Transcriptomic and metabolomic insights into the defense response to HFRs in Arabidopsis.

Tetrabromobisphenol A (TBBPA), Tetrachlorobisphenol A (TCBPA), Tetrabromobisphenol S (TBBPS) and their derivatives as the most widely used halogenated flame retardants (HFR), had been employed in the manufacturing industry to raise fire safety. HFRs have been shown to be developmentally toxic to animals and also affect plant growth. However, little was known about the molecular mechanism responded by when plants were treated with these compounds. In this study, when Arabidopsis was exposed to four HFRs (TBBPA, TCBPA, TBBPS-MDHP, TBBPS), the stress of these compounds had different inhibitory effects on seed germination and plant growth. Transcriptome and metabolome analysis showed that all four HFRs could influence the expression of transmembrane transporters to affect ion transport, Phenylpropanoid biosynthesis, Plant-pathogen interaction, MAPK signalling pathway and other pathways. In addition, the effects of different kinds of HFR on plants also have variant characteristics. It is very fascinating that Arabidopsis shows the response of biotic stress after exposure to these kinds of compounds, including the immune mechanism. Overall, the findings of the mechanism recovered by methods of transcriptome and metabolome analysis supplied a vital insight into the molecular perspective for Arabidopsis response to HFRs stress.

Identification and interaction mechanism of protein corona on silver nanoparticles with different sizes and the cellular responses.

With the potential biomedical applications of nanomaterials such as silver nanoparticles (SNPs), nanotoxicity concerns are growing, and the importance of NP and protein interactions is far from being addressed enough. Here, we identified the major binding protein on SNPs in blood as human serum albumin (HSA) using polyacrylamide gel electrophoresis and liquid chromatography-mass spectrometry/mass spectrometry. By comparing with the previous methods, we emphasized surface area concentration as a new dose metric to address the importance of NP curvature. SNPs interacted with cysteine and cystine, disrupting the secondary structure and conformation of HSA, and this tendency became stronger on small SNPs than large ones. The protein corona significantly alleviated the toxicity and decreased SNPs' internalization in a particle size-dependent manner, where more significant inhibition effects occurred on larger particles at the same area concentration. These findings may shed light on nanotoxicity and also the design of safe nanomaterials by a comprehensive preconsideration of the metrological method.

PM2.5 induces vascular permeability increase through activating MAPK/ERK signaling pathway and ROS generation.

Although in-vivo exposure of PM2.5 has been suggested to initiate a disorder on vascular permeability, the effects and related mechanism has not been well defined. In this work, an obvious increase on vascular permeability has been confirmed in vivo by vein injection of PM2.5 into Balb/c mouse. Human umbilical vein vascular endothelial cells and the consisted ex-vivo vascular endothelium were used as model to investigate the effects of PM2.5 on the vascular permeability and the underlying molecular mechanism. Upon PM2.5 exposure, the vascular endothelial growth factor receptor 2 on cell membrane phosphorylates and activates the downstream mitogen-activated protein kinase (MAPK)/ERK signaling. The adherens junction protein VE-cadherin sheds and the intercellular junction opens, damaging the integrity of vascular endothelium via paracellular pathway. Besides, PM2.5 induces the intracellular reactive oxygen species (ROS) production and triggers the oxidative stress including activity decrease of superoxide dismutase, lactate dehydrogenase release and permeability increase of cell membrane. Taken together, the paracellular and transcellular permeability enhancement jointly contributes to the significant increase of endothelium permeability and thus vascular permeability upon PM2.5 exposure. This work provides an insight into molecular mechanism of PM2.5 associated cardiovascular disease and offered a real-time screening method for the health risk of PM2.5.

Thiolation in arsenic metabolism: a chemical perspective.

In recent years, methylated thioarsenicals have been widely detected in various biological and environmental matrices, suggesting their broad involvement and biological importance in arsenic metabolism. However, very little is known about the formation mechanism of methylated thioarsenicals and the relation between arsenic methylation and thiolation processes. It is timely and necessary to summarize and synthesize the reported information on thiolated arsenicals for an improved understanding of arsenic thiolation. To this end, we examined the proposed formation pathways of methylated oxoarsenicals and thioarsenicals from a chemical perspective and proposed a novel arsenic metabolic scheme, in which arsenic thiolation is integrated with methylation (instead of being separated from methylation as currently reported). We suggest in the new scheme that protein-bound pentavalent arsenicals are critical intermediates that connect methylation and thiolation, with protein binding of pentavalent methylated thioarsenical being a key step for arsenic thiolation. This informative review on arsenic thiolation from the chemical perspective will be helpful to better understand the arsenic metabolism at the molecular level and the toxicological effects of arsenic species.

Perfluorohexadecanoic acid increases paracellular permeability in endothelial cells through the activation of plasma kallikrein-kinin system.

