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The pathology of psoriasis involves the over-proliferation of keratinocytes, exaggerated inflammation of keratinocytes, and infiltration of inflammatory cells such as macrophages (Mø), etc. The therapeutic outcomes of current treatment targeting one single pathological process are less than satisfactory. Based on their diverse biological activities, natural products offer a potential solution to this problem. In this study, we investigated the effects of β-Elemene (ELE) on both psoriatic keratinocytes and M1-type Mø (M1-Mø) in vitro. Hyaluronic acid (HA) microneedles loaded with ELE (HA-ELE-MN) were also fabricated and tested for the treatment of psoriasis in vivo using an imiquimod (IMQ)-induced psoriatic mice model. Our data suggest that ELE induces apoptosis and inhibits inflammation of psoriatic keratinocytes. In addition, ELE attenuates the expression of inflammatory cytokines secreted from M1-Mø, thus indirectly inhibiting the inflammation of keratinocytes. Furthermore, HA-ELE-MN has been found to significantly alleviate symptoms in an IMQinduced psoriatic mice model by inducing keratinocytes apoptosis, suppressing keratinocytes proliferation, and inhibiting M1-Mø infiltration. Taken together, this study demonstrates that ELE can be used for the treatment of psoriasis by targeting both keratinocytes and M1-Mø, which provides a potential novel reagent for psoriasis treatment. [ABSTRACT FROM AUTHOR]

The absorption of peptides and proteins delivered orally is minimum because of the intestine epithelial barrier. There are few known active transport mechanisms for macromolecules including the neonatal Fc Receptor (FcRn) for the absorption and secretion of IgGs in infant and adult intestine. We had previously described the FnAb-8 protein that could bind to hFcRn tightly at pH 6.0 but barely at pH 7.4. In this study, we examined its uptake, biodistribution and pharmacokinetics after peroral administration in both wild-type and human FcRn transgenic (Tg) mice. FnAb-8 was modified to contain trans-cyclooctene (TCO) which could interact with 18 F labeled tetrazine in situ via the bioorthogonal inverseelectron- demand Diels -Alder reaction. We showed that FnAb-8 had a tendency to distribute and persist in the Tg mice intestine for an extended duration of time. It could also be absorbed into the circulation and distributed systemically over a long period of time up to 172 h. The improvement in oral uptake and concentration in the intestine tissue may be valuable for designing oral delivery of biopharmaceuticals, especially for diseases involving the gastric intestinal tissue. [ABSTRACT FROM AUTHOR]

The retarding field analyzer (RFA) is considered to be one of the most effective tools to measure ion temperature (Ti) in the plasma boundary. However, there are some inaccuracies in the measured Ti by RFA caused by impurities in the plasma. In this paper, the influence of impurities on the measured Ti by RFA have been analyzed in hydrogen isotope plasmas with both low-Z and high-Z impurities. The analytical results show that Ti is underestimated in H+ (also D+ and T+) plasma when the fuel ion charge is taken as the charge number and the analyzed Ti in H+ plasma are all larger than that in D+ and T+ plasmas, exhibiting the isotope effect. With the concentration of low-Z impurity (ηl) increasing, the analyzed Ti decreases and is underestimated by about 20% with ηl ~ 12%. Following a comparison of different charge numbers and masses of low-Z impurities, it is found that larger charge numbers and smaller masses of low-Z impurities lead to greater underestimation of the analyzed Ti. High-Z impurities make almost no impact on the Ti, due to their small current contribution. Moreover, the Ti is measured by RFA and edge rotational diagnostic (ERD) systems through experiments. The results show good agreement with the analytical evaluations. [ABSTRACT FROM AUTHOR]

We consider the dynamic mean--variance portfolio choice without cash under a game theoretic framework. The mean--variance criterion is investigated in the situation where an investor allocates the wealth among risky assets while keeping no cash in a bank account. The problem is solved explicitly up to solutions of ordinary differential equations by applying the extended Hamilton-- Jacobi--Bellman equation system. Given a constant risk aversion coefficient, the optimal allocation without a risk-free asset depends linearly on the current wealth, while that with a risk-free asset turns out to be independent of the current wealth. We also study the minimum-variance criterion, which can be viewed as an extension of the mean--variance model when the risk aversion coefficient tends to infinity. Calibration exercises demonstrate that for large investments, the mean--variance model without cash yields the highest certainty equivalent return for both short-term and long-term investments. Furthermore, the mean--variance portfolio choices with and without cash yield almost the same Sharpe ratio for an investment with large initial wealth. [ABSTRACT FROM AUTHOR]

