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Aflatoxin B1 Discovery By using a Highly-Sensitive Molecularly-Imprinted Electrochemical Sensor Based on a great Electropolymerized Material Natural Framework.
© 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.Supported Catalytically Active Liquid Metal Solutions (SCALMS) were recently described as a new class of heterogeneous catalysts, where the catalytic transformation takes place at the highly dynamic interface of a liquid alloy. Their application in alkane dehydrogenation has been claimed to be superior to classical heterogeneous catalysts, because the single atom nature of Rh dissolved in liquid Ga hinders the formation of significant amounts of coke, e. g. by oligomerisation of carbon fragments and excessive dehydrogenation. In the present study, we investigate the coking behaviour of Ga-Rh SCALMS during dehydrogenation of propane in detail by means of high-resolution thermogravimetry. We report that the application of Ga-Rh SCALMS indeed limits the formation of coke when compared to the Ga-free Rh catalyst, in particular when relating coke formation to the catalytic performance. Furthermore, the formed coke has been shown to be highly reactive during temperature programmed oxidation in 21 % O2/He with onset temperatures of approx. 150 °C enabling a regeneration of the Ga-Rh SCALMS system under mild conditions. The activation energy of the oxidation lies in the lower range of values reported for spent cracking catalysts. Monitoring the formation of coke and performance of SCALMS in situ via thermogravimetry coupled with mass spectrometry revealed the continuous formation of coke, which becomes the only process affecting the net weight change after a certain time on stream. © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.Rationale Glioma is the most common primary malignant brain tumor in adults. Chemoresistance of temozolomide (TMZ), the first-line chemotherapeutic agent, is a major issue in the management of patients with glioma. Alterations of alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene constitute one of the most prevalent genetic abnormalities in gliomas. Therefore, elucidation of the role of ATRX contributing to TMZ resistance in glioma is urgently needed. Methods We performed the bioinformatics analysis of gene expression, and DNA methylation profiling, as well as RNA and ChIP-seq data sets. CRISPR-Cas9 gene editing system was used to achieve the ATRX knockout in TMZ resistant cells. In vitro and in vivo experiments were carried out to investigate the role of ATRX contributing to TMZ resistance in glioma. Results We found that ATRX expression was upregulated via DNA demethylation mediated by STAT5b/TET2 complex and strengthened DNA damage repair by stabilizing PARP1 protein in TMZ resistant cells. ATRX elicited PARP1 stabilization by the down-regulating of FADD expression via the H3K27me3 enrichment, which was dependent on ATRX/EZH2 complex in TMZ resistant cells. Magnetic resonance imaging (MRI) revealed that the PARP inhibitor together with TMZ inhibited glioma growth in ATRX wild type TMZ resistant intracranial xenograft models. Conclusions The present study further illustrated the novel mechanism of the ATRX/PARP1 axis contributing to TMZ resistance. Our results provided substantial new evidence that PARP inhibitor might be a potential adjuvant agent in overcoming ATRX mediated TMZ resistance in glioma. BAY 1217389 cell line © The author(s).Lymph node (LN) dissection followed by histological analysis is the current standard for diagnosis of LN metastasis but the method suffers from patient morbidity and low sensitivity of detection. Ultra-pH sensitive (UPS) nanoparticles show remarkable accuracy in the delineation of primary tumor margins for precision cancer surgery. Herein we investigate the effectiveness of UPS nanoparticles to detect cancer-involved LNs. Methods We synthesized a series of indocyanine green (ICG) conjugated UPS nanoparticles with distinct pKa (UPS5.3, UPS6.1, and UPS6.9). Systemically administered UPS-ICG nanoparticles in the 4T1.2-BALB/cj mouse model were imaged with real-time, near-infrared fluorescence (NIRF) to guide removal of LNs. Ex vivo imaging of gross tissue enabled quantification of fluorescence intensity. Histological analysis was used as the gold standard diagnostic test. Results Macrophage uptake of UPS nanoparticles elevates the background signal in benign LNs. However, cancer foci within LNs show distinctive clustering of UPS-ICG fluorescence. UPS5.3 achieves accurate detection of metastatic LNs as shown by a receiver operating characteristic (ROC) area under the curve (AUC) of 0.96 ± 0.03. UPS6.1 and UPS6.9 offer decreased discriminatory power at ROC AUC of 0.73 ± 0.1 and 0.88 ± 0.07, respectively. Conclusions All UPS compositions show cancer-specific discrimination of metastatic LNs over benign LNs with the best outcomes from UPS5.3. Detection of micro-metastatic LNs (cancer foci less then 2 mm) remains a challenge. This study provides information on the detection of LN status for image-guided resection of metastatic LNs. © The author(s).Because of the complexity of cancer, a combination of chemotherapy and gene therapy is an emerging treatment modality. To realize the full potential of this strategy, a smart, highly biocompatible nanosystem that enables the precise co-delivery of small-molecule anticancer drugs and small interfering RNA (siRNA) is urgently needed. This study aimed to improve the therapeutic effect against cervical cancer by using cancer cell membrane-camouflaged nanoparticles for simultaneous delivery of paclitaxel (PTX) and siRNA targeting E7. Methods By camouflaging HeLa cell membranes onto siRNA/PTX co-loaded (lactic-co-glycolic acid) (PLGA) nanoparticles, a biomimetic dual-drug delivery system (Si/PNPs@HeLa) was developed to simultaneously deliver PTX and siRNA targeting E7. After evaluating the physicochemical characteristics as well as their cell uptake and biodistribution behavior, studies on the RNA interference efficiency and antitumor ability of Si/PNPs@HeLa in vitro and in vivo were further carried out. Results The Si/PNPs@HeLa was capable of delivering PTX and siRNA simultaneously to HeLa cells both in vitro and in vivo. Moreover, benefiting from the recognition and adhesion molecules on the surface of HeLa cells, Si/PNPs@HeLa exhibited an improved immune escape ability and an increased tumor region accumulation (3-fold higher than bare nanoparticles). As a result, an excellent synergistic anti-tumor effect was observed in the HeLa tumor-bearing mice, with tumor volume inhibiting rates of 83.6% and no side effects in major organs. The mechanistic studies confirmed that E7 knockdown sensitized HeLa cells to PTX chemotherapy, mainly by inhibiting PTX-induced AKT pathway activation. Conclusion Si/PNPs@HeLa, by integrating immune escape and tumor-homing ability, can serve as an efficient dual-drug delivery system to achieve precise treatment of cervical cancer through chemo-gene combined therapy. © The author(s).
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