Search

The combination of chemotherapy and gene therapy has been indicated as a promising approach for cancer therapy. However, this combination strategy is still faced a challenge by the lack of suitable carriers to co-loaded chemotherapeutic drug and gene into one single nanoplatform. In this study, a tumor-targeted HC/pIL-12/polyMET micelleplexes were developed for the co-loading and co-delivery of cisplatin (CDDP) and plasmid encoding interleukin-12 gene (pIL-12), which would be utilized to generate synergistic actions through chemotherapy sensitization and microenvironment modulation. The HC/pIL-12/polyMET exhibited desirable particle size, superior serum stability, effective intracellular CDDP release and pIL-12 transfection efficiency. More important, the HC/pIL-12/polyMET generated the enhanced LLC cell proliferation inhibition and apoptosis induction efficiency. The long-circulating HC/pIL-12/polyMET micelleplexes promoted the accumulation of CDDP and pIL-12 in tumor site, which resulted in significantly inhibiting the growth of lung cancer, and prolonging the overall survival of tumor-bearing mice. The underlying immune mechanism demonstrated the combination of CDDP and pIL-12 activated immune effector cells to release IFN-γ and induced M1-type differentiation of tumor-related macrophages, thereby generating synergistic chemoimmunotherapy effect. Taken together, this study may provide an effective strategy for drug/gene co-delivery and cancer chemoimmunotherapy. STATEMENT OF SIGNIFICANCE: Chemoimmunotherapy has been indicated as an approach to improve efficacy of cancer therapy. Herein, a tumor-targeted micelleplexes (HC/pIL-12/polyMET) were developed for the co-delivery of cisplatin (CDDP) and plasmid encoding IL-12 gene (pIL-12), which can employ the synergistic effects through chemotherapy sensitization and microenvironment modulation. The HC/pIL-12/polyMET exhibited desirable particle size, superior serum stability, high gene transfection efficiency and antitumor activity on tumor cell proliferation inhibition and apoptosis induction. More importantly, the long-circulating HC/pIL-12/polyMET micelleplexes could effectively accumulate in tumor sites and then rapidly release the CDDP and pIL-12, significantly inhibit the growth of lung cancer. This strategy provides a new concept for chemo-gene combination with a strengthened overall therapeutic efficacy of chemoimmunotherapy.

Indoleamine 2,3-dioxygenase (IDO), an immune checkpoint protein, can cause the depletion of tryptophan (Trp) and accumulation of its metabolite of kynurenine (Kyn) in cancer cells, and generates the immunosuppressive microenvironment that supports tumor cell growth. A novel immunoregulatory prodrug micelle based on polyethylene glycol-derivatized an IDO-selective inhibitor of 1-methyltryptophan (1-MT), PEG-Fmoc-1-MT, was developed for inhibiting the IDO activity of the conversion of Trp to Kyn in tumor microenvironments. To investigate the 1-MT distribution and Trp/Kyn ratios in mice tumors with PEG-Fmoc-1-MT prodrug micelles treatment, a HPLC–MS/MS method for simultaneous determination of 1-MT and IDO biomakers of Trp and Kyn in mouse tumors was developed and validated. Triple-quadrupole mass spectrometry with positive electrospray ionization as source ionization in multiple reaction monitoring at m/z 219.0 → 160.1, 205.0 → 118.2, 209.0 → 146.1 and 249.3 → 148.3 was used for determination of 1-MT, Trp, Kyn and matrine (internal standard). The method demonstrated good linearity at the concentrations ranging from 10 to 10,000 ng/mL and lower limits of quantitation of 1 ng/mL for 1-MT, Trp and Kyn, respectively. The validated method was successfully applied to 1-MT tumor biodistribution and Trp/Kyn ratio studies in 4T1 tumor bearing mice i.v. with PEG-Fmoc-1-MT prodrug micelles. The mice tumors with PEG-Fmoc-1-MT prodrug micelles treatment exhibited higher 1-MT accumulation and lower Trp/Kyn ratio, in comparison with those of mice with 1-MT solution treatment. The developed PEG-Fmoc-1-MT prodrug micelles could be a promising IDO immunoregulatory prodrug micelles for cancer immunotherapy.

Charge density wave (CDW) in two-dimensional (2D) crystals plays a vital role in tuning the interface structures and properties. However, how the CDW tunes the self-assembled molecular superlattice still remains unclear. In this study, we investigated the self-assembled manganese phthalocyanine (MnPc) molecular superlattice on single-layered 1T- and 2H-NbSe2 crystals under regulation by distinct CDW patterns. We observe that, in low coverage, MnPc molecules preferentially adsorb on 2H-NbSe2 compared to 1T-NbSe2. With increasing coverage, MnPc can form a highly ordered superlattice on 2H-NbSe2; however, it is randomly distributed on 1T-NbSe2. We reveal a perfect geometric commensurability between the molecular superlattice and intrinsic CDW pattern in 2H-NbSe2 and a poor commensurability for that of 1T-NbSe2. We believe that the subtly different geometric commensurability dominates the different adsorption and arrangement of the molecular superlattices on 2D CDW patterns. Our study provides a pioneering approach for tuning the molecular superlattices using the CDW patterns.

Background: Conventional cancer therapeutics has enormous toxicity and severe side effects that generate multi-drug resistance. Therefore, an urgent need exists for new alternative therapeutic agents for cancer treatment. Cepharanthin (CEP) has anti-cancer potential but has poor aqueous solubility, which limits its clinical use. Nanosuspensions (NS) are attractive as insoluble drug delivery systems. Objectives: In this study, we used D-alpha Tocopherol acid Polyethylene Glycol Succinate (TPGS), Polyvinylpyrrolidone (PVP) VA64, and Croscamellose Sodium (CCS) as stabilizers to produce TPGS-CEP-NS, PVP VA64-CEP-NS, and CCS-CEP-NS by wet-milling technology, and then characterized the NS and evaluated their functional activities in vitro. Methods: EP Nanosuspensions (CEP-NS) were prepared by the wet-milling method. The prepared NS were characterized by particle size distribution, zeta potential, morphology, surface properties, and molecular interactions. The NS were evaluated for their effects on HepG2 cells in vitro. The evaluations included assessment of cellular cytotoxicity, cellular apoptosis, NS uptake by cells, and mitochondrial membrane potential changes. Results: CEP-NS showed an appropriate particle size and were physically stable. All CEP-NS exhibited HepG2 enhanced anti-proliferative effects by reducing cell viability, enhanced cellular uptake, induced cellular apoptosis, and mitochondrial membrane potential loss. Conclusion: : CEP-NS may be effective therapeutic agents for the treatment of hepatocellular carcinoma.

