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Abstract Background Ankyrin repeat domain 53 (ANKRD53) plays an important role in maintaining chromosome integrity and stability, and chromosome instability is associated with cancer. Through integrative analysis, this study investigates the potential value of ANKRD53 in stomach adenocarcinoma (STAD). Methods RNA-seq and scRNA-seq data were used for integrative analysis based on online databases. Expression of ANKRD53 was confirmed by RT-PCR after bioinformatic analysis. Kaplan–Meier and Cox regression analyses were performed to evaluate the prognostic value of ANKRD53 in STAD. Gene set enrichment analysis (GSEA) was performed to evaluate ANKRD53-related signaling pathways. In addition, the interaction of ANKRD53 with immunity was also investigated. Results RT-PCR in STAD cell lines confirmed that ANKRD53 was downregulated in STAD samples compared to normal samples in the online databases. As an independent predictive biomarker, ANKRD53 was combined with other clinicopathological parameters to create a prognostic nomogram. Using GSEA, ANKRD53 was found to be involved in five pathways, including the TGF-β signaling pathway. Further investigation revealed that ANKRD53 was associated with immune checkpoint molecules, immunological pathways, and immunotherapy, in addition to MSI, TMB and neoantigens. In addition, scRNA-seq data revealed that ANKRD53 is mainly expressed in CD8+ T and dendritic cells. Conclusions ANKRD53 is an important biomarker for STAD that deserves further attention.

Abstract Programmed cell death (PCD) is a basic process of life that is closely related to the growth, development, aging and disease of organisms and is one of the hotspots of life science research today. PCD is a kind of genetic control, autonomous and orderly important cell death that involves the activation, expression, and regulation of a series of genes. In recent years, with the deepening of research in this field, new mechanisms of multiple PCD pathways have been revealed. This article reviews and summarizes the multiple PCD pathways that have been discovered, analyses and compares the morphological characteristics and biomarkers of different types of PCD, and briefly discusses the role of various types of PCD in the diagnosis and treatment of different diseases, especially malignant tumors.

Abstract Background As a core member of the FA complex, in the Fanconi anemia pathway, FAAP24 plays an important role in DNA damage repair. However, the association between FAAP24 and patient prognosis in AML and immune infiltration remains unclear. The purpose of this study was to explore its expression characteristics, immune infiltration pattern, prognostic value and biological function using TCGA-AML and to verify it in the Beat AML cohort. Methods In this study, we examined the expression and prognostic value of FAAP24 across cancers using data from TCGA, TARGET, GTEx, and GEPIA2. To further investigate the prognosis in AML, development and validation of a nomogram containing FAAP24 were performed. GO/KEGG, ssGSEA, GSVA and xCell were utilized to explore the functional enrichment and immunological features of FAAP24 in AML. Drug sensitivity analysis used data from the CellMiner website, and the results were confirmed in vitro. Results Integrated analysis of the TCGA, TARGET and GTEx databases showed that FAAP24 is upregulated in AML; meanwhile, high FAAP24 expression was associated with poor prognosis according to GEPIA2. Gene set enrichment analysis revealed that FAAP24 is implicated in pathways involved in DNA damage repair, the cell cycle and cancer. Components of the immune microenvironment using xCell indicate that FAAP24 shapes an immunosuppressive tumor microenvironment (TME) in AML, which helps to promote AML progression. Drug sensitivity analysis showed a significant correlation between high FAAP24 expression and chelerythrine resistance. In conclusion, FAAP24 could serve as a novel prognostic biomarker and play an immunomodulatory role in AML. Conclusions In summary, FAAP24 is a promising prognostic biomarker in AML that requires further exploration and confirmation.

Background Immunotherapy is revolutionizing cancer treatment from conventional radiotherapies and chemotherapies to immune checkpoint inhibitors which use patients’ immune system to recognize and attack cancer cells. Despite the huge clinical success and vigorous development of immunotherapies, there is a significant unmet need for a robust tool to identify responders to specific immunotherapy. Early and accurate monitoring of immunotherapy response is indispensable for personalized treatment and effective drug development.Methods We established a label-free metabolic intravital imaging (LMII) technique to detect two-photon excited autofluorescence signals from two coenzymes, NAD(P)H (reduced nicotinamide adenine dinucleotide (phosphate) hydrogen) and FAD (flavin adenine dinucleotide) as robust imaging markers to monitor metabolic responses to immunotherapy. Murine models of triple-negative breast cancer (TNBC) were established and tested with different therapeutic regimens including anti-cluster of differentiation 47 (CD47) immunotherapy to monitor time-course treatment responses using the developed metabolic imaging technique.Results We first imaged the mechanisms of the CD47-signal regulatory protein alpha pathway in vivo, which unravels macrophage-mediated antibody-dependent cellular phagocytosis and illustrates the metabolism of TNBC cells and macrophages. We further visualized the autofluorescence of NAD(P)H and FAD and found a significant increase during tumor growth. Following anti-CD47 immunotherapy, the imaging signal was dramatically decreased demonstrating the sensitive monitoring capability of NAD(P)H and FAD imaging for therapeutic response. NAD(P)H and FAD intravital imaging also showed a marked decrease after chemotherapy and radiotherapy. A comparative study with conventional whole-body bioluminescence and fluorescent glucose imaging demonstrated superior sensitivity of metabolic imaging. Flow cytometry validated metabolic imaging results. In vivo immunofluorescent staining revealed the targeting ability of NAD(P)H imaging mainly for tumor cells and a small portion of immune-active cells and that of FAD imaging mainly for immunosuppressive cells such as M2-like tumor-associated macrophages.Conclusions Collectively, this study showcases the potential of the LMII technique as a powerful tool to visualize dynamic changes of heterogeneous cell metabolism of cancer cells and immune infiltrates in response to immunotherapy thus providing sensitive and complete monitoring. Leveraged on ability to differentiate cancer cells and immunosuppressive macrophages, the presented imaging approach provides particularly useful imaging biomarkers for emerged innate immune checkpoint inhibitors such as anti-CD47 therapy.

