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The subcellular localization of RNAs correlates with their function and how they are regulated. Most protein-coding mRNAs are exported into the cytoplasm for protein synthesis, while some mRNA species, long noncoding RNAs, and some regulatory element-associated unstable transcripts tend to be retained in the nucleus, where they function as a regulatory unit and/or are regulated by nuclear surveillance pathways. While the mechanisms regulating mRNA export and localization have been well summarized, the mechanisms governing nuclear retention of RNAs, especially of noncoding RNAs, are seldomly reviewed. In this review, we summarize recent advances in the mechanistic study of RNA nuclear retention, especially for noncoding RNAs, from the angle of cis-acting elements embedded in RNA transcripts and their interaction with trans-acting factors. We also try to illustrate the general principles of RNA nuclear retention and we discuss potential areas for future investigation.

PurposeMarket-oriented relations has been regarded as a kind of public relations practices widely performed by the practitioners of public relations and marketing. This study attempts to discuss market-oriented relations in the digital era in which public relations and marketing practitioners' involvement in managing market-oriented relations was simultaneously related to their perceptions of interactivity effects, value of public relations and benefits of digital media usage in public relations practices.Design/methodology/approachA self-administrated online survey targeting 241 practitioners engaged in coordinating public relations activities in Hong Kong was conducted in 2017.FindingsStructural equation modeling (SEM) analysis showed that practitioners' involvement in market-oriented relations practices had significant positive effects on their perceptions of interactivity effects, value of public relations and benefits of digital media usage. Practitioners' perceptions of interactivity effects and benefits of digital media usage were positively affected by their perceptions of public relations value, particularly public relations effectiveness. Clients' profitability and business intelligence, as well as interactivity effects in terms of involvement and perceived customization were practitioners' key concerns in managing market-oriented relations.Originality/valueThis study explores how practitioners of public relations and marketing perceived and practiced public relations in the digital era. Specifically, the conception of market-oriented relations in regard to the use of digital media was discussed in the proposed structural model.

A heterostructure of Sn-doped In2O3 (ITO)/Al-doped ZnO (AZO)/n-Si was proposed and studied for photovoltaics. The top ITO worked as a transparent conducting layer for excellent optical transparency and current collection. The AZO/n-Si served as the active junction and provided the built-in potential (qVbi) for the photovoltaic devices. To achieve a higher open circuit voltage (Voc), which is the main challenge for AZO/Si heterojunctions due to the junction interfacial defects, the AZO and AZO/Si junction properties were systematically investigated. By modulating the Al doping in the AZO thin films via a dual beam co-sputtering technique, the AZO/n-Si junction quality was significantly improved with qVbi increased from 0.21 eV to 0.74 eV. As a result, the Voc of our best device was enhanced from 0.14 V to 0.42 V, with a short circuit current (Jsc) of 26.04 mA/cm2 and a conversion efficiency (Eff) of 5.03%. To our best knowledge, this is the highest Voc reported for ZnO/Si heterojunctions prepared by the sputtering method. The results confirmed the validity of our proposed structure and junction engineering approach and provided new insights and opportunities for ZnO/Si heterojunction optoelectronics.

The coordinated heat-electricity dispatch of the urban integrated energy system (UIES) helps to improve the system flexibility, thereby overcoming the adverse effects caused by the random fluctuations of renewable energy (RE) and promoting the penetration of RE. Among them, the dynamic characteristics of the urban heat network (UHN) are important features that need to be considered for the operating scheduling of the UIES. This paper aims to establish a flexibility scheduling model for UIES based on the dynamic characteristics of the UHN. First, the typical structure and key equipment model of the urban integrated heat and power system (UIHPS) with the dynamic characteristics of the UHN is proposed. Then, the definition and model of the UIHPS flexibility and the assessment index of the flexibility are developed. Moreover, a flexibility scheduling model for a UIHPS that considers the dynamic characteristics of a UHN is established. Finally, the validity of the proposed model is validated by case studies, and the applicability of flexibility scheduling and the effect of heat load (HL) are analyzed.