The combination therapy of cisplatin (CDDP) and metformin (MET) is a clinical strategy to enhance therapeutic outcomes in lung cancer. However, the efficacy of this combination is limited due to the asynchronous pharmacokinetic behavior of CDDP and MET, used as free drugs. Therefore, in this work, hyaluronic acid-cisplatin/polystyrene-polymetformin (HA-CDDP/PMet) dual-prodrug co-assembled nanoparticles were developed, with precise ratiometric co-delivery of CDDP and MET for chemo-immunotherapy against lung cancer. The HA-CDDP/PMet NPs showed a spherical morphology with an average particle size of 166.5 nm and a zeta potential of -17.4 mV at an HA-CDDP and PMet mass ratio of 1/1. The content of CDDP and MET in HA-CDDP/PMet NPs was 3.7% and 15.2%, respectively. In vitro antitumor effects of CDDP and MET resulted in an improved synergistic action on proliferation inhibition and apoptosis induction on Lewis lung cancer cells. Moreover, in vivo by co-delivered HA-CDDP/PMet NPs into tumor cells, with an excellent intracellular CDDP and MET cleavage. These nanoparticles exhibited significantly increased tumor accumulation and tumor growth inhibition and prolonged animal overall survival in Lewis lung cancer bearing mice without nephrotoxicity, excess of free drugs and homo-prodrugs. The synergistic effect of MET and CDDP in HA-CDDP/PMet NPs resulted in up-regulation of the cleaved poly(ADP)-ribose polymerase (PARP) protein to induce tumor cell apoptosis, and down-regulation of the excision repair cross-complementation group 1 (ERCC1) protein level to decrease the resistance to CDDP. The synergistic effect of MET and CDDP in HA-CDDP/PMet NPs also resulted in induction of the adenosine monophosphate (AMP)-activated protein kinase-α (AMPK-α) pathway and inhibition of the mammalian target of rapamycin (mTOR), finally exerting a chemotherapeutic effect and modulating a potent immunotherapeutic function with an increase in CD4+ and CD8+ T cells, a concomitant decrease in regulatory T (Treg) cells, and an increased expression of the cytokines IFN-γ and TNF-α. Therefore, the immunochemotherapy using CDDP and MET mediated by this dual prodrug co-assembled nano-platform might provide a promising treatment strategy against lung cancer.

The alpine meadow ecosystem on the Qinghai-Tibetan Plateau (QTP) is very sensitive to warming and plays a key role in regulating global carbon (C) cycling. However, how warming affects the soil organic carbon (SOC) pool and related C inputs and outputs in alpine meadow ecosystems on the QTP remains unclear. Here, we combined two field experiments and a meta-analysis on field experiments to synthesize the responses of the SOC pool and related C cycling processes to warming in alpine meadow ecosystems on the QTP. We found that the SOC content of surface soil (0-10 cm) showed a minor response to warming, but plant respiration was accelerated by warming. In addition, the warming effect on SOC was not correlated with experimental and environmental variables, such as the method, magnitude and duration of warming, initial SOC content, mean annual temperature, and mean annual precipitation. We conclude that the surface soil organic carbon content is resistant to climate warming in alpine meadow ecosystems on the QTP.

Soil organic carbon (SOC) decomposition can potentially feedback to climate change. However, the biotic, abiotic and inherent factors controlling the stability of soil carbon, and changes in these factors with soil depth, remain poorly understood. In this study, we combined a number of complementary methods to quantify the biological, thermal, chemical, molecular and isotopic indices of soil organic matter (SOM) stability along the soil profile (0–70 cm) in two contrasting alpine ecosystems (meadow and shrubland) on the Tibetan Plateau. Firstly, we conducted an aerobic lab–incubation experiment on root–free, sieved soils. The number of days to respire 5% of initial SOC, a biological index of SOM stability, decreased with soil depth. Moreover, the temperature at which half of SOM mass loss (TG–T50), a thermal index of SOM stability, increased with soil depth. Additionally, hot–water extractable organic carbon (HWEOC) per gram SOC, a chemical index of SOM stability, showed weak (meadow) and little (shrubland) declining trend with depth. Further, we used Fourier–transform infrared spectroscopy (FTIR) and nuclear magnetic resonance (NMR) spectroscopy to characterize the molecular composition of SOM. The index of recalcitrance of FTIR spectra and the combined index of aliphaticity and aromaticity of NMR spectra both increased with depth, suggesting that the molecular composition of SOM was more complex with increasing depth. Finally, the isotopic values of SOM (13C and 15N) and the 14C–based SOC turnover time both increased with depth, indicating that the isotopic indices of SOM stability also increased with depth. Overall, our results suggest that the thermal, chemical, molecular and isotopic indices of SOM stability were mutually correlated and all showed increasing trend with increasing soil depth in the two alpine ecosystems, although the biological index (as measured by aerobic incubation of root–free sieved soils) showed the opposite results.

