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Porous gehlenite coatings on Al2O3–ZrO2–SiC composite ceramics were prepared by electro-spraying technique combined with reactive sintering method. The influences of gehlenite coating on the mechanical property of the ceramics and biological activity of the coating were investigated. The results indicated that the gehlenite coating has limited influences on flexural strength and fracture toughness of the ceramics, and the coating has elastic modulus of 82 GPa, hardness of 2.2 GPa, and adhesive strength of 1512 mN, suggesting its potential application in load-bearing ceramic implants. Simulated body fluid soaking test, CCK-8 and alkaline phosphatase activity assay demonstrated that the porous gehlenite coating has strong mineralization ability, which promotes proliferation and differentiation of MC3T3-E1 cells. These excellent biological performances can be attributed to the synergistic effect of the porous surface of the coating and its release of Ca2+ and Si4+.

Bioinspired intergranular mineral bridges were fabricated in alumina-based ceramics through in situ synthesis of Al2TiO5 whiskers. The effects of mineral bridges on the mechanical properties of ceramics were investigated. Results showed that the flexural strength and fracture toughness of the alumina-based ceramics increased by 33.97% and 33.52%, respectively, after introducing the mineral bridges under hot pressing. Moreover, the effects of the mineral bridges on the crack tip stress (CTS) of models were calculated by finite element method for the first time. The mineral bridge buds and mineral bridges reduced the CTS by 15.54% and 22.22%, respectively. This finding revealed the root cause of the crack deflection mechanism of the mineral bridges and directly confirmed their strengthening and toughening effects.

In this paper, the effects of tube feet pores on the mechanical properties of Sea Urchin Skeleton (SUS) have been studied. The pore structure of drop-like Tripnenstes gratilla (a sea urchin) skeleton is characterized by Scanning Electron Microscopy (SEM). Based upon the data, the finite element method has been employed to analyze the Maximum Tensile Stress (MTS) of SUS models with different pore positions, accompanied by compressive tests on SUS-like ceramics. Results indicate that for a drop-like SUS, the MTS keeps a linear relationship with the maximum load applied on the SUS. More importantly, the mechanical performances of some perforated SUSs are better than their non-perforated counterparts due to their lower MTS values, e.g. the maximum load can thus be increased by 35% when the pore is perforated at −10°. The strengthening is attributed to the introduced pore that causes the redistribution of stress and partly reduces the stress intensity on the original MTS position. By contrast, the pore only increases the MTS value of a spherical shell under isostatic pressure or unidirectional pressing. This is a strong hint that the drop-like shape of SUS has evolved to work with the tube feet pores to better protect their bodies.

In this study, the effects of SiC content, sintering temperature and Al2O3/SiO2 ratio on the microstructure and mechanical properties of hot-pressed alumina–mullite–zirconia–silicon carbide (Al2O3–mullite–ZrO2–SiC) composite ceramics were investigated systematically. The research results indicate that the composite ceramics have excellent combined properties when SiC content is 20 vol% and sintering temperature is 1530 °C, with Vickers hardness, fracture toughness and flexural strength of 17.5 GPa, 12.3 MPa m1/2 and 970 MPa, respectively. The fracture toughness and flexural strength are higher than those of monolithic Al2O3 ceramics and Al2O3-based composites, which are fairly attributed to the refined microstructures of composites and the synergistic effects of crack deflection, pull-out, branching, and phase transformation toughening mechanisms induced by short columnar Al2O3 grains and SiC platelets formed in the ceramics, as well as the ZrO2 particles existed in the ceramics.

Image contrast distortion is a common type of distortion in digital images. However, there is almost no research on the no-reference image quality assessment (NR-IQA) algorithm for image contrast. Therefore, we propose a histogram-based NR-IQA algorithm for contrast distorted images. Firstly, we analyze the image sequence with gradually changing contrast, and the image features are extracted from two aspects: objective statistical attribute, subjective perception attribute. And then we propose three statistical features, including image local contrast, histogram shape and image brightness, which can describe the image quality more simply and intuitively. Furthermore, we introduce the Just noticeable difference (JND) model, which makes the proposed algorithm have a higher matching degree between the human vision system (HVS) and the objective features in the algorithm. Finally, the support vector regression (SVR) is utilized to obtain the mapping relationship between the quantified features and the subjective scores to predict the quality of contrast distorted images. The outstanding performance of the proposed algorithm have been proved on CSIQ, TID2013 and CCID2014 databases.

