTC staining, echocardiography, Hematoxylin and Eosin (HE) staining, TUNEL staining, and ELISA assays. We further explored SKDW's influence on cardiomyocyte mitochondria and inflammatory factor expression. Moreover, oxidative stress-related parameters and differentially expressed genes were analyzed using bioinformatics approaches. RESULTS: SKDW significantly reduced myocardial infarct size and improved cardiac function, demonstrating a dose-dependent therapeutic potential. It ameliorated myocardial tissue damage at the histological level, inhibited cardiomyocyte apoptosis, and mitigated inflammatory response. SKDW also enhanced mitochondrial energy metabolism and suppressed the levels of oxidative stress markers. Bioinformatics analysis identified key differentially expressed genes (DEGs), including cbln1, Tgm1, Trh, and Ccl27, possibly mediating the therapeutic effects of SKDW. CONCLUSIONS: SKDW exerts its therapeutic effects on MIRI through the modulation of several genes and pathways related to inflammation, apoptosis, mitochondrial function, and oxidative stress. Our findings provide a scientific basis for the clinical application of SKDW in the treatment of MIRI. [ABSTRACT FROM AUTHOR]

Background Phytase supplementation in rations can reduce their phytic acid composition in order to enhance their nutritional value. Aspergillus niger is a fungus that can encode phytase. This study aims to determine the characteristics of its DNA sequences and amino acid composition that encode the phytase enzyme, as well as to determine the primer designs. Method This study used gene sequence data and protein-encoding phytase from Aspergillus niger that was collected manually from NCBI and PDB. The data was analyzed using SPDBV and then be aligned using the ClustalW Multiple Alignment features. The phylogenetic tree was built by Mega11 software. Primers were designed from selected candidate sequences that were analyzed. The designed primers were then simulated for PCR using FastPCR and SnapGene software. Results There are 18 Aspergillus niger phytases in NCBI which is 14.87% of the total Aspergillus. There are 14 Aspergillus niger phytases that have identity above 95%. Aspergillus niger 110. M94550.1 is the closest strain to the PDB template. Candidate sources of phytase genes are Aspergillus niger 110.M94550.1, 48.2.BCMY01000003.1, and 92.JQ654450.1. The primer design has 2 possibilities of self-annealing and high melting temperature on the reverse primer. PCR simulation shows that the primer design can attach completely but still has the possibility of mispriming. Conclusion This study suggests promising results for the future development of phytase enzyme production from Aspergillus niger as a feed additive using genetic engineering to enhance the quality of livestock feed in Indonesia. [ABSTRACT FROM AUTHOR]

Introduction: Females with Alzheimer's disease (AD) suffer accelerated dementia and loss of cholinergic neurons compared to males, but the underlying mechanisms are unknown. Seeking causal contributors to both these phenomena, we pursued changes in transfer RNS (tRNA) fragments (tRFs) targeting cholinergic transcripts (CholinotRFs). Methods: We analyzed small RNA‐sequencing (RNA‐Seq) data from the nucleus accumbens (NAc) brain region which is enriched in cholinergic neurons, compared to hypothalamic or cortical tissues from AD brains; and explored small RNA expression in neuronal cell lines undergoing cholinergic differentiation. Results: NAc CholinotRFs of mitochondrial genome origin showed reduced levels that correlated with elevations in their predicted cholinergic‐associated mRNA targets. Single‐cell RNA seq from AD temporal cortices showed altered sex‐specific levels of cholinergic transcripts in diverse cell types; inversely, human‐originated neuroblastoma cells under cholinergic differentiation presented sex‐specific CholinotRF elevations. Discussion: Our findings support CholinotRFs contributions to cholinergic regulation, predicting their involvement in AD sex‐specific cholinergic loss and dementia. [ABSTRACT FROM AUTHOR]

