Development of a Novel miR-3648-Related Gene Signature as a Prognostic Biomarker in Esophageal Adenocarcinoma

Background: Esophageal adenocarcinoma (EA) is a typical immunogenic malignant tumor with a dismal 5-year survival rate lower than 20%. Although miRNA-3648 (miR-3648) is expressed abnormally in EA, its impact on the tumor immune microenvironment remains unknown. In this study, we sought to identify immune-related genes (IRGs) that are targeted by miR-3648 and develop an EA multigene signature. Methods: The gene expression data of 87 EA tumor samples and 67 normal tissue samples from The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database were downloaded, respectively. Weighted gene co-expression network analysis (WGCNA), the CIBERSORT algorithm, and Cox regression analysis were applied to identify IRGs and to construct a prognostic signature and nomogram. Results: MiR-3648 was expectedly highly expressed in EA tumor tissues (P=2.6e-8), and related to the infiltration of activated natural killer cells (NK cells) and activated CD4 T lymphocytes (CD4 cells). A total of 70 miR-3648-targeted genes related to immune cell infiltration were identified. Among them, 4 genes (C10orf55, DLL4, PANX2, and NKAIN1) were closely related to overall survival (OS), and were thus selected to construct a 4-gene risk score (RS). The RS had a superior capability to predict OS [area under the curve (AUC) =0.740 for 1 year; AUC =0.717 for 3 years; AUC =0.622 for 5 years]. A higher score was indicative of a poorer prognosis than a lower score [hazard ratio (HR) =2.71; 95% confidence interval (CI): 1.45–5.09; P=0.002]. Furthermore, the nomogram formed by combining the RS and the TNM classification of malignant tumors (TNM stage) improved the accuracy of survival prediction [Harrell’s concordance index (C-index) =0.698]. Conclusions: MiR-3648 may play a critical role in EA pathogenesis. The novel 4-gene signature may serve as a prognostic tool to manage patients with EA

Multi-ancestry genome-wide association study of 21,000 cases and 95,000 controls identifies new risk loci for atopic dermatitis

Genetic association studies have identified 21 loci associated with atopic dermatitis risk predominantly in populations of European ancestry. To identify further susceptibility loci for this common, complex skin disease, we performed a meta-analysis of >15 million genetic variants in 21,399 cases and 95,464 controls from populations of European, African, Japanese and Latino ancestry, followed by replication in 32,059 cases and 228,628 controls from 18 studies. We identified ten new risk loci, bringing the total number of known atopic dermatitis risk loci to 31 (with new secondary signals at four of these loci). Notably, the new loci include candidate genes with roles in the regulation of innate host defenses and T cell function, underscoring the important contribution of (auto)immune mechanisms to atopic dermatitis pathogenesis

The Global Convergence of Self-scale BFGS Algorithm with Nonmonotone Line Search for Unconstrained Nonconvex Optimization Problems

The self-scaling quasi-Newton method solves an unconstrained optimization problem by scaling the Hessian approximation matrix before it is updated at each iteration to avoid the possible large eigenvalues in the Hessian approximation matrices of the objective function. It has been proved in the literature that this method has the global and superlinear convergence when the objective function is convex (or even uniformly convex). We propose to solve unconstrained nonconvex optimization problems by a self-scaling BFGS algorithm with nonmonotone linear search. Nonmonotone line search has been recognized in numerical practices as a competitive approach for solving large-scale nonlinear problems. We consider two different nonmonotone line search forms and study the global convergence of these nonmonotone self-scale BFGS algorithms. We prove that, under some weaker condition than that in the literature, both forms of the self-scaling BFGS algorithm are globally convergent for unconstrained nonconvex optimization problems

Fabrication of Au-Ag nanocage@NaYF4@NaYF4:Yb,Er core-shell hybrid and its tunable upconversion enhancement

Localized electric filed enhancement by surface plasmon resonance (SPR) of noble metal nanoparticles is an effective method to amplify the upconversion luminescence (UCL) strength of upconversion nanoparticles (UCNPs), whereas the highly effective UCL enhancement of UCNPs in colloids has not been realized until now. Here, we designed and fabricated the colloidal Au-Ag nanocage@NaYF4@NaYF4:Yb,Er core-shell hybrid with different intermediate thickness (NaYF4) and tunable SPR peaks from visible wavelength region to NIR region. After the optimization of the intermediate spacer thickness (~7.5 nm) of NaYF4 NPs and the SPR peak (~950 nm) of noble metal nanoparticles, an optimum enhancement as high as ~25 folds was obtained. Systematic investigation indicates that UCL enhancement mainly originates from the influence of the intermediate spacer and the coupling of Au-Ag nanocages with the excitation electromagnetic field of the UCNPs. Our findings may provide a new thinking on designing highly effective metal@UCNPs core-shell hybrid in colloids.Published versio

