Large scale, high concurrency, and vast amount of data are important trends for the new generation of website. Node.js becomes popular and successful to build data-intensive web applications. To study and compare the performance of Node.js, Python-Web and PHP, we used benchmark tests and scenario tests. The experimental results yield some valuable performance data, showing that PHP and Python-Web handle much less requests than that of Node.js in a certain time. In conclusion, our results clearly demonstrate that Node.js is quite lightweight and efficient, which is an idea fit for I/O intensive websites among the three, while PHP is only suitable for small and middle scale applications, and Python-Web is developer friendly and good for large web architectures . To the best of our knowledge, this is the first paper to evaluate these Web programming technologies with both objective systematic tests (benchmark) and realistic user behavior tests (scenario), especially taking Node.js as the main topic to discuss.
Combination therapy has been proved to be an effective strategy to inhibit metastasis, however, its efficacy was always compromised by the poor delivery efficiency of drugs. In this study, multi...
Cancer-associated fibroblasts (CAFs)
were believed to establish
a tight physical barrier and a dense scaffold for tumor cells to make
them maintain immunosuppression and drug resistance, strongly hindering
nanoparticles to penetrate into the core of tumor tissues and limiting
the performance of tumor cell-targeted nanoparticles. Here, we fabricated
the substrate Z-Gly-Pro of fibroblast activation protein α (FAPα)
and folic acid-codecorated pH-responsive polymeric micelles (dual
ligand-modified PEOz-PLA polymeric micelles, DL-PP-PMs) that possessed
nanodrill and tumor cell-targeted functions based on Z-Gly-pro-conjugated
poly(2-ethyl-2-oxazoline)-poly(D,l-lactide) (ZGP-PEOz-PLA),
folic acid (FA)-conjugated PEOz-PLA (FA-PEOz-PLA), and PEOz-PLA for
cancer therapy. The micelles with about 40 nm particle size and a
narrow distribution exhibited favorable pH-activated endo/lysosome
escape induced by their pH responsibility. In addition, the enhancement
of in vitro cellular uptake and cytotoxicity to folate receptors or
FAPα-positive cells for doxorubicin (DOX)/DL-PP-PMs compared
with DOX/PP-PMs evidenced the dual target ability of DOX/DL-PP-PMs,
which was further supported by in vivo biodistribution results. As
expected, in the human oral epidermal carcinoma (KB) cells xenograft
nude mice model, the remarkable enhancement of antitumor efficacy
for DOX/DL-PP-PMs with low toxicity was observed compared with DOX/FA-PP-PMs
and DOX/ZGP-PP-PMs. The possible mechanism was elucidated to be the
dismantling of the stromal barrier by nanodrill-like DOX/DL-PP-PMs
via the deletion of CAFs evidenced by the downregulation of α-SMA
and inhibition of their functions proved by the decrease in the microvascular
density labeled with CD31 and the reduction in the extracellular matrix
detected by the collagen content, thereby promoting tumor penetration
and enhancing their uptake by tumor cells. The present research offered
an alternative approach integrating anticancer and antifibrosis effects
in one delivery system to enhance the delivery efficiency and therapeutic
efficacy of anticancer drugs.
The intestinal epithelium is known
to be a main hindrance to oral
delivery of nanoparticles. Even though surface ligand modification
can enhance cellular uptake of nanoparticles, the “easy entry
and hard across” was frequently observed for many active targeting
nanoparticles. Here, we fabricated polymeric nanoparticles relayed
by bile acid transporters with monomethoxy poly(ethylene glycol)-poly(D,l-lactide) and deoxycholic acid-conjugated poly(2-ethyl-2-oxazoline)-poly(D,l-lactide) based on structural characteristics of intestine
epithelium and the absorption characteristics of endogenous substances.
As anticipated, deoxycholic acid-modified polymeric nanoparticles
featuring good stability in simulated gastrointestinal fluid could
notably promote the internalization of their payload by Caco-2 cells
through mediation of apical sodium-dependent bile acid transporter
(ASBT) and transmembrane transport of the nanoparticles across Caco-2
cell monolayers via relay-guide of ASBT, ileal bile acid-binding protein,
and the heteromeric organic solute transporter (OSTα-OSTβ)
along with multidrug resistance-associated protein 3 (MRP3) evidenced
by competitive inhibition and fluorescence immunoassay, which was
further visually confirmed by the stronger fluorescence from C6-labeled
nanoparticles inside enterocytes and the basal side of the intestinal
epithelium of mice. The transcellular transport of deoxycholic acid-modified
nanoparticles in an intact form was mediated by caveolin/lipid rafts
and clathrin with intracellular trafficking trace of endosome-lysosome-ER-Golgi
apparatus and bile acid transport route. Furthermore, the increased
uptake by HepG2 cells compared with unmodified nanoparticles evidenced
the target ability of deoxycholic acid-modified nanoparticles to the
liver, which was further supported by ex vivo imaging of excised major
organs of mice. Thus, this study provided a feasible and potential
strategy to further enhance transepithelial transport efficiency and
liver-targeted ability of nanoparticles by means of the specific enterohepatic
circulation pathways of bile acid.
Chain disasters often cause greater casualties and economic losses than single disasters. It plays an important role in the prevention and control to draw the susceptibility map and hazard map of geological hazards. To the best of our knowledge, the existing models are not suitable for the study of earthquake–geological disaster chains. Therefore, this study aims to establish a DNN model suitable for the study of earthquake–geological disaster chains. Firstly, nine key factors affecting geological disasters were selected and multi-source data sets were established based on geological disaster points in the study area. Secondly, the DNN model is trained to calculate the susceptibility of landslides and is discussed with the Support Vector Machine (SVM) model, Logistic Regression (LR) model, and Random Forest (RF) model. Finally, verify with the ROC curve. The verification results show that the DNN model has the highest accuracy among the proposed models. It is suitable for drawing geological hazard susceptibility maps and hazard maps. Therefore, it is proved that the model can be applied for the prediction of chain disasters and is a promising tool for geological hazard assessment.
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