Reprogrammable plasmonic topological insulators with ultrafast control

Topological photonics has revolutionized our understanding of light propagation, providing a robust way to manipulate light. So far, most of studies in this field are focused on designing a static photonic structure. Developing a dynamic photonic topological platform to switch multiple topological functionalities at ultrafast speed is still a great challenge. Here we theoretically propose and experimentally demonstrate a reprogrammable plasmonic topological insulator, where the topological propagation route can be dynamically changed at nanosecond-level switching time, leading to an experimental demonstration of ultrafast multi-channel optical analog-digital converter. Due to the innovative use of electric switches to implement the programmability of plasmonic topological insulator, each unit cell can be encoded by dynamically controlling its digital plasmonic states while keeping its geometry and material parameters unchanged. Our reprogrammable topological plasmonic platform is fabricated by the printed circuit board technology, making it much more compatible with integrated photoelectric systems. Furthermore, due to its flexible programmability, many photonic topological functionalities can be integrated into this versatile topological platform

Bevacizumab for newly diagnosed ovarian cancers: Best candidates among high-risk disease patients (icon-7)

Bevacizumab is approved as a maintenance treatment in first-line setting in advanced-stage III-IV ovarian cancers, because GOG-0218 and ICON-7 phase III trials demonstrated progression-free survival benefits. However, only the subgroup of patients with high-risk diseases (stage IV, and incompletely resected stage III) derived an overall survival (OS) gain in the ICON-7 trial (4.8 months). The modeled CA-125 elimination rate constant K (KELIM) parameter, based on the longitudinal CA- 125 kinetics during the first 100 days of chemotherapy, is a potential indicator of the tumor primary chemo-sensitivity. In the ICON-7 trial dataset, the OS of patients within the low- and high-risk disease groups was assessed according to treatment arms and KELIM. Among the patients with high-risk diseases, those with favorable standardized KELIM of at least 1.0 (n=214, 46.7%) had no survival benefit from bevacizumab, whereas those with unfavorable KELIM less than 1.0 (n=244, 53.2%) derived the highest OS benefit (absolute difference = 9.1 months, 2-sided log-rank P=.10; Cox hazard ratio = 0.78, 95% confidence interval = 0.58 to 1.04, 2-sided P=.09)

Bevacizumab for Newly Diagnosed Ovarian Cancers: Best Candidates Among High-Risk Disease Patients (ICON-7)

Bevacizumab is approved as a maintenance treatment in first-line setting in advanced-stage III-IV ovarian cancers, because GOG-0218 and ICON-7 phase III trials demonstrated progression-free survival benefits. However, only the subgroup of patients with high-risk diseases (stage IV, and incompletely resected stage III) derived an overall survival (OS) gain in the ICON-7 trial (4.8 months). The modeled CA-125 elimination rate constant K (KELIM) parameter, based on the longitudinal CA-125 kinetics during the first 100 days of chemotherapy, is a potential indicator of the tumor primary chemo-sensitivity. In the ICON-7 trial dataset, the OS of patients within the low- and high-risk disease groups was assessed according to treatment arms and KELIM. Among the patients with high-risk diseases, those with favorable standardized KELIM of at least 1.0 (n = 214, 46.7%) had no survival benefit from bevacizumab, whereas those with unfavorable KELIM less than 1.0 (n = 244, 53.2%) derived the highest OS benefit (absolute difference = 9.1 months, 2-sided log-rank P = .10; Cox hazard ratio = 0.78, 95% confidence interval = 0.58 to 1.04, 2-sided P = .09)

Inhibition of Osteoclastogenesis by Mechanically Loaded Osteocytes: Involvement of MEPE