Mollusk shells have highly complex hierarchical structures and unique mechanical properties, which have been widely studied, especially in fresh shells. However, few studies have revealed differences in the structure-property correlations of shells during the permineralization process, which occurs after organism death. To better understand the effect of permineralization on the microstructure and mechanical properties of shells, this study investigated and compared the compositions, microstructures, and mechanical properties of Tridacna gigas and permineralized J-Tridacna gigas. The results showed that permineralized J-Tridacna gigas possessed coarsened aragonite minerals, less anisotropy and organic matter, and higher hardness and strength than Tridacna gigas. The toughening mechanisms of Tridacna gigas, including crack deflection, aragonite platelet pull-out, and mineral bridges, were discovered during Vickers hardness tests. Moreover, the permineralization mechanism comprised three main steps: organic matter dissolution, aragonite plate compaction, and recrystallization. This work further elaborates the permineralization mechanism, which can help increase the crystal size and improve the strength and hardness of materials. Moreover, this study provides valuable insights into the design of bioinspired advanced materials with outstanding hardness and strength.

In the present study, chitosan based polymer-lipid hybrid nanoparticles (PLNs) were prepared by a self-assembly method and their use as the carrier for oral absorption enhancement of enoxaparin was evaluated. The enoxaparin-loaded nanoparticles were composed of chitosan as the polymer and glyceryl monooleate as the lipid with a lipid/polymer mass ratio ranging from 0 to 0.3, and F127 was added as a stabilizer. It was found that the PLNs showed a higher surface hydrophobicity but mucoadhesive properties similar to those of chitosan based nanocomplexes. Results from DSC experiments and NMR solvent relaxation study indicate that glyceryl monooleate was completely incorporated into the nanoparticles and the lipid/polymer ratio affected the extent of lipid-polymer interaction inside the nanoparticles and the resultant internal structures. The stability of the PLNs in simulated gastrointestinal fluids was also affected by the lipid/polymer ratio; the best stability was shown by nanoparticles with a lipid/polymer ratio of 0.2. Nanoparticles with the optimal composition significantly enhanced the oral bioavailability of enoxaparin with a 4.5-fold increase in AUC in comparison with a solution of enoxaparin. In conclusion, GMO/CS based PLNs can provide a new insight to develop orally applicable delivery system for hydrophilic macromolecules. Their absorption can be enhanced with proposed PLNs and preparation of this PLNs was also found to be easy comparing to other similar methods.

Chemotherapy is an important approach for clinical cancer treatment. However, the success of chemotherapy is usually hindered by the occurrence of intrinsic or acquired multidrug resistance of cancer cells. Herein, we reported an effective approach to overcome doxorubicin (DOX) resistance in MCF-7/ADR breast cancer using DOX-loaded pH-responsive micelles. The micelles were prepared from a pH-responsive diblock copolymer, poly(ethylene glycol)-block-poly(2-(diisopropylamino)ethyl methacrylate) (PEG-b-PDPA), and a vitamin E derivate (D-α-tocopheryl polyethylene glycol 1000 succinate, TPGS) (denoted as PDPA/TPGS micelles). At neutral pH of 7.4, DOX was loaded into the hydrophobic core of PDPA/TPGS micelles via a film sonication method. After cellular uptake, the DOX payload was released in early endosomes by acidic pH-triggered micelle dissociation. Meanwhile, the TPGS component synergistically improved the cytotoxicity of DOX by targeting mitochondrial organelles and reducing the mitochondrial transmembrane potential. In vitro cell culture experiments using DOX-resistant MCF-7/ADR cells demonstrated that PDPA/TPGS micelles reduced the IC50 of DOX by a sixfold magnitude. In vivo animal studies showed that DOX-loaded PDPA/TPGS micelles (PDPA/TPGS@DOX) inhibited tumor growth more efficiently than free DOX in a nude mouse model bearing orthotopic MCF-7/ADR tumor. All these results imply that the mitochondria-targeted pH-responsive PDPA/TPGS micelles have significant potential for efficiently combating DOX resistance in breast cancer cells.

