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A core-shell molecularly imprinted polymer nanoparticle with biological enzyme functional characteristics was developed by oxidative polymerization of template protein and polydopamine on the surface of protease-copper phosphate hybrid nanoflowers by molecular imprinting technology and enzyme immobilization technology. The obtained molecularly imprinted polymer showed specific binding characteristics with the template protein. It recognized and enriched the target molecules through the surface molecularly imprinted sites of the shell structure. In addition, the bound target molecules were further degraded into fragments by nanozymes with biological enzyme characteristics in the core. In this study, molecular imprinting technology and biotechnology were combined to obtain bifunctional molecularly imprinted polymer nanoparticles that can not only enrich template molecules but also degrade them into fragments. Herein, we selected interleukin 6 (IL-6), the target molecule of cytokine release syndrome (CRS), as a template molecule, and reported a molecularly imprinted polymer with degrading enzyme properties that can rapidly reduce IL-6 levels in vivo, including a molecularly imprinted layer that can recognize and bind IL-6 and nanozymes that can degrade IL-6 and deactivate it. It is used to clear the excessive secretion of IL-6 in CRS and reduce the level of IL-6 in the body to achieve the purpose of adjuvant treatment of CRS.

(a) Schematic illustration for the preparation of iRGD-R7-LAHP-M NPs. (b) The prepared NPs penetrated into the deep tumor, and released LAHP and metal ions in acid pH, inducing singlet oxygen-mediated cell death and evoking immunogenic cell death.

The glucagon-like peptide-1 receptor agonist exenatide (EXT) is an effective treatment for type 2 diabetes. However, this peptide has a short biological half-life and the delayed release characteristic of current formulations limit its clinical application. Herein, we prepared EXT-loaded inside-porous poly(d,l-lactic-co-glycolic acid (PLGA) microspheres with outside layers (EXT-PMS) using a W1/O/W2 emulsion method with a microfluidic technique and its fabrication and formulation conditions were systematically investigated. In vitro dissolution experiments showed that the PLGA concentration, proportion of drug and oil phase, and the number and size of pores strongly affected the release behaviors of EXT-PMS. In vitro, the optimized EXT-PMS with large internal pores exhibited rapid and stable release without a lag phase. In a rat model, subcutaneous administration of the product yielded plasma concentrations of EXT that was sustained for 30 days with low burst and no delayed-release effect. The preparation of inside-porous microspheres is lighting up the development of long-acting drug delivery systems for other drugs with favorable release characteristics.

Progesterone (PG) is an essential sex hormone with a variety of important biological functions, but its insolubility leads to low bioavailability of most water-based formulations. What is more, the commercial oil-based formulations often cause severe side effects after long-term injection due to poor tissue absorption of oil. Herein, we report an aseptic bottom-up method utilizing emulsion freeze-drying technology that produces size-controllable, highly bioavailable, and water-based PG nanocrystal injection. The key factors that can determine the features of nanocrystals were investigated, including solvents, water-to-oil ratio, drug concentrations, type of surfactants, temperature in freeze-drying process, and lyoprotectants. Mechanisms of crystal growth formation process for PG nanocrystals were also analyzed theoretically. The prepared water-based PG nanocrystal suspension injection (PG/NSI) not only showed quick dissolution behaviors but also had significantly improved bioavailability in vivo. Therefore, this method can effectively control the size of nanocrystals, enhance bioavailability of insoluble drugs, and produce aseptic water-based nanocrystals that can be directly used for injection. Moreover, this method can also be used to prepare nanocrystals with the desired size under aseptic conditions for other poorly water-soluble drugs.

Schizophrenia and bipolar disorder are severe chronic neuropsychiatric diseases, affecting hundreds of millions of people worldwide. Asenapine maleate (ASM) has been demonstrated as a safe and effective therapeutic agent under twice-daily administration. However, lower compliance is observed when patients are treated with ASM, which significantly limits its application in schizophrenia and bipolar disorder. Moreover, the low bioavailability of ASM caused by first-pass metabolism and poor aqueous solubility also impairs the treatment effect. A formulation of ASM with the property of long-term sustained release and improved bioavailability can be a solution to overcome these weaknesses. In this article, we prepared ASM-loaded poly(lactic-co-glycolic acid) (ASM-PLGA) microspheres through different techniques, including emulsification-solvent evaporation (ESE), Shirasu porous glass membrane emulsification (SPG-ME), and microfluidic method. In vitro and in vivo assessments demonstrated that uniform-sized microspheres generated by the microfluidic process sustainably released ASM throughout 40-days, showing low burst release and significantly improved bioavailability. The results suggest that ASM-PLGA microspheres prepared by the microfluidic method provide an efficient strategy to enhance the drug exposure of ASM as the treatment of chronic neuropsychiatric diseases. It is also evident that this microfluidic strategy has the potential to construct with other drugs, establishing long-acting formulations.

Based on the results of SSM, regional natural endowment conditions, the stage of economic development and the industrial structure evolution determine the energy consumption structure, while the changes in total energy consumption determine the changes in amount of carbon emissions. Under the premise of the total energy consumption is determined, the optimization of energy consumption structure will reduce the carbon intensity (emissions per unit of GDP), that is to achieve low-input, low-emission energy, high output, which is the essence of the low carbon economic development model. Hebei Energy consumption is heavily dependent on coal; however, coal utilization efficiency is low and unit energy carbon emissions are huge, therefore, energy structure dominated by carbon-based energy is a long-term constraint of the development of low carbon economy. Energy consumption structure is composed of regional natural endowments, the stage of economic development and industrial structure, and it is difficult to change in the short term.

