Rational Design of Conducting Polymer-Derived Tubular Carbon Nanoreactors for Enhanced Enzyme-like Catalysis and Total Antioxidant Capacity Bioassay Application.

The design of void-confined tubular nanostructures has aroused significant interest for catalytic applications because of their distinct microenvironment to modulate the reaction kinetics. Herein, we propose a facile wrapping-pyrolysis strategy to confine Fe0 nanoparticles (Fe NPs) inside N-doped carbon nanotubes (Fe@NC NTs) derived from Fe2O3@polypyrrole (PPy) core-sheath nanofibers (NFs). The resultant Fe@NC NTs can act as efficient enzyme mimics and exhibit a significantly higher peroxidase (POD)-like catalytic activity than unconfined Fe NPs and bare NC NTs. Kinetic experiments demonstrate that the optimized void structure benefits the affinity with the POD substrates and achieves excellent catalytic efficiency. The mechanism study reveals that the generation of •OH from H2O2 endows Fe@NC NTs with excellent POD-like performance. Furthermore, we develop a total antioxidant capacity (TAC) sensing platform on account of this efficient POD-like system, expanding their applications in the field of food safety and human healthcare.

Strongly coupled CeO2/Co3O4/poly(3,4-ethylenedioxythiophene) nanofibers with enhanced nanozyme activity for highly sensitive colorimetric detection.

In this work, we have prepared CeO2/Co3O4 composite nanofibers via an electrospinning technique followed by a calcination process. Then core-shell structured CeO2/Co3O4/poly(3,4-ethylenedioxythiophene) (PEDOT) composite nanofibers were fabricated through a redox reaction between the 3,4-ethylenedioxythiophene (EDOT) monomer and Co3O4 on the surface of CeO2/Co3O4 composite nanofibers. The morphology and composition of the two composite nanofibers were confirmed by field-emission scanning electron microscopy, transmission electron microscopy, x-ray diffraction, Fourier transform infrared spectroscopy, and x-ray photoelectron spectra measurements. Due to the synergistic effect between CeO2 and Co3O4, the catalytic activity was enhanced compared to that of independent oxide nanofibers. After the growth of PEDOT, the catalytic activity process was further improved, having achieved a secondary synergistic effect. Application of the two prepared composite nanofibers as peroxidase-like catalysts for the colorimetric detection of H2O2 was investigated. It is anticipated that this work can inspire researchers to develop various novel functional nanocomposites for applications in biosensing and environmental monitoring.

Pigment epithelium derived factor suppresses expression of Sost/Sclerostin by osteocytes: implication for its role in bone matrix mineralization.

Mutations in Serpinf1 gene which encodes pigment epithelium derived factor (PEDF) lead to osteogenesis imperfecta type VI whose hallmark is defective mineralization. Mechanisms by which PEDF regulates matrix mineralization remain unknown. We examined effect of exogenous PEDF on expression of osteoblastic and osteocytic related genes and proteins in mineralizing osteoblast culture. Mineralizing human osteoblasts supplemented with exogenous PEDF for 14 days deposited 47% more mineral than cells cultured without PEDF. Analysis of selected gene expression by cells in mineralizing cultures supplemented with exogenous PEDF showed reduction in expression of Sclerostin (Sost) by 70%, matrix extracellular phosphoglycoprotein (MEPE) by 75% and dentin matrix protein (DMP-1) by 20% at day 14 of culture. Phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) expression was not affected. Western blotting and immunoprecipitation showed that sclerostin and MEPE synthesis by osteocytes were reduced by 50% and 60% respectively in mineralizing osteoblasts containing exogenous PEDF. Primary osteocytes exposed to PEDF also reduced synthesis of Sost/sclerostin by 50% within 24 h. For osteoblastic genes, Bone sialoprotein (BSP) was expressed at 75% higher by day 7 in cultures containing exogenous PEDF while Col1A1 expression remained high at all-time points. Total beta-catenin was increased in mineralizing osteoblastic cells suggesting increased Wnt activity. Taken together, the data indicate that PEDF suppressed expression of factors that inhibit mineralization while enhancing those that promote mineralization. The findings also suggest that PEDF may regulate Sost expression by osteocytes leading to enhanced osteoblastic differentiation and increased matrix mineralization.