The characteristics of the energy transfer and nonlinear coupling among edge electromagnetic turbulence have been dedicatedly studied in various discharge stages at the sino-united spherical tokamak using multiple Langmuir and magnetic probe arrays. The wavelet bispectral analysis and the modified Kim's method are applied to investigate turbulence properties and their linear growth/damping and nonlinear energy transfer rates, along with multi-field turbulence interactions. The results show diverse features in the linear growth and nonlinear energy transfer between multi-field fluctuations during the current ramp-up, stationary, and internal connection event discharge phases. The diversity implies the importance to develop more sophisticated multi-field models to directly estimate the energy transfer rate among multiple turbulent fields. [ABSTRACT FROM AUTHOR]

Land resources and land use activities support the social and economic development in any region. In order to explore the distribution of land use structure, we can apply the Lorenz curves and Gini coefficient to accomplish. In this study, we selected the land use data in 14 prefecture cities in Liaoning Province of China from 2010 to 2015. Based on the Lorenz curve and the Gini coefficient, we analyzed quantitatively the land use structure in 14 prefecture cities of Liaoning province. Results indicated that cultivated land, forest land and construction land were evenly distributed, while garden land, grass land and unused land were distributed in a more concentrated state in space scale. On time scale, the Gini coefficient of forest land, garden land and grass land were increasing, and the degree of distribution dispersion has increased, while the Gini coefficient of cultivated land, construction land and unused land has reduced, whose distribution tended to equilibrium. Some suggestion for rational land use and structural adjustment has been provided by analyzing the spatial and temporal distribution of land use in Liaoning Province. [ABSTRACT FROM AUTHOR]

Fluorescence labeled small interfering RNAs (siRNAs) were loaded into lipopolyplexes modified with ApoA1 (named as rHDL) and administered by intravenous injection. The biodistribution with time of these lipopolyplexes inside the liver and among various cell types was followed using tissue sections by Confocal fluorescence microscopy. At about 0.5 h after tail vein injection at a dose of 0.408 mg/kg, very few fluorescence signals were found in the liver. But then the signals could be seen to accumulate inside hepatocytes as discrete spots and diffused signals at around 2-4 h after injection. Such a distribution and uptake pattern was significantly different from what were observed using the commercial agent Invivofectamine® 2.0 or DOTAP lipoplexes as the carriers. The differences indicated different mechanisms concerning the in vivo behavior of these carriers. The rHDL carrier system we developed was able to deliver siRNA specifically into hepatocytes while avoiding the uptake by REM cells especially the Kupffer cells. With it's low toxicity and off target effect, it may be suitable to be developed as a hepatocyte targeting delivery system for siRNA. [ABSTRACT FROM AUTHOR]

Huperzine A is a bioactive compound derived from traditional Chinese medicine plant Qian Ceng Ta (Huperzia serrata), and was found to have multiple neuroprotective effects. In addition to being a potent acetylcholinesterase inhibitor, it was thought to act through other mechanisms such as antioxidation, antiapoptosis, etc. However, the molecular targets involved with these mechanisms were not identified. In this study, we attempted to exam the interactome of Huperzine A using a cDNA phage display library and also mammalian brain tissue extracts. The drugs were chemically linked on the surface of magnetic particles and the interactive phages or proteins were collected and analyzed. Among the various cDNA expressing phages selected, one was identified to encode the mitochondria NADH dehydrogenase subunit 1. Specific bindings between the drug and the target phages and target proteins were confirmed. Another enriched phage clone was identified as mitochondria ATP synthase, which was also panned out from the proteome of mouse brain tissue lysate. These data indicated the possible involvement of mitochondrial respiratory chain matrix enzymes in Huperzine A's pharmacological effects. Such involvement had been suggested by previous studies based on enzyme activity changes. Our data supported the new mechanism. Overall we demonstrated the feasibility of using magnetic biopanning as a simple and viable method for investigating the complex molecular mechanisms of bioactive molecules. [ABSTRACT FROM AUTHOR]

This paper presents a new patch-based video restoration scheme. By grouping similar patches in the spatiotemporal domain, we formulate the video restoration problem as a joint sparse and low-rank matrix approximation problem. The resulting nuclear norm and ℓ1 norm related minimization problem can also be efficiently solved by many recently developed numerical methods. The effectiveness of the proposed video restoration scheme is illustrated on two applications: video denoising in the presence of random-valued noise, and video in-painting for archived films. The numerical experiments indicate that the proposed video restoration method compares favorably against many existing algorithms. [ABSTRACT FROM AUTHOR]

