用胶体金试纸法直接测定鱼肉中硝基呋喃类残留的方法探讨

目的:通过研究胶体金试纸条在硝基呋喃类代谢物残留量中呋喃它酮代谢物AMOZ的应用,并与高效液相色谱法比较。方法:用胶体金试纸半定量法直接测定鱼肉中硝基呋喃类代谢物残留量中呋喃它酮代谢物AMOZ含量。结果:本方法测定的结果与高效液相色谱法相符,并且结果差异无显著性。结论:用胶体金试纸条测定鱼肉中硝基呋喃类代谢物残留量中呋喃它酮代谢物AMOZ具有快速﹑省时﹑简单的优点。     

Combining multiple continuous tests for the diagnosis of kidney impairment in the absence of a gold standard

Receiver operating characteristic (ROC) curves are commonly used to summarize the classification accuracy of diagnostic tests. It is not uncommon in medical practice that multiple diagnostic tests are routinely performed or multiple disease markers are available for the same individuals. When the true disease status is verified by a gold standard (GS) test, a variety of methods have been proposed to combine such potential correlated tests to increase the accuracy of disease diagnosis. In this article, we propose a method of combining multiple diagnostic tests in the absence of a GS. We assume that the test values and their classification accuracies are dependent on covariates. Simulation studies are performed to examine the performance of the combination method. The proposed method is applied to data from a population-based aging study to compare the accuracy of three screening tests for kidney function and to estimate the prevalence of moderate kidney impairment.     

Highly efficient conversion of superoxide to oxygen using hydrophilic carbon clusters

Many diseases are associated with oxidative stress, which occurs when the production of reactive oxygen species (ROS) overwhelms the scavenging ability of an organism. Here, we evaluated the carbon nanoparticle antioxidant properties of poly(ethylene glycolated) hydrophilic carbon clusters (PEG-HCCs) by electron paramagnetic resonance (EPR) spectroscopy, oxygen electrode, and spectrophotometric assays. These carbon nanoparticles have 1 equivalent of stable radical and showed superoxide (O₂^•−) dismutase-like properties yet were inert to nitric oxide (NO^•) as well as peroxynitrite (ONOO⁻). Thus, PEG-HCCs can act as selective antioxidants that do not require regeneration by enzymes. Our steady-state kinetic assay using KO₂ and direct freeze-trap EPR to follow its decay removed the rate-limiting substrate provision, thus enabling determination of the remarkable intrinsic turnover numbers of O₂^•− to O₂ by PEG-HCCs at >20,000 s⁻¹. The major products of this catalytic turnover are O₂ and H₂O₂, making the PEG-HCCs a biomimetic superoxide dismutase.Reactive oxygen species (ROS), such as superoxide (O₂^•−), hydrogen peroxide (H₂O₂), organic peroxides, and hydroxyl radical (^•OH), are a consequence of aerobic metabolism (1, 2). These ROS are necessary for the signaling pathways in biological processes (3, 4) such as cell migration, circadian rhythm, stem cell proliferation, and neurogenesis (5). In healthy systems, ROS are efficiently regulated by the defensive enzymes superoxide dismutase (SOD) and catalase, and by antioxidants such as glutathione, vitamin A, ascorbic acid, uric acid, hydroquinones, and vitamin E (6). When the production of ROS overwhelms the scavenging ability of the defense system, oxidative stress occurs, causing dysfunctions in cell metabolism (7–16).In addition to ROS, reactive nitrogen species (RNS) such as nitric oxide (NO^•), nitrogen dioxide, and dinitrogen trioxide can be found in all organisms. NO^• can act as an oxidizing or reducing agent depending on the environment (17), is more stable than other radicals (half-life 4–15 s) (18), and is synthesized in small amounts in vivo (17–22). NO^• is a potent vasodilator and has an important role in neurotransmission and cytoprotection (17, 18, 22, 23). Owing to its biological importance and the low concentration found normally in vivo, it is often important to avoid alteration of NO^• levels in biological systems to prevent aggravation of acute pathologies including ischemia and reperfusion.One way to treat these detrimental pathologies is to supply antioxidant molecules or particles that renormalize the disturbed oxidative condition. We recently developed a biocompatible carbon nanoparticle, the poly(ethylene glycolated) hydrophilic carbon cluster (PEG-HCC), which has shown ability to scavenge oxyradicals and protect against oxyradical damage in rodent models and thus far has demonstrated no in vivo toxicity in laboratory rodents (24–27). The carbon cores of PEG-HCCs are ∼3 nm wide and range from 30 to 40 nm long. Based on these data, we estimate that there are 2,000–5,000 sp² carbon atoms on each PEG-HCC core. We have demonstrated the efficacy of PEG-HCCs for normalizing in vivo O₂^•− in models of traumatic brain injury with concomitant hypotension. Simultaneously, we observed normalization in NO^• levels in these experiments (26, 27). A better understanding of these materials is necessary to potentially translate these therapeutic findings to the clinic.In the present work, we evaluated antioxidant properties of PEG-HCCs. Using spin-trap EPR spectroscopy, we demonstrate that PEG-HCCs scavenge O₂^•− with high efficiency. X-ray photoelectron spectroscopy (XPS) indicates that covalent addition of ROS to the PEG-HCCs is not responsible for the observed activity. Direct measurement of O₂^•− concentration using freeze-trap EPR demonstrates that PEG-HCCs behave as catalysts, and measurements made with a Clark oxygen electrode during the reaction reveal that the rate of production of O₂ is above that expected due to self-dismutation of O₂^•− in water. An equivalent amount of H₂O₂ is also simultaneously produced. Finally, selectivity for ROS is confirmed using a hemoglobin and a pyrogallol red assay; PEG-HCCs are unreactive to both NO^• and ONOO⁻. These results clarify the fundamental processes involved in the previously observed in vivo protection against oxygen damage (26, 27).     

