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1.
Cancer-associated fibroblasts (CAFs) are one of the most abundant and critical components of the tumor stroma. CAFs can impact many important steps of cancerogenesis and may also influence treatment resistance. Some of these effects need the direct contact of CAFs and cancer cells, while some involve paracrine signals. In this study, we investigated the ability of head and neck squamous cell carcinomas (HNSCC) patient-derived CAFs to promote or inhibit the colony-forming ability of HNSCC cells. The effect of cisplatin on this promoting or inhibiting influence was also studied. The subsequent analysis focused on changes in the expression of genes associated with cancer progression. We found that cisplatin response in model HNSCC cancer cells was modified by coculture with CAFs, was CAF-specific, and different patient-derived CAFs had a different “sensitizing ratio”. Increased expression of VEGFA, PGE2S, COX2, EGFR, and NANOG in cancer cells was characteristic for the increase of resistance. On the other hand, CCL2 expression was associated with sensitizing effect. Significantly higher amounts of cisplatin were found in CAFs derived from patients who subsequently experienced a recurrence. In conclusion, our results showed that CAFs could promote and/or inhibit colony-forming capability and cisplatin resistance in HNSCC cells via paracrine effects and subsequent changes in gene expression of cancer-associated genes in cancer cells.  相似文献   
2.
An improved glucose-chelator-albumin bioconjugate (GluCAB) derivative, GluCAB-2Mal, has been synthesized and studied for in vivo 64Cu-PET/CT imaging in breast cancer mice models together with its first-generation analogue GluCAB-1Mal. The radioligand works on the principle of tumor targeting through the enhanced permeability and retention (EPR) effect with a supportive role played by glucose metabolism. [64Cu]Cu-GluCAB-2Mal (99 % RCP) exhibited high serum stability with immediate binding to serum proteins. In vivo experiments for comparison between tumor targeting of [64Cu]Cu-GluCAB-2Mal and previous-generation [64Cu]Cu-GluCAB-1Mal encompassed microPET/CT imaging and biodistribution analysis in an allograft E0771 breast cancer mouse model. Tumor uptake of [64Cu]Cu-GluCAB-2Mal was clearly evident with twice as much accumulation as compared to its predecessor and a tumor/muscle ratio of up to 5 after 24 h. Further comparison indicated a decrease in liver accumulation for [64Cu]Cu-Glu-CAB-2Mal.  相似文献   
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4.
Relatively recently, we advanced a route to create, in a controlled fashion, combined horizontal and vertical stratified structures by simple and energy-efficient processing operations employing static mixing elements. While in state-of-the-art static mixing the focus is on layer multiplication, here the aim is to create hierarchical fractal structures. Therefore, the main question addressed in this article is how structures, rather than layers, can be multiplied. The key aspect is the addition of layers on the sides or in the midplane of the flow during the process; every addition step increases the hierarchy by one level. This article derives the general formalism for forming fractal structures with controlled hierarchy, and we develop the language required to design and construct the dies. The main part of the article addresses this main topic and is based on the splitting serpentine static mixer geometry that can be easily made on the parting surfaces of a mold on both the micro- and the macroscale. The second part of the article addresses the strategy to minimize the number of mirroring steps, eventually avoiding mirroring completely, and is based on the rotation-free multiflux static mixer geometry. With the design language derived, complex hierarchical fractal structures can be generated simply by changing the number and sequence of operators within extrusion dies or molds, providing a one-step solution to produce material structures for potential use in diverse applications ranging from advanced mechanical systems to photovoltaic devices, where controlled assembly of dissimilar materials, and the realization of huge interfaces and genuine cocontinuity throughout the cross section, is critical.  相似文献   
5.
Journal of Chemical Ecology - There is increasing evidence that microorganisms, particularly fungi and bacteria, emit volatile compounds that mediate the foraging behaviour of insects and therefore...  相似文献   
6.
Liquid-phase adsorption has hardly been established in micro-flow, although this constitutes an industrially vital method for product separation. A micro-flow UV-photo isomerization process converts cis-cyclooctene partly into trans-cyclooctene, leaving an isomeric mixture. Trans-cyclooctene adsorption and thus separation was achieved in a fixed-bed micro-flow reactor, packed with AgNO3/SiO2 powder, while the cis-isomer stays in the flow. The closed-loop recycling-flow has been presented as systemic approach to enrich the trans-cyclooctene from its cis-isomer. In-flow adsorption in recycling-mode has hardly been reported so that a full theoretical study has been conducted. This insight is used to evaluate three process design options to reach an optimum yield of trans-cyclooctene. These differ firstly in the variation of the individual residence times in the reactor and separator, the additional process option of refreshing the adsorption column under use, and the periodicity of the recycle flow.  相似文献   
7.