Therapeutic proteins have become a highly attractive drug of choice due to minimal toxicity, high activity and exquisite specificity. Oral delivery of protein drugs is a very interesting area for research, and, naturally, numerous technologies are required to improve the oral bioavailability of therapeutic proteins.This review article systemically generalized the major physiological barriers facing oral macromolecule delivery as well as the current approaches and novel developments in the field, including permeation enhancers, enzyme inhibitors, particulate drug delivery system, ligand delivery system, mucoadhesive delivery system, mucus penetration delivery system and other strategies.The development of composite formulation methods need to meet regulatory requirements for reproducibility, manufacturing cost, and bioavailability. So far, oral delivery of protein and peptide drugs is still facing immense challenges despite of the fact that some clinical studies are undergoing. The most advanced clinical strategies for therapeutic proteins are co-administration of absorption enhancers or protease inhibitors. Besides, rising new technologies in the field also provides a growing opportunity, such as nanotechnology, mucoadhesive and mucus penetration particulate delivery system.

Cunfu Li,1 Aizhai Xiang,2 Xianzhi Chen,3 Kai Yin,4 Jinsong Lu,4 Wenjin Yin5,6 1Department of General Surgery, Weihai Central Hospital, Weihai, 2Department of Breast Surgery, Hangzhou First People’s Hospital, Nanjing Medical University, Hangzhou, 3Department of General Surgery, Huainan First People’s Hospital, Huainan, 4Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 5Department of Breast Surgery, Fudan University Shanghai Cancer Center, 6Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China Background: Manifold data have demonstrated that the addition of bevacizumab to chemotherapy improved progression-free survival (PFS), while few trials have revealed its significant overall survival (OS) benefit. Furthermore, it still remains suspended how to maximize the benefits of bevacizumab as first-line therapy for human epidermal growth factor receptor 2 (HER2)-negative breast cancer. We sought to conduct a meta-analysis to assess the benefits of bevacizumab with chemotherapy and to identify the ideal chemotherapy partner of bevacizumab in the first-line setting for HER2-negative advanced breast cancer patients.Methods: Computerized and manual searches were performed to identify randomized clinical trials evaluating the efficacy of bevacizumab plus chemotherapy versus chemotherapy alone or bevacizumab with different chemotherapy regimens as first-line therapy for HER2-negative locally recurrent or metastatic breast cancer patients. Risk ratios or odds ratios with their 95% CIs were used to estimate the association between multiple combinations of bevacizumab with chemotherapy and various clinical outcomes.Results: With 7 trials identified, this analysis included 3,984 eligible patients. The addition of bevacizumab to chemotherapy resulted in a statistically significant improvement in PFS (P=0.019) and objective response rate (ORR; P

Metastasis is one of the major obstacles for the successful therapy of breast cancer. Although increased candidate drugs targeting cancer metastasis are tested, their clinical translation is limited by either serve toxicity or low efficacy. In present work, a nano-drug delivery system loading atorvastatin calcium (Ator) was developed for the efficient suppression of the metastasis of breast cancer. The nano-drug delivery system was constructed by a amphiphilic copolymer of methoxy polyethylene glycol-s-s-vitamin E succinate (mPEG-s-s-VES, PSV), which was consisted of a hydrophilic mPEG1k segment and a hydrophobic VES head, which were conjugated with a linker bearing amide and disulfide groups simultaneously. Self-assembly of PSV and Ator formed Ator-loaded PSV micelles (ASM) with good colloidal stability, high drug loading content (up to 50%) and great encapsulation efficiency (99.09 ± 0.28%). In cellular level, it was found that the ASM could efficiently release the Ator payload into cytosol due to detachment of PEG shell at high intracellular glutathione condition. ASM could significantly inhibit the migration and invasion of 4T1 breast cancer cells with inhibitory rates of 79.2% and 88.5%, respectively. In a 4T1 orthotropic mammary tumor metastatic cancer model, it was demonstrated that ASM could completely blocked the lung and liver metastasis of breast cancer with minimal toxicity owing to enhanced Ator accumulation in tumor and lung as compared with that of free Ator. The down-regulations of metastasis-promoting MMP-9, Twist and uPA proteins were demonstrated as the main underlying mechanism. As a result, ASM could be a promising drug delivery system for the efficient therapy of breast cancer metastasis.