Background: Phenazines are important compounds produced by pseudomonads and other bacteria. Two phz gene clusters called phzA1-G1 and phzA2-G2, respectively, were found in the genome of Pseudomonas sp. M18, an effective biocontrol agent, which is highly homologous to the opportunistic human pathogen P. aeruginosa PAO1, however little is known about the correlation between the expressions of two phz gene clusters. Methodology/Principal Findings: Two chromosomal insertion inactivated mutants for the two gene clusters were constructed respectively and the correlation between the expressions of two phz gene clusters was investigated in strain M18. Phenazine-1-carboxylic acid (PCA) molecules produced from phzA2-G2 gene cluster are able to auto-regulate expression itself and activate the expression of phzA1-G1 gene cluster in a circulated amplification pattern. However, the post-transcriptional expression of phzA1-G1 transcript was blocked principally through 59-untranslated region (UTR). In contrast, the phzA2-G2 gene cluster was transcribed to a lesser extent and translated efficiently and was negatively regulated by the GacA signal transduction pathway, mainly at a post-transcriptional level. Conclusions/Significance: A single molecule, PCA, produced in different quantities by the two phz gene clusters acted as the functional mediator and the two phz gene clusters developed a specific regulatory mechanism which acts through 5′-UTR to transfer a single, but complex bacterial signaling event in Pseudomonas sp. strain M18. [ABSTRACT FROM AUTHOR]

Integrins play critical roles in the process of angiogenesis and are attractive targets for anticancer therapies. It is desirable to develop new types of small-molecule inhibitors of integrin. Herein, the binding features of several inhibitors to integrin αvβ3 have been studied by surface plasmon resonance (SPR) biosensor technology and molecular docking analyses. The SPR results indicated that the equilibrium dissociation constant (KD) values are evaluated for the inhibitors and showed that the KD value of cyclopeptide c-Lys is much lower than the reference molecule. In addition, the 3D structural model of integrin αvβ3 was generated according to the crystal structure of the integrin αvβ3 complex, and the molecular docking simulation analyses revealed that the predicted binding sites for the most active cyclopeptide c-Lys were consistent with the reported structure. These results thus implied that cyclopeptide c-Lys could be developed as a novel inhibitor for integrin αvβ3. The current work has potential for application in structure-based integrin αvβ3 inhibitor discovery. (Journal of Biomolecular Screening 2010:131-137) [ABSTRACT FROM AUTHOR]

J Oral Pathol Med (2010) 39: 63–68 Background: The chemokine SDF-1 and its receptor CXCR4 play active role in the metastasis and proliferation of several malignancies. Methods: In this study, we used an immunohistochemical technique in 91 specimens of oral squamous cell carcinoma (SCC), and flow cytometry technique in oral SCC cell line, and then evaluated the role of proliferation of CXCR4 using MTT assay in oral SCC cell line. Results: The expression of CXCR4 in 91 specimens of oral SCC was 62.6% and in oral SCC cell line was 68.6%. There was a significant association between the expression of CXCR4 and lymph node metastasis ( P = 0.012), tumor size ( P = 0.01), UICC stage ( P = 0.016), tumor histology grade ( P < 0.001). SDF-1 stimulated proliferation of oral SCC cell and CXCR4 neutralization by monoclonal antibodies decreased proliferation. Conclusions: Our results suggest that CXCR4 might be a novel biomarker to evaluate the biological behavior of oral SCC. CXCR4 inhibitors or antagonists might be potential anticancer agents to suppress tumor proliferation. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGF-R) is an important target in anticancer therapy. Here we report how a novel EGF-R peptide ligand (D4: Leu-Ala-Arg-Leu-Leu-Thr) is identified using a computer-aided design approach from a virtual peptide library of putative EGF-R binding peptides by screening against the EGF-R X-ray crystal structure in silico and in vitro. The selected peptide is conjugated with a polyethylene glycol (PEG) lipid, and the lipid moiety of the peptide-PEG-lipid conjugate is inserted into liposome membranes by a postmodification process. D4 peptide-conjugated liposomes are found to bind to and enter cells by endocytosis specifically and efficiently in vitro in a process apparently mediated by EGF-R high-expressing cancer cells (H1299). In vivo, the D4 peptide-conjugated liposomes are found to accumulate in EGF-R-expressing xenograft tumor tissues up to 80 h after intravenous delivery, in marked contrast to controls. These results demonstrate how structure-based peptide design can be an efficient approach to identify highly novel binding ligands against important receptors. These data could have important consequences for the development of peptide-directed drug delivery systems with engineered specificities and prolonged times of action. [ABSTRACT FROM AUTHOR]