Long-term nitrogen (N) addition can affect soil organic carbon (SOC) pool within different soil fractions with different turnover rates. However, the mechanisms of these effects, particularly in alpine grassland ecosystems, are not clear. We studied the responses of SOC content in different soil fractions to N addition based on a six-year N addition field experiment in an alpine meadow ecosystem on the Tibetan Plateau. We measured soil chemical and microbial properties, and SOC content in bulk soil, particular organic matter (POM) and mineral-associated organic matter (MAOM) fractions in response to N addition. N addition increased soil N availability, decreased soil pH and microbial biomass, but had minimal effect on plant biomass, soil enzyme activity, and SOC content in bulk soil. With increasing levels of N addition, SOC in the POM fraction (POC) showed a significant negative trend, while SOC in the MAOM fraction (MAOC) did not change significantly. As plant biomass input and soil enzyme activity were not significantly altered with N addition, the decline in POC was likely caused by changes in microbial physiology (carbon use efficiency), while the insignificant change in MAOC may be determined by the balance between input (from microbial necromass) and output (from microbial decomposition). Taken together, our study showed that the less-protected POC fraction is more vulnerable to N addition than the more-protected MAOC fraction in the alpine grassland. This finding may improve the prediction of soil C dynamics in response to N deposition in alpine grassland ecosystems on the Tibetan Plateau.

The mechanism of inclusion-induced initial pitting corrosion of Al-Ti-Ca complex deoxidized steel with Ce treatment was studied by the experimental investigation and theoretical calculation. To figure out which phases of complex inclusion containing different components induced initial pitting corrosion, the scanning electron microscope (SEM) analysis, the continuous immersion experiments and density functional theory (DFT) calculation were conducted. Two types of inclusions and different pit morphologies were observed. The pit initially occurred at the sulfide inclusions (MnS and Ce2O2S) rather than the steel matrix due to the lower the electronic work function (EWF) of this compound compare to the steel matrix and other phases. In addition, the Ce-rich inclusion possessed the higher pitting corrosion resistance than the same type of inclusions. Finally, a schematic diagram was established to explain the mechanism of the different inclusions in initiating and proceeding pitting corrosion.

The dose-related toxicity has been one of the major limiting factors in cisplatin (CDDP)-based cancer therapy. Based on it, a novel strategy of combination of CDDP and interleukin-12 (IL-12) gene is an effective treatment, which resulted in synergistic antitumor effects while avoiding dose-limiting toxicity in a cancer mice model. However, efficient encapsulation and co-delivery of CDDP and IL-12 gene while retaining their active remains a significant challenge. In this study, a tumor-targeted micelleplexes (HC/pIL-12/polyMET) were developed for the co-delivery of the chemotherapeutic drug CDDP and plasmid encoding IL-12 gene (pIL-12). The polymetformin (polyMET) were synthesized as the cationic polymer for condensation of pIL-12 to form a cationic pIL-12/polyMET micelleplexes, and the anionic HC prodrug was then collaboratively assembled to pIL-12/polyMET to stabilize the micelleplexes and co-delivery of CDDP. The HC/pIL-12/polyMET micelleplexes exhibited desirable particle size, excellent stability and high pIL-12 loading capacity. More importantly, in vitro cell experiments verified that HC/pIL-12/polyMET micelleplexes could significantly improve the uptake by LLC tumor cells and promote the endosomal escape of CDDP and pIL-12, resulting in enhanced cytotoxicity and apoptosis induction. Besides, this strategy significantly enhanced the pIL-12 transfection efficiency in LLC cells. In vivo studies further revealed that HC/pIL-12/polyMET micelleplexes possessed the highest drug accumulation and excellent pIL-12 transfection efficiency in tumors of LLC tumor-bearing mice. Consequently, the HC/pIL-12/polyMET micelleplexes exhibit significantly tumor growth inhibition, and prolong the overall survival of lung cancer mice model. The underlying immune mechanism demonstrated that the combination of CDDP and pIL-12 activated immune effector cells to release IFN-γ and induced M1-type differentiation of tumor-related macrophages, thereby generating synergistic chemoimmunotherapy effect. Taken together, this study may provide an effective strategy for drug/gene co-delivery and cancer chemoimmunotherapy.

In order to solve the problem of where, why, and how to start pitting, it is necessary to study the influence of different dissolution activity of the internal heterogeneous structures of the complex inclusions. In this paper, mechanism of internal activity difference of two typical Yttrium composite inclusions on pitting corrosion is revealed from atomic scale by using immersion test, FE-SEM/EDS analysis and first-principles calculations. The results show that, for Mg-Y-S composite inclusions, pitting potential is lower than that of the matrix, therefore, The matrix around the composite inclusions dissolves preferentially; for Y-S-O composite inclusions with core-shell structure, Y-O inclusions in the shell are deformed and cracked due to the internal stress of the matrix and Y-S during the immersion process, resulting in the simultaneous dissolution of inclusions and steel matrix.

The particles and microstructure characteristics of coarse-grained heat-affected zone (CGHAZ) in Al–Ti–Mg killed steels with different Al contents were investigated. The results show that inclusion in high Al steel consists of Al–Mg oxide surrounded with a layer of MnS. However, inclusion in low Al steel is Al–Ti–Mg oxide covered with a layer of MnS, effectively promoting the formation of acicular ferrite. The precipitates of both steels are (Ti, Nb)N, the finer and more dispersed inclusions and precipitates in low Al steel can effectively inhibit austenite grain growth by grain boundary pinning during the thermal cycle. The fine-grained microstructure is obtained in CGHAZ of the low Al steel due to the pinning effect of finer particles and the high density of acicular ferrite.