Integrated evaluation of the reactive oxygen species (ROS) production characteristics in one large lake under alternating flood and drought conditions.

Reactive oxygen species (ROS) are omnipresent in natural aquatic environments, and play an important role in biogeochemical cycles. One of the dominant sources of ROS in surface waters was thought to be from dissolved organic matter (DOM) interacting with photochemical process. The properties of DOM were different between the flood and drought periods in lakes; yet, information on how these variations influence ROS photoproduction is unknown. Through a three-year study, the photochemical properties of DOM and the resultant ROS photoproduction between the flood and drought period were determined in the largest freshwater lake in China (Lake Poyang). Results found that quantum yield coefficients of excited triplets (3CDOM*), apparent quantum yields of singlet oxygen (1O2) and hydroxyl radicals (•OH) were holistically higher in the flood period than those in the drought period. The optical properties of DOM showed that DOM in the flood period featured an allochthonous input, accompanied by higher molecular size (E2/E3), aromatic content (SUVA254), humification degree (HIX), while DOM in the drought period was mainly internal input. Fourier transform ion cyclotron resonance mass spectrometry (FI-ICR MS) further revealed that some refractory components, such as lignin-like and carboxyl-rich alicyclic molecules (CRAM) presented higher abundance in the flood period, and played the positive impacts on ROS production. Orthogonal partial least squares (OPLS) were used to build novel multivariate predictive models for indicating the spatio-temporal ROS production. Also, the relatively higher steady-state concentrations of 3CDOM* and 1O2 in the flood period could significantly diminish the half-lives of acetochlor. Considering the photochemical activity of DOM varied considerably at different periods, this study provided a new method to predict ROS production and contributed to a new insight into stage-specific emerging contaminants removing in natural aquatic environments.

Changes of the physicochemical properties of extracellular polymeric substances (EPS) from Microcystis aeruginosa in response to microplastics.

Microplastics (MPs) are ubiquitous in aquatic ecosystems and can significantly influence the growth, aggregation and functions of phytoplankton biomass. However, variations in the extracellular polymeric substances (EPS) of phytoplankton in terms of compositions and structures in response to MPs were still not reported. In this study, EPS matrix of Microsystis aeruginosa was applied and fractionated into loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS) fractions, with the time-dependent changes in response to different concentrations (10, 100 and 500 mg/L) of MPs being explored via using the fluorescence excitation emission matrix coupled with parallel factor (EEM-PARAFAC) and two-dimensional Fourier transform infrared correlation spectroscopy (2D-FTIR-COS) analysis. Results showed that 500 mg/L of MP concentration significantly inhibited Microcystis growth by 30.5% but enhanced EPS secretion. In addition, organic composition in LB-EPS and TB-EPS varied differently in response to increased MP exposure, as the ratio of polysaccharide/protein increased in the TB-EPS but decreased in LB-EPS. Further analysis revealed obvious heterogeneities in organic component variations in response to MPs, as the C-O functional groups and glycosidic bonds in the TB-EPS preferentially responded, which lead to the domination of polysaccharides and humus substances; while the carbonyl, carboxyl and amino functional groups in the LB-EPS exhibited a preferential response, which caused the enhanced percentage of the tryptophan-like proteins. In addition to organic compositions, the aromaticity, hydrophobicity and humification in the LB-EPS fraction increased with enhanced MP exposure, which, as a result, may influence the ecotoxicological risk of MPs. Therefore, Microcystis can dynamically adjust not only the EPS contents but also the compositions in response to MPs exposure. The results can improve our understanding on the eco-physiological impact of phytoplankton-MP interaction in aquatic environment, and indicate that the dose-dependent and long-term effects of MPs on phytoplankton should be considered in future study.

Folate-decorated hybrid polymeric nanoparticles for chemically and physically combined paclitaxel loading and targeted delivery.