The recent advances in RNA interference (RNAi) technology provided novel and promising solutions for human cancer treatment. In this study, the application of dual pH-responsive cationic micellar nanoparticles for small interfering RNA (siRNA) and paclitaxel (PTX) co-delivery to overcome cancer multidrug resistance (MDR) is reported. The in vitro siRNA transfection shows that siRNA-luciferase (Luc) loaded micelleplexes efficiently silences Luc expression in various carcinoma cell lines. The Luc knockdown ability of the micelleplexes can be enhanced by choloquine (CQ) co-incubation. However, is abolished by bafilomycin-A1 (Baf-A1) treatment. The micelleplexes are further exploited for co-delivery of siRNA-Bcl-2 and PTX to Bcl-2 overexpressing A549 lung cancer cells (A549-Bcl-2). The experimental results show that the micelleplexes could sensitize A549-Bcl-2 cells to PTX via down-regulation of anti-apoptosis gene of Bcl-2, suggesting that PDMA-b-PDPA micelleplexes are promising nanovectors for siRNA and anti-cancer drug co-delivery to overcome cancer MDR.

Fine-grained W–2Mo–7Ni–3Fe heavy alloys were fabricated by low-energy ball milling (LEBM)-assisted spark plasma sintering at a temperature range of 1000–1250 °C. The effects of sintering temperature on the phase evolution, microstructural characteristics, and mechanical properties of the alloys were studied by X-ray diffraction (XRD), scanning electron microscopy (SEM), hardness testing, and universal testing. The XRD results show that small intermetallic compounds, such as NiW and Ni 2 W 4 C, form in the alloys. The W–2Mo–7Ni–3Fe alloys are characterized by white W grains, a gray W-rich microstructure that contains Mo, and a black γ–(Ni, Fe, W, Mo) binding phase. The X-ray energy dispersive analysis (EDS) shows that the Mo, Ni, and Fe that form a solid solution with W in the gray structure gradually decrease with increasing temperature. The hardness and bending strength of the alloys initially increase and then decrease with rising sintering temperature. Moreover, the alloys sintered at different temperatures exhibit dissimilar bending fracture modes.

Objective : This study investigated functional and neuropsychological abilities in adults with mild to moderate fetal alcohol spectrum disorder (FASD). Method : Sixty-eight participants completed various neuropsychological tests such as the California Verbal Learning Test – 2 nd edition (CVLT-2), Trail Making Test parts A and B (TMTA/TMTB), Stroop Color and Word Test (Stroop), Grooved Pegboard Test (GPT), Finger Tapping Test (FTT), and Independent Living Scales (ILS). Independent samples t -tests were used to compare performance between brain scores 2 and 3. Hierarchical logistic regression was used to identify predictors for brain scores. Results : Adults with severe impairment (i.e., a brain score of 3) performed significantly worse than those with milder brain dysfunction (i.e., a brain score of 2) on TMTB, Stroop, CVLT-2, and ILS (money management, and managing home and transportation subscales). Test scores from the CVLT-2 (long-delay cued recall) and ILS (money management subscale) predicted brain scores. Conclusions : Psychosocial ability remained low in all participants and should be assessed as a discrete factor for guiding interventions in adults. The results provided an important piece of reference in support of the inclusion of psycho-emotional elements in the new diagnostic guidelines for FASD.

Yb 3+ and Er 3+ co-doped GdAlO 3 phosphors are prepared by the sol–gel method. The effect of doping concentration on the structure and fluorescence properties is investigated by X-ray diffraction (XRD) and photoluminescence, respectively. XRD pattern indicates that the sample structure belongs to orthorhombic. The photoluminescence results show that both green and red fluorescence emission and upconversion emission intensities decrease with an increase in Yb 3+ concentration due to the cross-relaxation process between Yb 3+ and Er 3+ ions. Based on the emission spectra, the mechanism of the upconversion emission is discussed, and we concluded that the upconversion emission is a two-photon process.

