Nanoindentation and Morphological Studies of Epoxy Nanocomposites

Summary: This paper investigates the mechanical properties of the epoxy–organoclay nanocomposites by the nanoindentation technique. The nanocomposites were prepared by in situ polymerization and a mixture of exfoliated and intercalated composites structure was obtained as evidenced by X‐ray diffraction (XRD) and transmission electron microscopy (TEM). The hardness, elastic modulus, and the creep behavior of the nanocomposites have been evaluated as a function of clay concentration. It has been found that incorporation of 7.5 wt.‐% of clay nanofiller enhances the elastic modulus and hardness of the epoxy matrix by about 20 and 6%, respectively. The elastic modulus data calculated from indentation experiments are comparable with those obtained from a tensile test. An optimum clay loading level was found to be 2.5 wt.‐% to maximum enhance the creep resistance of the epoxy matrix. The lowered creep resistance with higher clay loading could be due to the reduced crosslinking density near the clay surface caused by the plasticizing effect from the pending of alkyl ammonium chains on the clay surface. An attempt has been made to correlate the fracture toughness of the nanocomposites with the ratio of modulus to hardness obtained from nanoindentation experiments.

Ratio of modulus to hardness (E/H) and the fracture toughness (K_IC) versus clay loading for the epoxy nanocomposites.     

Aligned Nafion® Nanocomposites: Preparation and Morphological Characterization

A novel nanocomposite based on Nafion® (ionomer) and a layered silicate is studied. An innovative approach of processing a composite under electric field to induce orientation of the inorganic filler was carried out and accomplished in the present work. The morphology of oriented composites was analyzed by scanning electric potential microscopy (SEPM) and transmission electron microscopy (TEM). Films based on both plain ionomer and composite displayed fine contrast in SEPM, differentiating the phases, which could not be achieved using conventional atomic force microscopy. The orientation of the silicates in the composites is evident from the SEPM picture.

AFM of Nafion®/montmorillonite composite films prepared by solution casting under electric field (Image obtained by SEPM).     

基因治疗用质粒DNA的制备工艺

目的探索基因治疗用质粒DNA的制备工艺。方法以CaCl2沉淀法去除大分子RNA,Q-Sepharose和SOURCE两步离子交换层析法去除染色体DNA、小分子RNA、蛋白质等杂质,并对各步骤样品进行检测。结果质粒pIRVP3HNIL18终产品的产量为1.638mg质粒DNA/g细菌,纯度为1.839,相对回收率为12.55%,蛋白质含量为0.0028mg/ml,未检测到RNA和染色体DNA。结论此工艺可有效去除质粒DNA制备过程中产生的杂质,可应用于药剂水平质粒DNA的制备。     

Polyamide Nanocomposites: Investigation of Mechanical,Thermal and Morphological Characteristics

In the present work, polyamide/CaSO₄ nanocomposites were prepared via melt intercalation on twin-screw extruder. Different particle sizes (23, 15, 10 nm) of CaSO₄ were synthesized by in situ deposition technique and its sizes and shape were confirmed on a transmission electron microscope (TEM). The TEM study showed that nano-CaSO₄ has a needlelike or fiberlike structure. Nano-CaSO₄ was added from 1 to 4 wt% in the polyamide. Properties such as Tensile strength, Elongation at Break, Young's Modulus, and hardness were studied. These results were then compared with commercial CaSO₄-filled polyamide composites. There was a propounding effect to be observed on properties of polyamide nanocomposites due to uniform dispersion of nano-CaSO₄ and commercial CaSO₄. The 4 wt% of 10 nm CaSO₄ shows 16% improvement in Tensile Strength compared to commercial CaSO₄ (11%) filled in polyamide composites, whereas, Elongation at Break decreases drastically in 10 nm CaSO₄-filled polyamide nanocomposites up to 22% compared to commercial CaSO₄-filled polyamide composites at 4 wt% loading (11%). Among these properties, Young's Modulus was found to be more effective in 4 wt% loading of 10 nm CaSO₄ and was recorded to be 66% more compared to commercial CaSO₄-filled-in polyamide composites (22%). Moreover, thermal properties such as thermal degradation and flammability were studied by TGA and flame testers. It was found that nano-CaSO₄ was thermally more stable compared to commercial CaSO₄-filled polyamide composites. Extent of dispersion of nano-CaSO₄ was studied along with micro cracks generated during tensile testing using an Atomic Force Microscope (AFM).     