Design of a secure e-business application

The present economical situation in China asks the enterprises to change the traditional transaction style and implement e-business. The most important problems the e-business is facing are: the information confidentiality, the data availability, the data integrity, the user's identity, the non-repudiation of the data's original sender and the legal user, etc. The subject of this thesis analyzes the basic concepts, the security infrastructure and payment system of electronic commerce, makes a thorough and comprehensive research on the security technology, authentication and transaction process, points out some deficiencies in Secure Electronic Transaction (SET) protocol. Then an improved method is given out with the data flow and data structure, finally a secure electronic commerce payment system and its software based on the improved SET model are designed. This thesis brings forward the improved method for improving the speed of transaction, and strengthening the security of protocol and adapting it to any circumstance easily

Plasmon-Enhanced Upconversion Luminescence on Vertically Aligned Gold Nanorod Monolayer Supercrystals

Upconversion nanophosphor is attracting worldwide interests owing to its unique optical properties and great application potentials. However, it is still a great challenge to effectively improve the efficiency/strength of upconversion nanophosphor. Plasmonic modulation is a promising way to solve this bottleneck. In this work, we present a simple yet versatile concept on magnifying upconversion luminescence of NaYF₄:Yb³⁺, Er³⁺ nanocrystals through local field manipulation of surface plasmon. Gold nanorods were directionally assembled into a vertically aligned monolayer supercrystals over large areas. The FDTD simulation indicates that the electromagnetic field strength |E|² can be improved about 113 folds at the hot spots of monolayer supercrystals. After optimization, on the surface of the vertically aligned monolayer supercrystals, the overall upconversion luminescence intensity of NaYF₄:Yb³⁺, Er³⁺ under 980 nm excitation was improved more than 35 fold

Observation of Considerable Upconversion Enhancement Induced by Cu_2–<i>x</i>S Plasmon Nanoparticles

Localized surface plasmon resonances (LSPRs) are achieved in heavily doped semiconductor nanoparticles (NPs) with appreciable free carrier concentrations. In this paper, we present the photonic, electric, and photoelectric properties of plasmonic Cu_2–<i>x</i>S NPs/films and the utilization of LSPRs generated from semiconductor NPs as near-infrared antennas to enhance the upconversion luminescence (UCL) of NaYF₄:Yb³⁺,Er³⁺ NPs. Our results suggest that the LSPRs in Cu_2–<i>x</i>S NPs originate from ligand-confined carriers and that a heat treatment resulted in the decomposition of ligands and oxidation of Cu_2–<i>x</i>S NPs; these effects led to a decrease of the Cu²⁺/Cu⁺ ratio, which in turn resulted in the broadening, decrease in intensity, and red-shift of the LSPRs. In the presence of a MoO₃ spacer, the UCL intensity of NaYF₄:Yb³⁺,Er³⁺ NPs was substantially improved and exhibited extraordinary power-dependent behavior because of the energy band structure of the Cu_2–<i>x</i>S semiconductor. These findings provide insights into the nature of LSPR in semiconductors and their interaction with nearby emitters and highlight the possible application of LSPR in photonic and photoelectric devices

Higher levels of synergistic inhibition of TLR-mediated TNF and IL-1β production in newborn cord blood with combined (PTX+DEX).

<p>Higher levels of synergistic inhibition of TLR-mediated TNF and IL-1β production in newborn cord blood with combined (PTX+DEX).</p

Synergistic Upconversion Enhancement Induced by Multiple Physical Effects and an Angle-Dependent Anticounterfeit Application

Semiconductor plasmon nanoparticles are currently attracting extensive interest because of their unique double character as a semiconductor and metal. In this work, we report that Cu_2–<i>x</i>S nanoparticles (NPs) demonstrate not only tunable localized surface plasmon resonance (LSPR) but also a two-photon absorption effect under infrared light pumping, which depends strongly on the size, composition, and band gap of the NPs. This interaction with the upconversion nanoparticles NaYF₄:Yb³⁺,Er³⁺@NaYF₄:Yb³⁺,Nd³⁺ was systemically studied under excitation of multiwavelengths 808, 980, and 1540 nm. For the localized electromagnetic field to be enhanced further, the Cu_2–<i>x</i>S NPs were inlayed into the surfactant apertures of three-dimensional poly­(methyl methacrylate) opals. On the basis of the synergistic interaction of the LSPR effect, the nonlinear effect and the photonic crystal effect of the hybrids, an upconversion enhancement of up to 1500-fold was achieved with an absolute brightness of 1282 cd/m² under excitation by 1.25 W/mm² 980 nm light. The experimental results were analyzed through comparison with finite-difference time-domain calculations. Finally, on the basis of the hybrids, novel angle-dependent infrared anticounterfeiting was successfully performed, which is extremely difficult to simulate. Our discovery provides a new concept for designing and optimizing luminescent materials and highlights the novel application of plasmonic semiconductor NPs in photonics

Parameter estimate for PTX and DEX synergy model for separate newborn and adult cohorts.

<p>Parameter estimate for PTX and DEX synergy model for separate newborn and adult cohorts.</p