Cationic polymer nanogels, positively-charged submicrometer polymeric particles that swell in water, have attracted an increasing research attentions in recent years because of their potential applications as gene carriers. In this paper, we report a novel method to synthesize polyethylenimine (PEI) nanogels with sizes ranging from 80 nm to 200 nm via UV irradiation at room temperature in aqueous solution without adding any kind of surfactants. The morphology of the nanoparticles is determined to be spherical. The nanogels are of high stability, high transfection efficiency, low toxicity and low immunogenicity, as having been confirmed by in vivo tests with mice as an animal model, and by in vitro tests with human lung and liver cancer cells as well. [ABSTRACT FROM AUTHOR]

In recent years, capsid-modified filamentous bacteriophage has become a potential vector for gene delivery into mammalian cells. However, little was known about how the carried gene in the single-stranded genome expressed in mammalian cells. To explore whether the orientation of the carried gene affects its expression in the cells, we prepared EGF-displayed phagemid particles whose genome carried the GFP gene or luciferase gene. The phagemid carried reporter genes either in the same orientation (called (+)gene) or in the contrary orientation (called (−)gene) to filamentous origin. Using these phagemid particles to infect H1299 cells, we found that the phages with (−) reporter genes had about 2-fold transduction efficiency as those with (+) reporter genes. These results indicated that phagemid carrying (−)gene of interest presented a better procedure in phage-mediated gene therapy. Furthermore, camptothecin (CPT) treatment was also applied and found to enhance both kinds of phagemid particles, and (−)gene still produced about 1.5- to 2-fold transduction efficiency compared to those with (+)gene. Thus, it is imperative that we clone the genes of interest in the reverse orientation to filamentous origin to enhance their expressions when preparing phagemid gene delivery vectors. Also, the results suggested that CPT could enhance both the replication of single-stranded DNA and its transcription. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (ErbB1, EGFR) is overexpressed in a variety of human cancer cells. It has been considered as a rational target for drug delivery. To identify novel ligands with specific binding capabilities to EGFR, we screened a phage display peptide library and found an enriched phage clone encoding the amino acid sequence YHWYGYT-PQNVI (designated as GE11). Competitive binding assay and Scatchard analysis revealed that GE11 peptide bound specifically and efficiently to EGFR with a dissociation constant of ∼22 nM, but with much lower mitogenic activity than with EGF. We showed that the peptides were internalized preferentially into EGFR highly expressing cells, and they accumulated in EGFR overexpressing tumor xenografts after i.v. delivery in vivo. In gene delivery studies, GE11-conjugated polyethylenimine (PEI) vectors were less mitogenic, but still quite efficient at transfecting genes into EGFR highly expressing cells and tumor xenografts. Taken together, GE11 is a potentially safe and efficient targeting moiety for selective drug delivery systems mediated through EGFR. [ABSTRACT FROM AUTHOR]

In TEXTOR the long-range time dependence of edge plasma fluctuations has been investigated. The results indicate that the tail of the autocorrelation function decays as a power law for time lags longer than the local decorrelation time. The frequency spectra of the fluctuations show similar features to those obtained in "sandpile" models. Using rescaled range (R/S) analysis techniques the self-similarity parameters have been estimated for the potential fluctuation data detected by Langmuir probes. The results show that the Hurst exponents are well above 0.5 over the self-similarity range at all the measured radial locations. All these facts reveal the self-similar character of the electrostatic fluctuations at the plasma edge of TEXTOR, consistent with plasma transport as characterized by self-organized criticality (SOC). Furthermore, we have analyzed in this respect discharges in which an edge transport barrier was created by means of edge biasing, hitherto limited to floating potential measurements in the scrape off layer outside the barrier region. The results show a decrease of fluctuating amplitudes, a reduction of decorrelation time of local turbulence and, surprisingly, a concomitant increase of the Hurst exponent. This result implies that the mechanisms governing the decorrelation of local turbulence may differ from those governing the decorrelation of SOC transport events. [ABSTRACT FROM AUTHOR]