The cationic dimethyldioctadecylammonium/trehalose 6,6,9-dibehenate (DDA/TDB) liposome is as a strong adjuvant system for vaccines, with remarkable immunostimulatory activity. The mucosal administration of vaccines is a potential strategy for inducing earlier and stronger mucosal immune responses to infectious diseases. In this study, we assessed whether the intranasal administration of cationic DDA/TDB liposomes combined with influenza antigen A (H3N2) can be used as a highly efficacious vaccine to induce mucosal and systemic antibody responses. Confocal laser scanning microscopy and a flow-cytometric analysis showed that the uptake of the cationic DDA/TDB liposome carrier was significantly higher than that of neutral 1,2-distearoyl-sn-glycero-3-phosphocholine/cholesterol (DSPC/Chol) or cationic 1,2-dioleoyl-3-trimethylammonium-propane/3β-(N-[N',N'-dimethylaminoethane]-carbamoyl (DOTAP/DC-Chol) liposomes. Our results indicate that the cationic DDA/TDB liposome is more effective in facilitating its uptake by dendritic cells (DCs) in vitro than the DSPC/Chol or DOTAP/DC-Chol liposome. DCs treated with DDA/TDB liposomes strongly expressed CD80, CD86, and MHC II molecules, whereas those treated with DSPC/Chol or DOTAP/DC-Chol liposomes did not. C57BL/6 mice intranasally immunized with H3N2-encapsulating cationic DDA/TDB liposomes had significantly higher H3N2-specific s-IgA levels in their nasal wash fluid than those treated with other formulations. The DDA/TDB liposomes also simultaneously enhanced the serum IgG IgG2a, IgG1, and IgG2b antibody responses. In summary, DDA/TDB liposomes effectively facilitated their uptake by DCs and DCs maturation in vitro, and induced significantly higher mucosal IgA, systemic IgG, IgG1, and IgG2b antibody titres than other formulations after their intranasal administration in vivo. These results indicate that DDA/TDB liposomes are a promising antigen delivery carrier for clinical antiviral applications.

Ternary photocatalyst, reduced graphene oxide-ZnFe 2 O 4 -polyaniline (RZP), has been successfully developed by the in-situ polymerization of aniline on the reduced graphene oxide-ZnFe 2 O 4 (RG/ZF) surface for sewage purification. The SEM, TEM and STEM images suggest that PANI has coated the RG/ZF composite well. The XRD, TG-DTG and FT-IR analysis confirm that there are some interactions between RG/ZF composite and PANI. Importantly, the decontamination performance of RZP composites has been investigated using RhB as a model organic in view of adsorption and photocatalysis. On one hand, thermodynamic researches indicate that the adsorption behaviors of RZP composites conform to the Langmuir model, and their adsorption mechanism can be well described by the second-order kinetic model. On the other hand, RZP composites with different mass ratios of PANI to RG/ZF ( m P/RZ ) present a better photocatalytic activity than that of RG/ZF composites, and their photocatalytic behaviors under different pH could be described by the first-order kinetic model. Furthermore, it can be observed that the RZP composite with m P/RZ = 0.4 has the excellent photocatalytic activity and photocatalytic stability under pH = 1. Finally, the possible photocatalytic degradation mechanisms of the RZP composite on RhB have been discussed. These results can unveil that the prepared RZP photocatalyst is very promising for application in water purification.

In Al-Ti-Mg killed steels, the use of complex deoxidation products, which act as heterogeneous nucleation sites for fine intragranular ferrite, has been acknowledged as an effective way for grain refinement. In this study, we investigated the interaction between Mn solute atoms and different oxide inclusions (such as MgO, MgTi₂O₄, MgTiO₃, Ti₂O₃, Ti₃O₅, Al₂O₃, MgAl₂O₄) experimentally and using first-principles calculations, to identify the oxides that can effectively lead to the formation of local Mn-depleted zones promoting the nucleation of intragranular ferrite. The results show that MgTi₂O₄, MgTiO₃ are effective for partition of Mn atoms into oxides, while MgO, Al₂O₃, MgAl₂O₄ are ineffective for the formation of local Mn-depleted zones. Furthermore, the calculations show that Mn atoms exist as a simple solute by replacing Mg atoms in MgO, MgTi₂O₄ and MgTiO₃. Except by forming complex Ti-Mn oxides, such as MnTi₂O₄ and MnTiO₃, Mn atoms can also exist as a simple solute in Ti₂O₃ by occupying vacancy positions in their crystals. Ti₃O₅ oxides cannot absorb Mn atoms by replacing Ti atoms in it, meanwhile, the occupying vacancy pattern is not the main reason for Ti₃O₅ oxides absorb Mn atoms. ispartof: Acta Materialia vol:118 pages:8-16 status: published

ZnTixFe2–xO4 and ZnTi0.6Fe1.4O4/Carbon nanotubes (ZT0.6F1.4/CNTs) composites were prepared by chemical co-precipitation method. The composition, microstructure, magnetic property, adsorption and photocatalytic activity of the prepared samples were characterized by means of modern analytical techniques. The results indicated that ZT0.6F1.4/CNTs composites not only held the original special structure and excellent adsorption properties of CNTs, but also had suitable magnetic property and excellent photocatalytic activity. The removal rate of the samples on Rhodamine B (RhB) depended on the adsorption of CNTs and the photocatalytic degradation of ZT0.6F1.4 in the composites. The maximum adsorption amount (q m) of ZT0.6F1.4/CNTs with the mass ratios of ZT0.6F1.4 to CNTs (m Z/C)=1 was up to 17.153 mg g–1 for RhB, its adsorption behavior was in accord with Langmuir model, and its photocatalytic degradation activity on RhB had a positive correlation with the content of ZT0.6F1.4 in the sample. The experimental results indicate that the total removal rate of composite with m Z/C=1 on RhB was more than 95% and the composite had good decontamination capability on industrial dye wastewater. In addition, the samples can be recovered conveniently, activated easily and had good performance for recycling.

Ag x Zn1−x O1−0.5x and Ag0.02Z0.98O0.99/polyaniline (AZO/PANI) nanocomposites were prepared by citrate sol–gel method and in situ inverse microemulsion method, respectively. The composition, structure and morphology of the samples were characterized by means of modern testing techniques. The antibacterial activities of the as-prepared samples against Staphylococcus aureus, Escherichia coli and Candida albicans were carried out using inhibition zone, minimum inhibitory concentration and minimal bactericidal concentrations methods under the irradiation of sunlight. Results showed that the antibacterial activity of Ag x Zn1−x O1−0.5x was better than that of ZnO, and it was optimum when the mole ratio of Ag was 0.02. The AZO/PANI composites had preferable antibacterial effect than AZO, and shown the strongest antibacterial activity when the mass fraction of AZO was up to 60 %.

