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Alzheimer's disease (AD) is a neurodegenerative disorder with a distinct sex bias. Age‐related vascular alterations, a hallmark of AD onset and progression, are consistently associated with sexual dimorphism. Here, we conducted an integrative meta‐analysis of 335,803 single‐nucleus transcriptomes and 667 bulk transcriptomes from the vascular system in AD and normal aging to address the underlying sex‐dependent vascular aging in AD. All vascular cell types in male AD patients exhibited an activated hypoxia response and downstream signaling pathways including angiogenesis. The female AD vasculature is characterized by increased antigen presentation and decreased angiogenesis. We further confirmed that these sex‐biased alterations in the cerebral vascular emerged and were primarily determined in the early stages of AD. Sex‐stratified analysis of normal vascular aging revealed that angiogenesis and various stress‐response genes were downregulated concurrently with female aging. Conversely, the hypoxia response increased steadily in males upon aging. An investigation of upstream driver transcription factors (TFs) revealed that altered communication between estrogen receptor alpha (ESR1) and hypoxia induced factors during menopause contributes to the inhibition of angiogenesis during normal female vascular aging. Additionally, inhibition of CREB1, a TF that targets estrogen, is also related to female AD. Overall, our study revealed a distinct cerebral vascular profile in females and males, and revealed novel targets for precision medicine therapy for AD. [ABSTRACT FROM AUTHOR]

Background: Forkhead box (FOX) proteins belong to one of the largest transcription factor families and play crucial roles in the initiation and progression of cancer. Prior research has linked several FOX genes, such as FOXA1 and FOXM1, to the crucial process of carcinogenesis. However, the overall picture of FOX gene family across human cancers is far from clear. Methods: To investigate the broad molecular signatures of the FOX gene family, we conducted study on multi‐omics data (including genomics, epigenomics and transcriptomics) from over 11,000 patients with 33 different types of human cancers. Results: Pan‐cancer analysis reveals that FOX gene mutations were found in 17.4% of tumor patients with a substantial cancer type‐dependent pattern. Additionally, high expression heterogeneity of FOX genes across cancer types was discovered, which can be partially attributed to the genomic or epigenomic alteration. Co‐expression network analysis reveals that FOX genes may exert functions by regulating the expression of both their own and target genes. For a clinical standpoint, we provided 103 FOX gene‐drug target‐drug predictions and found FOX gene expression have potential survival predictive value. All of the results have been included in the FOX2Cancer database, which is freely accessible at http://hainmu‐biobigdata.com/FOX2Cancer. Conclusion: Our findings may provide a better understanding of roles FOX genes played in the development of tumors, and help to offer new avenues for uncovering tumorigenesis and unprecedented therapeutic targets. [ABSTRACT FROM AUTHOR]

Background: N6‐methyladenosine (m6A) plays an essential role in tumorigenesis and cancer progression. Long noncoding RNAs (lncRNAs) are discovered to be important targets of m6A modification, and they play fundamental roles in diverse biological processes. However, there is still a lack of knowledge with regards to the association between m6A and lncRNAs in human tumors. Methods: The relationship between lncRNAs and 21 m6A regulators was comprehensively explored, through the integration of multi‐omics data from M6A2Target, m6A‐Atlas, and TCGA (The Cancer Genome Atlas). In order to explore the potential roles of m6A‐related lncRNAs in human tumors, three applicable methods were introduced, which include the construction of ceRNA networks, drug sensitivity estimation, and survival analysis. Results: A substantial number of positive correlation events across 33 cancer types were found. Moreover, cancer‐specific lncRNAs were associated with tissue specificity, and cancer‐common lncRNAs were conserved in cancer‐related biological function. In particular, the m6A‐related lncRNA FGD5‐AS1 was found to be associated with cancer treatment, through its influence on cisplatin resistance in breast cancer patients. Finally, a user‐friendly interface Lnc2m6A, which is enriched with various browsing sections resource for the exhibition of relationships and putative biogenesis between lncRNAs and m6A modifications, is offered in http://hainmu‐biobigdata.com/Lnc2m6A. Conclusions: In summary, the results from this paper will provide a valuable resource that guides both mechanistic and therapeutic roles of m6A‐related lncRNAs in human tumors. [ABSTRACT FROM AUTHOR]