A facile method by combining bottom-up and top-down approaches was developed to construct uniform three-dimensional (3D) ZnO nanowires (NWs)/silicon microrod (SiMR) hybrid architectures. Patterned SiMR arrays with controlled geometry and density were structured by photolithography and chemical etching on single-crystal silicon wafers, which subsequently served as 3D scaffolds for the ZnO NW growth. In contrast to the top-down approach to fabricate SiMR scaffolds, the radial ZnO NWs grown conformally on the SiMRs follow a bottom-up method by employing a modified carbon-assisted self-catalytic growth via chemical vapor deposition. The light absorption and the photocatalytic capability of methyl red of ZnO NW arrays were demonstrated to improve significantly by the 3D constructions. The method is expected to be applicable to the synthesis of 3D hybrid structures of other nanomaterials. The heterojunction and ultralarge surface area of the 3D architectures are promising for diverse applications in photovoltai...

Acquiring stable binary wide band-gap semiconductor (WBS) materials with high p-type mobility is essential for the development of WBS optoelectronic devices. CuI is a p-type WBS material with a large band gap (3.1 eV) and high exciton binding energy (62 meV). However, the semiconductor characteristics of the CuI single crystal are unknown due to the lack of a large sized and high quality crystal. Our approach focuses on the design of the mineralizer for the hydrothermal method to effectively control the growth habit and the impurity concentration in the crystal. A large size (15 mm × 10 mm × 1 mm) and high quality CuI single crystal is obtained by using a new mineralizer (NH4I + KI). The crystal shows high p-type mobility (43.9 cm2·V−1·S1−). The strong and sharp band-edge emission at 410 nm indicates that the interband excitonic transition dominates the optical response in the spectrum. Such a binary crystalline material may open the way to new applications in optoelectronic devices.

The subsolidus phase relations of the ternary system ZnO–B2O3–V2O5 were investigated by means of X-ray diffraction (XRD). There is no ternary compound in the system. There are seven binary compounds which have been reported in the ZnO–B2O3–V2O5 system, which can be divided into eight 3-phase regions. The phase diagram of Zn4V2O9–Zn3B2O6 pseudo-binary system from 740 °C to 1250 °C has also been constructed through XRD and differential thermal analysis (DTA) methods, and the result reveals this system is eutectic system. The eutectic temperature is 780 °C and eutectic point comprises 55% Zn4V2O9 and 45% Zn3B2O6. The mixture with the composition near the eutectic point might be the suitable flux for ZnO crystal growth.

The subsolidus phase relations of the ternary system ZnO–V 2 O 5 –WO 3 was investigated by means of X-ray diffraction (XRD) analysis. The phase relations had been constructed. Five binary compounds, five tie lines and six three-phase regions were determined in this system. The possible component regions for ZnO single crystal flux growth were discussed. The phase diagram of Zn 4 V 2 O 9 –ZnWO 4 pseudo-binary system from 740 °C to 1300 °C was also determined through XRD and differential thermal analysis (DTA) methods. DTA results indicated this system was a eutectic system, and the eutectic temperature was 880 °C and eutectic point component was 78 mol% Zn 4 V 2 O 9 and 22 mol% ZnWO 4 . The compounds composed of 78 mol% Zn 4 V 2 O 9 and 22 mol% ZnWO 4 might be suitable flux for ZnO crystal growth.