Per- and polyfluoroalkyl substances (PFASs) are ubiquitous and high persistent in human blood, thus potentially inducing a myriad of deleterious consequences. Plasma kallikrein-kinin system (KKS), which physiologically regulates vascular permeability, is vulnerable to exogenous stimulators, like PFASs with long-chain alkyl backbone substituted by electronegative fluorine. The study on the interactions of PFASs with the KKS and the subsequent effects on vascular permeability would be helpful to illustrate how the chemicals penetrate the biological vascular barriers to reach different tissues. In present study, three representative PFASs, including perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and perfluorohexadecanoic acid (PFHxDA), were investigated for their effects on the activation of the KKS, paracellular permeability in human retina endothelial cells (HRECs) and integrity of the adherens junctions. In contrast to either PFOS or PFOA, PFHxDA efficiently triggered KKS activation in a concentration-dependent manner based on protease activity assays. The plasma activated by PFHxDA significantly increased paracellular permeability of HRECs through the degradation of adherens junctions. As evidenced by the antagonistic effect of aprotinin, PFHxDA-involved effects on vascular permeability were mediated by KKS activation. The results herein firstly revealed the mechanistic pathway for PFHxDA induced effects on vascular endothelial cells. Regarding the possible structure-related activities of the chemicals, this finding would be of great help in the risk assessment of PFASs.

Structure-Dependent Hematological Effects of Per- and Polyfluoroalkyl Substances on Activation of Plasma Kallikrein-Kinin System Cascade.

Per- and polyfluoroalkyl substances (PFASs) are a global concern because of their ubiquitous occurrence and high persistence in human blood, and increasing amounts of unidentified fluorinated compounds are now becoming new exposure issues. This study aims to investigate the structure-related effects of PFASs on the activation of the plasma kallikrein-kinin system (KKS). The effects of 20 PFASs and the related long-chain aliphatic compounds were screened, and their binding affinities for the initial zymogen, Hagmen factor XII (FXII) in the KKS, were evaluated by molecular docking analysis. PFASs were demonstrated to activate the KKS in a structure-dependent mode. More specifically, PFASs with longer carbon chain length, higher fluorine atom substitution degree, and terminal acid group exhibited relatively higher activities in activating the KKS. The binding affinities of PFASs with FXII determined their capabilities for inducing KKS activation. The alternative binding modes of PFASs with FXII, together with van der Waals and hydrogen bonds, specifically accommodated the distinctive chemical structures. To our knowledge, PFASs, for the first time, were found to induce the activation of the KKS in plasma, and their chemical structure-related effects would be extremely important for risk assessment on emerging PFASs in addition to the listing in Stockholm Convention.

Surface ligand controls silver ion release of nanosilver and its antibacterial activity against Escherichia coli.

Understanding the mechanism of nanosilver-dependent antibacterial activity against microorganisms helps optimize the design and usage of the related nanomaterials. In this study, we prepared four kinds of 10 nm-sized silver nanoparticles (AgNPs) with dictated surface chemistry by capping different ligands, including citrate, mercaptopropionic acid, mercaptohexanoic acid, and mercaptopropionic sulfonic acid. Their surface-dependent chemistry and antibacterial activities were investigated. Owing to the weak bond to surface Ag, short carbon chain, and low silver ion attraction, citrate-coated AgNPs caused the highest silver ion release and the strongest antibacterial activity against Escherichia coli, when compared to the other tested AgNPs. The study on the underlying antibacterial mechanisms indicated that cellular membrane uptake of Ag, NAD+/NADH ratio increase, and intracellular reactive oxygen species (ROS) generation were significantly induced in both AgNP and silver ion exposure groups. The released silver ions from AgNPs inside cells through a Trojan-horse-type mechanism were suggested to interact with respiratory chain proteins on the membrane, interrupt intracellular O2 reduction, and induce ROS production. The further oxidative damages of lipid peroxidation and membrane breakdown caused the lethal effect on E. coli. Altogether, this study demonstrated that AgNPs exerted antibacterial activity through the release of silver ions and the subsequent induction of intracellular ROS generation by interacting with the cell membrane. The findings are helpful in guiding the controllable synthesis through the regulation of surface coating for medical care purpose.

Distribution, Bioaccumulation, Trophic Transfer, and Influences of CeO2 Nanoparticles in a Constructed Aquatic Food Web.

In view of the final destination of nanomaterials, the water system would be an important sink. However, the environmental behavior of nanomaterials is rather confusing due to the complexity of the real environment. In this study, a freshwater ecosystem, including water, sediment, water lettuce, water silk, Asian clams, snails, water fleas, Japanese medaka, and Yamato shrimp, was constructed to study the distribution, bioaccumulation, and potential impacts of CeO2 nanoparticles (CeO2 NPs) via long-term exposure. The results demonstrated most of the CeO2 NPs deposited in the sediment (88.7%) when the partition approached to the constant 30 days later. The bioaccumulated Ce in six tested biota species was negatively correlated with its trophic level, showing no biomagnification of CeO2 NPs through this food web. CeO2 NP exposure induced visual abnormalities in hydrophytes, including chlorophyll loss in water silk and water lettuce, ultrastructural changes in pyrenoids of water silk, and root elongation in water lettuce. The generation of hydroxyl radical (·OH) and cell-wall loosening induced by CeO2 NP exposure might mediate the root growth in water lettuce. The findings on the environmental behavior of CeO2 NPs in water system have provided useful information on the risk assessment of nanomaterials.