The purpose of this work was to develop and characterize the fibrauretine (FN) loaded propylene glycol-embodying deformable liposomes (FDL), and evaluate the pharmacokinetic behavior and safety of FDL for vaginal drug delivery applications. FDL was characterized for structure, particle size, zeta potential, deformability and encapsulation efficiency; the ability of FDL to deliver FN across vagina tissue in vitro and the distribution behavior of FN in rat by vaginal drug delivery were investigated, the safety of FDL to the vagina of rabbits and rats as well as human vaginal epithelial cells (VK2/E6E7) were also evaluated. Results revealed that: (i) the FDL have a closed spherical shape and lamellar structure with a homogeneous size of 185±19nm, and exhibited a negative charge of -53±2.7mV, FDL also have a good flexibility with a deformability of 92±5.6 (%phospholipids/min); (ii) the dissolving capacity of inner water phase and hydrophilicity of phospholipid bilayers of deformable liposomes were increased by the presence of propylene glycol, this may be elucidated by the fluorescent probes both lipophilic Nile red and hydrophilic calcein that were filled up the entire volume of the FDL uniformly, so the FDL with a high entrapment capacity (were calculated as percentages of total drug) for FN was 78±2.14%; (iii) the permeability of FN through vaginal mucosa was obviously improved by propylene glycol-embodying deformable liposomes, no matter whether the FN loaded in liposomes or not, although FN loaded in liposomes caused the highest permeability and drug reservoir in vagina; (iv) the FN mainly aggregated in the vagina and uterus, then the blood, spleen, liver, kidney, heart and lungs for vaginal drug delivery, this indicating vaginal delivery of FDL have a better 'vaginal local targeting effect'; and (v) the results of safety evaluation illustrate that the FDL is non-irritant and well tolerated in vivo, thereby establishing its vaginal drug delivery potential. These results indicate that the propylene glycol-embodying deformable liposomes may be a promising drug delivery carrier for vaginal delivery of fibrauretine.

In the paper, a new method for semi-fragile watermarking of color image based on Slant Transform and channel coding is proposed. This technique certifies the belongings of images by using authentication watermarks that are embedded in IF of Slant Transform regions. Recover manipulated regions by restore watermarks that are extracted from the former 11 coefficients of each block. Restore watermarks are embedded in the least significant bits of each pixels. For increasing robustness of the algorithm, calculate error correction coding and spread spectrum modulation to authentication watermarks before embedding them. Watermarking extraction does not need original image, it belongs to blind extraction.

To solve the problems of most communication signals modulation recognition methods' computational complexity and classifier training difficulties, a method of modulation recognition is proposed based on particle swarm optimization(PSO) and support vector machine (SVM). Combine wavelet decomposition theory with the modulated signals' instantaneous characteristics, high-order cumulants and fractal theory to obtain a hybrid model of feature vector, and use PSO-SVM classifier to identify ten kinds of modulation signals as 2ASK, 4ASK, 2PSK, 4PSK, 8PSK, 2FSK, 4FSK, 8FSK, 16QAM, MSK. The simulation results show that the recognition rates are all over 98% at SNR 5dB.

In this paper, a combination method is presented to estimate the PN sequence's period of the direct sequence spread spectrum (DSSS) signal in strong narrow-band interference environment. An overlapping windowed FFT algorithm is first used to transform the received data signals to the frequency-domain where the elimination or drastical attenuation of the strong narrow-band interference is performed. Then a reprocessing of the power spectrum density algorithm is proposed to detect and estimate the Pseudo-random code (PN) sequence's period of the DSSS signal in low SNR, which solves the difficult problem of PN sequence's periodic detection and estimation of weak DSSS signals with interference. Theoretical analysis and simulation results show that the proposed algorithm can effectively estimate the PN sequence's period of DSSS signal, and the estimating performance closely relates the low SNR.

In a traditional quartz crystal microbalance (QCM), an AT-cut (cut angle phi=35.25 degrees in yxl orientation) quartz wafer is employed because it has low frequency-temperature coefficients (dF/dT) at room temperature region. But when a QCM is in contact with a liquid phase, its frequency is also related to the properties of the liquid, which are temperature dependent. The value of dF/dT is about 20 Hz/ degrees C for a 9 MHz AT-cut QCM with one side facing water. In this work, a group of QCMs in new cut angles were prepared. The influence of the cut angle on the frequency-temperature characteristic, response sensitivities to surface mass loading and viscodensity of liquid were investigated. An intrinsically temperature-compensated QCM sensor that possesses low dF/dT values in aqueous solution was reported. When a 9 MHz QCM with phi=35.65 degrees was contacted with water with one side, its dF/dT value is close to zero at ca. 25 degrees C and its averaged value of |dF/dT| is only 0.6 Hz/ degrees C in the temperature range of 23-27 degrees C. The frequency responses to surface mass loading and viscodensity of liquid phase are very close among the QCMs with the cut angles in the range of 35.15-35.7 degrees . The intrinsically temperature-compensated QCM was applied to investigate the alternate adsorption processes of cationic polyelectrolyte and silica nanoparticle.

To prepare human interferon-k (hIFN-kappa) and study its biological activities.Whole length of hIFN-kappa's cDNA was cloned, and its sequence was chemically synthesized according to the optimized codons of E.coli, then was expressed in E.coli DH5alpha. After purified, the rhIFN-kappa protein was tested for its various kinds of biological activities.The purity of rhIFN-kappa was above 90%. In WHIS-VSV system, the antiviral activity of rhIFN-kappa was 2.0 x 10(6) IU/mg. Compared with rhIFN-alpha-2b, the biological activities of rhIFN-kappa were all feeble, including antiviral activity, promoting NK cell activity and anti-proliferation activity.Antiviral activities of rhIFN-kappa on cell lines of different species are different, different viruses show different sensitivity to rhIFN-kappa.