Development of optical nanoprobes for molecular imaging of reactive oxygen and nitrogen species

Reactive oxygen and nitrogen species (RONS) play important roles in cell signal transduction. However, overproduction of RONS is associated with a series of pathological processes and may disrupt cellular homeostasis, causing oxidative and nitrosative stress. Accurate methods to selectively and specifically monitor RONS in living systems are required to further elucidate the biological functions of these species. Optical imaging possesses high sensitivity, high spatiotemporal resolution, and real-time imaging capability. These qualities are advantageous for the detection of RONS in living systems. This review summarizes the development of optical nanoprobes with near-infrared (NIR) fluorescent, upconversion luminescent, chemiluminescent, or photoacoustic signals for molecular imaging of RONS in living systems. In this review, we discuss the design principles and advantages of RONS-responsive activatable nanoprobes, as well as applications of these optical imaging modalities in different disease models.     

新型抗氧剂研究进展

近几十年来,高分子材料因具有高性能、易改性、质量轻等特点,已成为人们生产和生活中必不可少的一类材料.但高分子材料在加工、储存和使用过程中会发生氧化老化,延缓高分子材料氧化的方法较多,添加抗氧剂是其中简单且有效的方法.因此,对近10 a高分子材料抗氧剂的研究进行梳理,将其分为抗析出型、高效型和无毒环保型3类进行详细分析.根据高分子材料抗氧剂最新的发展动态,认为抗析出、高效和无毒环保是其研发的主要方向.大分子型抗氧剂、负载型抗氧剂和反应型抗氧剂能有效提升小分子抗氧剂的抗析出性能,其中,大分子型抗氧剂具有更好的发展潜力;分子内协同作用是抗氧剂高效化的有效手段;生物基抗氧剂是无毒环保型抗氧剂的主要研发方向.     

Antioxidant technology for durability enhancement in polymer electrolyte membranes for fuel cell applications

While polymer electrolyte membrane fuel cells (PEMFCs) have surged in popularity due to their low environmental impact and high efficiency, their susceptibility to degradation by in-situ generated peroxide and oxygen radical species has prevented their widespread adoption. To alleviate chemical attack on components of PEMFCs, particularly on polymer electrolyte membranes (PEMs), antioxidant approaches have been the subject of enormous interest as a key solution because they can directly scavenge and remove detrimental peroxide and oxygen radical species. However, a consequence is that long-term PEMFC device operation can cause undesirable adverse degradation of antioxidant additives provoked by the distinctive chemical/electrochemical environment of low pH, electric potential, water flux, and ion exchange/concentration gradient. Moreover, changes in the physical state such as migration, agglomeration, and dissolution of antioxidants by mechanical or chemical pressures are serious problems that gradually deteriorate antioxidant activity and capacity. This review presents current opportunities for and limitations to antioxidant therapy for durability enhancement in PEMs for electrochemical device applications. We also provide a summary of advanced synthetic design strategies and in-depth analyses of antioxidants regarding optimizing activity-stability factors. This review will bring new insight into the design to realization of ideal antioxidant nanostructures for PEMs and open up new opportunities for enhancing proliferation of durable PEMFCs.     

Towards complete descriptions of the free-energy landscapes of proteins

In recent years increasingly detailed information about the structures and dynamics of protein molecules has been obtained by innovative applications of experimental techniques, in particular nuclear magnetic resonance spectroscopy and protein engineering, and theoretical methods, notably molecular dynamics simulations. In this article we discuss how such approaches can be combined by incorporating a wide range of different types of experimental data as restraints in computer simulations to provide unprecedented detail about the ensembles of structures that describe proteins in a wide variety of states from the native structure to highly unfolded species. Knowledge of these ensembles is beginning to enable the complete free-energy landscapes of individual proteins to be defined at atomic resolution. This strategy has provided new insights into the mechanism by which proteins are able to fold into their native states, or by which they fail to do so and give rise to harmful aggregates that are associated with a wide range of debilitating human diseases.     

