M35 Oxidation Induces Aβ40-like Structural and Dynamical Changes in Aβ42

M35 Oxidation Induces Aβ40-like Structural and Dynamical Changes in Aβ4

Development of a Fluorescent Biosensor Based on DNAzyme for Tracing the Release of Zinc in Maize Leaves

A fluorescent biosensor for real-time monitoring the release of Zn2+ in plants was constructed through immobilization of DNAzyme-containing hairpin DNA on nanofertilizer ZnO@Au nanoparticles (ZnO@Au NPs). A specially designed hairpin DNA containing both DNAzyme and its substrate sequence, which was also labeled with 5′-FAM and 3′-SH groups, was modified on ZnO@Au NPs through the Au–S bond. The fluorescent signal of FAM was initially quenched by AuNPs. When Zn2+ was released from ZnO@Au NPs, DNAzyme was activated and the substrate sequence in hairpin DNA was cleaved. The restored fluorescent signal in Tris–HCl buffer (pH 6.5) was correlated with the concentration of the released Zn2+. The performance of the biosensor was first demonstrated in the solution. The linear detection range was from 50 nM to 1.5 μM, with a detection limit of 30 nM. The biosensor system can penetrate into maize leaves with ZnO@Au NPs. With the release of Zn2+ in leaves, the restored fluorescence can be imaged by a confocal laser scanning microscope and used for monitoring the release and distribution of Zn2+. This work may provide a novel strategy for tracing and understanding the mechanism of nanofertilizers in organisms

Additional file 3 of Identification of ENO1 as a prognostic biomarker and molecular target among ENOs in bladder cancer

Additional file 3: Figure S2. The originally western blotting images were presented

Table_1_A Novel Ferroptosis-Related Prognostic Signature Reveals Macrophage Infiltration and EMT Status in Bladder Cancer.DOCX

Bladder cancer (BC) belongs to one of the most common and highly heterogeneous malignancies. Ferroptosis is a newly discovered regulated cell death (RCD), characterized by accumulation of toxic lipid peroxides, and plays a crucial role in tumor progression. Here, we conducted a comprehensive analysis on the transcriptomics data of ferroptosis-related genes in BC based on The Cancer Genome Atlas (TCGA) and three Gene Expression Omnibus (GEO) datasets. In our study, a 6-gene signature was identified based on the potential prognostic ferroptotic regulatory genes. Furthermore, our signature revealed a good independent prognostic ability in BC. Patients with low-risk score exhibited higher FGFR3 mutation rates while high risk score had a positive association with higher RB1 mutation rates. Meanwhile, higher proportions of macrophages were observed in high BC risk group simultaneously with four methods. Unexpectedly, the risk score showed a significant positive correlation with epithelial-mesenchymal transition (EMT) status. Functional assays indicated that CRYAB and SQLE knockdown was associated with attenuated invasion capacity. Our study revealed a ferroptosis-related risk model for predicting prognostic and BC progression. Our results indicate that targeting ferroptosis may be a therapeutic strategy for BC.</p

DataSheet1_Pyroptosis-Related Patterns Predict Tumor Immune Landscape and Immunotherapy Response in Bladder Cancer.docx

Background: Bladder cancer (BC) is a leading cause of death from malignancy, with significant heterogeneity in the immunotherapeutic responsiveness of advanced status. Pyroptosis, a newly discovered inflammatory programmed cell death, is confirmed to play an indispensable role in tumorigenesis and anti-tumor activity. However, the effect of pyroptosis on the tumor-immune landscape remodeling and immunotherapy in BC remains elusive.Methods: We comprehensively evaluated the mRNA expression and genomic alterations of 33 pyroptosis-related genes (PRGs) in BC and evaluated the patterns of pyroptosis in publicly available BC datasets. An unsupervised clustering method was used to classify patients into distinct patterns. Then, we established a pyroptosis-related signature score (PS-score) model to quantify the pyroptosis-related patterns of individual BC patients using principal component analysis. Furthermore, we correlated the patterns with the immune landscape and response efficacy of immunotherapy.Results: Two pyroptosis-related patterns were identified in BC, and distinct patterns showed various immune characteristics. Patterns with a high expression level of PRGs exhibited a survival advantage and showed higher infiltration of cytotoxic lymphocytes. Tumors with a low PS-score were characterized by high tumor-infiltrating lymphocytes and considered “hot.” Further analysis revealed that the PS-score was an independent prognostic factor and could predict the response to immunotherapy for patients with advanced BC. We found a significant positive association between AHNAK2, AHNAK nucleoprotein 2, expression, and PS-score. Functional assays showed that AHNAK2 knockdown was correlated with attenuated invasive ability.Conclusion: This work comprehensively demonstrated the potential function of pyroptosis-related patterns in the bladder tumor-immune landscape and identified their therapeutic liability in immunotherapy. Our study enhanced our understanding of the immune landscape and provided a new approach toward more effective immunotherapy strategies.</p