Objectives Multidrug resistance (MDR) remains a primary challenge in breast cancer treatment. In the present study, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS)-coated docetaxel-loaded liposomes were developed as a novel drug delivery system to reverse MDR and enhance breast cancer therapy compared with the traditional liposomes, DSPE-mPEG-coated liposomes (stealth liposomes) and commercial Taxotere®. Key findings Liposomes were prepared by thin – film dispersion method. Evaluations were performed using human breast cancer MCF-7 and resistant MCF-7/ADR cells. The reversal multidrug-resistant effect was assessed by P-gp inhibition assay, cytotoxicity, cellular uptake and apoptosis assay. Results The TPGS-chol-liposomes were of an appropriate particle size (140.0 ± 6.0 nm), zeta potential (−0.196 ± 0.08 mv), high encapsulation efficiency (99.0 ± 0.9) and favourable in vitro sustained release. The TPGS-coated liposomes significantly improved cytotoxicity and increased the intracellular accumulation of docetaxel in both types of breast cancer cells. The TPGS-coated liposomes were confirmed to induce apoptosis via a synergistic effect between docetaxel and TPGS. It was demonstrated that TPGS enhanced the intracellular accumulation of drug by inhibiting overexpressed P-glycoprotein. Conclusions The TPGS-conjugated liposomes showed significant advantages in vitro compared with the PEG-conjugated liposomes. The TPGS-conjugated liposomes could reverse the MDR and enhance breast cancer therapy.

The drug efflux mediated by P-glycoprotein (P-gp) transporter is a major factor responsible for multidrug resistance (MDR) of paclitaxel (PTX). The efficient intracellular PTX delivery is a promising strategy for overcoming the MDR of tumor cells. A CD44 receptor targeting and endosome-pH sensitive dual functionalized hyaluronic acid-deoxycholic acid-histidine (HA-DOCA-His) micellar formulation was developed to overcome MDR, and a CD44 receptor targeting hyaluronic acid-deoxycholic acid (HA-DOCA) micelles was used as a comparison. Compared with Taxol solution and HA-DOCA micelles, the cytotoxicity of PTX loaded in HA-DOCA-His micelles against drug-resistant tumor cells was improved significantly and possessed superior MDR-overcoming performance; this phenomenon is due to the increased intracellular PTX delivery by CD44 receptor-mediated endocytosis pathway and endosome-pH sensitivity-mediated PTX triggering release. Upon pharmacokinetic study, PTX/HA-DOCA-His micelles demonstrated longer blood circulation time, larger AUC, decreased Vd and CL than the Taxol solution. More importantly, PTX/HA-DOCA-His micelles were more effective in tumor growth inhibition in MCF-7/Adr tumor-bearing mice compared with PTX/HA-DOCA micelles and Taxol solution. Dual targeting strategy-functionalized HA-DOCA-His micelles demonstrated excellent MDR-reversing ability for therapeutic efficacy and improvement on MDR tumors, thereby providing an effective targeting strategy for PTX delivery of nano-drug delivery system in MDR cancer chemotherapy.

The layered oxyselenide BiCuSeO thermoelectric ceramics are attracting more and more attention due to intrinsically low thermal conductivity. In this work, Bi1−x−yBaxPbyCuSeO (x = y = 0, 0.01, 0.02, 0.04, 0.06, 0.08; x = 0, y = 0.08; x = 0.08, y = 0) bulks have been prepared by mechanical alloying (MA) and resistance pressing sintering (RPS) process, and the effects of Ba/Pb doping on the thermoelectric properties and Vickers hardness of p-type BiCuSeO ceramics have been investigated systematically. The results indicated that the substitution of Bi3+ by Ba2+/Pb2+ resulted in the significantly increase of electrical conductivity and power factor due to the introduction of the carriers into the conductive (Cu2Se2)2− layers as the result of the introduction of negative charge into the carrier-storaging (Bi2O2)2+ layers. Specifically, the room temperature electrical conductivity significantly increases from ∼8 Scm−1 for pristine BiCuSeO to ∼244 Scm−1 for Bi0.92Ba0.04Pb0.04CuSeO, and further up to ∼443 Scm−1 for Bi0.84Ba0.08Pb0.08CuSeO. The maximum power factor of 0.66 mWm−1K−2 and dimensionless figure of merit (ZT) value of 1.01 were obtained for the Bi0.88Ba0.06Pb0.06CuSeO at 873 K.

Oxymatrine (OM) can be metabolized to matrine in gastrointestinal ileocecal valve after oral administration, which affects pharmacological activity and reduce bioavailability of OM. A type of multiple-unit alginate-chitosan (Alg-Cs) floating beads was prepared by the ionotropic gelation method for gastroretention delivery of OM. A solid dispersion technique was applied and incorporated into beads to enhance the OM encapsulation efficiency (EE) and sustain the drug release. The surface morphology and internal hollow structure of beads were evaluated using optical microscopy and scanning electron microscopy (SEM). The developed Alg-Cs beads were spherical in shape with hollow internal structure and had particle size of 3.49 ± 0.09 mm and 1.33 ± 0.09 mm for wet and dried beads. Over 84% of the optimized OM solid dispersion-loaded Alg-Cs beads were able to continuously float over the simulated gastric fluid for 12 h in vitro. The OM solid dispersion-loaded Alg-Cs beads showed drug EE of 67.07%, which was much higher than that of beads loading with pure OM. Compared with the immediate release of OM capsules and pure OM-loaded beads, the release of OM from solid dispersion-loaded Alg-Cs beads was in a sustained-release manner for 12 h. Prolonged gastric retention time of over 8.5 h was achieved for OM solid dispersion-loaded Alg-Cs floating beads in healthy rabbit in in vivo floating ability evaluated by X-ray imaging. The developed Alg-Cs beads loading with OM solid dispersion displayed excellent performance features characterized by excellent gastric floating ability, high drug EE and sustained-release pattern. The study illustrated the potential use of Alg-Cs floating beads combined with the solid dispersion technique for prolonging gastric retention and sustaining release of OM, which could provide a promising drug delivery system for gastric-specific delivery of OM for bioavailability enhancement.