In regions of high bone loading, the mechanoresponsive osteocytes inhibit osteoclastic bone resorption by producing signaling molecules. One possible candidate is matrix extracellular phosphoglycoprotein (MEPE) because acidic serine- and aspartate-rich MEPE-associated motif peptides upregulate osteoprotegerin (OPG) gene expression, a negative regulator of osteoclastogenesis. These peptides are cleaved from MEPE when relatively more MEPE than PHEX (phosphate-regulating gene with homology to endopeptidases on the X chromosome) is present. We investigated whether mechanical loading of osteocytes affects osteocyte-stimulated osteoclastogenesis by involvement of MEPE. MLO-Y4 osteocytes were mechanically loaded by 1-h pulsating fluid flow (PFF; 0.7 ± 0.3 Pa, 5 Hz) or kept under static control conditions. Recombinant MEPE (0.05, 0.5, or 5 μg/ml) was added to some static cultures. Mouse bone marrow cells were seeded on top of the osteocytes to determine osteoclastogenesis. Gene expression of MEPE, PHEX, receptor activator of nuclear factor kappa-B ligand (RANKL), and OPG by osteocytes was determined after PFF. Osteocytes supported osteoclast formation under static control conditions. Both PFF and recombinant MEPE inhibited osteocyte-stimulated osteoclastogenesis. PFF upregulated MEPE gene expression by 2.5-fold, but not PHEX expression. PFF decreased the RANKL/OPG ratio at 1-h PFF treatment. Our data suggest that mechanical loading induces changes in gene expression by osteocytes, which likely contributes to the inhibition of osteoclastogenesis after mechanical loading of bone. Because mechanical loading upregulated gene expression of MEPE but not PHEX, possibly resulting in the upregulation of OPG gene expression, we speculate that MEPE is a soluble factor involved in the inhibition of osteoclastogenesis by osteocytes

Computational Fitness Landscape for All Gene-Order Permutations of an RNA Virus

How does the growth of a virus depend on the linear arrangement of genes in its genome? Answering this question may enhance our basic understanding of virus evolution and advance applications of viruses as live attenuated vaccines, gene-therapy vectors, or anti-tumor therapeutics. We used a mathematical model for vesicular stomatitis virus (VSV), a prototype RNA virus that encodes five genes (N-P-M-G-L), to simulate the intracellular growth of all 120 possible gene-order variants. Simulated yields of virus infection varied by 6,000-fold and were found to be most sensitive to gene-order permutations that increased levels of the L gene transcript or reduced levels of the N gene transcript, the lowest and highest expressed genes of the wild-type virus, respectively. Effects of gene order on virus growth also depended upon the host-cell environment, reflecting different resources for protein synthesis and different cell susceptibilities to infection. Moreover, by computationally deleting intergenic attenuations, which define a key mechanism of transcriptional regulation in VSV, the variation in growth associated with the 120 gene-order variants was drastically narrowed from 6,000- to 20-fold, and many variants produced higher progeny yields than wild-type. These results suggest that regulation by intergenic attenuation preceded or co-evolved with the fixation of the wild type gene order in the evolution of VSV. In summary, our models have begun to reveal how gene functions, gene regulation, and genomic organization of viruses interact with their host environments to define processes of viral growth and evolution

NS3 protease from flavivirus as a target for designing antiviral inhibitors against dengue virus

The development of novel therapeutic agents is essential for combating the increasing number of cases of dengue fever in endemic countries and among a large number of travelers from non-endemic countries. The dengue virus has three structural proteins and seven non-structural (NS) proteins. NS3 is a multifunctional protein with an N-terminal protease domain (NS3pro) that is responsible for proteolytic processing of the viral polyprotein, and a C-terminal region that contains an RNA triphosphatase, RNA helicase and RNA-stimulated NTPase domain that are essential for RNA replication. The serine protease domain of NS3 plays a central role in the replicative cycle of dengue virus. This review discusses the recent structural and biological studies on the NS2B-NS3 protease-helicase and considers the prospects for the development of small molecules as antiviral drugs to target this fascinating, multifunctional protein

Controllable Synthesis of Single-Crystalline CdO and Cd(OH)2Nanowires by a Simple Hydrothermal Approach

Single-crystalline Cd(OH)2 or CdO nanowires can be selectively synthesized at 150 °C by a simple hydrothermal method using aqueous Cd(NO3)2 as precursor. The method is biosafe, and compared to the conventional oil-water surfactant approach, more environmental-benign. As revealed by the XRD results, CdO or Cd(OH)2 nanowires can be generated in high purity by varying the time of synthesis. The results of FESEM and HRTEM analysis show that the CdO nanowires are formed in bundles. Over the CdO-nanowire bundles, photoluminescence at ~517 nm attributable to near band-edge emission of CdO was recorded. Based on the experimental results, a possible growth mechanism of the products is proposed