Patterning the Stiffness of Elastomeric Nanocomposites by Magnetophoretic Control of Cross-linking Impeder Distribution

We report a novel method to pattern the stiffness of an elastomeric nanocomposite by selectively impeding the cross-linking reactions at desired locations while curing. This is accomplished by using a magnetic field to enforce a desired concentration distribution of colloidal magnetite nanoparticles (MNPs) in the liquid precursor of polydimethysiloxane (PDMS) elastomer. MNPs impede the cross-linking of PDMS; when they are dispersed in liquid PDMS, the cured elastomer exhibits lower stiffness in portions containing a higher nanoparticle concentration. Consequently, a desired stiffness pattern is produced by selecting the required magnetic field distribution a priori. Up to 200% variation in the reduced modulus is observed over a 2 mm length, and gradients of up to 12.6 MPa·mm⁻¹ are obtained. This is a significant improvement over conventional nanocomposite systems where only small unidirectional variations can be achieved by varying nanoparticle concentration. The method has promising prospects in additive manufacturing; it can be integrated with existing systems thereby adding the capability to produce microscale heterogeneities in mechanical properties.     

Growth of Ceria Nano-Islands on a Stepped Au(788) Surface

The growth morphology and structure of ceria nano-islands on a stepped Au(788) surface has been investigated by scanning tunneling microscopy (STM) and low-energy electron diffraction (LEED). Within the concept of physical vapor deposition, different kinetic routes have been employed to design ceria-Au inverse model catalysts with different ceria nanoparticle shapes and arrangements. A two-dimensional superlattice of ceria nano-islands with a relatively narrow size distribution (5 ± 2 nm²) has been generated on the Au(788) surface by the postoxidation method. This reflects the periodic anisotropy of the template surface and has been ascribed to the pinning of ceria clusters and thus nucleation on the fcc domains of the herringbone reconstruction on the Au terraces. In contrast, the reactive evaporation method yields ceria islands elongated in [01-1] direction, i.e., parallel to the step edges, with high aspect ratios (~6). Diffusion along the Au step edges of ceria clusters and their limited step crossing in conjunction with a growth front perpendicular to the step edges is tentatively proposed to control the ceria growth under reactive evaporation conditions. Both deposition recipes generate two-dimensional islands of CeO₂(111)-type O–Ce–O single and double trilayer structures for submonolayer coverages.     