This study aims at examining the effects of expert endorsement, corporate image and investment knowledge on individuals’ perceived risk in mutual fund advertising. Based on the results from a content analysis of 341 print advertisements of mutual funds in Hong Kong, a 3 (advertising texts about corporate image: corporate management, financial performance, corporate responsibility) × 2 (visual of expert endorser: presence, absence) between-subjects online experiment was subsequently conducted. The content analysis showed that visuals of experts had a significant relationship with corporate attributes in the advertisements. Results from the experimental study revealed that the participants reading the expert-endorsed advertisement about corporate management were more favorable toward the advertiser’s corporate image. The participants’ investment confidence posed a significant effect to their favorability toward the advertiser’s corporate image and subsequently their willingness to invest. When formulating communication strategies for financial products and services, practitioners should pay attention to the effect of expert endorsement in enhancing individuals’ favorability of the corporate image, as well as the effect of individuals’ investment confidence on individuals’ willingness to invest.

// Xilan Yu 1, * , Wuxiang Mao 1, * , Yansheng Zhai 1 , Chong Tong 1 , Min Liu 1 , Lixin Ma 1 , Xiaolan Yu 1 , Shanshan Li 1 1 Hubei Collaborative Innovation Center for Green Transformation of Bio-Resources, College of Life Sciences, Hubei University, Wuhan, Hubei, China * These authors have equally contributed to this work Correspondence to: Xiaolan Yu, email: yxiaolan@163.com Shanshan Li, email: shl@hubu.edu.cn Keywords: metformin, therapeutic targets, metabolism, epigenetic modifications Received: September 22, 2016 Accepted: November 03, 2016 Published: November 26, 2016 ABSTRACT Metformin has been used to treat type 2 diabetes for over 50 years. Epidemiological, preclinical and clinical studies suggest that metformin treatment reduces cancer incidence in diabetes patients. Due to its potential as an anti-cancer agent and its low cost, metformin has gained intense research interest. Its traditional anti-cancer mechanisms involve both indirect and direct insulin-dependent pathways. Here, we discussed the anti-tumor mechanism of metformin from the aspects of cell metabolism and epigenetic modifications. The effects of metformin on anti-cancer immunity and apoptosis were also described. Understanding these mechanisms will shed lights on application of metformin in clinical trials and development of anti-cancer therapy.

A facile and green route to prepare reduced graphene oxide (RGO) is reported. The graphite oxide is firstly pretreated by detonating exfoliation in muffle furnace at low temperature and then is completely reduced to RGO in hydrogen atmosphere at high temperature, namely two-step method. Extensive characterisations show that the as-prepared RGO with high ratio of C/O and surface area consists of crumpled and few-layer thick graphitic sheets. The RGO is used to electrocatalyse nitrobenzene (NB) to P-aminophenol (PAP). High catalytic activity and stability obtained in the electrochemical measurement indicate that the RGO could be a promising alternative catalyst toward the electroreduction of NB to PAP.

Here, we report an approach to realize highly transparent low resistance Al-doped ZnO (AZO) films for broadband transparent conductors. Thin Al films are deposited on ZnO surfaces, followed by thermal diffusion processes, introducing the Al doping into ZnO thin films. By utilizing the interdiffusion of Al, Zn, and O, the chemical state of Al on the surfaces can be converted to a fully oxidized state, resulting in a low sheet resistance of 6.2 Ω/sq and an excellent transparency (i.e., 96.5% at 550 nm and higher than 85% up to 2500 nm), which is superior compared with some previously reported values for indium tin oxide, solution processed AZO, and many transparent conducting materials using novel nanostructures. Such AZO films are also applied as transparent conducting layers for AZO/Si heterojunction solar cells, demonstrating their applications in optoelectronic devices.

The Park Integrated Energy System (PIES) is essential to increase the economic energy supply for the coupling of multiple energy sources. Thus, this paper firstly analyzed the integrated demand response function of park energy users, and then constructed the optimal scheduling model of PIES aiming at the economy of PIES. Finally, an improved non-dominated scheduling genetic algorithm with elite strategy (NSGA-II) was proposed to solve the optimization problem. The results show that the model can effectively solve the optimal scheduling problem of PIES, and the integrated demand response can effectively improve the economic figure of PIES.