Microbial infections of the brain can lead to dementia, and for many decades microbial infections have been implicated in Alzheimer's disease (AD) pathology. However, a causal role for infection in AD remains contentious, and the lack of standardized detection methodologies has led to inconsistent detection/identification of microbes in AD brains. There is a need for a consensus methodology; the Alzheimer's Pathobiome Initiative aims to perform comparative molecular analyses of microbes in post mortem brains versus cerebrospinal fluid, blood, olfactory neuroepithelium, oral/nasopharyngeal tissue, bronchoalveolar, urinary, and gut/stool samples. Diverse extraction methodologies, polymerase chain reaction and sequencing techniques, and bioinformatic tools will be evaluated, in addition to direct microbial culture and metabolomic techniques. The goal is to provide a roadmap for detecting infectious agents in patients with mild cognitive impairment or AD. Positive findings would then prompt tailoring of antimicrobial treatments that might attenuate or remit mounting clinical deficits in a subset of patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to research gene expression profiles and diagnostic applications of meningeal carcinoma based on bioinformatics. MATERIALS AND METHODS: We used the Gene Expression Omnibus (GEO) database to obtain the GSE43290 dataset based on the expression data of normal meninges and meningiomas consisting of 51 samples divided into two groups (47 samples of meningioma tumors and four samples of normal meninges). We used the GEO2R tool to identify differentially expressed genes (DEGs) by setting the log2 fold change as greater than two and an adjusted p-value lower than 0.05. We used the database for annotation, visualization and integrated discovery (DAVID) to perform gene ontology, biological pathways and functional annotation of the DEGs. A search Tool for the Retrieval of Interacting Gene database (STRING) was used to obtain Protein-Protein Interaction (PPI) and modular networks based on the Markov clustering algorithm. RESULTS: Our study identified 358 significant DEGs, of which 343 were downregulated genes while 15 were upregulated. Five significant hub genes (CXCL8, AGT, CXCR4, CXCL12 and CXCL2) were associated with various biological pathways, molecular functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The DEGs were enriched in biological pathways of chemokine-mediated signaling, positive regulation of leukocyte chemotaxis, second messenger-mediated signaling, induction of positive chemotaxis, CXCR chemokine receptor binding and activities of cytokines. CONCLUSIONS: These hub genes and pathways could be targeted in clinical research to discover new treatments for meningeal carcinoma. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Vacuolar protein sorting-associated protein 29 (VPS29) plays a certain role in cancer, but its biological significance in hepatocellular carcinoma (HCC) has not been studied. We utilized bioinformatics and Mendelian randomization (MR) analysis to explore the potential function of the VPS29 gene in HCC, as well as the causal relationship between VPS29 protein and HCC. MATERIALS AND METHODS: We downloaded the raw data from TCGA, GEO, and IEU OpenGWAS databases. We used R software for data processing and analysis to explore the relationship between the VPS29 gene and the expression, prognosis, clinical features, methylation, immune microenvironment, tumor mutation burden, and drug sensitivity in HCC patients. Additionally, a two-sample Mendelian randomization analysis was conducted to investigate the causal relationship between the VPS29 protein and HCC. RESULTS: VPS29 was found to be overexpressed in various types of cancer, including HCC, and its elevated expression often predicts poor prognosis in HCC patients. Univariate and multivariate Cox analysis demonstrated that VPS29 was an independent prognostic factor in HCC patients. The ROC curve indicated that VPS29 has a high diagnostic value in HCC. There were differential expressions of VPS29 in various clinical feature subgroups. The expression of VPS29 was negatively correlated with methylation levels, and multiple methylation sites were identified in the promoter region, including cg20877181, cg03867797, cg10025392, cg21605021, which were associated with poorer overall survival (OS) at low methylation levels. VPS29 was associated with immune cell infiltration disorders, including CD8+ T cells, Eosinophils, Neutrophils, Tcm, NK CD56bright cells, TFH, Th2 cells, Th17 cells, etc. Drug sensitivity analysis showed that VPS29 could be indicative of treatment response to 10 common antineoplastic drugs in different expression subgroups. Inverse variance weighted (IVW) analysis revealed a significant increase in HCC risk associated with VPS29 [odds ratio (OR): 1.440; 95% confidence interval (CI): 1.195-1.736], and sensitivity analysis showed no heterogeneity or pleiotropy. CONCLUSIONS: VPS29 is a risk factor for the occurrence and progression of HCC and may serve as a molecular biomarker for the diagnosis and prognosis of HCC. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to analyze the cross-presentation of allopeptides derived from donor major histocompatibility (MHC) molecules by recipient class I MHC molecules in the context of transplantation rejection. Materials and Methods: The MHC molecules were selected based on frequency distribution in the Kerala (India) population using the "allelefrequency. net" database. The most frequent alleles were chosen as donor and recipient alleles. Different immunoinformatics servers such as Netcytotoxic T lymphocyte, NetMHCpan, and Immune Epitope Database MHC I were used for predicting potential T-cell epitopes, and MHC class I epitopes, respectively, from the chosen donor MHC molecule. Three peptides with strong binding affinities in all three predictions were selected for further analysis. The binding of these peptides to the second MHC class I molecule, the recipient one, and transporter associated with antigen processing protein was confirmed by molecular docking using the "AutoDockVina" tool. The binding interactions were visualized using the "Discovery Studio Visualizer" platform. Results: The ability of the selected class I MHC molecule, human leukocyte antigens (HLAs)-A* 11:01, considered the donor allele, to act as an exogenous antigen and to get processed into peptides and presented on the second class I MHC molecule, HLA-A*02:01, considered the recipient allele was confirmed. This immunoinformatics approach could help us to identify potential epitopes from an HLA class I molecule and to measure its ability to get cross-presented on a second HLA class I molecule to trigger the process of cell-mediated rejection. Conclusion: This immunoinformatics approach could help us to identify potential epitopes from an HLA class I molecule and to measure its ability to get cross-presented on a second HLA class I molecule to trigger the process of cell-mediated rejection. Our study provides an easy in silico method for predicting the chances of cell mediated rejection in organ transplantations involving an unrelated donor. We hope that this computational analysis will pave the way for simplifying the process involved in organ rejection prediction. [ABSTRACT FROM AUTHOR]

Background and objective Lung adenocarcinoma (LUAD) is a major subtype of lung cancer, and its treatment and diagnosis remain a hot research topic. Targeting protein for Xenopus kinesin-like protein 2 (TPX2) is highly expressed in a variety of cancer cells and may be associated with the progression of LUAD. This study aimed to investigate the effect of TPX2 on the malignant progression of LUAD cells and the regulatory mechanisms. Methods The expression of gene TPX2 in LUAD tissues from The Cancer Genome Atlas (TCGA) database was analyzed by bioinformatics analysis techniques. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of TPX2 and miR-218-5p in human lung normal cell lines and human LUAD cell lines. Western blot was used to detect TPX2 protein expression in cell lines and its effect on the expression of key proteins in the p53 signaling pathway. The relationship between TPX2 and miR-218-5p was predicted using bioinformatics and verified by dual luciferase reporter gene assay. Cell counting kit-8 (CCK-8) assay, cell clone formation, cell scratching, Transwell assay, and flow cytometry were used to detect the effects of miR-218-5p and TPX2 on LUAD cell function. Results TPX2 was significantly overexpressed in LUAD cells, and knockdown of TPX2 inhibited LUAD cell proliferation, migration, and invasion, promoted apoptosis and induced G2/M phase block, and promoted the expression of key proteins in the p53 signaling pathway. miR-218-5p, an upstream regulator of TPX2, could inhibit its expression. Overexpression of miR-218-5p eliminated the malignant development caused by high expression of TPX2, inhibited the malignant processes of LUAD cells such as proliferation and migration as well as promoted the p53 signaling pathway. Conclu- sion miR-218-5p targets and inhibits TPX2 expression and exerts an inhibitory effect on the malignant progression of LUAD cells via p53. [ABSTRACT FROM AUTHOR]