Application of Turkevich Method for Gold Nanoparticles Synthesis to Fabrication of SiO2@Au and TiO2@Au Core-Shell Nanostructures

The Turkevich synthesis method of Au nanoparticles (AuNPs) was adopted for direct fabrication of SiO₂@Au and TiO₂@Au core-shell nanostructures. In this method, chloroauric acid was reduced with trisodium citrate in the presence of amine-functionalized silica or titania submicroparticles. Core-shells obtained in this way were compared to structures fabricated by mixing of Turkevich AuNPs with amine-functionalized silica or titania submicroparticles. It was found that by modification of reaction conditions of the first method, such as temperature and concentration of reagents, control over gold coverage on silicon dioxide particles has been achieved. Described method under certain conditions allows fabrication of semicontinuous gold films on the surface of silicon dioxide particles. To the best of our knowledge, this is the first report describing use of Turkevich method to direct fabrication of TiO₂@Au core-shell nanostructures.     

Magnetic Control of Fe3O4 Nanomaterial for Fat Ablation in Microchannel

In this study, surface modification of iron (II, III) oxide Fe₃O₄ nanoparticles by oleic acid (OA) coating is investigated for the microablation of fat in a microchannel. The nanoparticles are synthesized by the co-precipitation method and then dispersed in organic solvent prior to mixing with the OA. The magnetization, agglomeration, and particle size distribution properties of the OA-coated Fe₃O₄ nanoparticles are characterized. The surface modification of the Fe₃O₄ nanoparticles reveals that upon injection into a microchannel, the lipophilicity of the OA coating influences the movement of the nanoparticles across an oil-phase barrier. The motion of the nanoparticles is controlled using an AC magnetic field to induce magnetic torque and a static gradient field to control linear translation. The fat microablation process in a microchannel is demonstrated using an oscillating driving field of less than 1200 Am⁻¹.     

Enhanced Erbium-Doped Ceria Nanostructure Coating to Improve Solar Cell Performance

This paper discusses the effect of adding reduced erbium-doped ceria nanoparticles (REDC NPs) as a coating on silicon solar cells. Reduced ceria nanoparticles doped with erbium have the advantages of both improving conductivity and optical conversion of solar cells. Oxygen vacancies in ceria nanoparticles reduce Ce⁴⁺ to Ce³⁺ which follow the rule of improving conductivity of solar cells through the hopping mechanism. The existence of Ce³⁺ helps in the down-conversion from 430 nm excitation to 530 nm emission. The erbium dopant forms energy levels inside the low-phonon ceria host to up-convert the 780 nm excitations into green and red emissions. When coating reduced erbium-doped ceria nanoparticles on the back side of a solar cell, a promising improvement in the solar cell efficiency has been observed from 15% to 16.5% due to the mutual impact of improved electric conductivity and multi-optical conversions. Finally, the impact of the added coater on the electric field distribution inside the solar cell has been studied.     

Polymeric synthetic nanoparticles for the induction of antigen-specific immunological tolerance

