The interactions between drugs and their target proteins induce altered expression of genes involved in complex intracellular networks. The properties of these functional network modules are critical for the identification of drug targets, for drug repurposing, and for understanding the underlying mode of action of the drug. The topological modules generated by a computational approach are defined as functional clusters. However, the functions inferred for these topological modules extracted from a large-scale molecular interaction network, such as a protein–protein interaction (PPI) network, could differ depending on different cluster detection algorithms. Moreover, the dynamic gene expression profiles among tissues or cell types causes differential functional interaction patterns between the molecular components. Thus, the connections in the PPI network should be modified by the transcriptomic landscape of specific cell lines before producing topological clusters. Here, we systematically investigated the clusters of a cell-based PPI network by using four cluster detection algorithms. We subsequently compared the performance of these algorithms for target gene prediction, which integrates gene perturbation data with the cell-based PPI network using two drug target prioritization methods, shortest path and diffusion correlation. In addition, we validated the proportion of perturbed genes in clusters by finding candidate anti-breast cancer drugs and confirming our predictions using literature evidence and cases in the ClinicalTrials.gov. Our results indicate that the Walktrap (CW) clustering algorithm achieved the best performance overall in our comparative study.

Carbon dots (CDs) with deep-blue thermally activated delayed fluorescence (TADF) of more than 2 s were developed, exhibiting the longest lifetime to date. In contrast to the established deep-blue TADF systems, this developed CD-based system (BNCDs) could be facilely and effectively synthesized, and more impressively, the emission lasted for more than 16 s (to the naked eye). XRD, TEM, FT-IR, and XPS analyses were conducted, and structural characterizations indicated that the CDs formed hydrogen bonding with B₂O₃. The temperature-dependent photoluminescence (PL) spectra demonstrated the existence of thermally activated delayed fluorescence in the composite. Further studies revealed that the B₂O₃ matrix restricted the vibration and rotation of CD chromophores and suppressed the non-radiative recombination of triplet excitons. Last but not least, potential applications in bioimaging, anti-counterfeiting, and information encryption were also explored. This work can provide new insights for developing metal-free and ultralong lifetime afterglow materials.

Aberrant hypermethylation of Wnt antagonists has been observed in gastric cancer. A number of studies have focused on the hypermethylation of a single Wnt antagonist and its role in regulating the activation of signaling. However, how the Wnt antagonists interacted to regulate the signaling pathway has not been reported. In the present study, we systematically investigated the methylation of some Wnt antagonist genes (SFRP2, SFRP4, SFRP5, DKK1, DKK2, and APC) and their regulatory role in carcinogenesis. We found that aberrant promoter methylation of SFRP2, SFRP4, DKK1, and DKK2 was significantly increased in gastric cancer. Moreover, concurrent hypermethylation of SFRP2 and DKK2 was observed in gastric cancer and this was significantly associated with increased expression of β-catenin, indicating that the joint inactivation of these two genes promoted the activation of the Wnt signaling pathway. Further analysis using a multivariate Cox proportional hazards model showed that DKK2 methylation was an independent prognostic factor for poor overall survival, and the predictive value was markedly enhanced when the combined methylation status of SFRP2 and DKK2 was considered. In addition, the methylation level of SFRP4 and DKK2 was correlated with the patient's age and tumor differentiation, respectively. In conclusion, epigenetic silencing of Wnt antagonists was associated with gastric carcinogenesis, and concurrent hypermethylation of SFRP2 and DKK2 could be a potential marker for a prognosis of poor overall survival.

Oxaliplatin resistance limits the efficiency of treatment for colorectal cancer (CRC). Studies have shown that abnormal expression of microRNAs (miRNAs) were associated with tumorigenesis, cancer development and chemoresistance. The purpose of this study was to identify potential miRNAs related to oxaliplatin resistance in CRC cells. In this work, using small RNA sequencing (small RNA-Seq) and transcriptome sequencing (RNA-Seq), we found that down-regulated miR-483-3p was concurrent with up-regulated FAM171B in oxaliplatin-resistant colorectal cancer cell line HCT116/L as compared with its parental cell line HCT116. Transient transfection of miR-483-3p mimics markedly decreased the levels of FAM171B and restored oxaliplatin responsiveness of HCT116/L cells, and this alteration enhanced cell apoptosis and weakened cell migration. Whereas miR-483-3p inhibitor dramatically promoted the expression of FAM171B and enhanced oxaliplatin resistance of HCT116 cells by repressing cell apoptosis. Furthermore, knockdown of FAM171B in HCT116/L cells could also sensitize its reaction of the treatment with oxaliplatin, which was verified by the reduced cell migration. These findings demonstrate that FAM171B is a functional target of miR-483-3p in the regulation of oxaliplatin resistance in human CRC cells.

Transcriptome profiling identified differentially expressed genes and pathways associated with tamoxifen resistance in human breast cancer Transcriptome profiling identified differentially expressed genes and pathways associated with tamoxifen resistance in human breast cancer