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Oxaliplatin (L‐OHP), a third‐generation platinum‐based anti‐tumor drug, finds widespread application in the first‐line treatment of metastatic colorectal cancer. Despite its efficacy, the drug's usage is curtailed by a litany of side effects, with L‐OHP‐induced peripheral neuropathy (OIPN) being the most debilitating. This condition can be classified into varying degrees of severity. Employing serum metabolomics, a high‐sensitivity, high‐throughput technique, holds promise as a method to identify biomarkers for clinical assessment and monitoring of OIPN patients across different severity levels. In our study, we analyzed serum metabolites in patients with different OIPN levels using ultra‐performance liquid chromatography‐high resolution mass spectrometry. By employing statistical analyses and pathway enrichment studies, we aimed to identify potential biomarkers and metabolic pathways. Our findings characterized the serum metabolic profiles of patients with varying OIPN levels. Notably, pathway analysis revealed a significant correlation with lipid metabolism, amino acid metabolism, and energy metabolism. Multivariate statistical analysis and receiver operator characteristic curve evaluation pointed to anhalamine and glycochenodeoxycholic acid as potential biomarkers for OIPN C and A, which suggest that serum metabolomics may serve as a potent tool for exploring the metabolic status of patients suffering from diverse diseases and for discovering novel biomarkers. [ABSTRACT FROM AUTHOR]

The traditional Chinese herb Rubus chingii Hu (R. chingii) is widely used in clinical practice due to its beneficial effects. Flavonoids are the important class of pharmacological substances in R. chingii , however, the molecular mechanism underlying the differences in active flavonoid contents in R. chingii at different developmental stages remain poorly understood. In this experiment, we selected four developmental stages (GG, GY, YR, RR) of R. chingii as the research material. We studied the untargeted and targeted metabolic profiles of flavonoids in different periods of R. chingii , combining full-length and comparative transcriptome analyses. Functional analyses were conducted on genes implicated in flavonoid differences. GG and RR displayed relatively higher and lower contents of flavonols, flavones, flavanols, flavanones, and isoflavonoid, respectively. RNA-seq analyses showed structural genes such as RcPAL, RcC4H, Rc4CL, RcCHS, RcCHI, RcF3H, RcF3′H, and RcFLS in flavonoid biosynthesis pathway were upregulated in GG, which were essential for the accumulation flavanones, flavones, and flavonols (effective components). qRT-PCR analyses investigated that six structural genes RcCHI, RcF3H, 2 RcCHS, and 2 Rc4CL, two TFs RcMYB308 and RcMYB123 had a consistent expression pattern with which in transcriptome. Also, an interaction network showed that the RcMYB308 could positively regulate Ka3R, Qu, Qu3G, AS, Hy, Ti through RcF3H. Furthermore, Subcellular localization analysis revealed that RcMYB308 was localization to the nucleus. In tobacco, RcMYB308 was overexpressed, resulting in higher flavonoids, RcF3H, RcF3′H, RcCHI, and RcFLS. RcMYB308 upregulated RcF3H in dual-luciferase assays. These results provide new insights for further understanding the molecular mechanism regulating flavonol biosynthesis in R. chingii fruit, and also provide a potential MYB regulator for molecular breeding of R. chingii. • Metabolic profiles with transcriptome analyses were performed in R. chingii. • GG and RR displayed relatively higher and lower contents of flavonoids. • Important structural genes in flavonoid biosynthesis were upregulated in GG. • RcMYB308 led to increased flavonols, RcF3H, RcF3′H, RcCHI, and RcFLS. • Dual-luciferase assays confirmed that RcMYB308 upregulated RcF3H. [ABSTRACT FROM AUTHOR]