It has been reported that enzymatic-catalyzed reduction of CO 2 is feasible. Most of literature focuses on the conversion of CO 2 to methanol. Herein we put emphasis on the sequential conversion of CO 2 to formaldehyde and its single reactions. It appears that CO 2 pressure plays a critical role and higher pressure is greatly helpful to form more HCOOH as well as HCHO. The reverse reaction became severe in the reduction of CO 2 to formaldehyde after 10 h, decreasing HCHO production. Increasing the mass ratio of formate dehydrogenase to formaldehyde dehydrogenase could promote the sequential reaction. At concentrations of nicotinamide adenine dinucleotide lower than 100 mmol·L − 1 , the reduction of CO 2 was accelerated by increasing cofactor concentration. The optimum pH value and concentration of phosphate buffer were determined as 6.0 and 0.05 mol·L − 1 , respectively, for the overall reaction. It seems that thermodynamic factor such as pH is restrictive to the sequential reaction due to distinct divergence in appropriate pH range between its single reactions.

Multicomponent formulations have attracted increasing attention because of their favourable patient compliance and greater therapeutic effect. The aim of this study was to develop a multicomponent nanosuspension formulation of bufadienolides, the antitumor components of a traditional Chinese medicine, toad venom, using a wet-milling technique to improve its dissolution behaviour. Croscarmellose sodium (CCS) and sodium lauryl sulfate (SLS) were chosen as the combined stabilizers of the nanosuspension. A Taguchi orthogonal array design was used for this study to optimize the formulation and process parameters. The optimized nanosuspension was characterized by its particle size distribution, zeta potential, morphology, crystallinity, molecular interactions, stability and dissolution. The results showed that the nanosuspension was a homogeneous amorphous system with average particle sizes of100 nm and significantly improved dissolution behaviour. It was also physically stable for at least 2 months; steric and kinetic stabilization were its main stability mechanisms. These findings suggested that the use of wet milling to fabricate nanosuspensions is a promising method for achieving the fast and synchronized dissolution of multicomponent formulations, presumably increasing the bioavailability of poorly water-soluble drugs.

Oxymatrine (OM) is an alkaloid extracted from a Chinese herb that has been found to possess an anti-hepatic fibrosis effect, although its anti-fibrotic potential is limited due to a lack of targeting specificity, a short half-life and adverse effects. Polymersomes (PM) assembled from amphiphilic block copolymers represent promising vesicles for applications that include drug delivery and surface functionalization. The aim of this study was to develop a novel drug carrier based on PM modified with the peptide RGD and evaluate its therapeutic effect on liver fibrosis. A series of PM based on poly(ethylene glycol)-b-poly(ε-caprolactone) (PEG-b-PCL) were prepared and characterized. OM was loaded into PM by a pH-gradient method then the OM-loaded PM was modified with RGD peptide to obtain RGD-PM-OM. The average drug loading of RGD-PM-OM, with a size of 95 nm, was 6.8%. The targeting effects of the system were determined in cultured hepatic stellate cells (HSCs) and bile duct-ligated rats (BLD). RGD-PM-OM displayed better suppression of HSCs proliferation and significantly reduced the expression of the genes for α-SMA and collagen lα1 in cultured HSCs. Furthermore, RGD-PM-OM exhibited markedly superior anti-fibrosis activity by reducing the levels of PC-III and IV-C in serum and connective tissue deposition in BLD compared with PM-OM and OM. These results indicate that targeted RGD-PM-OM markedly attenuates the effects of hepatic fibrosis.

Oxymatrine (OM) is an alkaloid extracted from a Chinese herb that has been found to possess anti-hepatic fibrosis effects. To support a pharmacokinetic study for OM-loaded polymersome-based poly(ethylene glycol)-b-poly(e-caprolactone) (mPEG-b-PCL) in rats, a rapid, highly selective ultra-performance liquid chromatography-tandem mass spectrometry method (UPLC-MS/MS) to quantify OM in rat plasma was developed and validated. Tetrahydropalmatine was employed as the internal standard (IS). Protein precipitation with acetonitrile was used for preparation of plasma samples. OM and the IS were separated on an ACQUITY UPLC™ BEH C18 column (2.1 mm × 50 mm i.d., 1.7 μm), with a gradient elution of acetonitrile and 0.1% formic acid (aq), within a run time of 2.5 min. Tandem mass detection was carried out using electrospray ionization (ESI) in positive ion-selected multiple reaction monitoring (MRM) mode. The peak area of the m/z 265.20 → 148.07 transition of OM was evaluated versus that of the m/z 356.15 → 192.07 transition of the IS to generate the standard curve. In plasma, the linear range was 4–1000 ng mL−1, with a lower limit of quantitation (LLOQ) of 4.0 ng mL−1 for OM using 100 μL of plasma. The intra- and inter-day precision (RSD) were

Heterogeneous photo-Fenton SiO2/Fe3O4/C@TiO2 (SFCT) catalyst with a core-multishell structure and a diameter of about 550 nm was successfully prepared and was characterized by scanning electron microscopy (SEM), TEM, XRD, Raman, and Fourier transform infrared (FT-IR). The results illustrated that anatase TiO2 coexisted with rutile TiO2, in which the anatase phase was the main crystal phase. In addition, the catalytic activity of SFCT catalyst had been evaluated in the catalytic degradation on p-nitrophenol (PNP). The influence factors on the PNP degradation, including SFCT component ratio (m SFC/ m TiO2), H2O2 dosage, solution pH, and PNP concentration, had been investigated. And the contrast experiments about the photo-Fenton catalytic mechanism revealed that the SFCT-2 catalyst possessed a superior activity in the neutral environment due to the optimal activity matching between Fe3O4 and TiO2, and it exhibited the stable catalytic performance after five successive recycles. Therefore, the SFCT-2 catalyst had a promising application for the photo-Fenton degradation of organic contaminant.

A trifunctional 1,9-dithiophenalenylium salt with benzene spacer has been prepared as the precursor for a phenalenyl-based high spin radical. Electrochemical studies show that this salt undergoes two three-electron reduction steps and generate its corresponding neutral radical, which has been studied by quantum chemical calculations. The investigation of the spin density distribution of the radical revealed that the spin and electronic properties of molecules based on phenalenyl systems are strongly influenced by intramolecular topology connection.