小鼠神经生长因子基因治疗型DNA质粒的质量控制

目的对小鼠神经生长因子(NGF)基因治疗型DNA质粒进行质量控制。方法用酶切鉴定法和PCR法进行DNA质粒的结构确认,鸡胚背根神经节法和免疫印迹测定DNA质粒表达产物的生物学活性,分光光度法测定浓度,琼脂糖凝胶电泳法和DNA-NPR-HPLC法测定纯度,气相色谱法测定乙醇和异丙醇残留量,琼脂糖凝胶电泳法测定RNA残留量,其余检测项目按《中国药典》三部(2005版)规定进行。结果用上述方法对原液和成品进行了检定,各项指标均符合《预防用DNA疫苗临床前研究技术指导原则》和《中国药典》三部(2005版)的要求。结论所采用的质控方法和质量标准能够保证该DNA质粒的安全、有效,可用于治疗型DNA质粒的质控。     

Solid State Viscoelastic Properties,Morphological and Melt Rheological Studies on PLA/TPU/POSS Nanocomposites

Effects of trifluoropropyl-substituted polyhedral oligomeric Silsesquioxane (POSS), on the morphological, rheological and dynamic mechanical properties of a series of poly(lactic acid)

(PLA)/thermoplastic polyurethane (TPU) blends were explored, thoroughly. Microscopic techniques including scanning electron microscope (SEM) and transmission electron microscope (TEM) utilized in conjunction with viscosity measurements to explain morphological dissimilarities between different samples. A remarkable morphological refinement was observed upon addition of POSS into the 50/50 PLA/TPU blend. This morphological change was detected by means of frequency sweep rheological experiments, where the shoulder-like plateau appears as a result of increase in the contribution from the interfacial component of elasticity in the enhancement of storage modulus. Based on the results of the dynamic time sweep small amplitude oscillatory shear (SAOS) experiments, a scaling relation was proposed to quantify the kinetics of phase separation and the associate time evolution of elasticity. It turned out that POSS particles can slow down the rate of morphological coarsening up to the 50%. Using dynamic mechanical thermal analysis (DMTA) and rheological experiments, the differences in the rate of undergoing dynamics in all the length scales, starting from segmental up to the chain level, were compared for various compositions and the discrepancies were fully described based on the dissimilarities in the entanglement densities, combinatorial effects of soft and hard segments of TPU, lubricating role of POSS particles, crystallinity, and morphological characteristics of samples.     

Cell and Gene Therapy for Anemia: Hematopoietic Stem Cells and Gene Editing

Hereditary anemia has various manifestations, such as sickle cell disease (SCD), Fanconi anemia, glucose-6-phosphate dehydrogenase deficiency (G6PDD), and thalassemia. The available management strategies for these disorders are still unsatisfactory and do not eliminate the main causes. As genetic aberrations are the main causes of all forms of hereditary anemia, the optimal approach involves repairing the defective gene, possibly through the transplantation of normal hematopoietic stem cells (HSCs) from a normal matching donor or through gene therapy approaches (either in vivo or ex vivo) to correct the patient’s HSCs. To clearly illustrate the importance of cell and gene therapy in hereditary anemia, this paper provides a review of the genetic aberration, epidemiology, clinical features, current management, and cell and gene therapy endeavors related to SCD, thalassemia, Fanconi anemia, and G6PDD. Moreover, we expound the future research direction of HSC derivation from induced pluripotent stem cells (iPSCs), strategies to edit HSCs, gene therapy risk mitigation, and their clinical perspectives. In conclusion, gene-corrected hematopoietic stem cell transplantation has promising outcomes for SCD, Fanconi anemia, and thalassemia, and it may overcome the limitation of the source of allogenic bone marrow transplantation.     

Microstructural and Optoelectronic Studies on Polyaniline: TiO2 Nanocomposites

Thin films of polyaniline (PANi) and PANi: titanium oxide (TiO₂) composites have been synthesized by sol–gel spin coating technique. The TiO₂ powder of particle size 50–60 nm was synthesized by the sol–gel technique and the polyaniline was synthesized by the chemical oxidative polymerization of aniline. The composite films were characterized by X-ray diffraction (XRD), atomic force microscopy (AFM), scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, UV-vis spectroscopy and the four-probe method. The results were compared with corresponding data on pure polyaniline films. The intensity of diffraction peaks for PANi:TiO₂ composites is lower than that for TiO₂. The characteristic FTIR peaks of pure PANi are observed to shift to a higher wavenumber in PANi:TiO₂ composite, which is attributed to the interaction of TiO₂ particles with PANi molecular chains. The resistivity measurement shows that the molecular chain constitution of polyaniline is the most important carrier in the polyaniline: nano-TiO₂ composite.     