Background: Neuropsychiatric symptoms (NPS) and cognitive impairments are both common in patients with late-life depression (LLD). However, the relationship between NPS and cognitive functions in LLD patients remains unclear. The current study aims to explore the effects of NPS on cognitive impairments in LLD patients.Methods: Two hundred and sixty-two LLD patients and 141 normal controls (NC) were recruited. Exploratory factor analysis was used to extract factors from the Neuropsychiatric Inventory (NPI). Correlation, mediation, and moderation analyses were used to explore whether NPS exacerbated the cognitive impairments in LLD and whether NPS exhibited different effects on cognitive impairments in acute-state LLD (aLLD) and recovery-state LLD (rLLD).Results: Three main factors were extracted from the NPI, including emotional, behavioral, and psychotic factors. The patients with LLD exhibited worse cognition and higher NPI scores, and the scores of NPI-total and three extracted factors were negatively associated with cognitive scores. The mediation analyses exhibited that NPI-total and behavioral factor scores increase the difference in cognition scores between LLD and NC groups. The mediation analyses exhibited that behavioral factor score played a greater effect on impairing MMSE in the rLLD group than in the aLLD group. Additionally, behavioral factor score was in a trend to be negatively associated with Mini-Mental State Examination (MMSE) score changes at a one-year follow-up (p = 0.051).Conclusions: NPS, especially behavioral symptoms, exacerbate cognitive impairments in LLD and may contribute to residual cognitive impairment in rLLD patients. Early intervention for behavioral symptoms in LLD patients may be beneficial to their long-term clinical prognosis.

Abstract Growing evidence indicates that the tumor biomarker cytokeratin 19 fragment (CYFRA21-1) is significant for a variety of cancers. However, its role in epithelial ovarian cancer (EOC) has rarely been reported. In this study, a receiver operating characteristic (ROC) curve was utilized to estimate the diagnostic efficiency of CYFRA21-1. The correlation between the CYFRA21-1 level and prognosis was analyzed by Kaplan-Meier survival analysis and univariable and multivariable analyses. The relationship between serum CYFRA21-1 levels and different clinicopathological variables was also analyzed. At the same time, the standard serum marker cancer antigen 125 (CA125) was measured. The results demonstrated that CYFRA21-1 expression was significantly increased in EOC compared with expression in benign ovarian diseases and healthy controls, which was similar to CA125 (P

(1) Background: Odor identification (OI) dysfunction is a potential predictor of developing dementia in late life depression (LLD). However, it is not clear whether patients with early onset depression (EOD) and late onset depression (LOD) may exhibit different OI dysfunctions. The aim of this study was to compare OI between EOD patients and LOD patients and its relationship with cognitive function. (2) Methods: A total of 179 patients with LLD and 189 normal controls were recruited. Participants underwent clinical assessment, olfactory testing, and comprehensive neuropsychological assessment. The OI scores of EOD patients and LOD patients were compared, and correlation analyses and mediation analyses were used to explore the relationship between OI and cognition. (3) Result: LOD patients exhibited lower OI scores than EOD patients and normal controls (NCs). Additionally, the LOD patients exhibited a higher percentage of OI dysfunction than the EOD patients. Moreover, OI scores were associated with global cognition, memory, language, and visuospatial ability in the EOD group (p < 0.05) but were not associated with any cognitive score in the LOD patients (p > 0.05). Finally, the scores of the Auditory Verbal Learning Test Immediate recall and Boston Naming Test exhibited a partially mediating effect on the difference in OI scores between the EOD and LOD patients. (4) Conclusions: LOD patients exhibited worse OI than EOD patients, and their difference in OI was mediated by their memory and language function.

Molecular dynamics (MD) simulation were performed on wild-type transthyretin (TTR) and two pathogenic variants to investigate how single-point mutations influence the effective energy landscapes of TTR monomers. Principle coordinate analysis on MD-generated ensembles has revealed multiple unfolding pathways for each protein.