Melioidosis is a serious infectious disease caused by the environmental Gram-negative bacillus Burkholderia pseudomallei. It has been shown that the host immune system, mainly comprising various types of immune cells, fights against the disease. The present study was to specify correlation between septicemic melioidosis and the levels of multiple immune cells. First, the genes with differential expression patterns between patients with septicemic melioidosis (B. pseudomallei) and health donors (control/healthy) were identified. These genes being related to cytokine binding, cell adhesion molecule binding, and MHC relevant proteins may influence immune response. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed 23 enriched immune response pathways. We further leveraged the microarray data to investigate the relationship between immune response and septicemic melioidosis, using the CIBERSORT analysis. Comparison of the percentages of 22 immune cell types in B. pseudomallei vs. control/healthy revealed that those of CD4 memory resting cells, CD8+ T cells, B memory cells, and CD4 memory activated cells were low, whereas those of M0 macrophages, neutrophils, and gamma delta T cells were high. The multivariate logistic regression analysis further revealed that CD8+ T cells, M0 macrophages, neutrophils, and naive CD4+ cells were strongly associated with the onset of septicemic melioidosis, and M2 macrophages and neutrophils were associated with the survival in septicemic melioidosis. Taken together, these data point to a complex role of immune cells on the development and progression of melioidosis. [ABSTRACT FROM AUTHOR]

Lymph node metastasis contributed to the leading cause and treatment failure in nasopharyngeal carcinoma (NPC). The microenvironment and the cellular communications of lymph node metastasized tumours determine the tumour progression and therapeutic effect, but the ecosystems about the lymph node metastasis (LNM) for NPC patients remain poorly characterized. Here, we integrated the transcriptomes of 47,618 single cells from eight samples related to NPC LNM. The dynamic immune ecosystems and immunosuppressive microenvironment including T cells, myeloid cells and B cells were observed in the lymph node metastatic samples compared with primary tumours. Additionally, the heterogeneity of epithelial cells was also revealed, and several clusters with expression programs that were associated with the progression-free survival of NPC patients were identified. Additionally, our data revealed the complex intercellular communications from primary to lymph node metastasis. The rewiring of CCL signalling which plays an important role in tumour metastasis was further identified. Altogether, we systematically characterized the ecosystem of NPC primary and lymph node metastasized tumours, which may shed light on the development of a therapeutic strategy to improve clinical outcomes of NPC patients with lymph node metastasis., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: N6-methyladenosine (m 6 A) plays an essential role in tumorigenesis and cancer progression. Long noncoding RNAs (lncRNAs) are discovered to be important targets of m 6 A modification, and they play fundamental roles in diverse biological processes. However, there is still a lack of knowledge with regards to the association between m 6 A and lncRNAs in human tumors., Methods: The relationship between lncRNAs and 21 m 6 A regulators was comprehensively explored, through the integration of multi-omics data from M6A2Target, m6A-Atlas, and TCGA (The Cancer Genome Atlas). In order to explore the potential roles of m6A-related lncRNAs in human tumors, three applicable methods were introduced, which include the construction of ceRNA networks, drug sensitivity estimation, and survival analysis., Results: A substantial number of positive correlation events across 33 cancer types were found. Moreover, cancer-specific lncRNAs were associated with tissue specificity, and cancer-common lncRNAs were conserved in cancer-related biological function. In particular, the m 6 A-related lncRNA FGD5-AS1 was found to be associated with cancer treatment, through its influence on cisplatin resistance in breast cancer patients. Finally, a user-friendly interface Lnc2m6A, which is enriched with various browsing sections resource for the exhibition of relationships and putative biogenesis between lncRNAs and m 6 A modifications, is offered in http://hainmu-biobigdata.com/Lnc2m6A., Conclusions: In summary, the results from this paper will provide a valuable resource that guides both mechanistic and therapeutic roles of m 6 A-related lncRNAs in human tumors., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Increasing evidence has revealed that RNA subcellular localization is a very important feature for deeply understanding RNA's biological functions after being transported into intra- or extra-cellular regions. RNALocate is a web-accessible database that aims to provide a high-quality RNA subcellular localization resource and facilitate future researches on RNA function or structure. The current version of RNALocate documents more than 37 700 manually curated RNA subcellular localization entries with experimental evidence, involving more than 21 800 RNAs with 42 subcellular localizations in 65 species, mainly including Homo sapiens, Mus musculus and Saccharomyces cerevisiae etc. Besides, RNA homology, sequence and interaction data have also been integrated into RNALocate. Users can access these data through online search, browse, blast and visualization tools. In conclusion, RNALocate will be of help in elucidating the entirety of RNA subcellular localization, and developing new prediction methods. The database is available at http://www.rna-society.org/rnalocate/., (© The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.)