In this study, folate-functionalized hybrid polymeric nanoparticles (NPs) were prepared as carriers of low water solubility paclitaxel for tumor targeting, which were composed of monomethoxy-poly(ethylene glycol)-b-poly(lactide)-paclitaxel (MPEG-PLA-paclitaxel) and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS)-folate (TPGS-FOL). NPs with various weight ratios of MPEG-PLA-paclitaxel and TPGS-FOL were prepared using a solvent extraction/evaporation method, which can also physically encapsulate paclitaxel. The size, size distribution, surface charge, and morphology of the drug-loaded NPs were characterized using a Zetasizer Nano ZS, scanning electron microscope (SEM), and atomic force microscopy (AFM). The encapsulation and drug loading efficiencies of these polymeric NPs are analyzed using high-performance liquid chromatography (HPLC) at 227 nm. The combination of covalent coupling and physical encapsulation is found to improve the loading of paclitaxel in NPs greatly. The in vitro antitumor activity of the drug-loaded NPs is assessed using a standard method of transcriptional and translational (MTT) assays against HeLa and glioma C6 cells. When the cells were exposed to NPs with the same paclitaxel weights, cell viability decreases in relation to the increase in TPGS-FOL in drug-loaded NPs. To investigate drug-loaded NP cellular uptake, the fluorescent dye coumarin-6 is utilized as a model drug and enveloped in NPs with 0 or 50% TPGS-FOL. Confocal laser scanning microscopy (CLSM) analysis shows that cellular uptake is lower for coumarin-6-loaded NPs with 0% TPGS-FOL than those with 50% TPGS-FOL. However, no difference for NIH 3T3 cells with normally expressed folate receptors is found. Results from in vitro antitumor activity and cellular uptake assay demonstrate that folic acid promotes drug-loaded NP cellular uptake through folate receptor-mediated endocytosis (RME). All of these results demonstrate that folate-decorated hybrid polymeric NPs are potential carriers for tumor-targeted drug delivery.

Influence of the structure and properties of lignocellulose on the physicochemical characteristics of lignocellulose-based residues used as an environmentally friendly substrate.

The extensive use of nonrenewable peat does not meet the strategic goals of sustainable development. This study explores the advantages and disadvantages of using lignocellulose-based agricultural and forestry wastes as peat substitute in substrates for soilless cultivation; further, it also investigates the key factors influencing the physical and chemical properties of the substrates. Accordingly, the physical and chemical properties of four gramineous crop straws and two woody forestry wastes were determined and compared with those of peat and coconut bran. In addition, cellulose, hemicellulose, and lignin were extracted from wheat straw and pine sawdust, and their basic characteristics and structures were compared and analyzed. The results showed that the influence of particle size on the physical properties of substrates was significantly higher (P < 0.01) than the influence of the substrate type, especially with respect to the water-holding and aeration porosities, which had effect sizes (Eta2) of 73.8% and 68.2%, respectively. The electrical conductivity values of the four straws (1.87-3.42 mS/cm) were higher than those of peat and coconut bran (0.50-0.96 mS/cm), which was mainly due to the high hemicellulose contents (28.52%-30.10%) and total nutrient contents (28.46-47.81 g/kg) of the straws. In contrast, the electrical conductivity values of the woody waste substrates were lower (0.28-0.33 mS/cm) than those of peat and coconut bran. Peat and coconut bran contained the lowest cellulose (17.84%-20.95%) and hemicellulose contents (5.14%-7.19%) of all substrates, resulting in a low degradability and good stability. The crystallinity of coconut bran (23.06%) was significantly lower than that of all other substrates (30.36%-43.03%), which mainly contributed to the superior compressibility of coconut bran. The best pretreatment method for biomass waste used as a substrate should be selected according to the target properties of the corresponding components.

Role of Vitamin D Receptor Gene Polymorphisms on the Susceptibility to Periodontitis: A Meta-Analysis of a Controversial Issue.