DataSheet1_PDE4B Induces Epithelial-to-Mesenchymal Transition in Bladder Cancer Cells and Is Transcriptionally Suppressed by CBX7.docx

Urinary bladder cancer (UBC) is a common malignant tumor with high incidence. Advances in the diagnosis and treatment of this disease demand the identification of novel therapeutic targets. Multiple studies demonstrated that PDE4B level was upregulated in malignancies and high PDE4B expression was correlated with poor outcomes. Herein, we identified that PDE4B was a potential therapeutic target in UBC. We confirmed that PDE4B expression was correlated with aggressive clinicopathological characteristics and unfavorable prognosis. Functional studies demonstrated that ectopic expression of PDE4B promoted UBC cells proliferation, migration and invasion, whereas PDE4B depletion suppressed cancer cell aggressiveness. We also identified CBX7 as a regulator of PDE4B to suppress the expression of PDE4B at the transcription level in a PRC1-dependent manner. Moreover, our results indicated that PDE4B induced epithelial-to-mesenchymal transition (EMT) in UBC cells via β-catenin pathway, whereas inhibition of PDE4B by its small molecule inhibitor, rolipram, effectively reversed the PDE4B overexpression-induced effects. To sum up, our results indicated that PDE4B acts as an oncogene by promoting UBC cell migration and invasion via β-catenin/EMT pathway.</p

Additional file 2 of Identification of ENO1 as a prognostic biomarker and molecular target among ENOs in bladder cancer

Additional file 2: Figure S1. Prognostic analysis of ENO1 in the BLCA patients. A, B Univariate (A) and Multivariate (B) Cox regression analyses of ENO1 along with clinicopathological characteristics for overall survival in GEO13507. C Time-dependent ROC analysis of ENO1 in estimating the prognostic performance of the BLCA patients in GEO13507. D Multi-variable time-dependent ROC analysis of ENO1 in predicting the overall survival of the BLCA patients in GEO13507

Enzyme Reaction-Assisted Programmable Transcriptional Switches for Bioactive Molecule Detection

Bioactive molecules are highly worthwhile to recognize and explore the latent pathogenic mechanism. Conventional methods for bioactive molecule detection, including mass spectrometry and fluorescent probe imaging, are limited due to the complex processing and signal interference. Here, we designed enzyme-reaction-assisted programmable transcriptional switches for the detection of bioactive molecules. The approach is based on the use of programmable enzyme site-specific cleavage-assisted DNA triplex-based conformational switches that, upon responding to bioactive molecules, can trigger the transcription of fluorescent light-up aptamers. Thanks to the programmable nature of the sensing platform, the method can be adapted to different bioactive molecules, and we demonstrated the enzyme-small molecule catalytic reaction combination of myeloperoxidase (MPO)–hydrogen peroxide (H2O2) as a model that transcriptional switches was capable of detecting H2O2 and possessed the specificity and anti-interference ability in vitro. Furthermore, we successfully applied the switches into cells to observe the detection feasibility in vivo, and dynamically monitored changes of H2O2 in cellular oxidative stress levels. Therefore, we attempt to amalgamate the advantages of enzyme reaction with the pluripotency of programmable transcriptional switches, which can take both fields a step further, which may promote the research of biostimuli and the construction of DNA molecular devices

Additional file 1 of Identification of ENO1 as a prognostic biomarker and molecular target among ENOs in bladder cancer

Additional file 1: Table S1. List for sequences of primer sets and siRNAs

Table3_A novel cuproptosis-related lncRNA signature predicts prognosis and therapeutic response in bladder cancer.XLSX

Bladder cancer (BC) ranks the tenth in the incidence of global tumor epidemiology. LncRNAs and cuproptosis were discovered to regulate the cell death. Herein, we downloaded transcriptome profiling, mutational data, and clinical data on patients from The Cancer Genome Atlas (TCGA). High- and low-risk BC patients were categorized. Three CRLs (AL590428.1, AL138756.1 and GUSBP11) were taken into prognostic signature through least absolute shrinkage and selection operator (LASSO) Cox regression. Worse OS and PFS were shown in high-risk group (p < 0.05). ROC, independent prognostic analyses, nomogram and C-index were predicted via CRLs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated IncRNAs play a biological role in BC progression. Immune-related functions showed the high-risk group received more benefit from immunotherapy and had stronger immune responses, and the overall survival was better (p < 0.05). Finally, a more effective outcome (p < 0.05) was found from clinical immunotherapy via the TIDE algorithm and many potential anti-tumor drugs were identified. In our study, the cuproptosis-related signature provided a novel tool to predict the prognosis in BC patients accurately and provided a novel strategy for clinical immunotherapy and clinical applications.</p