Ceria Nanoparticles Meet Hepatic Ischemia‐Reperfusion Injury: The Perfect Imperfection

The mononuclear phagocyte system (MPS, e.g., liver, spleen) is often treated as a “blackbox” by nanoresearchers in translating nanomedicines. Often, most of the injected nanomaterials are sequestered by the MPS, preventing their delivery to the desired disease areas. Here, this imperfection is exploited by applying nano‐antioxidants with preferential liver uptake to directly prevent hepatic ischemia‐reperfusion injury (IRI), which is a reactive oxygen species (ROS)‐related disease. Ceria nanoparticles (NPs) are selected as a representative nano‐antioxidant and the detailed mechanism of preventing IRI is investigated. It is found that ceria NPs effectively alleviate the clinical symptoms of hepatic IRI by scavenging ROS, inhibiting activation of Kupffer cells and monocyte/macrophage cells. The released pro‐inflammatory cytokines are then significantly reduced and the recruitment and infiltration of neutrophils are minimized, which suppress subsequent inflammatory reaction involved in the liver. The protective effect of nano‐antioxidants against hepatic IRI in living animals and the revealed mechanism herein suggests their future use for the treatment of hepatic IRI in the clinic.     

Stimulus‐Responsive Anti‐Oxidizing Drug Crystals and their Ecological Implication

Various antioxidants are being used to neutralize the harmful effects of reactive oxygen species (ROS) overproduced in diseased tissues and contaminated environments. Polymer‐directed crystallization of antioxidants has attracted attention as a way to control drug efficacy through molecular dissolution. However, most recrystallized antioxidants undertake continuous dissolution independent of the ROS level, thus causing side‐effects. This study demonstrates a unique method to assemble antioxidant crystals that modulate their dissolution rate in response to the ROS level. We hypothesized that antioxidants recrystallized using a ROS‐labile polymer would be triggered to dissolve when the ROS level increases. We examined this hypothesis by using catechin as a model antioxidant. Catechin was recrystallized using polyethylenimine cross‐linked with ROS‐labile diselanediylbis‐(ethane‐2,1‐diyl)‐diacrylate. Catechin crystallized with the ROS‐labile polymer displays accelerated dissolution proportional to the H₂O₂ concentration. The ROS‐responsive catechin crystals protect vascular cells from oxidative insults by activating intracellular glutathione peroxidase expression and, in turn, inhibiting an increase in the intracellular oxidative stress. In addition, ROS‐responsive catechin crystals alleviate changes in the heart rate of Daphnia magna in oxidative media. We propose that the results of this study would be broadly useful for improving the therapeutic efficacy of a broad array of drug compounds.     

In vivo imaging of hydrogen peroxide with chemiluminescent nanoparticles

The overproduction of hydrogen peroxide is implicated in the development of numerous diseases and there is currently great interest in developing contrast agents that can image hydrogen peroxide in vivo. In this report, we demonstrate that nanoparticles formulated from peroxalate esters and fluorescent dyes can image hydrogen peroxide in vivo with high specificity and sensitivity. The peroxalate nanoparticles image hydrogen peroxide by undergoing a three-component chemiluminescent reaction between hydrogen peroxide, peroxalate esters and fluorescent dyes. The peroxalate nanoparticles have several attractive properties for in vivo imaging, such as tunable wavelength emission (460-630 nm), nanomolar sensitivity for hydrogen peroxide and excellent specificity for hydrogen peroxide over other reactive oxygen species. The peroxalate nanoparticles were capable of imaging hydrogen peroxide in the peritoneal cavity of mice during a lipopolysaccharide-induced inflammatory response. We anticipate numerous applications of peroxalate nanoparticles for in vivo imaging of hydrogen peroxide, given their high specificity and sensitivity and deep-tissue-imaging capability.     

Determining the effects of antioxidants on oxidative stress induced carbonylation of proteins

There is potential that the pathological effects of oxidative stress (OS) associated diseases such as diabetes could be ameliorated with antioxidants, but this will require a clearer understanding of the pathway(s) by which proteins are damaged by OS. This study reports the development and use of methods that assess the efficacy of dietary antioxidant supplementation at a mechanistic level. Data reported here evaluate the impact of green tea supplementation on oxidative stress induced post-translational modifications (OSi-PTMs) in plasma proteins of Zucker diabetic fatty (ZDF) rats. The mechanism of antioxidant protection was examined through both the type and amount of OSi-PTMs using mass spectrometry based identification and quantification. Carbonylated proteins in freshly drawn blood samples were derivatized with biotin hydrazide. Proteins thus biotinylated were selected from plasma samples of green tea fed diabetic rats and control animals by avidin affinity chromatography, further fractionated by reversed phase chromatography (RPC); fractions from the RPC column were tryptic digested, and the tryptic digest was fractionated by RPC before being identified by tandem mass spectrometry (MS/MS). Relative quantification of peptides bearing carbonylation sites was achieved for the first time by RPC-MS/MS using selective reaction monitoring (SRM). Seventeen carbonylated peptides were detected and quantified in both control and treated plasma. The relative concentration of eight was dramatically different between control and green tea treated animals. Seven of the OSi-PTM bearing peptides had dropped dramatically in concentration with treatment while one increased, indicating differential regulation of carbonylation by antioxidants. Green tea antioxidants were found to reduce carbonylation of proteins by lipid peroxidation end products most, followed by advanced glycation end products to a slightly lower extent. Direct oxidation of proteins by reactive oxygen species (ROS) was protected the least by green tea.     

