Adsorption and Desorption Mechanisms of Methylene Blue Removal with Iron-Oxide Coated Porous Ceramic Filter

Adsorption and desorption mechanisms of methylene blue (MB) removal with iron-oxide coated porous ce-ramics filter (IOCPCF) were investigated in batch and column mode. The results revealed that MB removal mechanisms included physical adsorption and chemical adsorption, of which chemical adsorption by surface ligand complex reaction played a dominant role after infrared spectrum analysis. Recycling agents were se-lected from dilute nitric acid (pH=3), sodium hydroxide solution (pH=12) and distilled water. Among three agents, dilute metric acid (pH=3) was the best recycling agent. Regeneration rate of IOCPCF arrived at 82.56% at batch adsorption and regeneration was finished in 75min at column adsorption. Adsorp-tion-desorption cycles of IOCPCF after batch and column adsorption were four and three times, respectively. Further, compared with fresh IOCPCF, MB removal rate with these desorbed IOCPCF adsorption only slightly decreased, which suggested that IOCPCF should be used repeatedly.

Difluorocarbene-derived rapid late-stage trifluoromethylation of 5-iodotriazoles for the synthesis of^(18)F-labeled radiotracers

Difluorocarbene has emerged as a valuable intermediate to synthesize fluorides.However,difluorocarbene-derived synthesis of^(19)F/^(18)F-trifluoromethyl triazoles has not been explored.Herein,we reported the Cu(I)-promoted difluorocarbene-derived^(19)F/^(18)F-trifluoromethylation of iodotriazoles using KF/K^(18)F as the fluorine source.This approach rapidly generated a wide range of 5-trifluoromethyl-1,2,3-triazoles in good yields showing high functional group compatibility.The reaction was effective for late-stage functionalization of bioactive molecules and^(18)F-trifluoromethylation of iodotriazoles.This work provides a practical synthetic methodology for the development of triazole drugs and^(18)F-radiotracers for positron emission tomography.

Multi-responsive nanotheranostics with enhanced tumor penetration and oxygen self-producing capacities for multimodal synergistic cancer therapy

Incorporation of multiple functions into one nanoplatform can improve cancer diagnostic efficacy and enhance anti-cancer outcomes. Here, we constructed doxorubicin(DOX)-loaded silk fibroinbased nanoparticles(NPs) with surface functionalization by photosensitizer(N770). The obtained nanotheranostics(N770-DOX@NPs) had desirable particle size(157 nm) and negative surface charge(-25 m V). These NPs presented excellent oxygen-generating capacity and responded to a quadruple of stimuli(acidic solution, reactive oxygen species, glutathione, and hyperthermia). Surface functionalization of DOX@NPs with N770 could endow them with active internalization by cancerous cell lines, but not by normal cells. Furthermore, the intracellular NPs were found to be preferentially retained in mitochondria, which were also efficient for near-infrared(NIR) fluorescence imaging, photothermal imaging,and photoacoustic imaging. Meanwhile, DOX could spontaneously accumulate in the nucleus. Importantly, a mouse test group treated with N770-DOX@NPs plus NIR irradiation achieved the best tumorretardation effect among all treatment groups based on tumor-bearing mouse models and a patientderived xenograft model, demonstrating the unprecedented therapeutic effects of trimodal imagingguided mitochondrial phototherapy(photothermal therapy and photodynamic therapy) and chemotherapy.Therefore, the present study brings new insight into the exploitation of an easy-to-use, versatile, and robust nanoplatform for programmable targeting, imaging, and applying synergistic therapy to tumors.

Jumonji domain-containing 6 (JMJD6) identified as a potential therapeutic target in ovarian cancer

Jumonji domain-containing 6(JMJD6)is a candidate gene associated with tumorigenesis,and JMJD6 overexpression predicts poor differentiation and unfavorable survival in some cancers.However,there are no studies reporting the expression of JMJD6 in ovarian cancer,and no JMJD6 inhibitors have been developed and applied to targeted cancer therapy research.In the present study,we found that the high expression of JMJD6 in ovarian cancer was correlated with poor prognosis in ovarian cancer.A potential inhibitor(SKLB325)was designed based on the crystal structure of the jmjC domain of JMJD6.This molecule significantly suppressed proliferation and induced apoptosis in a dose-dependent manner in SKOV3 cell lines as detected by CCK-8 cell proliferation assays and flow cytometry.A Matrigel endothelial tube formation assay showed that SKLB325 inhibited capillary tube organization and migration in HUVECs in vitro.We also observed that JMJD6 colocalized with p53 protein in the nucleus,with mRNA and protein expression of p53 as well as its downstream effectors significantly increasing both in vitro and in intraperitoneal tumor tissues treated with SKLB325.In addition,SKLB325 significantly reduced the intraperitoneal tumor weight and markedly prolonged the survival of tumor-bearing mice.Taken together,our findings suggest that JMJD6 may be a marker of poor prognosis in ovarian cancer and that SKLB325 may be a potential candidate drug for the treatment of ovarian cancer.

Cotransfecting norepinephrine transporter and vesicular monoamine transporter 2 genes for increased retention of metaiodobenzylguanidine labeled with iodine 131 in malignant hepatocarcinoma cells

Norepinephrine transporter （NET） transfection leads to significant uptake of iodine-131-labeled metaiodobenzylguanidine （^131I-MIBG） in non-neuroendocrine tumors. However, the use of ^131I-MIBG is limited by its short retention time in target cells. To prolong the retention of ^131I-MIBG in target cells, we infected hepatocarcinoma （HepG2） cells with Lentivirus-encoding human NET and vesicular monoamine transporter 2 （VMAT2） genes to obtain NET-expressing, NET-VMAT2-coexpressing, and negative-control cell lines. We evaluated the uptake and efflux of 131I-MIBG both in vitro and in vivo in mice bearing transfected tumors. NET- expressing and NET-VMAT2-coexpressing cells respectively showed 2.24 and 2.22 times higher ^131I-MIBG uptake than controls. Two hours after removal of ^131I-MIBG-containing medium, 25.4% efflux was observed in NET- VMAT2-coexpressing cells and 38.6% in NET-expressing cells. In vivo experiments were performed in nude mice bearing transfected tumors; results revealed that NET-VMAT2-coexpressing tumors had longer ^131I-MIBG retention time than NET-expressing tumors. Meanwhile, NET-VMAT2-coexpressing and NET-expressing tumors displayed 0.54% and 0.19%, respectively, of the injected dose per gram of tissue 24 h after ^131I-MIBG administration. Cotransfection of HepG2 cells with NET and VMAT2 resulted in increased ^131I-MIBG uptake and retention. However, the degree of increase was insufficient to be therapeutically effective in target cells.