NF-κB is a promising target for cancer treatment because of its overactivation in almost all cancers but countless NF-κB inhibitors rarely became clinical drugs due to side effects. In contrast to traditional cancer treatments aimed at inhibiting NF-κB activity, this study develop a novel approach termed HOPE, which focuses on activating the exogenous effector gene CRISPR-Cas13a within cancer cells, achieved by utilizing the NF-κB-specific promoter DMP previously constructed, then targets and suppresses the expression of oncogenes TERT, PLK1, KRAS and MYC at mRNA level. We evaluated the antitumour effects of HOPE in various cultured cells and confirmed it could induce obvious the death of cancer cells without affecting normal cells. By packaging HOPE into adeno-associated virus (AAV) and intravenously injected it to treat mice that were subcutaneously transplanted with colorectal cancer. This validated that rAAV-HOPE could significantly inhibit tumour growth without side effects. Based on the scRNA-seq data, we observed that HOPE could activate the immune system and decrease the proportion of cancer cells, particularly reducing the stemness of cancer cells. This study elucidates an important role of HOPE in inhibiting cancer cell growth both in vitro and in vivo, additionally provides a novel therapeutic technology for cancer gene therapy.

Background: Antibiotics were extensively used in the pigeon breeding industry previously to promote growth and prevent disease, leading to the spread of antibiotic-resistant genes (ARGs) in gut microbes, which has become a major public health concern. Methods: A metagenomic analysis was performed to investigate the gut microbial communities and ARGs in young and older pigeons in Nanjing, Jiangsu Province, China. Results: There were obviously distinct gut microbiota and functional compositions between young and older pigeons. Both Pseudomonadota and Uroviricota were dominant in young and older pigeons. Although sharing 24 gut microbiota phyla between young and older pigeons, Bacillota and Pseudomonadota were the dominant microbial phyla in them, respectively. Besides the shared metabolic pathways and biosynthesis of secondary metabolites, biosynthesis of amino acids was the most abundant Kyoto Encyclopedia of Genes and Genomes (KEGG) function in young pigeons, while microbial metabolism in diverse environments was abundant in older pigeons. A total of 142 ARGs conferring multidrug resistance, tetracycline, and aminoglycoside resistance were identified; the most abundant gene in young pigeons was tetracycline-tetW, while in older pigeons, it was multidrug-acrB. Conclusions: Our findings revealed significant differences in the gut microbial communities and ARGs between young and older pigeons. This study enhances our understanding of pigeon gut microbiota and antibiotic resistomes, contributing to knowledge-based sustainable pigeon meat production.

Background: Characterization of the molecular features of a brain tumor is a critical step for patient treatment. Tissue-based detection methods are limited by the location of brain tumors and high intratumor heterogeneity, which also preclude repeat sampling to monitor tumor progression. Cerebrospinal fluid (CSF)-based noninvasive methods may provide an opportunity to solve these problems, but efficient markers are lacking. This study aims to develop and validate a CSF-based liquid biopsy approach to investigate the molecular characterization and transcriptional regulation features of brain tumors. Methods: In this study, we conducted genome wide analysis of CSF cell free DNA (cfDNA) data collected from Sonic hedgehog (SHH) pathway-activated medulloblastoma (MB) patients sourced from gene expression omnibus (GEO) database, to identify genome features that differed significantly between patients with MB and those with hydrocephalus (P<0.001) using the whole genome bisulfite sequencing (WGBS) dataset. Results: A total of 397 differential cfDNA genomic loci were identified and verified by assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) as SHH-MB specific; 114 were located in promoter regions, and related to genes specifically expressed in SHH-MB and, combined with DNA methylation state in these regions, could be used to classify the SHH-MB subtype from 763 samples. Twelve of 283 non-promoter loci were identified as super-enhancers and binding sites for transcription factors related to brain tumors were also identified in associated genomic regions. Patients with SHH-MB were then classified using these CSF cfDNA derived transcription regulation features. Conclusions: CSF cfDNA from patients with brain tumors was used to determine transcription regulation features, which could reflect the molecular characteristics of brain tumors. Further, these features represent biomarkers with potential to identify patients with tumors. Our study provides a new application for CSF cfDNA and extends its use for investigating tumor-specific gene transcription regulation.