In a recent article, we presented evidence demonstrating the existence of hidden γ-stories within the genomes of humans and canines. These stories were found not only in the non-protein-coding regions but also within the genetic regions and the sequence of exons. Consequently, we are now exploring whether these discoveries are unique to humans and dogs or if they are more widely distributed throughout the cellular world. To approach this question, we embarked on an investigation of the genomes of various species across Whittaker's five kingdoms, namely Animalia, Plantae, Fungi, Protista, and Monera. Through online resources, we obtained and analysed whole-genome sequences of one avian species, one fish species, one reptile species, and one invertebrate species within the Animalia kingdom. Furthermore, we examined the genomes of one plant species, one fungus species, one protozoan species, and two bacterial species. Employing the same methods as in our prior studies, our findings in this study align with our proto knowledge hypothesis, suggesting that all living cells possess a repository of hidden γ-information which determines the cellular design, sustains its overall functionality, and governs its performance and behaviour throughout its lifespan until death. We briefly explain life as a bio-linguistic phenomenon and future projects. [ABSTRACT FROM AUTHOR]

The carriage of multidrug-resistant (MDR) pathogens in medical students has not been studied extensively, despite the fact that they are in contact with patients and exposed to a hospital environment. To investigate the intestinal and nasal carriage of MDR pathogens among medical students and its association with their lifestyle and demographic data. In 2021, first- and final-year medical students were invited to the study. Two rectal swabs were used for detection of extended-spectrum β-lactamase (ESBL)-producing, colistin-, tigecycline- or carbapenem-resistant Gram-negative bacteria and vancomycin-resistant enterococci. Nasal swab was used for Staphylococcus aureus culture. S. aureus isolates were characterized by spa typing; Gram-negative resistant isolates and meticillin-resistant S. aureus (MRSA) were subjected to whole-genome short and/or long sequencing. From 178 students, 80 (44.9%) showed nasal carriage of S. aureus ; two isolates were MRSA. In rectal swabs, seven ESBL-producing strains were detected. Sixteen students were colonized by colistin-resistant bacteria, three isolates carried the mcr-1 gene (1.7%). The mcr-9 (10.7%, 19/178) and mcr-10 (2.2%, 4/178) genes were detected by quantitative polymerase chain reaction, but only two colistin-susceptible mcr-10 -positive isolates were cultured. The S. aureus nasal carriage was negatively associated with antibiotic and probiotic consumption. S. aureus and colistin-resistant bacteria were detected more frequently among students in contact with livestock. Medical students can be colonized by (multi)drug-resistant bacteria with no difference between first- and final-year students. The participation of students in self-screening increases their awareness of possible colonization by resistant strains and their potential transmission due to poor hand hygiene. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: To investigate the clinical relevance of intratumoral tumor infiltrating lymphocytes (TILs) in breast cancer as measured by computational deconvolution of bulk tumor transcriptomes. Summary Background Data: Commonly assessed TILs, located in tumor stroma without direct contact with cancer cells (stromal TILs), correlate with breast cancer treatment response and survival. The clinical relevance of intratumoral TILs has been less studied partly due to their rarity; however, they may have nonnegligible effects given their direct contact with cancer cells. Methods: In all, 5870 breast cancer patients from TCGA, METABRIC, GSE96058, GSE25066, GSE163882, GSE123845, and GSE20271 cohorts were analyzed and validated. Results: The intratumoral TIL score was established by the sum of all types of lymphocytes using the xCell algorithm. This score was the highest in triple-negative breast cancer (TNBC) and the lowest in the ER-positive/HER2-negative subtype. It correlated with cytolytic activity and infiltrations of dendritic cells, macrophages, and monocytes, and uniformly enriched immune-related gene sets regardless of subtype. Intratumoral TIL-high tumors correlated with higher mutation rates and significant cell proliferation on biological, pathological, and molecular analyses only in the ER-positive/HER2-negative subtype. It was significantly associated with pathological complete response after anthracycline- and taxane-based neoadjuvant chemotherapy in about half of the cohorts, regardless of the subtype. Intratumoral TIL-high tumors correlated with better overall survival in HER2-positive and TNBC subtypes consistently in 3 cohorts. Conclusions: Intratumoral TILs estimated by transcriptome computation were associated with increased immune response and cell proliferation in ER-positive/HER2-negative and better survival in HER2-positive and TNBC subtypes, but not always with pathological complete response after neoadjuvant chemotherapy. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Ulcerative colitis (UC), a chronic inflammatory disease of the colon with unknown etiology, is characterized by remission and recurrence. At present, a considerable number of UC cases are misdiagnosed or delayed in diagnosis and treatment. We aimed to identify UC-related genes to aid the development of drugs for this condition. PATIENTS AND METHODS: Transcriptome data of 362 patients with UC and 126 control subjects were obtained from the Gene Expression Omnibus. The 362 patients with UC were subgrouped using unsupervised machine learning. R software was used to analyze the clinical characteristics of the subgroups, screen subgroup-specific genes, assess the relationships between gene modules and clinical characteristics using weighted gene co-expression network analysis, and perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the subgroups. RESULTS: Patients w ith UC were c lassified into two subgroups. Genes specific to subgroup I included IL21R, ATP8B2, and PLEKHO1. Severe disease tended to be associated with immune cell infiltration; anti-tumor necrosis factor (TNF)-a antibodies and ustekinumab may have been effective in this subgroup. Subgroup II-specific genes included SLC4A4, EPB41L4B, and PLCE1. Patients in this subgroup had mild clinical conditions; however, their disease was more likely to progress to colorectal cancer. Thus, 5-aminosalicylic acid-based drugs may be effective for the treatment of UC in these patients. CONCLUSIONS: We divided UC into two molecular subgroups based on transcriptome data, providing molecular evidence for the development of diagnostic methods and individualized treatment strategies for UC. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The crosstalk between age and immunity in the context of ulcerative colitis (UC) remains incompletely understood. Our objective is to elucidate the specific age-associated genetic factors that modulate immune cell infiltration in UC, with the aim of identifying innovative therapeutic targets for the treatment of this disease. MATERIALS AND METHODS: Potential batch effects between samples were removed by R package "inSilicoMerging". Unsupervised clustering analysis via the "ConsensusClusterPlus" R package was utilized to perform consensus molecular subtyping of immune subtypes in UC. The construction of a heat map was accomplished through the utilization of the R package "pheatmap", while functional enrichment analysis was executed by means of the Metascape database. The identification of the age-related gene module was achieved by performing weighted gene co-expression network analysis (WGCNA) analysis using the R package "WGCNA". The support vector machine (SVM), least absolute shrinkage and selector operation (LASSO), and random forest algorithms were performed via the "e1071", "glmnet" and "randomForest" packages in R, respectively. The diagnostic performance of the parameter was assessed using the receiver operating characteristic (ROC) curve. Correlation analysis was performed by Spearman correlation. The "XSum" package in R was employed to identify potential small-molecule drugs for UC utilizing the Connectivity Map (CMap) database. Molecular docking was performed with Autodock Vina molecular docking software. RESULTS: A significantly greater frequency of UC patients aged below 40 years was observed in the group with extensive disease extent as compared to those with non-extensive disease extent (70% vs. 47%; Chi-square test, p = 0.02). The application of unsupervised clustering analysis allowed for the stratification of UC patients into two distinct immune subtypes, namely cluster C1 and cluster C2. The distribution of immune subtypes was significantly different between different age categories (Chi-square test, p = 0.00219). The UC samples that were grouped under cluster C1 were distinguished