The combination of chemotherapy and RNA interference is a promising approach for efficient cancer therapy. However, the success of such a strategy is hampered by the lack of suitable vectors to coordinate small interfering RNA (siRNA) and chemotherapeutic drug into one single platform. We herein report a novel triple-layered pH-responsive micelleplex loading siRNA and alkylated cisplatin prodrug for NF-Kappa B targeted treatment of metastatic breast cancer. The micelles were self-assembled from poly(ethylene glycol)-block-poly(aminolated glycidyl methacrylate)-block-poly(2-(diisopropyl amino) ethyl methacrylate) (PEG-b-PAGA-b-PDPA) triblock copolymers. At pH 7.4, the cisplatin prodrug was encapsulated in the hydrophobic PDPA core and siRNA was loaded on the positively charged PAGA interlayer to form the micelleplexes. The PEG corona can prevent protein absorption during blood circulation, minimize non-specific interaction with the reticuloendothelial system, and prolong the systemic circulation of the micelleplexes. The positively charged PAGA interlayer can facilitate deep tumor penetration of the micelleplexes, which, upon cellular uptake, are dissociated in the early endosomes to release anticancer drug payload due to protonation of the PDPA core. Using a 4T1 breast cancer model, we demonstrate that this novel micelleplex co-loaded with cisplatin prodrug and siRNA-p65 is able to simultaneously inhibit tumor growth and suppress distant metastasis of the cancer cells by downregulating NF-kappa B expression. The results reported in this study suggest that siRNA and anticancer drug co-delivery using pH-responsive micelleplexes is a promising strategy for efficient treatment of metastatic cancer.

Heat shock factors (HSFs) are ubiquitous in eukaryotes with diversification in structural feature and biological function in plants. Based on the availability of whole cucumber genome sequences, we characterized the cucumber HSFs gene family which contains at least 21 members. Sequence alignments show that all HSFs possess a specific DNA binding domain (DBD). These HSFs genes are unevenly distributed in the seven cucumber chromosomes except for Csa026480 (located on Scaffold_repeat037858). Phylogenetic analysis shows that HSFs in cucumber could be divided into three families, in which family I included three categories (A, B and C). Phylogenetic tree also reveals nine pairs of orthologous genes and three pairs of paralogous genes, suggesting that HSFs gene family have existed before the separation of cucumber and Arabidopsis thaliana. EST analysis shows that cucumber HSFs may be involved in the development of fruit, female flower and hermaphrodite flower. qRT-PCR analysis demonstrated that these genes exhibit different expression levels in heat stress treatment. These results will provide a foundation for the functions of the HSF gene family.

1. In this article, the modulatory effects of extracts from vinegar-baked Radix Bupleuri (VBRB) and saikosaponins on the activity of CYP1A2, CYP2C9 and CYP3A4 were investigated in vitro. 2. Microsomal in vitro incubation method was utilized to simulate metabolic reaction under physiological environment by incubating the marker with liver microsomes in the absence or presence of VBRB and saikosaponins. The contents of 4-acetamidophenol, 6β-hydroxyltestosterone and 4-hydroxydiclofenac, the metabolites of phenacetin, testosterone and diclofenac, which were selected as specific probe drugs of CYP1A2, CYP2C9 and CYP3A4, respectively, were analyzed by high-performance liquid chromatography. 3. The production of the metabolites was incubation time dependent. The modulatory effects of different VBRB extracts and saikosaponins on CYP isoforms increased with concentration. Among all the extracts studied, BC1 has a strong inhibition effect compared to the three CYP isoforms tested, while the others have only significant inhibition on the activity of CYP2C9. 4. This in vitro study demonstrated that various extracts of VBRB tested in this study have negligible potential to interfere with CYP1A2- and CYP3A4-metabolized drugs; risk of herb-drug interaction might occur when VBRB is concurrently taken with CYP2C9 substrates.

Despite the exciting advances in cancer therapy over past decades, tumor metastasis remains the dominate reason for cancer-related mortality. In present work, DNA-wrapped gold nanorods with doxorubicin (DOX)-loading (GNR@DOX) were developed for treatment of metastatic breast cancer via a combination of chemotherapy and photothermal ablation. The GNR@DOX nanoparticles induced significant temperature elevation and DOX release upon irradiation with near infrared (NIR) light as shown in the test tube studies. It was found that GNR@DOX nanoparticles in combination with laser irradiation caused higher cytotoxicity than free DOX in 4T1 breast cancer cells. Animal experiment with an orthotropic 4T1 mammary tumor model demonstrated that GNR@DOX nanoplatform significantly reduced the growth of primary tumors and suppressed their lung metastasis. The Hematoxylin and Eosin (H&E) and immunohistochemistry (IHC) staining assays confirmed that the tumor growth inhibition and metastasis prevention of GNR@DOX nanoparticles were attributed to their abilities to induce cellular apoptosis/necrosis and ablate intratumoral blood vessels. All these results suggested a considerable potential of GNR@DOX nanoplatform for treatment of metastatic breast cancer.