Electrical,Morphological and Rheological Study of Melt‐Mixed Polystyrene/Copper Nanowire Nanocomposites

Polystyrene and copper nanowires were melt‐mixedat 200 °C and 50 rpm in 5 mL and 15 mL DSM co‐rotating conical micro‐compounders (DSM5 and DSM 15), respectively. The electrical, morphological and rheological properties of the resulting nanocomposites were studied. The electrical percolation of nanocomposites is between 1.0 and 2.0 vol.‐% for the composites prepared in DSM5 and above 2.0 vol.‐% for the composites prepared in DSM15. SEM micrographs show smaller copper nanowire agglomerates inside polystyrene from DSM15 than those from DSM5. However, TEM micrographs reveal that both single copper nanowires and nanowire bundles coexist in the polymer matrix for the samples prepared in both micro‐compounders. No obvious microstructure transition is detected by the dynamic rheological data at 200 °C.

     

PVA,PVA Blends,and Their Nanocomposites for Biodegradable Packaging Application

This review exclusively addresses material systems primarily based on poly(vinyl alcohol) (PVA), one of the most popular water-soluble biopolymers, for their use in packaging applications with the primary objective of reducing petrobased plastic waste. In addition, some typical PVA blends and nanocomposites are discussed as comparative studies for material packaging. Structural characteristics, mechanical, thermal, and barrier properties, in addition to biodegradation of these multiple material systems are summarized in a systematic manner. Finally, associated fabrication processing methods together with the most popular theoretical models used for the permeability of PVA nanocomposites are also reviewed in detail.     

Increased Circulatory Asymmetric Dimethylarginine and Multiple Organ Failure: Bile Duct Ligation in Rat as a Model

Bile duct ligation (BDL)-treated rats exhibit cholestasis, increased systemic oxidative stress, and liver fibrosis, which ultimately lead to liver cirrhosis. Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of nitric oxide synthase that can decrease the synthesis of nitric oxide. BDL rats have higher plasma and hepatic ADMA levels, which may be due to increased hepatic protein arginine methyltransferase-1 and decreased dimethylarginine dimethylaminohydrolase expression. BDL rats also exhibit renal and brain damage characterized by increased tissue ADMA concentrations. The increased plasma ADMA levels and multiple organ damages seen here are also observed following multiple organ failures associated with critical illness. This review discusses the dysregulation of ADMA in major organs in BDL rats and the role of increased ADMA in multiple organ damages.     

Studies on Preparation of Photosensitizer Loaded Magnetic Silica Nanoparticles and Their Anti-Tumor Effects for Targeting Photodynamic Therapy

Abstract  As a fast developing alternative of traditional therapeutics, photodynamic therapy (PDT) is an effective, noninvasive, nontoxic therapeutics for cancer, senile macular degeneration, and so on. But the efficacy of PDT was compromised by insufficient selectivity and low solubility. In this study, novel multifunctional silica-based magnetic nanoparticles (SMNPs) were strategically designed and prepared as targeting drug delivery system to achieve higher specificity and better solubility. 2,7,12,18-Tetramethyl-3,8-di-(1-propoxyethyl)-13,17-bis-(3-hydroxypropyl) porphyrin, shorted as PHPP, was used as photosensitizer, which was first synthesized by our lab with good PDT effects. Magnetite nanoparticles (Fe₃O₄) and PHPP were incorporated into silica nanoparticles by microemulsion and sol–gel methods. The prepared nanoparticles were characterized by transmission electron microscopy, X-ray diffraction, Fourier transform infrared spectroscopy and fluorescence spectroscopy. The nanoparticles were approximately spherical with 20–30 nm diameter. Intense fluorescence of PHPP was monitored in the cytoplasm of SW480 cells. The nanoparticles possessed good biocompatibility and could generate singlet oxygen to cause remarkable photodynamic anti-tumor effects. These suggested that PHPP-SMNPs had great potential as effective drug delivery system in targeting photodynamic therapy, diagnostic magnetic resonance imaging and magnetic hyperthermia therapy. Graphical Abstract   Novel multifunctional photosensitizer loaded magnetic silica nanoparticles were strategically prepared with low toxicity, good biocompatibility and remarkable photodynamic anti-tumor efficacy. The nanoparticles were believed to be of great value as drug delivery system in targeting photodynamic therapy, diagnostic magnetic resonance imaging and magnetic hyperthermia therapy.      