A Graphene Quantum Dots–Hypochlorite Hybrid System for the Quantitative Fluorescent Determination of Total Antioxidant Capacity

Antioxidants play a major part in the prevention and impairment of oxidative stress‐induced damages and diseases. Evaluating the antioxidants activity/capacity in food and biological fluid is proved to be useful for the diagnosis and treatment of these oxidative stress‐induced diseases. Herein, a graphene quantum dots (GQDs)–hypochlorite system to detect the antioxidants including nonenzymatic and enzymatic antioxidants in the biological fluid is proposed. The detection principle is based on the fact that antioxidants can protect the fluorescence of GQDs from hypochlorite‐caused quenching by acting as the scavengers of hypochlorite. The GQDs–hypochlorite system allows the accurate quantification of the total antioxidant capacity (TAC) of commercial drinks as well as the extracellular superoxide dismutase (SOD) secretion upon stimulation of cytokines or hyperglycemia. This system shows the excellent analytical recoveries for commercial drinks (>89.9%) and good consistency with ELISA testing for SOD secretion in cell‐conditioned medium. These results demonstrate the ability and reliability of the GQD–hypochlorite system for detecting and quantifying TAC in real drinks and complex biological fluids.     

γ辐射下HALS与抗氧剂在PP中的并用效应及机理研究——Ⅱ．γ辐照下HALS与抗氧剂在PP中的并用机理

通过测定在聚丙烯（PP）中生成的氢过氧化物的浓度，辐照后P宾质量变化以及羰基的生成等，研究了受阻胺光稳定剂PDS[4－（甲基丙烯酸）－2，2，6，6－四甲基哌啶醇酯和苯乙烯的共聚物]与几种类型抗氧剂在γ－辐射下在PP中的并用机理。发现并用效果越好的体系中氢过氧化物的生成浓度越低，PP质量增加越少。认为PDS与大多数抗氧剂并用得到协同效应的原因是更能有效地清除在PP中生成的氢过氧化物和过氧自由基。     

Biological Functions and Current Advances in Isolation and Detection Strategies for Exosome Nanovesicles

Exosomes are nanoscale (≈30–150 nm) extracellular vesicles of endocytic origin that are shed by most types of cells and circulate in bodily fluids. Exosomes carry a specific composition of proteins, lipids, RNA, and DNA and can work as cargo to transfer this information to recipient cells. Recent studies on exosomes have shown that they play an important role in various biological processes, such as intercellular signaling, coagulation, inflammation, and cellular homeostasis. These functional roles are attributed to their ability to transfer RNA, proteins, enzymes, and lipids, thereby affecting the physiological and pathological conditions in various diseases, including cancer and neurodegenerative, infectious, and autoimmune diseases (e.g., cancer initiation, progression, and metastasis). Due to these unique characteristics, exosomes are considered promising biomarkers for the diagnosis and prognosis of various diseases via noninvasive or minimally invasive procedures. Over the last decade, a plethora of methodologies have been developed for analyzing disease‐specific exosomes using optical and nonoptical tools. Here, the major biological functions, significance, and potential role of exosomes as biomarkers and therapeutics are discussed. Furthermore, an overview of the most commonly used techniques for exosome analysis, highlighting the major technical challenges and limitations of existing techniques, is presented.     

高密度聚乙烯/木粉复合材料的热氧老化(Ⅱ)——热氧老化对木塑复合材料力学性能的影响

以高密度聚乙烯和木粉为原料、马来酸酐接枝聚乙烯为界面增溶剂,采用热压成型的方法制备了木塑复合材料.通过添加不同抗氧刺及调节抗氧剂比例来对比分析各种抗氧剂对木塑复合材料耐老化性能的效果.结果表明,使用抗氧剂可有效改善木塑复合材料的热氧老化性能,其中使用1.5%～2.0%(质量分数)β-(3,5-二叔丁基-4-羟基苯基)丙酸正十八碳醇酯(1076)的效果最好.     