Toll-like receptor-2 deficiency enhances non-alcoholic steatohepatitis

<p>Abstract</p> <p>Background</p> <p>Previously we reported that mice deficient in toll-like receptor 4 (TLR-4) signalling were protected from diet-induced non-alcoholic steatohepatitis (NASH). Another member of the toll-like receptor family, TLR-2, has been shown to play a role in lipid trafficking via uptake of diacylated lipoproteins. However, a role for TLR-2 in NASH has not been elucidated. The objectives of the current study were to examine the influence of dietary fat quality and TLR-2 on NASH pathogenesis.</p> <p>Methods</p> <p>Steatohepatitis was induced in male Db, C57BL/6 and TLR-2^-/-mice by feeding an L-amino acid-defined diet that was deficient in methionine and choline (MCDD). Mice fed the base diet supplemented with methionine and choline (control diet; CD) were used as controls. To determine the role of fat quality, MCDD was enriched with polyunsaturated corn oil (PUFA) or coconut oil that is comprised mostly of saturated fat (SAFA); the total amount of each fat was 112.9 g/kg of diet. After 8 weeks of feeding CD or MCDD, hepatic steatosis, inflammation and necrosis were evaluated in histological sections. Total RNA was extracted from frozen liver samples and mRNA expression of TNFα, collagen α1, IL-10, peroxisome proliferator-activated receptor-γ (PPAR-γ), TLR-4, and CD14, was analyzed via real-time PCR. Protein levels of TLR-2 were analyzed by western blot.</p> <p>Results</p> <p>Panlobular macrovessicular steatosis and diffuse leukocyte infiltration were noted in PUFA-fed Db mice. Histological scores demonstrated significantly less steatosis, inflammation and necrosis in SAFA-fed mice of all mouse strains. However, compared to wild type mice, hepatocellular damage was notably more severe in TLR-2^-/-mice. Consistent with histological findings, mRNA expression of TNFα was elevated by approximately 3-fold in TLR-2^-/-mice; PPAR-γ expression was blunted in this strain compared to wild type. Expression of the matrix protein collagen αI was also significantly higher in TLR-2^-/-mice, indicating a pro-fibrogenic state. Sensitivity to steatohepatitis due to dietary fat or TLR-2 deficiency correlated significantly with alterations in the expression of TLR-4 as well as the co-receptor CD-14.</p> <p>Conclusions</p> <p>Our findings suggest that dietary saturated fat plays a protective role against MCDD-induced steatohepatitis, whereas TLR-2 deficiency exacerbated NASH. The mechanism underlying the response to dietary fat and TLR-2 likely involves altered signalling via the TLR-4 pathway.</p

The number and microlocalization of tumor-associated immune cells are associated with patient's survival time in non-small cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Tumor microenvironment is composed of tumor cells, fibroblasts, endothelial cells, and infiltrating immune cells. Tumor-associated immune cells may inhibit or promote tumor growth and progression. This study was conducted to determine whether the number and microlocalization of macrophages, mature dendritic cells and cytotoxic T cells in non-small cell lung cancer are associated with patient's survival time.</p> <p>Methods</p> <p>Ninety-nine patients with non-small cell lung cancer (NSCLC) were included in this retrospective study. Paraffin-embedded NSCLC specimens and their clinicopathological data including up to 8-year follow-up information were used. Immunohistochemical staining for CD68 (marker for macrophages), CD83 (marker for mature dendritic cells), and CD8 (marker for cytotoxic T cells) was performed and evaluated in a blinded fashion. The numbers of immune cells in tumor islets and stroma, tumor islets, or tumor stroma were counted under a microscope. Correlation of the cell numbers and patient's survival time was analyzed using the Statistical Package for the Social Sciences (version 13.0).</p> <p>Results</p> <p>The numbers of macrophages, mature dendritic cells and cytotoxic T cells were significantly more in the tumor stroma than in the tumor islets. The number of macrophages in the tumor islets was positively associated with patient's survival time, whereas the number of macrophages in the tumor stroma was negatively associated with patient's survival time in both univariate and multivariate analyses. The number of mature dendritic cells in the tumor islets and stroma, tumor islets only, or tumor stroma only was positively associated with patient's survival time in a univariate analysis but not in a multivariate analysis. The number of cytotoxic T cells in the tumor islets and stroma was positively associated with patient's survival time in a univariate analysis but not in a multivariate analysis. The number of cytotoxic T cells in the tumor islets only or stroma only was not associated with patient's survival time.</p> <p>Conclusions</p> <p>The number of macrophages in the tumor islets or stroma is an independent predictor of survival time in NSCLC patients. Counting macrophages in the tumor islets or stroma is more useful in predicting patient's survival time than counting mature dendritic cells or cytotoxic T cells.</p