Ventricular fibrillation (VF) is one of the most serious malignant arrhythmias usually resulting from immediate degeneration of ventricular tachycardia (VT). In order to analyse the nonlinear dynamics of the cardiac micro-mechanism under VT and VT rhythm, at the cellular level, myocardial cell action potentials are investigated under different rhythm, normal sinus rhythm, VT and VT. On the basis of nonlinear chaotic theory and symbolic dynamics, we put forward new definitions, complexity rate, etc, and obtained some useful properties for cellular electrophysiological analysis. The results of the experiments and computation show that the myocardial cellular signals under VT and VF rhythm are different kinds of chaotic signals in that the cardiac chaos attractor under VF is higher than that under VT. The analytical complexity theory has been promising in the clinical application. [ABSTRACT FROM AUTHOR]

Examines the improvement of the Ohmic confinement phase during the turbulent heating pulse in the Hefei Tokamak-6M. Factor affecting the steepness of the electron temperature and density profiles; Role of the radial electric field during the transition of L mode and H mode; Effect of radial electric field on the suppression of the plasma potential fluctuation.

Discusses the measurement of temperature, density and potential fluctuations in both the plasma edge and core of the Keda Tokamak-5C. Use of swept double probe and triple probe technique; Estimation of fluctuation-driven particle and energy fluxes; Existence of substantial electron temperature fluctuations.

The transition of trapped-particle orbit topologies has been investigated in quasi-axisymmetric (QA) configurations, such as the Chinese First Quasi-axisymmetric Stellarator (CFQS). It is found that the axisymmetry-breaking phenomenon in QA configurations is of great significance at some specific locations, which could easily induce blocked particles to transit into localized particles. A novel aspect is presented to interpret the transition mechanism of trapped-particle orbit topologies in this paper, i.e., as the amplitudes of non-axisymmetric field increase along the radius direction, the region of large toroidal inhomogeneity is gradually generated, which makes the length of the trapped-particle trajectory substantially short, and hence, may restrict particles to a single helical field period. Meanwhile, at such locations the “pseudo-axisymmetric” field results in coupling of the maximum radial drift and the minimum poloidal drift, which enables the transition of trapped-particle orbit topologies considerably and forms specific loss channels, degrading plasma confinement. These results may shed light on the optimization of QA configurations via avoidance of such coupling with respect to energetic particle confinement. Moreover, this work is also relevant to the generation of inhomogeneity of particle flux deposition on the devertor plates. [ABSTRACT FROM AUTHOR]

Error fields are predominantly attributed to inevitable coil imperfections. Controlling error fields during coil fabrication and assembly is crucial for stellarators. Excessively tight coil tolerance increases time and cost, and, in part, led to the cancellation of the National Compact Stellarator Experiment and delay of W7-X. In this paper, we improve the recently proposed Hessian matrix method to rapidly identify important coil deviations. Two of the most common figures of merit, magnetic island size and quasi-symmetry, are analytically differentiated over coil parameters. By extracting the eigenvectors of the Hessian matrix, we can directly identify sensitive coil deviations in the order of the eigenvalues. The new method is applied to the upcoming Chinese First Quasi-axisymmetric Stellarator configuration. Important perturbations that enlarge n/m  =  4/11 islands and deteriorate quasi-axisymmetry of the magnetic field are successfully determined. The results suggest each modular coil should have separate tolerance and some certain perturbation combinations will produce significant error fields. By relaxing unnecessary coil tolerance, this method will hopefully lead to a substantial reduction in time and cost. [ABSTRACT FROM AUTHOR]

The toroidal rotation modulation and momentum transport have been investigated in the J-TEXT tokamak using a modulated electrode biasing (EB) along with measurements of the toroidal rotation (Vϕ) by a spectrometer and a Langmuir-Mach probe array. The amplitude Av and phase delay ϕv (relative to the phase of the biasing current, IEB) of the rotation modulation are extracted through sine-fitting approaches. It is found that the Av increases with increasing IEB and the ϕv becomes larger when the modulation frequency increases. It has been estimated that the momentum transport time across a radial range from r/a ∼ 0.9 to 0.65 is about 10 ms, shorter than the half of modulation period (∼30 ms). Using the perturbation analysis technique, the toroidal momentum transport coefficients, including momentum diffusivity χϕ and convective velocity Vconv, have been calculated and an inward pinch effect has been observed. In addition, the impact of the EB on the ion temperature and intrinsic rotation and the toroidal rotation difference between impurity and main ions are analyzed and discussed. [ABSTRACT FROM AUTHOR]