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Both G9a and NSD2 have been recognized as promising therapeutic targets for cancer treatment. However, G9a inhibitors only showed moderate inhibitory activity against solid tumors and NSD2 inhibitors were limited to the treatment of hematological malignancies. Inspired by the advantages of dual-target inhibitors that show great potential in enhancing efficiency, we developed a series of highly potent G9a/NSD2 dual inhibitors to treat solid tumors. The candidate 16demonstrated much enhanced antiproliferative activity compared to the selective G9a inhibitor 3and NSD2 inhibitor 15. In addition, it exhibited superior potency in inhibiting colony formation, inducing cell apoptosis, and blocking cancer cell metastasis. Furthermore, it effectively inhibited the catalytic functions of both G9a and NSD2 in cells and exhibited significant antitumor efficacy in the PANC-1 xenograft model with good safety. Therefore, compound 16as a highly potent G9a/NSD2 dual inhibitor presents an attractive anticancer drug candidate for the treatment of solid tumors.

Understanding the genetic and metabolic elements that impact the quality of meat is crucial in order to improve production and satisfy consumer demands in the beef sector. Differences in meat quality among various muscle areas in beef cattle can impact pricing in the market. Despite progress in genomics, the specific genes and metabolites that affect meat quality characteristics in Qinchuan cattle remain inadequately understood. Therefore, this study aimed to evaluate the meat quality characteristics of four specific muscle locations (tenderloin, striploin, high rib and ribeye muscles) in Qinchuan bulls, including ten traits (total protein content (TPC), intramuscular fat (IMF), non-esterified fatty acid (NEFA), meat color (L*, a* and b*), shear force (SF), cooking loss (CL), pH0 and pH24). In this experiment, transcriptome, metabolome sequencing, and sophisticated analytical methodologies such as weighted gene co-expression network analysis (WGCNA) and protein-protein interaction networks (PPI) were used to identify the key genes and metabolites associated with specific traits. The findings highlighted three notable genes (NDUFAB1, NDUFA12, and NDUFB7) linked to intramuscular fat (IMF), three key genes (CSRP3, ACAA3, ACADVL) correlated with non-esterified fatty acids (NEFA), and one crucial gene (CREBBP) influencing meat color. In conclusion, this investigation offers a new perspective on the differences in bovine muscle locations and contributes to the molecular understanding of bovine meat quality. Future research endeavors could delve deeper into the identified genes and pathways to enhance both the quality and yield of beef cattle.