We report the finding of the presence of fluorescent carbon dots in commercial beer and TEM analysis reveals that the beer carbon dots (BCDs) have an average size of 2.5 nm. The BCDs possessed high solubility and excellent fluorescence properties under the excitation of ultra-violet light with a quantum yield of approximately 7.39%. X-ray photoelectron spectroscopy (XPS) characterization demonstrated that the BCDs contain carbon, oxygen and nitrogen, three elements with the relative contents ca. 59.52%, 36.71% and 3.77%, respectively. X-ray diffraction (XRD) analysis indicated that the BCDs are amorphous. Fourier transform infrared (FTIR) spectroscopy was employed to characterize the surface groups of the BCDs. The BCDs showed excellent stability under different conditions (high ion strength, extreme pH and laser exposure). The cytotoxicity study revealed that there was no obvious inhibition of cell viability with a concentration as high as 12.5 mg mL⁻¹ for 48 h, so that the BCDs could be directly applied in live cell imaging. Moreover, the BCDs could be used as efficient nanocarriers for the purpose of anticancer therapy. Doxorubicin-conjugated BCDs (BCD-DOX) induced prolonged cytotoxicity compared to free doxorubicin (DOX) due to the slow release of DOX from the BCD-DOX. The internalization of BCD-DOX by MCF-7 cells was further confirmed by using a laser scanning confocal microscope. All these results indicated that the BCDs present in beer have good biocompatibility and excellent fluorescence properties and may be considered as a safe material for bio-imaging and image-guided drug delivery in cancer therapy.

As an atypical member of cyclin dependent kinase family, Cyclin dependent kinase 5 (Cdk5) is considered as a neuron-specific kinase in the past decade due to the abundant existence of its activator p35 in post-mitotic neurons. Recent studies show that Cdk5 participates in a series of biological and pathological processes in non-neuronal cells, and is generally dysregulated in various cancer cells. The inhibition or knockdown of Cdk5 has been proven to play an anti-cancer role through various mechanisms, and can synergize the killing effect of chemotherapeutics. DNA damage response (DDR) is a series of regulatory events including DNA damage, cell-cycle arrest, regulation of DNA replication, and repair or bypass of DNA damage to ensure the maintenance of genomic stability and cell viability. Here we describe the regulatory mechanisms of Cdk5, its controversial roles in apoptosis and focus on its links to DDR and cancer.

Background: Breast cancer (BC) remains a prevalent and common form of cancer with high heterogeneity. Making efforts to explore novel molecular biomarkers and serve as potential disease indicators, which is essential to effectively enhance the prognosis and individualized treatment of BC. FBXO proteins act as the core component of E3 ubiquitin ligase, which play essential regulators roles in multiple cellular processes. Recently, research has indicated that FBXOs also play significant roles in cancer development. However, the molecular functions of these family members in BC have not been fully elucidated.Methods: In this research, we investigated the expression data, survival relevance and mutation situation of 10 FBXO members (FBXO1, 2, 5, 6, 16, 17, 22, 28, 31 and 45) in patients with BC from the Oncomine, GEPIA, HPA, Kaplan–Meier Plotter, UALCAN and cBioPortal databases. The high transcriptional levels of FBXO1 in different subtypes of BC were verified by immunohistochemical staining and the specific mutations of FBXO1 were obtained from COSMIC database. Top 10 genes with the highest correlation to FBXO1 were identified through cBioPortal and COXPRESdb tools. Additionally, functional enrichment analysis, PPI network and survival relevance of FBXO1 and co-expressed genes in BC were obtained from DAVID, STRING, UCSC Xena, GEPIA, bc-GenExMiner and Kaplan–Meier Plotter databases. FBXO1 siRNAs were transfected into MCF-7 and MDA-MB-231 cell lines. Expression of FBXO1 in BC cell lines was detected by western-blot and RT-qPCR. Cell proliferation was detected by using CCK-8 kit and colony formation assay. Cell migration was detected by wound‐healing and transwell migration assay.Results: We found that FBXO2, FBXO6, FBXO16 and FBXO17 were potential favorable prognostic factors for BC. FBXO1, FBXO5, FBXO22, FBXO28, FBXO31 and FBXO45 may be the independent poor prognostic factors for BC. All of them were correlated to clinicopathological staging. Moreover, knockdown of FBXO1 in MCF7 and MDA-MB-231 cell lines resulted in decreased cell proliferation and migration in vitro. We identified that FBXO1 was an excellent molecular biomarker and therapeutic target for different molecular typing of BC.Conclusion: This study implies that FBXO1, FBXO2, FBXO5, FBXO6, FBXO16, FBXO17, FBXO22, FBXO28, FBXO31 and FBXO45 genes are potential clinical targets and prognostic biomarkers for patients with different molecular typing of BC. In addition, the overexpression of FBXO1 is always found in breast cancer and predicts disadvantageous prognosis, implicating it could as an appealing therapeutic target for breast cancer patients.

Breast cancer (BC), an extremely aggressive malignant tumor, causes a large number of deaths worldwide. In this study, we pooled profile datasets from three cohorts to illuminate the underlying key genes and pathways of BC. Expression profiles GSE42568, GSE45827, and GSE124646, including 244 BC tissues and 28 normal breast tissues, were integrated and analyzed. Differentially expressed genes (DEGs) were screened out based on these three datasets. Functional analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway were performed using The Database for Annotation, Visualization and Integrated Discovery (DAVID). Moreover, Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING) and Molecular Complex Detection (MCODE) plugin were utilized to visualize protein protein interaction (PPI) of these DEGs. The module with the highest connectivity of gene interactions was selected for further analysis. All of these hub genes had a significantly worse prognosis in BC by survival analysis. Additionally, four genes (CDK1, CDC20, AURKA, and MCM4) dramatically were enriched in oocyte meiosis and cell cycle pathways through re-analysis of DAVID. Moreover, the mRNA and protein levels of CDK1, CDC20, AURKA, and MCM4 were significantly increased in BC patients. In addition, knockdown of CDK1 and CDC20 by small interfering RNA remarkably suppressed cell migration and invasion in MCF-7 and MDA-MB-231 cells. In conclusion, our results suggested that CDK1, CDC20, AURKA, and MCM4 were reliable biomarkers of BC via bioinformatics analysis and experimental validation and may act as prospective targets for BC diagnosis and treatment.