In Traditional Chinese Medicine, liver targeting is usually achieved by coadministration with Vinegar-baked Radix Bupleuri (VBRB), but the mechanism is unclear. In this paper, the influence of VBRB on the activity of β-glucuronidase was investigated and compared with that of saikosaponins. The activity of β-glucuronidase was measured by microplate reader using a 4-nitrophenyl-β-d-glucuronide substrate. The change of 4-nitrophenol content was used to characterize the activity of β-glucuronidase. Bupleurum chinenes were found to be the inhibitor of β-glucuronidase. The inhibition rate of Bupleurum chinenes extracts BC1 (high molecular weight polysaccharides), BC2 (ethanol soluble/water insoluble component), BC3 (extracted by n-butanol, soluble in water), and BC4 (low molecular weight water soluble parts) on the activity of β-glucuronidase was found to be 45.15%, 33.94%, 24.94%, and 34.54%, respectively, after 1 h incubation, with BC1 showing the highest inhibition rate. In contrast, the saikosaponins were demonstrated to be the promoter of β-glucuronidase, with promotion rates of 333.56%, 217.04%, 247.87%, 149.75%, and 92.50% for saikosaponin standard samples A, B, B2, C, and D, respectively, (p0.05). In conclusion, inhibiting the activity of β-glucuronidase might be one of the reasons why VBRB could influence drug distribution upon its coadministration with other drugs. Since saikosaponins and VBRB extracts have opposite effect, more attention should be paid to the content of saikosaponins in the extracts upon its application.

An appropriate co-delivery system for chemotherapeutic agents and nucleic acid drugs will provide a more efficacious approach for the treatment of breast cancer by reversing multidrug resistance (MDR). In this work, a new amphiphilic poly (β-amino ester), poly[(1,4-butanediol)-diacrylate-β-5-polyethylenimine]-block-poly[(1,4-butanediol)-diacrylate-β-5-hydroxy amylamine] (PDP-PDHA) was synthesized, and the doxorubicin (DOX) and survivin-targeting shRNA (shSur) co-loading nanoparticle (PDNs) were prepared. The pH-sensitive poly[(1,4-butanediol) diacrylate-β-5-hydroxy amylamine] (PDHA) endowed PDNs both pH-triggered drug release characteristics and enhanced endo/lysosomal escape ability, thus improving the cytotoxicity of DOX and the transfection efficiency. PDNs also increased the DOX accumulation, down-regulated 57.7% survivin expression, induced 80.8% cell apoptosis and changed the cell cycle in MCF-7/ADR cells. In the MCF-7/ADR tumor-bearing mice models, after administrated intravenously, PDNs raised the accumulation of DOX and shSur in the tumor tissue by 10.4 and 20.2 folds, respectively, resulting in obvious inhibition of the tumor growth with tumor inhibiting rate of 95.9%. The combination of DOX and RNA interference showed synergistic effect on overcoming MDR. Therefore, PDNs could be a promising co-delivery vector for effective therapy of drug resistant breast cancer.

The recent advances in RNA interference (RNAi) technology provided novel and promising solutions for human cancer treatment. In this study, the application of dual pH-responsive cationic micellar nanoparticles for small interfering RNA (siRNA) and paclitaxel (PTX) co-delivery to overcome cancer multidrug resistance (MDR) is reported. The in vitro siRNA transfection shows that siRNA-luciferase (Luc) loaded micelleplexes efficiently silences Luc expression in various carcinoma cell lines. The Luc knockdown ability of the micelleplexes can be enhanced by choloquine (CQ) co-incubation. However, is abolished by bafilomycin-A1 (Baf-A1) treatment. The micelleplexes are further exploited for co-delivery of siRNA-Bcl-2 and PTX to Bcl-2 overexpressing A549 lung cancer cells (A549-Bcl-2). The experimental results show that the micelleplexes could sensitize A549-Bcl-2 cells to PTX via down-regulation of anti-apoptosis gene of Bcl-2, suggesting that PDMA-b-PDPA micelleplexes are promising nanovectors for siRNA and anti-cancer drug co-delivery to overcome cancer MDR.