Background: To assess whether vitamin D receptor (VDR) gene polymorphisms influence the susceptibility to periodontitis. Methods: We retrieved 34 relevant studies, comprising a total of 3848 subjects suffering from periodontitis and 3470 controls for this meta-analysis. The pooled data were analyzed using STATA software. Results: Among all ethnic groups examined, the VDR BsmI polymorphism was associated with periodontitis under the recessive model (odds ratio [OR] = 0.722, 95% confidence interval [CI]: 0.532-0.980, p = 0.037). There was also a link between the VDR FokI polymorphism and periodontitis in the overall population (dominant model: OR = 1.459, 95% CI: 1.050-2.028, p = 0.025 and allelic model: OR = 1.386, 95% CI: 1.026-1.874, p = 0.034) and in Chinese participants (dominant model: OR = 1.813, 95% CI: 1.185-2.774, p = 0.006; allelic model: OR = 1.602, 95% CI: 1.044-2.459, p = 0.031) when stratified by race. The FokI variant was also correlated with aggressive periodontitis (AP) (dominant model: OR = 2.204, 95% CI: 1.148-4.231, p = 0.018; allelic model: OR = 2.017, 95% CI: 1.365-2.980, p = 0.000; and recessive model: OR = 2.903, 95% CI: 1.520-5.542, p = 0.001). We also showed a correlation between the VDR TaqI variant and periodontitis susceptibility in Caucasian populations (dominant model: OR = 0.525, 95% CI: 0.318-0.866, p = 0.012). The results revealed that there was no relationship between the VDR ApaI gene polymorphism and periodontitis. Conclusions: There was a link between the VDR BsmI and FokI gene polymorphisms and periodontitis in the overall population. In addition, the FokI polymorphism was correlated with AP. There was a link between the TaqI polymorphism and periodontitis in the Caucasian population. The VDR Apal variant, however, was not correlated with periodontitis.

CCL28-induced RARß expression inhibits oral squamous cell carcinoma bone invasion.

Oral squamous cell carcinoma (OSCC) frequently invades the maxillary or mandibular bone, and this bone invasion is closely associated with poor prognosis and survival. Here, we show that CCL28 functions as a negative regulator of OSCC bone invasion. CCL28 inhibited invasion and epithelial-mesenchymal transition (EMT), and its inhibition of EMT was characterized by induced E-cadherin expression and reduced nuclear localization of ß-catenin in OSCC cells with detectable RUNX3 expression levels. CCL28 signaling via CCR10 increased retinoic acid receptor-ß (RARß) expression by reducing the interaction between RARα and HDAC1. In addition, CCL28 reduced RANKL production in OSCC and osteoblastic cells and blocked RANKL-induced osteoclastogenesis in osteoclast precursors. Intraperitoneally administered CCL28 inhibited tumor growth and osteolysis in mouse calvaria and tibia inoculated with OSCC cells. RARß expression was also increased in tumor tissues. In patients with OSCC, low CCL28, CCR10, and RARß expression levels were highly correlated with bone invasion. Patients with OSCC who had higher expression of CCL28, CCR10, or RARß had significantly better overall survival. These findings suggest that CCL28, CCR10, and RARß are useful markers for the prediction and treatment of OSCC bone invasion. Furthermore, CCL28 upregulation in OSCC cells or CCL28 treatment can be a therapeutic strategy for OSCC bone invasion.

A degradable triple temperature-, pH-, and redox-responsive drug system for cancer chemotherapy.

In order to achieve a precise therapeutic effect of cancer treatment and improve the utilization of drugs, a temperature-, pH-, and redox-responsive drug delivery system were synthesized. Methacrylic acid (MAA), poly(N-isopropylacrylamide) (PNIPAM), 2-hydroxyethylmethacrylate (HEMA), and N,N'-bis(acryloyl)cystamine (BACy), a disulfide bond contained cross-linker, were polymerized by a distillation-precipitation polymerization. Doxorubicin (DOX), an anti-cancer drug, can be loaded into the loose nanoparticle (NP) effectively. The prepared drug delivery remains stable during blood circulation and, when the vectors accumulated at tumor tissues, the pH-response of MMA and temperature-response of PNIPAM makes volume shrinkage of vectors which benefit the diffusion of vectors into tumor tissues. After being endocytosed into tumor cell, the disulfide bond that contained in the drug delivery can be cleaved by glutathione (GSH), causing the decomposition of NPs, and then release all of the drug. Under the influence of three trigger factors, the triple stimuli-responsive drug delivery vectors can realize tumor accumulation, tumor penetration and controlled drug release. Thus, the prepared multi-responsive NP is ideal drug carriers for developing novel drug delivery systems. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3203-3210, 2018.