Alcohol dehydrogenase (ADH) catalyzes the final step in the biosynthesis of methanol from CO2. Here, we report the steady-state kinetics for ADH, using a homogeneous enzyme preparation with formaldehyde as the substrate and nicotinamide adenine dinucleotide (NADH) as the cofactor. When changing NADH concentrations with the fixed concentrations of HCHO (more or less than NADH), kinetic studies revealed a particular zigzag phenomenon for the first time. Increasing formaldehyde concentration can weaken substrate inhibition and improve catalytic efficiency. The kinetic mechanism of ADH was analyzed using the secondary fitting method. The double reciprocal plots (1/v∼1/[HCHO] and 1/[NADH]) strongly demonstrated that the substrate inhibition by NADH was uncompetitive versus formaldehyde and partial. In the direction of formaldehyde reduction, ADH has an ordered kinetic mechanism with formaldehyde adding to enzyme first and product methanol released last. The second reactant NADH can combine with the enzyme-methanol complex and then methanol dissociates from it at a slower rate than from enzyme-methanol. The reaction velocity depends on the relative rates of the alternative pathways. The addition of NADH also accelerates the releasing of methanol. As a result, substrate inhibition and activation occurred intermittently, and the zigzag double reciprocal plot (1/v∼1/[NADH]) was obtained.

A highly pure red luminescent heterobimetallic complex [EuZnL(tta)2(μ-tfa)] (L = N,N′-bis(salicylidene)-2,3-propanediamine, tta = 2-thenoyltrifluoroacetonate, tfa = trifluoroacetate) was synthesized. The EL device with this complex exhibits an inspiring current efficiency of 3.7 cd A−1 at a brightness of 300 cd m−2 and gives a maximum Eu(III)-based pure red emitting luminance of 1982.5 cd m−2 at 13.8 V.

Two novel copolymers PBDT-DEAITN and PBDT-DOAITN containing the same backbone of isothianaphthene (ITN) quinoidal and benzodithiophene (BDT) donor units are synthesized and their organic photovoltaic (OPV) devices are fabricated. Although these two polymers have rather low optical bandgaps, 1.52 and 1.58 eV for PBDT-DEAITN and PBDT-DOAITN, respectively, their OPV cells exhibit rather limited power conversion effi ciencies of 1.25% and 1.20% under an AM1.5G simulated solar light. The reasons for the low OPV performance are investigated by structure modeling calculation. Based on this and the screening results for the representative quinoidal polymers in the literatures, a strategy of designing highperformance planar polymers based on ITN unit is proposed.

Stable phenalenyl (PLY) radicals without sterically bulky substituents need to be synthesized for application as neutral organic molecular conductors. Verdazyl radicals, which have high stability even without sterically bulky substituents, were combined with PLY radicals to produce two novel radicals. The stability of the dimethylthiourea substituted PLY radical is supported by the experimental results and quantum chemical calculations.

The effects of rare earth erbium (Er) on microstructures and fatigue fracture behavior of an Al–Cu–Mg–Ag alloy were investigated. Microstructural examinations first revealed that the precipitation kinetics of Ω phase was distinctly retarded by promoting the formation of θ′ phase with the Er addition during the initial aging. The fatigue crack propagation resistance of Er-containing microstructure was significantly enhanced arising from the presence of the crystallographic secondary cracks, which was directly relative to the large grain size. Results also suggested that the dendritic substructure of as-cast Al–Cu–Mg–Ag alloy was refined remarkably by Er addition.

Two oligo-(aryleneethynylene)s, with coplanarity of main chain and tetrathiafulvalene (TTF) side chains, have been prepared and characterized. The X-ray diffractions (XRDs) show that their π-extended coplanar backbones can form continuous π-stacking. For the two oligomers, one stacks in the inter-digitation packing mode; another stacks in the end-to-end packing mode. Cyclic voltammetries reveal that the two oligomers have almost the same reversible electroactive properties. The TTF units of the two oligomers can be oxidized to TTF •1+ by Fe(bpy) 3 (PF 6 ) 3 (bpy = 2,2'-bipyridine). The band gaps, deduced from UV-Vis absorption spectra, are 1.92 and 2.03 eV, respectively. The conductivities of the two oligomers are 1 × 10 ―5 and 6 x 10 ―8 S. cm ―1 at room temperature. The charge transfer (CT) complexes of the oligomers and tetracyanoquinodimethane (TCNO) exhibit higher conductivity up to 0.2 S ·cm ―1 .

5,12-Diphenyl-6,11-bis(thien-2-yl)tetracene ( 1 ) was prepared by reduction of 5,12-diphenyl-6,11-bis(thien-2-yl)-6,11-tetracenediol ( 3 ) with NaBH 3 CN in the presence of weak Lewis acid ZnI 2 . A rearranged byproduct, 6,11-dihydro-5,12-diphenyl-6,6′-bis(thien-2-yl)-11,11′-dihydrotetracene ( 5 ), was also obtained under this condition. Treatment of compound 3 with HI or other strong Lewis acid led to rearrangement and afforded 5,12-diphenyl-6,6′-bis(thien-2-yl)tetracene-11-one ( 4 ). The structures of compounds 1 , 4 and 5 were confirmed by single crystal X-ray diffraction. The central tetracene rings of molecules 1 are twisted and assemble into arrays with slip parallel molecules in the crystal structure. There is no π–π overlap among the tetracene rings or among the pendant phenyl rings and thienyl rings.

A novel poly(aryleneethynylene), in which the main chain and the tetrathiafulvalene (TTF) side chains are coplanar, has been prepared and characterized. The polymer can self-assemble in tetrahydrofuran (THF) and the p-extended coplanar backbones adopt good face-to-face stacking, which is confirmed by X-ray diffraction (XRD) analysis. Cyclic voltammetry has revealed that the polymer has reversible electroactive properties. The optical bandgap deduced by UV-vis absorption spectroscopy and the electrochemical bandgap are 2.03 and 2.14 eV. The conductivities of the powder and the realigning solid of the polymer are 6 � 10 � 8 and 4 � 10 � 6 Sc m � 1 .