Current treatments to control pathological or unwanted immune responses often use broadly immunosuppressive drugs. New approaches to induce antigen-specific immunological tolerance that control both cellular and humoral immune responses are desirable. Here we describe the use of synthetic, biodegradable nanoparticles carrying either protein or peptide antigens and a tolerogenic immunomodulator, rapamycin, to induce durable and antigen-specific immune tolerance, even in the presence of potent Toll-like receptor agonists. Treatment with tolerogenic nanoparticles results in the inhibition of CD4+ and CD8+ T-cell activation, an increase in regulatory cells, durable B-cell tolerance resistant to multiple immunogenic challenges, and the inhibition of antigen-specific hypersensitivity reactions, relapsing experimental autoimmune encephalomyelitis, and antibody responses against coagulation factor VIII in hemophilia A mice, even in animals previously sensitized to antigen. Only encapsulated rapamycin, not the free form, could induce immunological tolerance. Tolerogenic nanoparticle therapy represents a potential novel approach for the treatment of allergies, autoimmune diseases, and prevention of antidrug antibodies against biologic therapies.Undesired immunogenicity can have a profound impact on human health. Allergies, including allergic asthma and severe food allergies, affect ∼20% of the population, and the prevalence has been steadily increasing over the past several decades (1). The prevalence of autoimmune diseases, including multiple sclerosis and type 1 diabetes, is ∼4.5% (2). Unwanted immunogenicity can also affect both efficacy and safety of biologic drugs (3), particularly in the case of protein replacement therapies for the treatment of genetic deficiencies, such as hemophilia A (4) and Pompe Disease (5). Immunomodulatory agents commonly used to control immunogenicity are often broadly immunosuppressive and typically require chronic administration that can lead to reactivation of latent pathogens, development of tumors, and opportunistic infections (6, 7). Therefore, antigen-specific, durable tolerogenic therapy would be highly desirable from an efficacy and safety perspective.Multiple techniques for antigen-specific immunotherapy have been described, although only allergen immunotherapy, wherein low doses of antigen are delivered in the absence of immunomodulating agents, is currently used in the clinic (1). Experimental approaches have included oral administration of antigen, high dose tolerance, and the use of altered peptide ligands (8). Although these methods have been successful in preclinical models, translation to human clinical trials has been largely disappointing (8). Alternative strategies to leverage tolerogenic programming associated with apoptotic cells include conjugating antigen to splenocytes (9–12) or synthetic microparticles (13, 14) or targeting antigen to the surface of red blood cells (15). Other approaches include loading particles with MHC complexes that present relevant peptides in the absence of costimulation (16, 17), liposomal copresentation of antigen with a ligand specific for the negative signaling receptor CD22 on B cells (18), codelivery of peptide antigen with an aryl hydrocarbon receptor agonist (19), and cotreatment with pharmacological agents, such as methotrexate (20). A major concern for antigen immunotherapy is the ability to induce and maintain tolerance in the presence of proinflammatory stimuli caused by tissue stress, injury, or concurrent infections. We sought to develop an antigen-specific tolerogenic technology that could control both T-cell– and B-cell–mediated immunity and that was durable over time and to multiple challenges with the antigen, even in the presence of strong innate immune stimulants.Dendritic cells (DCs) are an attractive target for immunotherapies due to their central role in antigen presentation to T cells and their ability to induce and control regulatory responses to secure self-tolerance (21–25). Thomson and colleagues (26, 27) demonstrated that treating DCs with rapamycin, an inhibitor of the mTOR pathway, induces a tolerogenic DC phenotype capable of inducing Treg differentiation and antigen-specific immune tolerance that is resistant to the proinflammatory cascade triggered by TLR signaling. However, conventional therapy with free rapamycin requires chronic systemic administration, resulting in broad immunosuppression due to its direct effect on lymphocytes (28), whereas low doses of rapamycin may paradoxically augment effector T-cell memory (29). Thus, it would be desirable to transiently target rapamycin’s effects to DCs and other antigen-presenting cells (APCs) at the time of antigen encounter. Nanoparticles (NPs) are an ideal mechanism to deliver antigen (16, 30, 31) and drugs (32) to APCs, as these cells are keyed to capture and internalize nanoparticulates such as viruses.Here we describe the development of tolerogenic NPs (tNPs) using materials and compounds that have been well validated in the clinic. These self-assembling, biodegradable poly(lactide-coglycolide) (PLGA) tNPs containing either protein or peptide antigens and rapamycin are capable of inducing durable antigen-specific tolerance that control adaptive immune responses and withstand multiple immunogenic challenges with antigen. We demonstrate that either s.c. or i.v. administration of tNPs inhibits the activation of antigen-specific CD4+ and CD8+ T cells and B cells while inducing antigen-specific Tregs and Bregs. Swiss Jack Lambert (SJL) mice immunized with the myelin proteolipid protein 139–151 peptide in complete Freud’s adjuvant (PLP_139–151/CFA) and treated therapeutically with a single dose of tNPs at the peak of disease are completely protected from developing relapsing paralysis. In hemophilia A animals, administration of tNP before or after the establishment of an anti-factor VIII (FVIII) antibody response led to a significant reduction of the neutralizing antibody response against FVIII. Treatment of mice with tNP prevents both cellular and humoral immunity even in the presence of potent TLR agonists. These effects are dependent on the presence of the encapsulated rapamycin (not free in solution).