The generation of high-energy dual-wavelength domain wall pulse with a low repetition rate is demonstrated in a highly nonlinear fiber (HNLF)-based fiber ring laser. By introducing the intracavity birefringence-induced spectral filtering effect, the dual-wavelength lasing operation can be achieved. In order to enhance the cross coupling effect between the two lasing beams for domain wall pulse formation, a 215-m HNLF is incorporated into the laser cavity. Experimentally, it is found that the dual-wavelength domain wall pulse with a repetition rate of 77.67 kHz could be efficiently obtained through simply rotating the polarization controller (PC). At a maximum pump power of 322 mW, the 655-nJ single pulse energy in cavity is obtained. The proposed configuration provides a simpler and more efficient way to generate high energy pulse with a low repetition rate.
Background: Chemotherapy for non-small-cell lung cancer (NSCLC) still leads to unsatisfactory clinical prognosis because of poor active targeting and tumor metastasis. Purpose: The objective of this study was to construct a kind of PFV peptide modified targeted daunorubicin and dioscin codelivery liposomes, which could enhance tumor targeting and inhibit tumor cell metastasis. Methods and results: Targeted daunorubicin and dioscin codelivery liposomes were prepared by film dispersion and the ammonium sulfate gradient method. With the ideal physicochemical properties, targeted daunorubicin and dioscin codelivery liposomes exhibited enhanced cellular uptake and showed strong cytotoxicity to tumor cells. The encapsulation of dioscin increased the inhibitory effects of daunorubicin on A549 cells, vasculogenic mimicry (VM) channels and tumor metastasis. The enhanced antimetastatic mechanism of the targeted liposomes was attributed to the downregulation of matrix metalloproteinase-2 (MMP-2), vascular endothelial cadherin (VE-Cad), transforming growth factor-β1 (TGF-β1) and hypoxia inducible factor-1α (HIF-1α). Meanwhile, the targeted daunorubicin and dioscin codelivery liposomes exhibited significant antitumor effects in tumor-bearing mice. H&E staining, immunohistochemistry with Ki-67 and TUNEL assay also showed the promoted antitumor activity of the targeted liposomes. Conclusion: Targeted daunorubicin and dioscin codelivery liposomes may provide an effective strategy for the treatment of NSCLC.
Hydrogen sulfide (H2S) is a hazardous and corrosive byproduct generated during heavy oil recovery, particularly during hot water flooding. Previous studies on factors influencing H2S generation during hot water flooding have been mainly focused on high temperatures (>250 °C), which may not accurately represent reservoir conditions. Moreover, the concentration of H2S produced by hot water flooding at low temperatures exceeds the standard. In this study, experiments were conducted on hot water flooding at low temperatures (110–150 °C). The mechanism of reactants and reaction conditions on H2S generation was investigated. The results showed that thermochemical sulfate reduction (TSR) was the primary reaction type responsible for H2S generation, while aquathermolysis and pyrite oxidation reactions weakly or did not occur. The reactivity of TSR was directly proportional to reaction temperature and time, while inversely proportional to reaction pH. The formation of oxidants ([MgSO4]CIP and HSO4–) was also found to be crucial for TSR initiation. Unstable organic sulfur-containing compounds were oxidized to produce CO2, H2S, SO3, and solid bitumen, which further sustained the autocatalytic reaction. Low temperature TSR was found to consume the saturated fraction in heavy oil and convert inorganic sulfur to organic sulfide. The increase in pH inhibited the conversion of inorganic sulfur to organic sulfur, resulting in a higher percentage of the saturated fraction. This study provides new insights into the low temperature TSR reaction mechanism and the origin of H2S, which can aid in better understanding and mitigation of the associated risks during heavy oil recovery.
Hepatocellular carcinoma (HCC), the most common malignancy of the liver, exhibits high recurrence and metastasis. Structural modifications of natural products are crucial resources of antitumor drugs. This study aimed to synthesize C-14 derivatives of tetrandrine and evaluate their effects on HCC. Forty C-14 sulfonate tetrandrine derivatives were synthesized and their in vitro antiproliferative was evaluated against four hepatoma (HepG-2, SMMC-7721, QGY-7701, and SK-Hep-1) cell lines. For all tested cells, most of the modified compounds were more active than the lead compound, tetrandrine. In particular, 14-O-(5-chlorothiophene-2-sulfonyl)-tetrandrine (33) exhibited the strongest antiproliferative effect, with half-maximal inhibitory concentration values of 1.65, 2.89, 1.77, and 2.41 μM for the four hepatoma cell lines, respectively. Moreover, 33 was found to induce apoptosis via a mitochondria-mediated intrinsic pathway via flow cytometry and western blotting analysis. In addition, colony formation, wound healing, and transwell assays demonstrated that 33 significantly inhibited HepG-2 and SMMC-7721 cell proliferation, migration, and invasion, indicating that it might potentially be a candidate for an anti-HCC therapy in the future.