A novel tetrathiafulvalene- (TTF-) fused poly(aryleneethynylene) with an acceptor main chain and donor side chains has been prepared and characterized. The EPR and UV–vis spectra show that there exists intramolecular charge transfer (CT) between the electron-rich TTF side chains and the electron-deficient main chain. The band gaps deduced from UV–vis absorption spectroscopy and electrochemical studies are 1.78 and 1.84 eV, respectively. Powder X-ray diffraction analysis indicate that the polymer forms a self-assembled π-stacking structure and the polymer takes an interdigitation packing mode. Polymer solar cell has been fabricated with the blend of the TTF-fused polymer and C60 as the photosensitive layer. The power conversion efficiency is 0.25% under AM 1.5 simulated sun light (100 mW/cm2). The intramolecular charge transfer was also confirmed by the chemical oxidation of the polymer with Fe(bpy)3(PF6)3 (bpy = 2,2′-bipyridine).

The study on the dynamic viscoelastic properties of grafted carbon black (g-CB) filled low-density polyethylene (LDPE) was carried out. Because of formation of CB networking, the characteristic modulus plateau and loss tangent arc appears. Addition of grafting monomer like butyl acrylate (BA) and acroleic acid (AA) enhances the interaction between particles and matrix due to accelerated formation of micronetworking in the composites induced by forming branch chains of AA and BA with multiunit. The decrease of the temperature corresponding to αc mechanical relaxation together with AA (BA) addition given by the position of loss tangent (tan δ) peak for LDPE is owed to the formation of long-chain polymer grafted between CB and the matrix, which facilitates the slip of the lamella of LDPE. The influence of maleic anhydride (MA) on enhancing interaction between LDPE and CB is not so pronounced, as compared with AA and BA because of no formation of long chain between CB particle and polymer matrix. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 100: 4127–4132, 2006

A novel fluorine derivative 4,5‐diaza‐9‐(4‐methylphenyl) imino fluorene has been synthesized and evaluated as a lead (II) ion‐selective ionophore in PVC membrane electrode. The influence of the nature of the plasticizers (o‐NPOE, DBP, and DOS) and of the amount of incorporated ionophore and KTpClPB on the characteristics of the electrode were discussed. The electrode prepared with 5.7 mg ionophore, 187 mg o‐NPOE, 92 mg PVC, and 0.11 mg KTpClPB gave a good Nernstian response of 28.8 mV/decade for lead (II) in the concentration range 1.0 × 10−6–1.0 × 10−2 mol dm−3. The limit of detection reached 1.0 × 10−7 mol dm−3. The electrode showed high selectivity toward lead over alkali, alkaline earth, and some transition metal ions. The influence of pH has been studied. The electrode exhibited better potential stability and reproducibility. The electrode was used to determine lead levels in polluted water using the developed electrode.

Two similar dithiafulvalene-fused conjugated polymers, with different donor–acceptor (D–A) structures, were synthesised. The polymers have different band gaps and stacking structures, as proven by the experimental results and computational studies.

A simplified triple-layered pure red organic light-emitting diode with high efficiency and a slow efficiency roll-off was fabricated by using Eu(DBM)3(sbf) (DBM = dibenzoylmethane, sbf = 4,5-diaza-9,9′-spirobifluorene) as emitter. In particular, an impressive current efficiency of 3.31 cd A−1 and an external quantum efficiency of 1.8% were maintained at a high luminance of 100 cd m−2.

In the title centrosymmetric compound, C(28)H(32)N(4)O(2) (2+) 2I(-), the two midazole rings are approximately perpendicular to the central anthracene ring system [dihedral angle = 86.6 (2)°]. The ionic units are linked into a two-dimensional network parallel to (01) by C-H⋯I hydrogen bonds and π-π inter-actions involving the anthracene ring system and imidazole rings [centroid-centroid distance = 3.717 (3) Å].

With N-(5-phenyl-1,3,4-oxadiazol-2-yl)-benzamide (HL1) as the first ligand, three new luminescent europium complexes Eu2Na2(L1)6(OH)(2).2C2H5OH.2CHCl3 (1), Eu(L1)3(phen) (phen = 1,10-phenanthroline) (2) and Eu2Na2(L1)6(L2)2(OH)(2).8CHCl3 [L2 = 2,5-bis(2-pyridyl)-1,3,4-oxadiazole] (3) have been prepared and structurally characterized. Each ligand L1 coordinates with a Eu3+ ion through a carbonyl oxygen atom and oxadiazol nitrogen atom, the coordination geometry at europium is a distorted square antiprism. Complexes 1 and 3 have centrosymmetric dimeric structural features with OH- as the bridging ligand, while 2 is mononuclear with phen as the neutral ligand. All these complexes show efficient red emissions typical of Eu3+ ions at room temperature, the overall quantum yields of complexes 1, 2 and 3 were 0.15, 0.37 and 0.23, respectively. Using Eu(L1)3(phen) as the emitting material, an electroluminescent device with the structure ITO/TPD (30 nm)/Eu(L1)3(phen): TPD (1 : 3, 50 nm)/AlQ (30 nm)/Mg(0.9)Ag(0.1)/Ag was fabricated. The device emits sharp red light originating from europium complex, demonstrating that Eu(L1)3(phen) is a promising red emitter with good electron-transporting property.

In the title compound, Na+·4C7H5N6+·5BF4−, the Na+ ion lies on a fourfold rotation axis and one of the tetrafluoridoborate ions lies on a site of symmetry overline{4}. Each Na+ ion is surrounded by four symmetry-related tetrafluoridoborate ions, and is eight-coordinated by F atoms, the Na...F separation being 2.3956 (15) or 2.4347 (17) Å. The hexaazaphenalenium ring system is essentially planar. In the crystal structure, the cations and anions are linked into a three-dimensional network by N—H...N and C—H...F hydrogen bonds.