Purpose – The purpose of this paper is to propose a model of financial communication to investigate the process of communicating risk signals between listed companies and their individual retail investors in initial public offerings (IPOs). Design/methodology/approach – A survey study on individual IPO investors (n=212) in the Hong Kong Stock Exchange was conducted to examine how risk estimates of individual retail investors were affected by three factors of financial communication, namely organizational trust, organizational reputation and investors’ trust in the media specialists. Structural equation modeling analysis was conducted. Findings – Respondents’ perceived risks of below-target returns and perceived risks of losses of principals were significantly affected by their perceived market risks. Respondents relied significantly on organizational trust to estimate their amounts of target returns and mitigate their perceived risks of losses of principals. Organizational reputation, which could be possibly reinforced by respondents’ trust in the media specialists, could enhance organizational trust. Practical implications – Corporate communications practitioners should pay attention to the effect of perceived market risk on risk estimate. As organizational trust is a significant precondition of risk taking in IPOs, practitioners should rethink the effectiveness of financial communication in which organizational trust, organizational reputation and investors’ trust in the media specialists are interrelated. Originality/value – There is a lack of research in financial communication from the organization-stakeholders perspective. This paper conceptualizes financial communication and provides insights to both scholars and practitioners in corporate communications on how significant factors of financial communication affect risk estimate in the financial market.

Energy internet and energy system integration with multi-energy complementation are vital developing directions of future energy supply systems. Combined cooling, heating and power(CCHP) realizes the coupling use of various forms of energy, and is one of the fundamental elements of the energy internet. During the concentrated CCHP operation analysis, due to the restriction of the fixed heat-electricity ratio, the coordination of the system and the combustion units will greatly impact the running efficiency of concentrated CCHP. In this paper, optimal operation strategy for the concentrated CCHP with the incorporation of the phase-change energy storage devices is analyzed. The flexible load participating in the demand response is also taken into consideration. On this basis, the economy objective function of CCHP is established and the units' output is scheduled. The results of an example in a micro grid applying CCHP show that the energy consumption is reduced, and the working efficiency of the system is improved.

Direct power purchase by large consumers is a good attempt to adjust the power price by market means, which is in favor of exploring a reasonable price formation mechanism and promotes the establishment of an open electricity market. To make the wheeling price and power loss minimum as the target, the paper presents a method based on the flow tracing, tracing the source of large power users, establishing the power grid optimization scheduling model considering the direct power purchase by large consumers. This paper simulates and analyzes the power grid optimization scheduling strategy under different numbers of large consumers in IEEE 30-bus system, the results demonstrate that the model presented can achieve comprehensive optimization of power loss and wheeling price satisfying the requirements of large consumers.

Benefited from the flexibility of Smart Grids, various dynamic lightning protection and Artificial Intelligence-based lightning protection methods become available. Based on Artificial Intelligence technologies, the paper proposes a method of lightning-caused faults forecasting for Smart Grid distribution systems. A self-balancing dynamic lightning protection, which assists the self-healing function of a Smart Grid distribution network, is also presented in the paper. The Artificial Intelligence-based Lightning Protection, which is defined and described in the paper, provides more comprehensive lightning protection solutions to improve system reliability for the Smart Grids.

The current–voltage–temperature (I-V-T) characteristics of transparent Al-doped ZnO (AZO) on n-Si heterojunction structures were analyzed with respect to two different Al diffusion temperatures, 200°C and 600°C. Thin films of Al were deposited on top of the ZnO/Si structures, followed by introducing the Al atoms into the ZnO to form AZO through a process of thermal diffusion. Measurements at temperatures of 150–400 K were carried out in order to understand the temperature dependence of the heterostructure diode characteristics for photovoltaic applications. The results indicated the difference in current mechanisms observed in the two diodes with different Al-diffusion temperatures and Al thicknesses. The charge transport mechanism in the 200°C diodes indicated thermionic field emission (TFE) as the dominating mechanism, whereas the 600°C diodes resulted in field emission (FE) as the dominating current transport. The differences in conduction mechanisms explain the better solar cell performance using the 200°C process.

With the integration of renewable resources, distributed generation (DG) and Microgrids, the Smart Grid distribution systems are more decentralized and interactive. As a System-level protection mode, the Dynamic Lightning Protection (DLP) focuses on the preventive actions for improving lightning performance of the whole system. In this paper, the DLP for Smart Grid distribution system is discussed. Taking advantage of the flexibility and interactivity of Smart Grid, the mode aims to maintain the system dynamic balance and minimize the lightning disturbance during the lightning storms. A dynamic hierarchical multilevel control model is also proposed in the paper, which could coordinate with a Dynamic Lightning Protection System (DLPS) to switch the control strategies, control the power exchange and improve the system reliability.