Physicochemical and Biological Properties of Biomimetic Mineralo‐Protein Nanoparticles Formed Spontaneously in Biological Fluids

Recent studies indicate that mineral nanoparticles (NPs) form spontaneously in human body fluids. These biological NPs represent mineral precursors that are associated with ectopic calcifications seen in various human diseases. However, the parameters that control the formation of mineral NPs and their possible effects on human cells remain poorly understood. Here a nanomaterial approach to study the formation of biomimetic calcium phosphate NPs comparable to their physiological counterparts is described. Particle sizing using dynamic light scattering reveals that serum and ion concentrations within the physiological range yield NPs below 100 nm in diameter. While the particles are phagocytosed by macrophages in a size‐independent manner, only large particles or NP aggregates in the micrometer range induce cellular responses that include production of mitochondrial reactive oxygen species, caspase‐1 activation, and secretion of interleukin‐1β (IL‐1β). A comprehensive proteomic analysis reveals that the particle‐bound proteins are similar in terms of their identity and number, regardless of particle size, suggesting that protein adsorption is independent of particle size and curvature. In conclusion, the conditions underlying the formation of mineralo‐protein particles are similar to the ones that form in vivo. While mineral NPs do not activate immune cells, they may become pro‐inflammatory and contribute to pathological processes once they aggregate and form larger mineral particles.     

聚烯烃抗氧剂1076和168在食用油中的迁移研究

借助HPLC分析仪器试验研究了不同温度下聚烯烃抗氧剂1076和168向食用调和油、玉米油和菜籽油的迁移,讨论了不同油类、温度对迁移的影响,并将所得结果与用100%乙醇作为脂肪模拟物取得的结果进行对比.结果表明:油的种类对抗氧剂的迁移过程影响较小;温度对迁移动力学过程起到决定性作用,迁移速度随温度的升高而加快,达到迁移平衡所需的时间也越短;2种抗氧剂在食用油和100%乙醇中的迁移行为相似,总体说来100%乙醇可以作为脂肪模拟物来替代食用油用于抗氧剂的迁移试验研究.     

Overproduction of reactive oxygen species in end-stage renal disease patients: a potential component of hemodialysis-associated inflammation

During the past decade, hemodialysis (HD)-induced inflammation has been linked to the development of long-term morbidity in end-stage renal disease (ESRD) patients on regular renal replacement therapy. Because interleukins and anaphylatoxins produced during HD sessions are potent activators for nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, an example of an enzyme that is responsible for overproduction of reactive oxygen species (ROS), this may constitute a link between leukocyte activation and cell or organ toxicity. Oxidative stress, which results from an imbalance between oxidant production and antioxidant defense mechanisms, has been documented in ESRD patients using lipid and/or protein oxidative markers. Characterization of HD-induced oxidative stress has included identification of potential activators for NADPH oxidase. Uremia per se could prime phagocyte oxidative burst. HD, far from improving the oxidative status, results in an enhancement of ROS owing to hemoincompatibility of the dialysis system, hemoreactivity of the membrane, and trace amounts of endotoxins in the dialysate. In addition, the HD process is associated with an impairment in antioxidant mechanisms. The resulting oxidative stress has been implicated in long-term complications including anemia, amyloidosis, accelerated atherosclerosis, and malnutrition. Prevention of oxidative stress in HD might focus on improving the hemocompatibility of the dialysis system, supplementation of deficient patients with antioxidants, and modulation of NADPH oxidase by pharmacologic approaches.     

The modelling of a primitive 'sustainable' conservative cell

The simple sustainable or 'eternal' cell model, assuming preservation of all proteins, is designed as a building block, a primitive element upon which one can build more complete functional cell models of various types, representing various species. In the modelling we emphasize the electrophysiological aspects, in part because these are a well-developed component of cell models and because membrane potentials and their fluctuations have been generally omitted from metabolically oriented cell models in the past. Fluctuations in membrane potential deserve heightened consideration because probably all cells have negative intracellular potentials and most cells demonstrate electrical activity with vesicular extrusion, receptor occupancy, as well as with stimulated excitation resulting in regenerative depolarization. The emphasis is on the balances of mass, charge, and of chemical species while accounting for substrate uptake, metabolism and metabolite loss from the cell. By starting with a primitive representation we emphasize the conservation ideas. As more advanced models are generated they must adhere to the same basic principles as are required for the most primitive incomplete model.     

