New agents with particular specificity toward targeted bacteria and superefficacy in antibacterial activity are urgently needed in facing the crisis of worldwide antibiotic resistance. Herein, a novel strategy by equipping bacteriophage (PAP) with photodynamic inactivation (PDI)active AIEgens (luminogens with aggregation-induced emission property) was presented to generate a type of AIE−PAP bioconjugate with superior capability for both targeted imaging and synergistic killing of certain species of bacteria. The targeting ability inherited from the bacteriophage enabled the bioconjugates to specifically recognize the host bacteria with preserved infection activity of phage itself. Meanwhile, the AIE characteristic empowered them a monitoring functionality, and the realtime tracking of their interactions with targets was therefore realized via convenient fluorescence imaging. More importantly, the PDI-active AIEgens could serve as powerful in situ photosensitizers producing high-efficiency reactive oxygen species (ROS) under white light irradiation. As a result, selective targeting and synergistic killing of both antibiotic-sensitive and multi-drug-resistant (MDR) bacteria were successfully achieved in in vitro and in vivo antibacterial tests with excellent biocompatibility. This novel AIE−phage integrated strategy would diversify the existing pool of antibacterial agents and inspire the development of promising drug candidates in the future.

Efficient signal amplification is essential to construct ultrasensitive biosensors for biologically relevant species with abundant concomitant interferences. Here, we apply LbaCas12a as a signal amplifier to develop a versatile CRISPR-Cas12a platform to detect a wide range of analytes in ultralow concentrations. The platform relies on the indiscriminate single-stranded DNase activity of LbaCas12a, which recognizes single-stranded DNA intermediates generated by non-DNA targets down to femtomolar concentrations and subsequently enhances the fluorescence signal output. With the help of functional nucleotides (DNAzyme and aptamer), ultrasensitive bioassays for Pb 2+ and Acinetobacter baumannii have been designed with a limit of detection down to ∼0.053 nM and ∼3 CFU/mL, respectively. It also allows simultaneous detection of four microRNAs (miRNAs) at a picomolar concentration without significant interferences by other counterparts, suggesting the potential of multiplexed miRNA expression profiles analysis in high throughput. Given the versatility and generality of the CRISPR-Cas12a platform, we expect the current work to advance the application of CRISPR-Cas-based platforms in bioanalysis and provide new insights into ultrasensitive biosensor design.

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Glioma is one of the most common types of human brain tumor, with high mortality in high-grade gliomas (HGG). Low-grade gliomas (LGG) can progress into HGG, leading to poor prognosis. However, it is unclear what factors affect the progression of LGG to HGG. This study aims to explore the function of the crosstalk genes on the progression and prognosis of LGG using bioinformatics analysis. Integrated transcriptome analysis was used to screen differentially expressed genes (DEGs). Then, gene ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to investigate the association between DEGs and gene functions and pathways by ClusterProfiler package and ClueGO plug-in. Protein-protein interaction (PPI) network analysis was applied to explore the connection between genes and biological processes. Subsequently, the gene clusters were analyzed using the Centiscape and molecular complex detection (MCODE) plug-in in Cytoscape software, where the crosstalk genes were identified for further study. Ultimately, the UALCAN website and Gene Expression Profiling Interactive Analysis (GEPIA) website were performed to visualize the expression levels and survival curves of genes, respectively. There were 74DEGs identified in glioma, including 55 upregulated genes and 19 downregulated genes, which mainly were enriched in extracellular matrix (ECM)receptor interaction, focal adhesion, PI3K-Akt signaling pathway, and so on. Then, six crosstalk genes were selected, including COL1A1, COL1A2, COL3A1, COL4A1, COL4A2, and COL5A2 genes. Overall survival (OS) analysis of crosstalk genes was conducted on the GEPIA website. High expression levels of crosstalk genes were closely related to the low survival rate of patients withLGG. The overexpressed crosstalk genes, such as COL1A1, COL1A2, COL3A1, COL4A1, COL4A2, and COL5A2 may participate in the progression and poor prognosis of LGG through the ECM-receptor interaction pathway. K E Y W O R D S bioinformatics, crosstalk genes, glioma, prognosis, progression Yongcan Guo and Hualin Tao contributed equally to this study.Glioma is the most common primary tumor of the central nervous system, 1 diagnosed based on pathological grade and molecular subtype. And gliomas are classified into grades I to IV by World Health Organization (WHO), including low-grade (WHO grades I-II) and high-grade (WHO grades III-IV) gliomas. 2 High-grade gliomas (HGG) have a high mortality rate and low five-year survival rate with less than 10%. 3 The effect of radiotherapy and chemotherapy is not obvious for HGG, leading to the median survival time of 14 to 17 months, 4 less than the low-grade glioma (LGG), of which the average survival time is approximately 10 years. By contrast, in case the LGG progress into HGG, the mortality rate will increase. 5 Therefore, it is necessary to explore the factors that have an influence on the progression of LGG to HGG, aiming at slowing down the progression and extending survival time of patients with LGG. In recent years, most ...

Background Renal cell carcinoma (RCC) is a common urological cancer. circular RNAs (circRNAs) is involved in the development of various types of cancers. However, the roles and underlying mechanisms of circRNAs in RCC are not fully elucidated. Herein, we aimed to examine the potential effect of circ_001287 on RCC progression. Materials and Methods Microarray-based gene expression profiling of RCC was initially employed in order to identify differentially expressed genes. Next, the expression of circ_001287 was examined, and the cell line with the highest circ_001287 expression was selected for subsequent investigation. The interaction among circ_001287, miR-144, and CEP55 was identified by conducting luciferase reporter assay, RNA-pull down, RIP, RT-qPCR and FISH. The effect of circ_001287 on proliferative, invasive and migratory capacities as well as tumorigenicity of transfected cells in mice was examined using gain- and loss-of-function experiments. Results circ_001287 and CEP55 were highly expressed while miR-144 was decreased in RCC tissues and cell lines. circ_001287 can up-regulate CEP55 by binding to miR-144, which resulted in increased proliferative, invasive and migratory capacities and tumor growth in vivo. In addition, down-regulation of miR-144 was also observed to promote these biological activities. Conclusions Overall, these results elucidate a new mechanism for circ_001287 in RCC development and provide a potential therapeutic target for RCC patients.

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