Through an initiate pilot screening with around 100 compounds, Flupirtine, a selective neuronal potassium channel opener, was identified as a potential TMPRSS2 inhibitor from an FDA-approved drug library by using this screening platform, and showed inhibitory effect on the TMPRSS-dependent infection of SARS-CoV-2 Spike-pseudotyped lentiviral particles. This study describes a platform proven effective for rapidly screening of TMPRSS2 inhibitors, and suggests that Flupirtine may be worthy of further consideration of repurposing to treat COVID-19 patients.Breast cancer is the leading cause of cancer-related deaths in women worldwide. Several studies have indicated that abnormal chondroitin sulfate (CS) chains accumulate in breast cancer tissues; however, the functions and dysregulation of CS synthases are largely unknown. Here, we demonstrate that chondroitin polymerising factor (CHPF) is frequently upregulated in breast cancer tissues and that its high expression is positively associated with tumor metastasis, high stages, and short survival time. CHPF modulates CS formation in breast cancer cells. Additionally, we found that CHPF promotes tumor growth and metastasis accompanied by an increase in G-CSF levels and the number of myeloid-derived suppressor cells in tumor tissue. We revealed that tumor cell-derived G-CSF is co-localised with CS on the cell surface. Interestingly, our study is the first to identify that syndecan-4 (SDC4) is modified by CHPF and that it is involved in CHPF-mediated phenotypes. Moreover, breast cancer patients with high expression of both SDC4 and CHPF had worse overall survival compared to other subsets, which implied the synergistic effects of these two genes. In summary, our results indicated that the upregulation of CHPF in breast cancer contributes to the malignant behaviour of cancer cells, thereby providing novel insights on the significance of CHPF-modified SDC4 in breast cancer pathogenesis.Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide although its pathogenic mechanism remains to be fully understood. Unlike normal cells, most cancer cells rely on aerobic glycolysis and are more adaptable to the microenvironment of hypoxia and hypoglycemia. Bone Morphogenetic Protein 4 (BMP4) plays important roles in regulating proliferation, differentiation, invasion and migration of HCC cells. https://www.selleckchem.com/products/mitoquinone-mesylate.html We have recently shown that BMP4 plays an important role in regulating glucose metabolism although the effect of BMP4 on glucose metabolic reprogramming of HCC is poorly understood. In this study, we found that BMP4 was highly expressed in HCC tumor tissues, as well as HCC cell lines that were tolerant to hypoxia and hypoglycemia. Mechanistically, we demonstrated that BMP4 protected HCC cells from hypoxia and hypoglycemia by promoting glycolysis since BMP4 up-regulated glucose uptake, the lactic acid production, the ATP level, and the activities of rate limiting enzymes of glycolysis (including HK2, PFK and PK). Furthermore, we demonstrated that BMP4 up-regulated HK2, PFKFB3 and PKM2 through the canonical Smad signal pathway as SMAD5 directly bound to the promoter of PKM. Collectively, our findings shown that BMP4 may play an important role in regulating glycolysis of HCC cells under hypoxia and hypoglycemia condition, indicating that novel therapeutics may be developed to target BMP4-regulated glucose metabolic reprogramming in HCC.Due to the difficulties and long periods of establishment, preclinical animal models of adenoid cystic carcinoma (ACC) are scarce but imperative. The researches involving molecular features and therapeutic targets of ACC require an integrated group of preclinical animal models which can credibly retain the heterogeneity of this tumor. Currently chemotherapies and targeting therapies have modest efficacy in ACC and the overall response rate is rather low. Therefore, novel therapeutic regimen of ACC is urgently needed and remains a major clinical challenge. We transplanted a group of tumor samples from human salivary ACC into immunodeficient mice to establish patient-derived xenografts (PDXs). Patient tumors and their matched PDXs were conducted histological analyses, whole-exome sequencing (WES) and RNA-seq respectively. 13 PDXs were successfully established from 34 ACC, involved in 3 histological types, including cribriform, tubular, and solid. These ACC PDXs generally reflected the histopathological and molecular features of their corresponding original tumors. MYB/MYBL1-NFIB fusion (53.85%) and high-frequency mutation genes, such as KDM6A, KMT2C, KMT2D, NOTCH1, NOTCH2, SMARCA4 and PIK3CA were mainly conserved in PDXs. Guided by the genetic alterations, the efficiencies of retinoic acid (RA) and a PI3K inhibitor were evaluated in ACC PDX models harboring both MYB fusion and PIK3CA amplification/mutation. Combination treatment of the PI3K inhibitor and RA demonstrated remarkable inhibition of tumors in PDXs harboring both PIK3CA mutation/amplification and MYB-NFIB fusion gene in vivo and in vitro. In this study, we displayed the morphologically and genetic featured PDXs which recapitulated the heterogeneity of original ACC tumors, indicating that the models could be used as a platform for drug screening for therapy response. The feasibility of combination treatment approaches for dual targets were confirmed, providing new regimens for personalized therapies in ACC.Sex-determining region Y (SRY)-related high mobility group (HMG) box (SOX) proteins are pivotal transcriptional factors that play essential roles in embryonic development, cell fate decisions and cancer development. The molecular mechanism of SOX13, a member of the SOX family, in hepatocellular carcinoma (HCC) remains largely unknown. In the current study, we found that HCC cells were able to form spheroids in serum-free suspension culture and that SOX13 expression was upregulated in spheroids enriched for cancer stem cells (CSCs). Inhibition of SOX13 in HCC-LM3 and MHCC-97H cells decreased the expression of stemness-related genes; attenuated spheroid formation, anchor-dependent and anchor-independent cell proliferation and tumorigenicity; and enhanced sensitivity to drug treatment. Furthermore, based on analysis of TCGA dataset, the results indicated that SOX13 expression was obviously upregulated and closely associated with poor prognosis in HCC patients. Moreover, SOX13 was correlated with TAZ and CD24 expression.