Fluoro-substituted and heteroaromatic compounds are valuable intermediates for a variety of applications in pharma- and agrochemistry and synthetic chemistry. This study investigates the chemoenzymatic preparation of chiral alcohols bearing a heteroaromatic ring with an increasing degree of fluorination in α-position. Starting from readily available picoline derivatives prochiral α-halogenated acyl moieties were introduced with excellent selectivity and 64–95 % yield. The formed carbonyl group was subsequently reduced to the corresponding alcohols using the alcohol dehydrogenase from Lactobacillus kefir, yielding an enantiomeric excess of 95–>99 % and up to 98 % yield.  相似文献   
8.
The lysosomal storage disease Niemann–Pick type C (NPC) is caused by impaired cholesterol efflux from lysosomes, which is accompanied by secondary lysosomal accumulation of sphingomyelin and glucosylceramide (GlcCer). Similar to Gaucher disease (GD), patients deficient in glucocerebrosidase (GCase) degrading GlcCer, NPC patients show an elevated glucosylsphingosine and glucosylated cholesterol. In livers of mice lacking the lysosomal cholesterol efflux transporter NPC1, we investigated the expression of established biomarkers of lipid-laden macrophages of GD patients, their GCase status, and content on the cytosol facing glucosylceramidase GBA2 and lysosomal integral membrane protein type B (LIMP2), a transporter of newly formed GCase to lysosomes. Livers of 80-week-old Npc1−/− mice showed a partially reduced GCase protein and enzymatic activity. In contrast, GBA2 levels tended to be reciprocally increased with the GCase deficiency. In Npc1−/− liver, increased expression of lysosomal enzymes (cathepsin D, acid ceramidase) was observed as well as increased markers of lipid-stressed macrophages (GPNMB and galectin-3). Immunohistochemistry showed that the latter markers are expressed by lipid laden Kupffer cells. Earlier reported increase of LIMP2 in Npc1−/− liver was confirmed. Unexpectedly, immunohistochemistry showed that LIMP2 is particularly overexpressed in the hepatocytes of the Npc1−/− liver. LIMP2 in these hepatocytes seems not to only localize to (endo)lysosomes. The recent recognition that LIMP2 harbors a cholesterol channel prompts the speculation that LIMP2 in Npc1−/− hepatocytes might mediate export of cholesterol into the bile and thus protects the hepatocytes.  相似文献   
9.
Polyoxometalates (POMs), molecular metal oxide anions, are inorganic clusters with promising antiviral activity. Herein we report increased anti-HIV-1 activity of a POM when electrostatically combined with organic counter-cations. To this end, Keggin-type cerium tungstate POMs have been combined with organic methyl-caffeinium (Caf) cations, and their cytotoxicity, antiviral activity and mode of action have been studied. The novel compound, Caf4K[β2-CeSiW11O39]×H2O, exhibits sub-nanomolar antiviral activity and inhibits HIV-1 infectivity by acting on an early step of the viral infection cycle. This work demonstrates that combination of POM anions and organic bioactive cations can be a powerful new strategy to increase antiviral activity of these inorganic compounds.  相似文献   
10.
Freezing methods have evolved over the last 30 years. This review states the effect of various freezing methods on the quality of fish and seafood. Freezing temperatures, freezing, and frozen storage temperatures were also analyzed and reviewed. The changes in the ice crystal, protein, and lipid affect the fish quality and nutritional value during freezing and frozen storage. Freezing methods when combined with various additives or preprocessing approaches help improve the efficacy of freezing and frozen storage. Several experimental or emerging methods also have positive effects on the products' quality. According to the metadata reanalysis of quality markers, freshly frozen fish using different freezing methods may vary much in terms of ice diameter, but not others. High pressure freezing or immersion freezing-derived fish retains the best quality through frozen storage. More data are required on freezing methods (electrical-assisted freezing, microwave-assisted freezing, magnetic-assisted freezing, radiofrequency-assisted freezing, and the commercial's application and investment should be considered in the future. This review sheds light on finding a balanced initial shear force during freezing and the use of certain additives to control freezing-related damages. Focusing on ice diameter alone may be futile (e.g., liquid N2 freezing). Future optimization of technologies should be in a way that several processes along the farm to fork such as freezing, frozen storage, thawing, thermal processing of fish, and even refabrication of food should mutually complement each other's needs to deliver safe and high-quality fish to the consumer's plate, even after a prolonged shelf-life.  相似文献   
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