by a higher abundance of macrophages and an elevated number of neutrophils relative to those in cluster C2. Based on both WGCNA and Limma analysis, 146 age-related genes were identified, which exhibited a predominant enrichment in the biological process of cellular senescence. Two age-related genes (MIDN, and PLD6) affecting the immune cell infiltration in UC were identified based on machine learning algorithms (SVM, LASSO, and random forest). The diagnostic performance of MIDN (AUC = 0.93) and PLD6 (AUC = 0.90) in discerning UC patients belonging to cluster C1 was found to be satisfactory, as demonstrated by ROC curve analysis. MIDN demonstrated a positive correlation (r = 0.50, p < 0.0001) with Neutrophil, while PLD6 exhibited a negative correlation (r = -0.52, p < 0.0001) with Neutrophil levels. The "XSum" algorithm revealed that Entinostat has therapeutic potential for UC. The docking glide score between Entinostat and MIDN, and PLD6 protein was -8.9 kcal/mol and -6.8 kcal/mol, respectively. CONCLUSIONS: We have identified two age-related genes, MIDN and PLD6, that are involved in immune cell infiltration in patients with ulcerative colitis. Furthermore, a small molecule drug (Entinostat) with potential therapeutic effects for UC was screened out. This study presented new perspectives on personalized clinical management and therapy research for UC. [ABSTRACT FROM AUTHOR]

In modern data analysis and machine learning, data are often represented in the form of pairwise comparisons of the elements of the data set. The pairwise comparisons immediately correspond to the similarity or dissimilarity of objects under investigation, and such a situation regularly arises in the domains of image and signal analysis, bioinformatics, expert evaluation, etc. The practical pairwise comparison functions may be incorrect in terms of potentially using them as scalar products or distances. In contrast to other approaches, we develop in this paper a technique based on the so-called metric approach, which proposes to modify the values of empirical functions so as to get scalar products or distances. The methods for obtaining the correct matrices of pairwise comparisons and for improving their conditionality are developed here. [ABSTRACT FROM AUTHOR]

Background and objective Idiopathic pulmonary fibrosis (IPF) is an idiopathic chronic, progressive interstitial lung disease with a diagnosed median survival of 3-5 years. IPF is associated with an increased risk of lung cancer. Therefore, exploring the shared pathogenic genes and molecular pathways between IPF and lung adenocarcinoma (LUAD) holds significant importance for the development of novel therapeutic approaches and personalized precision treatment strategies for IPF combined with lung cancer. Methods Bioinformatics analysis was conducted using publicly available gene expression datasets of IPF and LUAD from the Gene Expression Omnibus (GEO) database. Weighted gene co-expression network analysis was employed to identify common genes involved in the progression of both diseases, followed by functional enrichment analysis. Subsequently, additional datasets were used to pinpoint the core shared genes between the two diseases. The relationship between core shared genes and prognosis, as well as their expression patterns, clinical relevance, genetic characteristics, and immune-related functions in LUAD, were analyzed using The Cancer Genome Atlas (TCGA) database and single-cell RNA sequencing datasets. Finally, potential therapeutic drugs related to the identified genes were screened through drug databases. Results A total of 529 shared genes between IPF and LUAD were identified. Among them, SULF1 emerged as a core shared gene associated with poor prognosis. It exhibited significantly elevated expression levels in LUAD tissues, concomitant with high mutation rates, genomic heterogeneity, and an immunosuppressive microen-vironment. Subsequent single-cell RNA-seq analysis revealed that the high expression of SULF1 primarily originated from tumor-associated fibroblasts. This study further demonstrated an association between SULF1 expression and tumor drug sensitivity, and it identified potential small-molecule drugs targeting SULF1 highly expressed fibroblasts. Conclusions This study identified a set of shared molecular pathways and core genes between IPF and LUAD. Notably, SULF1 may serve as a potential immune-related biomarker and therapeutic target for both diseases. [ABSTRACT FROM AUTHOR]