Effect of stearic acid modified HAp nanoparticles in different solvents on the properties of Pickering emulsions and HAp/PLLA composites.

Stearic acid (Sa) was used to modify the surface properties of hydroxyapatite (HAp) in different solvents (water, ethanol or dichloromethane(CH2Cl2)). Effect of different solvents on the properties of HAp particles (activation ratio, grafting ratio, chemical properties), emulsion properties (emulsion stability, emulsion type, droplet morphology) as well as the cured materials (morphology, average pore size) were studied. FT-IR and XPS results confirmed the interaction occurred between stearic acid and HAp particles. Stable O/W and W/O type Pickering emulsions were prepared using unmodified and Sa modified HAp nanoparticles respectively, which indicated a catastrophic inversion of the Pickering emulsion happened possibly because of the enhanced hydrophobicity of HAp particles after surface modification. Porous materials with different structures and pore sizes were obtained using Pickering emulsion as the template via in situ evaporation solvent method. The results indicated the microstructures of cured samples are different form each other when HAp was surface modified in different solvents. HAp particles fabricated using ethanol as solvent has higher activation ratio and grafting ratio. Pickering emulsion with higher stability and cured porous materials with uniform morphology were obtained compared with samples prepared using water and CH2Cl2 as solvents. In conclusion, surface modification of HAp in different solvents played a very important role for its stabilized Pickering emulsion as well as the microstructure of cured samples. It is better to use ethanol as the solvent for Sa modified HAp particles, which could increase the stability of Pickering emulsion and obtain cured samples with uniform pore size.

Factors influencing the stability and type of hydroxyapatite stabilized Pickering emulsion.

Hydroxyapatite (HAp) nanoparticle stabilized Pickering emulsion was fabricated with poly(l-lactic acid) dissolved in dichloromethane (CH2Cl2) solution as oil phase and HAp aqueous dispersion as aqueous phase. Pickering emulsion was cured via in situ solvent evaporation method. Effect of PLLA concentrations, pH value, HAp concentrations, oil-water ratio, emulsification rates and times were studied on emulsion stability and emulsion type, etc. The results indicated emulsion stability increased with the increase of HAp concentration, emulsification rate and time; it is very stable when pH value of aqueous phase was adjusted to 10. Stable W/O and O/W emulsions were fabricated successfully using as-received HAp particles as stabilizer by adjusting the fabricating parameters. The interaction between HAp and PLLA played an important role to stabilize Pickering emulsions. SEM results indicated that both microsphere and porous materials were fabricated using emulsion stabilized by unmodified HAp nanoparticles, implying that both W/O and O/W emulsion type were obtained.

A novel GNRs-PEI/GNRs-PEI-folate for efficiently delivering siRNA.

