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Cisplatin has been reported to promote the expression of programmed cell death ligand-1 (PD-L1) in some cancer cells. However, the underlying mechanism through which PD-L1 is transcriptionally regulated by cisplatin in hepatocellular carcinoma (HCC) cells remains largely unknown. In the present study, we found that the expression of hepatocyte growth factor (HGF), p-Akt, p-ERK, and PD-L1 was increased in cisplatin-treated SNU-368 and SNU-739 cells. HGF stimulation also increased PD-L1 expression in these cells. Moreover, Inhibition of HGF/c-MET, PI3K/Akt, and MEK/ERK signaling pathways can dramatically block cisplatin or HGF-induced PD-L1 expression in SNU-368 and SNU-739 cells. In vivo, combination PHA665752 with cisplatin significantly reduced tumor weight with increased infiltration of CD8+ T cells in the tumor. Taken together, our study suggested that HGF/c-Met axis-induced the activation of PI3K/Akt and MEK/ERK pathways contributes to cisplatin-mediated PD-L1 expression. These findings may provide an alternative avenue for the treatment of HCC.

3-Hydroxypropionic acid (3-HP) and 1,3-propanediol (1,3-PDO) are value-added chemicals with versatile applications in the chemical, pharmaceutical, and food industries. Nevertheless, sustainable production of 3-HP and 1,3-PDO is often limited by the lack of efficient strains and suitable fermentation configurations. Herein, attempts have been made to improve the co-production of both metabolites through metabolic engineering of Escherichia coli and process optimization. First, the 3-HP and 1,3-PDO co-biosynthetic pathways were recruited and optimized in E. coli, followed by coupling the pathways to the transhydrogenase-mediated cofactor regeneration systems that increased cofactor availability and product synthesis. Next, pathway rebalancing and block of by-product formation significantly improved 3-HP and 1,3-PDO net titer. Subsequently, glycerol flux toward 3-HP and 1,3-PDO synthesis was maximized by removing metabolic repression and fine-tuning the glycerol oxidation pathway. Lastly, the combined fermentation process optimization and two-stage pH-controlled fed-batch fermentation co-produced 140.50 g/L 3-HP and 1,3-PDO, with 0.85 mol/mol net yield.

Multicistronic vectors can increase transgene expression and decrease the imbalance of gene expression in the Chinese hamster ovary (CHO) cell expression system. Small, self-cleaving 2A peptides have a high cleavage efficiency and are essential for constructing high-expression multicistronic vectors. In this study, we investigated the effects of two different 2A peptides on transgene expression in CHO cells via their mediating action on tricistronic vectors. The enhanced green fluorescent protein (eGFP) and red fluorescent protein (RFP) genes were linked by the porcine teschovirus-1 (P2A) and Thosea asigna virus (T2A) peptides in a multicistronic vector. We transfected CHO cells with these vectors and screened for the presence of blasticidin-resistant colonies. Flow cytometry and real-time quantitative PCR (qPCR) were used to detect the expression levels of eGFP and RFP and the copy numbers of stably transfected cells. The results showed that P2A could enhance eGFP and RFP expression by 1.48- and 1.47-fold, respectively, compared to T2A. The expression levels of the genes were not proportional to their copy numbers. In conclusion, we found that P2A can effectively drive transgene expression in CHO cells and a potent 2A peptide can be used for recombinant protein production in the CHO cell system.

Trace antiviral drug contamination in aquatic ecosystems is becoming a significant environmental concern that requires an urgent efficient determination method. Here we developed sensitive and robust multi-residue determination methods to simultaneously extract and analyze 9 commonly used antiviral drugs (abacavir, zidovudine, efavirenz, nevirapine, ritonavir, lopinavir, lamivudine, telbivudine and entecavir) in surface water, wastewater, sediment, and sludge. Water samples were extracted with solid-phase extraction (SPE) technique using tandem hydrophilic–lipophilic balance and graphitized carbon black cartridges, while sediment and sludge samples were extracted using QuEChERS (quick, easy, cheap, effective, rugged, and safe) method. The extraction conditions of SPE (pH and cartridge type) and QuEChERS (acetic acid content, salts reagent, and purification sorbent) methods were carefully optimized. We observed that under optimum conditions, the method quantification limits of the 9 antiviral drugs in water and solid samples ranged from 0.05 to 19.23 ng L−1 and from 0.02 to 7.38 ng g−1, respectively. For environmental samples spiking 3 different concentrations, the recovery values for the most targeted antiviral drugs ranged from 70 to 130%, except for efavirenz. All targeted antiviral drugs were detected in wastewater samples except for entecavir. We also found abacavir, efavirenz, ritonavir, lopinavir, and telbivudine in sediment and sludge samples. Notably, telbivudine was identified in all environmental matrices, with a high concentration of 127 ng L−1 and 222 ng g−1 in water and sediment samples, respectively.

The long term evolution (LTE) based smart grid communication network is a promising candidate solution for the future power grid. In this paper, we discuss three channel estimation schemes for the LTE-based smart grids, including least square (LS), minimum mean square error (MMSE), and discrete Fourier transform (DFT) based channel estimators. In the simulations, we compare these three estimators, the results show that the DFT-based channel estimator can achieve the best tradeoff between the performance and the implementation complexity.

The chemical constituents of 95% EtOH extract of yacon leaves were separated to yield two new sesquiterpene lactones, together with three known compounds. The two new compounds were characterized to be 8β-angeloyloxy-13-methoxyl-11, 13-dihydromelampolid-14-oic acid methyl ester (1) and 8β-(3-methylbut-2-enoyl) oxy-13-methoxyl-11, 13-dihydromelampolid-14-oic acid methyl ester (2) on the basis of NMR spectra, HR-MS and other spectroscopic methods. The cytotoxicity of compounds 1–5 were evaluated on human hepatoma cell Bel-7402 and all the compounds showed moderate cytotoxicity.

A novel TiO 2 /diatomite composite (TD) was prepared and then characterized by scanning electron microscope (SEM) and Fourier Transform Infrared (FTIR). The results of SEM showed that after modification, the porous surface of diatomite was covered with TiO 2 . Both diatomite and TD had clear disc-shaped structures with average grain diameters of around 25 μm. Then TD and pure TiO 2 were applied in the purification of phosvitin phosphopeptides (PPPs) from the digest of egg yolk protein, and a comparative study of adsorption properties of PPPs on TD and TiO 2 was performed. In the study of adsorption kinetics, the adsorption equilibrium of PPPs on TD and TiO 2 fitted well with the Langmuir model, and the time needed to reach adsorption equilibrium were both around 10 min. The maximum dynamic adsorption capacity of TD (8.15 mg/g) was higher than that of TiO 2 (4.96 mg/g). The results of repeated use showed that TD and TiO 2 were very stable after being subjected to ten repeated adsorption–elution cycles, and TD could easily be separated from aqueous solution by filtration. On the other hand, the present synthetic technology of TD was very simple, cost-effective, organic solvent-free and available for large-scale preparation. Thus, this separation method not only brings great advantages in the purification of PPPs from egg yolk protein but also provides a promising purification material for the enrichment of phosphopeptides in proteomic researches.

The computation and evaluation of color difference for images is a hot topic. In order to explore the calculation method of evaluating color difference sensation for similar images, 68 pairs of test images were made, which were made from ISO SCID 400 color images by altering their lightness and chroma respectively to cause different color difference scales, and tested by psychophysical experiment. The experiment results showed that the calculated color difference by each formula had a relation to the color difference sensation and the color difference formulae were optimized based on the experimental data.