By introducing silver nanoparticles (NPs) and SiO 2 spacer layers on top of Si-based Schottky barrier solar cells, we demonstrated a positive and tunable light trapping effect introduced by metallic NPs. A redshift of the surface plasmon resonant wavelength of Ag NPs from 550 nm to 650 nm, corresponding to the optical absorption peak of the solar cell, was observed with an increased average particle diameter from 19.7 nm to 85 nm. Enhanced light trapping effects at distinct resonance wavelengths were observed in the optical spectra of the plasmonic-enhanced devices. Electrical measurements confirmed the expected photocurrent improvement at these corresponding wavelengths. It was also revealed that the Ag NPs enhance the carrier generation rate inside of the Si active layer without sacrificing carrier collection efficiency of the device. The short-circuit current density of the best cell we obtained in this work was improved from 13.7 mA/cm 2 to 19.7 mA/cm 2 , with an enhancement factor of 43.7%.

This study investigated media reputation in initial public offerings (IPOs) by proposing eight attributes of substantive media reputation from environmental and product-resource perspectives. A content analysis on financial news coverage (2281 newspaper articles from 2004 to 2010) in Hong Kong was conducted to examine how print media reported financial and nonfinancial information on 38 IPO firms in the sectors of financial, properties and construction, and consumer goods. Results from partial least squares analysis showed that, although substantive media reputation and recency of news coverage together only explained a small proportion of changes in IPO share price, substantive media reputation has a significant positive effect on changes in IPO share price. Apart from the significant positive effect from the presentation tone of environmental attributes, the tone of social attributes had a significant negative effect on substantive media reputation. With the increasing concern on measuring media reputation attributes in financial news coverage across different contexts, this study contributes to the applicability of environmental and product-resource attributes in the specific context of IPOs.

To improve Plasmonic energy harvesting, the Al doped ZnO (AZO) and Si heterojunction was studied for plasmonic photovoltaic applications. Silver nanoparticles (Ag NPs) were embedded in AZO, resulting in direct energy absoption from Ag NPs, positioned close to the junction. This structure has a benefit of avoiding highly doped lossy layers of conventional solar cell structures. Al doped ZnO (AZO) was deposited on n-Si substrate by dual beam sputtering method to fabricate AZO/Si heterojunction solar cells. AZO provides a transparent current spreading effect and rectifying junction with n type silicon (Si). Silver nanoparticles (Ag NPs) were embedded in AZO film (240-270 nm thick) with a sandwich-like structure. The position of Ag NPs in the AZO film was controlled to be located at 10, 20 and 40 nm distance from the Si absorber layer. Fabricated solar cells show improved performance in terms of the short circuit current (J(sc)) and the quantum efficiency (QE). Finite difference time domain (FDTD) simulations were carried out to investigate the QE enhancement and optimize photocurrent gain under an AM1.5G solar spectrum. In calculation, absorption enhancement is maximized when Ag NPs are located close to the Si layer in the range of 10-40 nm. Experimentally, 20 nm distance of Ag NPs from the Si showed the best performance with 0.36 V of open circuit voltage (V(oc)), 28.3 mA/cm2 of J(sc) and 5.91% of coversion efficiency. The QE showed 15% of enhancement around lambda = 435 nm and 5-10% of enhancement within lambda = 600-1000 nm.

With the significance of risk-related information in the financial market, the purpose of this study is to explore the conception of corporate risk transparency from the perspective of individual retail investors. The conception of corporate risk transparency was discussed based on the interrelationships among the effects of risk disclosure, namely corporate reputation, corporate trust and media visibility, in the financial market. A survey study on individual initial public offering (IPO) investors (N=212) in the Hong Kong Stock Exchange was conducted. Structural equation modeling analyses showed that perceived importance of corporate reputation and perceived importance of corporate trust were indeed interrelated in forms of corporate attributes in risk disclosure. Diversity of media used by individual IPO investors, which was a factor of media visibility, would positively affect perceived importance of both corporate reputation and corporate trust.

This paper presents a nanoplasmonic enhanced ZnO/Si heterojunction metal–semiconductor–metal (MSM) photodetector (PD). By depositing different thicknesses of Ag thin film and annealing at a moderate temperature, well-defined silver (Ag) nanoparticles (NPs) with different diameters, densities, and size distributions were produced on the surface of ZnO/Si MSM photodetector devices. By tuning the characteristics of these NPs, a higher-performance ZnO/Si MSM photodetector has been realized. The photocurrent of the detector with NPs was increased by 160% to 680%, depending on the applied voltage. The spectral photocurrent enhancement by a factor of 7 to 18 was broadband from 350 nm to 850 nm.