Method for the comparative glycomic analyses of O-linked, mucin-type oligosaccharides

A method is presented for the direct relative quantitation of distinct O-linked mucin-type oligosaccharides. Mucin-type oligosaccharides are found in a host of tissues from anuran to humans. Because they are often associated with extracellular matrix, they play important roles in cell-cell recognition. Changes in glycosylation of O-linked oligosaccharides are associated with diseases such as cancer. In fertilization, they play an active role in sperm-egg recognition. We describe a method for observing changes in glycosylation of mucin-type oligosaccharides by incorporating deuterium in the release procedure. Oligosaccharides from two different sources are released separately by sodium tetrahydroborate and sodium tetradeuterioborate. The oligosaccharides are combined and separated into components by HPLC. By observing the ratio of deuterated and undeuterated species, changes in glycosylation are precisely quantified. This method is illustrated with mucin-type oligosaccharides from the egg jelly coat of the anuran Xenopus laevis.     

Hyaluronic Acid–Based Activatable Nanomaterials for Stimuli‐Responsive Imaging and Therapeutics: Beyond CD44‐Mediated Drug Delivery

There is a rapidly increasing interest in developing stimuli‐responsive nanomaterials for treating a variety of diseases. By enabling the activation of function locally at the sites of interest, it is possible to increase therapeutic efficacy significantly while simultaneously reducing adverse side effects. While there are many sophisticated nanomaterials available, they are often highly complex and not easily transferrable to industrial scales and clinical settings. However, nanomaterials based on hyaluronic acid offer a compelling strategy for reducing their complexity while retaining several desirable benefits such as active targeting and stimuli‐responsive degradation. Herein, the basic properties of hyaluronic acid, its binding partners, and natural routes for degradation by hyaluronidases—hyaluronic‐acid‐degrading enzymes—and oxidative stresses are discussed. Recent advances in designing hyaluronic acid–based, actively targeted, hyaluronidase‐ or reactive‐oxygen‐species‐responsive nanomaterials for both diagnostic imaging and therapeutic delivery, which go beyond merely the classical targeting of CD44, are summarized.     

Toxic effects of metals: modulation of intracellular calcium homeostasis

Metals and metalloids with their organic derivatives are part of the environment occurring naturally or being introduced upon human activity (e.g. industry, agriculture or medicine). Even if they are useful for humans, these chemicals could be highly toxic (e.g. mercury, lead, arsenic, tin) acting as neurotoxins or carcinogens. Several human cases of metal derived intoxication have been documented resulting in health complications or ending with death. The mechanisms of toxicity are not well understood. Since calcium is a universal second messenger in all cell types it is a good candidate to investigate how changes in the intracellular calcium homeostasis are involved in metal(loid) toxicity. In this mini‐overview the interaction of metallic species with channel proteins at the outer cell membrane, as well as with calcium release sides from the calcium stores and the impairment with calcium extrusion mechanism is discussed.     

Effects of antioxidants and the solid component on the thermal stability of polyol-ester-based thermal pastes

The thermal stability of polyol-ester-based thermal pastes is evaluated by weight loss, viscosity and thermal contact conductance measurements. A high degree of thermal stability has been attained by using a half-hindered phenolic primary antioxidant and a thiopropionate secondary antioxidant. By using either carbon black or boron nitride particles as the solid component, a thermally conductive paste with a high degree of thermal stability has been attained. The antioxidants cause the residual weight (excluding the solid component) after oven aging at 200 °C for 24 h to increase from 36 to 97 wt.%. They cause the viscosity not to increase upon heating and they reduce the thermal cracking tendency. They do not affect the thermal contact conductance measured across mating surfaces that sandwich the paste. The use of a fully-hindered phenolic primary antioxidant is less effective. Both carbon black and boron nitride serve as antioxidants in the presence of either primary antioxidant or secondary antioxidant at 200 °C, though, in most cases, they degrade the thermal stability in the presence of both primary and secondary antioxidants, particularly at 220 °C. Below 180 °C and in the presence of primary and secondary antioxidants, boron nitride is particularly effective in promoting the thermal stability. Boron nitride paste shows an estimated lifetime of 19 years at 100 °C, compared to 1.3 years for the carbon black paste, and 0.10 year for commercial polyol-ester-based Arctic Silver 5. Carbon black paste has a lower tendency for cracking after heating than boron nitride paste, due to the low volume fraction of the solid component.