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Probiotics play an important role in the host and have attracted widespread attention as an alternative to antibiotics. Arbor Acres broilers were used in the present experiment and fed different doses of compound probiotics at 1, 5, and 10g kgWe discovered 425 differentially expressed genes (DEGs; upregulated: 256, downregulated: 169) in the cecal transcriptome study. These DEGs were assigned to fat metabolic pathways, such as the PPAR signaling pathway, according to KEGG analysis. Probiotics downregulated LPL and up-regulated PPARα expression in the cecum. In metabolome analysis of broilers cecum, we screened 86 differential metabolites and performed KEGG enrichment analysis of these metabolites. The KEGG analysis showed that these differentially expressed metabolites were annotated to nucleotide metabolism-related pathways, such as purine metabolism. In the cecum, probiotics upregulated the content of guanine, AMP, 3'-AMP, adenylosuccinate, deoxyguanosine, and ADP-ribose, whereas downregulated the content of 5-hydroxyisourate. Comprehensive transcriptome and metabolome analysis revealed that glycolysis, gluconeogenesis, and glycerophospholipid metabolism pathways were jointly enriched in cecum of broilers fed probiotics-containing diet.This study provides valuable information for studying the regulation and gene metabolism network of probiotics on caecal metabolism in broilers. This article is protected by copyright. All rights reserved.

Pre-existing drug resistance and tumorigenicity of cancer cells are highly correlated with therapeutic failure and tumor growth. However, current cancer models are limited in their application to the study of intratumor functional heterogeneity in personalized oncology. Here, an innovative two-dimensional (2D) and three-dimensional (3D) model for patient-derived cancer cells (PDCCs) and air-liquid interface (ALI) organotypic culture is established from colorectal cancer (CRC). The PDCCs recapitulate the genomic landscape of their parental tumors with high efficiency, high proliferation rate, and long-term stability, while corresponding ALI organotypic cultures retain histological architecture of their original tumors. Interestingly, both 2D and 3D models maintain the transcriptomic profile of the corresponding primary tumors and display the same trend in response to 5-Fluoruracil, regardless of their difference in gene expression profiles. Furthermore, single-cell-derived clones() are efficiently established and pre-existing drug-resistant clones and highly tumorigenic clones within individual CRC tumors are identified. It is found that tumorigenic cancer cells do not necessarily possess the stem cells characteristics in gene expression. This study provides valuable platform and resource for exploring the molecular mechanisms underlying the pre-existing drug resistance and tumorigenicity in cancer cells, as well as for developing therapeutic targets specifically for pre-existing drug-resistant or highly tumorigenic clones.