Chromosome instability functions as a potential therapeutic reference by enhancing chemosensitivity to BCL-XL inhibitors in colorectal carcinoma.

Chromosome instability (CIN) and subsequent aneuploidy are prevalent in various human malignancies, influencing tumor progression such as metastases and relapses. Extensive studies demonstrate the development of chemoresistance in high-CIN tumors, which poses significant therapeutic challenges. Given the association of CIN with poorer prognosis and suppressed immune microenvironment observed in colorectal carcinoma (CRC), here we aimed to discover chemotherapeutic drugs exhibiting increased inhibition against high-CIN CRC cells. By using machine learning methods, we screened out two BCL-XL inhibitors Navitoclax and WEHI-539 as CIN-sensitive reagents in CRC. Subsequent analyses using a CIN-aneuploidy cell model confirmed the vulnerability of high-CIN CRC cells to these drugs. We further revealed the critical role of BCL-XL in the viability of high-CIN CRC cells. In addition, to ease the evaluation of CIN levels in clinic, we developed a three-gene signature as a CIN surrogate to predict prognosis, chemotherapeutic and immune responses in CRC samples. Our results demonstrate the potential value of CIN as a therapeutic target in CRC treatment and the importance of BCL-XL in regulating survival of high-CIN CRC cells, therefore representing a valuable attempt to translate a common trait of heterogeneous tumor cells into an effective therapeutic target.

Supramolecular Room-Temperature Phosphorescent Hydrogel Based on Hexamethyl Cucurbit[5]uril for Cell Imaging.

The host-guest interaction between hexamethyl cucurbit[5]uril (HmeQ[5]) and 1,4-diaminobenzene (DB) was investigated, and a new low-molecular-weight supramolecular gel was prepared by a simple heating/mixing cooling method. The structure and properties of the supramolecular gel were characterized. Results revealed that DB molecules did not enter the cavity of HmeQ[5] and that hydrogen bonding between the carbonyl group at the HmeQ[5] port and the DB amino groups, together with dipole-dipole interactions and outer wall interactions, were the main driving forces for the formation of the supramolecular gel. The HmeQ[5]/DB gel system exhibits temperature sensitivity. The phosphor 6-bromo-2-naphthol (BrNp) was embedded in the gel to give the gel fluorescent phosphorescence double emission. The double emission ability at room temperature can be attributed to the ordered microstructure of the supramolecular gel, which effectively avoids the nonradiative transition of BrNp. Meanwhile, HmeQ[5]/DB-BrNp has good biocompatibility and low biotoxicity, which is compatible with HeLa cells to achieve cytoplasmic staining of HeLa in the red channel. The supramolecular gels constructed by this supramolecular assembly strategy not only have good temperature sensitivity but also extend the application of Q[n]s in biomedical fields.