RNA interference (RNAi) employs double-stranded RNA or siRNA (small interfering RNA) to silence gene expression in cells. The widespread use of RNAi therapeutics requires the development of clinically suitable, safe and effective delivery vehicles. PEI (Poly(ethylene imine)) carrying the positive charges has attracted considerable attention for siRNA delivery. Gold nanorods (GNRs) exhibit specially localized surface plasmon resonance when excited by the visible and near-infrared laser, which is useful for photothermal therapy. However, the toxicity derived from a large amount of the surfactant cetyltrimethylammonium bromide (CTAB) during GNR synthesis severely limits their medical applications. Here, we report the synthesis of GNRs-PEI/GNRs-PEI-folate to improve biocompatibility, siRNA delivery and photothermal therapy of GNRs. Firstly, GNRs were synthesized according to the seed-mediated template-assisted protocol. The characterization results of GNRs showed: the size was length about 218 nm and width about 26.8 nm; the Zeta potential was +38.1 mV derived from CTAB on their surface; the dipole resonance extinction spectrum peak was 752 nm which is effective for photothermal therapy in vivo. Secondly, we synthesized PEI-MUA (Mercaptoundecanoic acid) and PEI-MUA-folate based on the chemical reaction between amino group of PEI and carboxyl group of MUA or Folate. PEI-MUA or PEI-MUA-folate to replace CTAB on GNRs obtained the GNRs-MUA-PEI system or the GNRs-MUA-PEI-folate system due to the solid conjugation between the thiol group of MUA and GNRs. The products were measured using the FTIR Spectrometer, and the spectra suggest MUA-PEI or PEI-MUA-folate has successfully replaced CTAB on the surface of GNRs. Finally, GNRs-MUA-PEI was incubated with siRNA-Cy3. The unbound siRNA-Cy3 was measured the intensity of fluorescence for calculating the uploaded amount of siRNA by GNRs-MUA-PEI, and the results indicate that the uploaded percentage of siRNA is about 70%. We conclude that the GNRs-MUA-PEI system is an effective siRNA loading vehicle.

Cellulose degradation by one mesophilic strain Caulobacter sp. FMC1 under both aerobic and anaerobic conditions.

Caulobacteria are presumed to be responsible for considerable mineralization of organic material in aquatic environments. In this study, a facultative, mesophilic and cellulolytic bacterium Caulobacter sp. FMC1 was isolated from sediments which were taken from a shallow freshwater lake and then enriched with amendment of submerged macrophyte for three months. This strain seemed to evolve a capacity to adapt redox-fluctuating environments, and could degrade cellulose both aerobically and anaerobically. Cellulose degradation percentages under aerobic and anaerobic conditions were approximately 27% and 10% after a 240-h incubation in liquid mediums containing 0.5% cellulose, respectively. Either cellulose or cellobiose alone was able to induce activities of endoglucanase, exoglucanase, and ß-1,4-glucosidase. Interestingly, ethanol was produced as the main fermentative product under anaerobic incubation on cellulose. These results could improve our understanding about cellulose-degrading process in aquatic environments, and were also useful in optimizing cellulose bioconversion process for bioethanol production.

Preparation and in vitro properties of redox-responsive polymeric nanoparticles for paclitaxel delivery.

Rice-like polymeric nanoparticles (NPs) composed of a new redox-responsive polymer, poly(ethylene glycol)-b-poly(lactic acid) (MPEG-SS-PLA), were prepared to carry paclitaxel (PTX) for glutathione (GSH)-regulated drug delivery. The PTX-loaded MPEG-SS-PLA NPs were fabricated using an optimized oil-in-water emulsion/solvent evaporation method. The size and morphology of the prepared NPs were characterized by scanning electron microscopy (SEM). The SEM results demonstrate that the NPs were dispersed as individual particles and were rice-shaped. The PTX loading efficiency, in vitro release, and stability of the NPs were analyzed by high-performance liquid chromatography (HPLC). The HPLC results revealed that the NPs released almost 90% PTX within 96 h when GSH presented at intracellular concentrations, whereas only a very small PTX amount was released at plasma GSH levels. The in vitro cytotoxicities of the NPs against A549, MCF-7, and HeLa carcinoma cells were assessed using a standard methyl thiazolyl tetrazoliun (MTT) assay. The MTT assay results show that the NPs caused concentration- and time-dependent changes in cell viability. To investigate the cellular uptake of the PTX-loaded NPs, visual endocytosis assay was performed using the fluorescent dye coumarin-6 as a model drug. The endocytosis assay results reveal rapid penetration and intracellular accumulation of coumarin-6-loaded NPs, as well as rapid coumarin-6 dispersion from the NPs. Overall, these findings establish that the NPs containing the synthesized redox-responsive polymer MPEG-SS-PLA can be used as potential carrier systems for antitumor drug delivery.