Cancer cells prefer aerobic glycolysis, but little is known about the underlying mechanism. Recent studies showed that the rate-limiting glycolytic enzymes, pyruvate kinase M2 (PKM2) directly phosphorylates H3 at threonine 11 (H3T11) to regulate gene expression and cell proliferation, revealing its non-metabolic functions in connecting glycolysis and histone modifications. We have reported that the yeast homolog of PKM2, Pyk1 phosphorylates H3T11 to regulate gene expression and oxidative stress resistance. But how glycolysis regulates H3T11 phosphorylation remains unclear. Here, using a series of glycolytic enzyme mutants and commercial available metabolites, we investigated the role of glycolytic enzymes and metabolites on H3T11 phosphorylation. Mutation of glycolytic genes including phosphoglucose isomerase (PGI1), enolase (ENO2), triosephosphate isomerase (TPI1), or folate biosynthesis enzyme (FOL3) significantly reduced H3T11 phosphorylation. Further study demonstrated that glycolysis regulates H3T11 phosphorylation by fueling the substrate, phosphoenonylpyruvate and the coactivator, FBP to Pyk1. Thus, our results provide a comprehensive view of how glycolysis modulates H3T11 phosphorylation.

We propose a theoretical design principle of polarization-insensitive metal–semiconductor–metal (MSM) structure for ultraviolet photodetectors based on one-dimensional nanogratings. Because the Fabry–Perot cavity modes supported by a 100-nm-thick ZnO layer with nanostructures for transverse electric and transverse magnetic polarized incidence overlap with each other, a polarization-insensitive absorption enhancement for the ZnO layer at UV wavelengths is achieved, which can be implemented as a nano-interdigitated electrode to address a long-existing limitation between the speed and the responsivity for conventional MSM photodetectors.

Traditional orthoimage mosaic methods do not perform well in computational speed and geometric precision. This paper proposed a fast orthoimage mosaic method for the application of grid. First of all, down-sample the original images and extracts feature, and adopt SANSAC to estimate the relative initial homography; second, refine homography matrix by Levenberg-Marquardt method and use the sparse bundle adjustment method to estimate the precise homography matrix; Third, passed the homography matrix to the original level of image by the homography relationship of the down-sampling and original image. Finally, synthesize the mosaic image. Our experiments showed that the method combined the down-sampling homography relationship of original image with sparse bundle adjustment organically, which effectively improved the speed and obtained geometric seamless mosaic.

This study attempts to investigate the transdermal permeability, the bioavailability and gene expression of plasmid formulated with nonionic poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) polymeric micelles (PM). Dynamic light scattering (DLS) and atomic force microscopy (AFM) were used to analyze the PM formulated pCMV-Lac Z (P/PM) containing the gene for β-galactosidase (β-Gal) driven by cytomegalovirus early promoter. Franz diffusion cell was used for in vitro transdermal permeability analysis. Real-time PCR was used to quantify the permeated plasmid in vitro and in vivo. β-Gal activity assay was performed to evaluate transgene expression in vivo. The size of P/PM was ~50 nm with round shape. PM significantly enhanced the in vitro transdermal permeability of plasmid in a direction- and temperature-dependent manner. Following transdermal application of P/PM, higher area under the curve (AUC(P/PM): 98.34 h·ng/mL) and longer half-life of plasmid were detected compared with that of plasmid alone (AUC(P): 10.12 h·ng/mL). Additionally, the β-Gal activity was significantly increased in skin, stomach, brain and spinal cord at both 48 and 72 h after P/PM application and in testis and spleen at 72 h postapplication. In conclusion, PM formulation enhanced the permeation of plasmid through skin into blood circulation, increasing its absorption and the transgene expression in various tissues.

Stromal keratocyte apoptosis triggered by epithelial injury is one mechanism of corneal disorders. A model of epithelial injury by epithelial debridement is established, and keratocyte apoptosis is evidenced by DNA fragmentation and cellular morphological changes in the anterior stroma underlying the injured epithelium. Delivery of plasmid (pCMV-bcl-x(L)-eGFP) encoding an anti-apoptotic gene, the bcl-x(L) with a nano-carrier, polymeric micelles (PM) via eye drop to cornea after epithelial debridement, the mRNA level of bcl-x(L) was significantly increased (2.2-fold, P0.05) at 48 h and the eGFP mRNA was detected (4571.7 ± 1194.5 copies/μg total RNA). The bcl-x(L)-eGFP fusion protein was also detected in wounded cornea at 48 h after delivery, accompanying with decreased DNA fragmentation and lower caspase-3 activity (P0.05). In conclusion, eye drop of pCMV-bcl-x(L)-eGFP/PM reduced corneal apoptosis following epithelial debridement.