The subsolidus phase relations of the ternary system ZnO–V 2 O 5 –WO 3 was investigated by means of X-ray diffraction (XRD) analysis. The phase relations had been constructed. Five binary compounds, five tie lines and six three-phase regions were determined in this system. The possible component regions for ZnO single crystal flux growth were discussed. The phase diagram of Zn 4 V 2 O 9 –ZnWO 4 pseudo-binary system from 740 °C to 1300 °C was also determined through XRD and differential thermal analysis (DTA) methods. DTA results indicated this system was a eutectic system, and the eutectic temperature was 880 °C and eutectic point component was 78 mol% Zn 4 V 2 O 9 and 22 mol% ZnWO 4 . The compounds composed of 78 mol% Zn 4 V 2 O 9 and 22 mol% ZnWO 4 might be suitable flux for ZnO crystal growth.

Bitespiramycin is a macrolide antibiotic consisting of a mixture of some nine spiramycin ester derivatives. It has a similar spectrum of antibiotic activity to that of spiramycin but has superior pharmacokinetic properties. In this study, a rapid and facile LC/ESI-MSn method was applied to study the metabolism of bitespiramycin in rat following a single oral dose (80 mg kg-1). Concentrations of parent drug constituents and metabolites were determined in plasma, urine, feces and bile. Concentrations of parent drug constituents and metabolites in plasma were very low. In urine, feces and bile, parent drug constituents and 38 metabolites were identified on the basis of their chromatographic and mass spectrometric properties. The identity of 17 metabolites was confirmed by comparison with reference substances. The principal metabolites were the corresponding spiramycins formed by hydrolysis of the 4''-(3-methylbutanoate) groups. Other important metabolic pathways were: hydrolytic loss of the forosamine and mycarose sugars; aldehyde reduction; cysteine conjugation of the aldehyde group; and hydrolysis of the lactone ring. Products formed by lactone ring opening were found only in urine, and those formed by aldehyde reduction were found only in feces. Aldehyde reduction and hydrolytic loss of forosamine represent novel biotransformation pathways for spiramycin derivatives.

1. A sensitive liquid chromatographic-tandem mas spectrometric assay was developed and validated to determine the major metabolite of betahistine, 2-pyridylacetic acid, in human plasma. 2. The analyte was extracted from plasma samples by liquid-liquid extraction and analysed using liquid chromatography-tandem mass spectrometry with an electrospray ionization interface. The method has a lower limit of quantitation of 1 ng ml(-1) fir a 0.5-ml plasma aliquot. The intra- and interday precision (relative standard deviation), calculated from quality control (QC) samples, was less than 10%. Accuracy as determined from QC samples was within +/-7%. 3. The validated method was successfully applied to a pharmacokinetic study of betahistine in healthy volunteers. After oral administration of a single dose of 24 mg betahistine mesylate to 20 healthy Chinese male volunteers, Cmax was 339.4 ng ml(-1) (range 77.3-776.4 ng ml(-1)). The t(1/2) was 5.2 h (range 2.0(-1)-11.4h). The AUC(0-t) obtained was 1153.5 ng ml(-1) h (range 278.5-3150.8 ng ml(-1)). The disposition of the metabolite exhibited a marked interindividual variation. 4. The plasma concentrations of the parent drug were less than 0.5 ng ml(-1), suggesting that it undergoes almost complete first-pass metabolism. The reported two active metabolites were not detected in the plasma of any volunteer. Although there is no evidence that the major metabolite has pharmacological activity, the clinical importance of 2-pyridylacetic acid in humans should be reinvestigated.

Wormlike micelles with intracellular pH-activating properties were developed. The micelles remained in a “silent” state at physiological pH conditions (i.e. pH 7.4), but were activated in the acidic microenvironment of endocytic vesicles. The wormlike micelles could be employed as nanovectors for the intracellular delivery of hydrophobic drugs for cancer therapy.