Protein disulfide isomerase (PDI) is a vital oxidoreductase. Extracellular PDI promotes thrombus formation but does not affect physiological blood hemostasis. Inhibition of extracellular PDI has been demonstrated as a promising strategy for antithrombotic treatment. Herein, we focused on the major substrate binding site, a unique pocket in the PDI b' domain, and identified four natural products binding to PDI by combining virtual screening with tryptophan fluorescence-based assays against a customized natural product library. These hits all directly bound to the PDI-b' domain and inhibited the reductase activity of PDI. Among them, galangin showed the most prominent potency (5.9 μM) against PDI and as a broad-spectrum inhibitor for vascular thiol isomerases. In vivo studies manifested that galangin delayed the time of blood vessel occlusion in an electricity-induced mouse thrombosis model. Molecular docking and dynamics simulation further revealed that the hydroxyl-substituted benzopyrone moiety of galangin deeply inserted into the interface between the PDI-b' substrate-binding pocket and the a' domain. Together, these findings provide a potential antithrombotic drug candidate and demonstrate that the PDI b' domain is a critical domain for inhibitor development. Besides, we also report an innovative high-throughput screening method for the rapid discovery of PDI b' targeted inhibitors.
Abstract Recent RNA sequencing (RNASeq) studies from Bailey et al., 2016, Moffitt et al., 2015 and Collisson et al., 2011 reported that mRNA expression from bulk tumor defines molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) that are highly correlated with patient survival. These studies independently identified Keratin 17 (K17) mRNA overexpression as one of over 20 upregulated transcripts that define the RNA signature of the most lethal PDACs. Studies in our lab determined that neither K17 gene missense mutations nor copy-number alterations explain the upregulation of K17 mRNA expression by malignant cells. In addition, we found that K17 expression, measured at the protein level by immunohistochemistry or at the level of mRNA by RNASeq, is sufficient to stratify patients by short- vs long- term survival at baseline after resection. These retrospective survival analyses were performed in four independent patient cohorts using a uniform threshold to define low- vs high- K17 patients (total n= 558). High-K17 cases were twice as likely to die from this disease compared to stage-matched low-K17 cases (P values < 0.05). Furthermore, we determined that K17 expression is associated with outcome after Gemcitabine treatment using the Bailey et al., 2016 patient cohort (n= 94). This is the first study to show that the expression of a single gene, K17, can accurately subtype PDAC at initial diagnosis. In conclusion, K17 was identified as a robust and independent, clinically relevant, prognostic and predictive biomarker to stratify clinical outcome at the time of initial diagnosis and to potentially inform clinical decisions regarding chemotherapeutic intervention. Citation Format: Luisa F. Escobar-Hoyos, Cindy Leiton, Elizabeth Vanner, Lucia Roa-Pena, Jinyu Li, Scott Powers, Ali Akalin, Jela Bandovic, Peter Bailey, David Chang, Richard Moffitt, Jen Jen Yeh, Andrew Biankin, Kenneth Shroyer. Keratin 17 identifies prognostic subtypes of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1762. doi:10.1158/1538-7445.AM2017-1762
Indium cluster in InGaN epilayers prepared with different H2-treating times was investigated. In cluster with the form of lower atom bonds was evidenced by Raman spectra. Carrier lifetime was found to increase with the H2-treating time.
Two-dimensional nanoporous membranes are promising materials for seawater desalination. However, the effect of nanopore charge properties on desalination performance, especially on water permeability, has not yet been systematically investigated. In this work, molecular dynamics simulations were carried out to elucidate the impact of nanopore charge modification (variated from 0 to 1.0e) on water permeability and ions conduction. The highest water permeability was observed when the modification was approximately 0.25e. The nanopore charge conditions significantly impacted water dynamic behaviors, leading to the transition of water transport processes from continuum state to non-continuum state as the increase of nanopore charge. In addition, we found that the positively charged nanopores not only effectively impede cation permeation, but also strongly impact the diffusion behavior of anions. This work unveils in-depth insights into the mechanism of saline water transport through the charge-modified nanopores and highlights the importance of the nanopore charge states for desalination. Meanwhile, it provides useful guidelines for the rational design of optimal nanoporous membranes in the future.
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