This study evaluates the eye drop delivery of genes with cornea-specific promoters, i.e., keratin 12 (K12) and keratocan (Kera3.2) promoters, by non-ionic poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) polymeric micelles (PM) to mouse and rabbit eyes, and investigates the underlying mechanisms.Three PM-formulated plasmids (pCMV-Lac Z, pK12-Lac Z and pKera3.2-Lac Z) containing the Lac Z gene for beta-galactosidase (beta-Gal) whose expression was driven by the promoter of either the cytomegalovirus early gene, the keratin 12 gene or the keratocan gene, were characterized by critical micelle concentration (CMC), dynamic light scattering (DLS), and atomic force microscopy (AFM). Transgene expression in ocular tissue after gene delivery was analyzed by 5-bromo-4-chloro-3-indolyl-beta-D-galactoside (X-Gal) color staining, 1,2-dioxetane beta-Gal enzymatic activity measurement, and real-time polymerase chain reaction (PCR) analysis. The delivery mechanisms of plasmid-PM on mouse and rabbit corneas were evaluated by EDTA and RGD (arginine-glycine-aspartic acid) peptide.The sizes of the three plasmid-PM complexes were around 150-200 nm with unimodal distribution. Enhanced stability was found for three plasmid-PM formulations after DNase I treatment. After six doses of eye drop delivery of pK12-Lac Z-PM three times a day, beta-Gal activity was significantly increased in both mouse and rabbit corneas. Stroma-specific Lac Z expression was only found in pKera3.2-Lac Z-PM-treated animals with pretreatment by 5 mM EDTA, an opener of junctions. Lac Z gene expression in both pK12-Lac Z-PM and pKera3.2-Lac Z-PM delivery groups was decreased by RGD peptide pretreatment.Cornea epithelium- and stroma-specific gene expression could be achieved using cornea-specific promoters of keratin 12 and keratocan genes, and the gene was delivered with PM formulation through non-invasive, eye drop in mice and rabbits. The transfection mechanism of plasmid-PM may involve endocytosis and particle size dependent paracellular transport.

The main aim of this study was to investigate the feasibility of using nonionic polymeric micelles of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) as a carrier for oral DNA delivery in vivo. The size and appearance of DNA/PEO-PPO-PEO polymeric micelles were examined, respectively, by dynamic light scattering and atomic force microscopy, and their zeta potential was measured. Expression of the delivered lacZ gene in various tissues of nude mice was assessed qualitatively by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside staining of sections and quantitatively by measuring enzyme activity in tissue extracts, using the substrate of beta-galactosidase, chlorophenol red-beta-D-galactopyranoside. In addition, the types of cells expressing the lacZ gene in the duodenum were identified by histological analysis. DNA/PEO-PPO-PEO polymeric micelles are a single population of rounded micelles with a mean diameter of 170 nm and a zeta potential of -4.3 mV. Duodenal penetration of DNA/PEO-PPO-PEO polymeric micelles was evaluated in vitro by calculating the apparent permeability coefficient. The results showed a dose-independent penetration rate of (5.75 +/- 0.37) x 10(-5) cm/sec at low DNA concentrations (0.026-0.26 microg/microl), but a decrease to (2.89 +/- 0.37) x 10(-5) cm/sec at a concentration of 1.3 microg/microl. Furthermore, when 10 mM RGD peptide or 10 mM EDTA was administered before and concurrent with the administration of DNA/PEO-PPO-PEO polymeric micelles, transport was inhibited ([0.95 +/- 0.57] x 10(-5) cm/sec) by blocking endocytosis or enhanced ([29.8 +/- 5.7] x 10(-5) cm/sec) by opening tight junctions, respectively. After oral administration of six doses at 8-hr intervals, the highest expression of transferred gene lacZ was seen 48 hr after administration of the first dose, with gene expression detected in the villi, crypts, and goblet cells of the duodenum and in the crypt cells of the stomach. Reporter gene activity was seen in the duodenum, stomach, and liver. Activity was also seen in the brain and testis when mice were administered 10 mM EDTA before and concurrent with DNA/PEO-PPO-PEO polymeric micelle administration. lacZ mRNA was detected in these five organs and in the blood by reverse transcription-polymerase chain reaction. Taken together, these results show efficient, stable gene transfer can be achieved in mice by oral delivery of PEO-PPO-PEO polymeric micelles.