Thin Film Nanocomposites Based on SBM Triblock Copolymer and Silver Nanoparticles: Morphological and Dielectric Analysis

Hybrid organic/inorganic thin film nanocomposites based on poly(styrene)‐b‐poly(butadiene)‐b‐poly(methyl methacrylate) triblock copolymer and silver nanoparticles are prepared and characterized. In order to improve the compatibility of nanoparticles with the polymeric matrix, their surface is modified with dodecanethiol surfactant, which enables a good dispersion of nanoparticles through the triblock copolymer, without the formation of aggregates. By atomic force microscopy (AFM), the dispersion level of nanoparticles is analyzed, together with their effect on the thin film surface morphology, for nanocomposites up to 15 wt% of nanoparticles. Dielectric properties of nanocomposites are studied by dielectric relaxation spectroscopy (DRS), analyzing the effect of nanoparticles on dielectric properties. Even if conductivity and permittivity of composites increase with nanoparticle content, percolation threshold is found to be at around 15% in volume. Morphologically analyzed nanocomposites are, in this way, below the threshold.     

Synthetic Nucleic Acid Analogues in Gene Therapy: An Update for Peptide–Oligonucleotide Conjugates

The main objective of this work is to provide an update on synthetic nucleic acid analogues and nanoassemblies as tools in gene therapy. In particular, the synthesis and properties of peptide–oligonucleotide conjugates (POCs), which have high potential in research and as therapeutics, are described in detail. The exploration of POCs has already led to fruitful results in the treatment of neurological diseases, lung disorders, cancer, leukemia, viral, and bacterial infections. However, delivery and in vivo stability are the major barriers to the clinical application of POCs and other analogues that still have to be overcome. This review summarizes recent achievements in the delivery and in vivo administration of synthetic nucleic acid analogues, focusing on POCs, and compares their efficiency.     

用于基因转运和治疗的多功能纳米复合物的制备及应用

基因治疗是将DNA转染进入目的细胞,修复遗传错误或者产生治疗因子。目前基因治疗研究的热点是利用纳米颗粒作为载体,将特异性基因转染到细胞内,从而达到基因治疗的目的。纳米颗粒作为载体可使基因的转染效率提高、增强其稳定性、靶向型。就纳米复合物的组成及在基因治疗方面的应用、面临的问题与挑战进行了综述。     

Gene Therapy for Progressive Familial Intrahepatic Cholestasis: Current Progress and Future Prospects

Progressive Familial Intrahepatic Cholestasis (PFIC) are inherited severe liver disorders presenting early in life, with high serum bile salt and bilirubin levels. Six types have been reported, two of these are caused by deficiency of an ABC transporter; ABCB11 (bile salt export pump) in type 2; ABCB4 (phosphatidylcholine floppase) in type 3. In addition, ABCB11 function is affected in 3 other types of PFIC. A lack of effective treatment makes a liver transplantation necessary in most patients. In view of long-term adverse effects, for instance due to life-long immune suppression needed to prevent organ rejection, gene therapy could be a preferable approach, as supported by proof of concept in animal models for PFIC3. This review discusses the feasibility of gene therapy as an alternative for liver transplantation for all forms of PFIC based on their pathological mechanism. Conclusion: Using presently available gene therapy vectors, major hurdles need to be overcome to make gene therapy for all types of PFIC a reality.     

On Processing and Impact Deformation Behavior of High Density Polyethylene (HDPE)–Calcium Carbonate Nanocomposites

Different processing approaches were adopted to obtain the best combination of strength and toughness. The approach that yielded superior properties was examined in detail to study the mechanical response of nanoscale calcium carbonate‐reinforced high density polyethylene in conjunction with unreinforced high density polyethylene. The reinforcement of high density polyethylene with nanoscale calcium carbonate increases impact strength and is not accompanied by decrease in yield strength. The addition of nanoscale calcium carbonate to high density polyethylene alters the micromechanism of deformation from crazing‐tearing in high density polyethylene to fibrillation in high density polyethylene–calcium carbonate nanocomposite.

     

Gene Therapy for Mucopolysaccharidosis Type II—A Review of the Current Possibilities

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder based on a mutation in the IDS gene that encodes iduronate 2-sulphatase. As a result, there is an accumulation of glycosaminoglycans—heparan sulphate and dermatan sulphate—in almost all body tissues, which leads to their dysfunction. Currently, the primary treatment is enzyme replacement therapy, which improves the course of the disease by reducing somatic symptoms, including hepatomegaly and splenomegaly. The enzyme, however, does not cross the blood–brain barrier, and no improvement in the function of the central nervous system has been observed in patients with the severe form of the disease. An alternative method of treatment that solves typical problems of enzyme replacement therapy is gene therapy, i.e., delivery of the correct gene to target cells through an appropriate vector. Much progress has been made in applying gene therapy for MPS II, from cellular models to human clinical trials. In this article, we briefly present the history and basics of gene therapy and discuss the current state of knowledge about the methods of this therapy in mucopolysaccharidosis type II.