<p>Supplementary Figure S2. Distribution of carbohydrates, xenobiotics, cofactors and vitamins, and energy in tumor and normal. (A-D): Heatmap of 8 carbohydrates (A), 7 xenobiotics (B), 7 cofactors and vitamins (C), and 7 energy metabolites (D) sorted by sample types and then tissue types. Heat-map colors represent z-score values of raw detection amount. FFPE, formalin-fixed paraffin-embedded; N, normal; T, tumor.</p>
To investigate the optimization of extraction conditions of safflower yellow from Cartbamus tirwtorius by response surface methodology.Experimental factors and levels were selected by one-factor test, and then according to the central composite experimental design principle, response surface'-methodology with three factors and three levels was used to establish a mathematical model to obtain the optimal extraction conditions with hydroxysafflower yellow A being the target and its extraction yield as response value.The optimal extraction conditions of safflower yellow were as follows: extraction temperature was 55 t, ratio of water to raw material was 16:1 and extraction time was 39 mm for three times.Under these conditions, the extraction yield of safflower yellow is 1.798%, and the relative error between the predicted value with actual value is 2.758%. The optimized method can provide reference for the efficient extraction of safflower yellow from Carthomos tinctorius
Several crucial stromal cell populations regulate hematopoiesis and malignant diseases in bone marrow niches. Precise regulation of these cell types can remodel niches and develop new therapeutics. Multiple nanocarriers have been developed to transport drugs into the bone marrow selectively. However, the delivery efficiency of these nanotherapeutics into crucial niche cells is still unknown, and there is no method available for predicting delivery efficiency in these cell types. Here, we constructed a three-dimensional bone marrow niche composed of three crucial cell populations: endothelial cells (ECs), mesenchymal stromal cells (MSCs), and osteoblasts (OBs). Mimetic niches were used to detect the cellular uptake of three typical drug nanocarriers into ECs/MSCs/OBs in vitro. Less than 5% of nanocarriers were taken up by three stromal cell types, and most of them were located in the extracellular matrix. Delivery efficiency in sinusoidal ECs, arteriole ECs, MSCs, and OBs in vivo was analyzed. The correlation analysis showed that the cellular uptake of three nanocarriers in crucial cell types in vitro is positively linear correlated with its delivery efficiency in vivo. The delivery efficiency into MSCs was remarkably higher than that into ECs and OBs, no matter what kind of nanocarrier. The overall efficiency into sinusoidal ECs was greatly lower than that into arteriole ECs. All nanocarriers were hard to be delivered into OBs (<1%). Our findings revealed that cell tropisms of nanocarriers with different compositions and ligand attachments in vivo could be predicted via detecting their cellular uptake in bone marrow niches in vitro. This study provided the methodology for niche-directed nanotherapeutics development.
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