The potential neurotoxicity of emerging tetrabromobisphenol A derivatives based on rat pheochromocytoma cells.

Tetrabromobisphenol A (TBBPA) can cause diverse adverse effects including neurotoxicity. Emerging TBBPA derivatives, with high structure similarity to the parent compound, are now being concerned. In this study, the potential neurotoxicities of four TBBPA derivatives and their parent compound were studied by cell viability inhibition in rat pheochromocytoma cells (PC12) and the corresponding molecular mechanisms were investigated. The cellular toxicity was correlated with the chemical hydrophobicity. Tetrabromobisphenol A bis(2-hydroxyethyl ether) (TBBPA-BHEE) exhibited the highest cellular toxicity to PC12 due to its lowest hydrophobicity among these 5 tested compounds. Further experiments showed that TBBPA-BHEE disturbed dopamine (DA) secretion and altered acetylcholinesterase (AChE) enzymatic activity in PC12 cells. The molecular mechanism study indicated that TBBPA-BHEE induced cellular toxicity to PC12 cells through ROS-mediated caspase activation to a large extent, which was partially attenuated by the anti-oxidation of Vitamin E. Moreover, in contrast to TBBPA, the occurrence of TBBPA-BHEE toxicity to PC12 was not attributed to activation of mitogen-activated protein kinases (MAPKs) or thyroid hormone (TH) signaling pathway. These findings suggest TBBPA derivatives, especially TBBPA-BHEE, as potential neurotoxins need urgent attention.

Negatively charged silver nanoparticles cause retinal vascular permeability by activating plasma contact system and disrupting adherens junction.

Silver nanoparticles (AgNPs) have been extensively used as antibacterial component in numerous healthcare, biomedical and consumer products. Therefore, their adverse effects to biological systems have become a major concern. AgNPs have been shown to be absorbed into circulation and redistributed into various organs. It is thus of great importance to understand how these nanoparticles affect vascular permeability and uncover the underlying molecular mechanisms. A negatively charged mecaptoundeonic acid-capped silver nanoparticle (MUA@AgNP) was investigated in this work. Ex vivo experiments in mouse plasma revealed that MUA@AgNPs caused plasma prekallikrein cleavage, while positively charged or neutral AgNPs, as well as Ag ions had no effect. In vitro tests revealed that MUA@AgNPs activated the plasma kallikrein-kinin system (KKS) by triggering Hageman factor autoactivation. By using specific inhibitors aprotinin and HOE 140, we demonstrated that KKS activation caused the release of bradykinin, which activated B2 receptors and induced the shedding of adherens junction protein, VE-cadherin. These biological perturbations eventually resulted in endothelial paracellular permeability in mouse retina after intravitreal injection of MUA@AgNPs. The findings from this work provided key insights for toxicity modulation and biomedical applications of AgNPs.

Identification and accurate size characterization of nanoparticles in complex media.

We have developed a new method for the identification and accurate size characterization of nanoparticles (NPs) in complex media based on capillary electrokinetic (CE) separation coupled to inductively coupled plasma mass spectrometry (ICP-MS). Through mass scanning and Gaussian fitting of electropherogram peaks, we can obtain multidimensional information on chemical compositions, size distributions, and ionic species of multiple NPs in a single run. The results are more accurate than those obtained by using conventional methods. This method provides a powerful tool for investigating polydisperse NP systems and rapid screening of NP-containing products.

Revealing carbon nanodots as coreactants of the anodic electrochemiluminescence of Ru(bpy)3²âº.

Recently, research on carbon nanodots (C-dots), a new type of luminescent nanoparticles with superior optical properties, biocompatibility, and low cost, has been focused on exploring novel properties and structure-related mechanisms to extend their scope. Herein, electrochemiluminescence, a surface-sensitive tool, is used to probe the unrevealed property of carbon nanodots which is characterized by surface oxygen-containing groups. Together with chemiluminescence, carbon nanodots as the coreactants for the anodic electrochemiluminescence of Ru(bpy)3(2+) are demonstrated for the first time. During the anodic scan, the benzylic alcohol units on the C-dots surface are oxidized "homogeneously" by electrogenerated-Ru(bpy)3(3+) to form reductive radical intermediate, which further reduce Ru(bpy)3(3+) into Ru(bpy)3(2+)* that produces a strong ECL emission. This work has provided an insight into the ECL mechanism of the C-dots-involved system, which will be beneficial for in-depth understanding of some peculiar phenomena of C-dots, such as photocatalytic activity and redox properties. Moreover, because of the features of C-dots, the ECL system of Ru(bpy)3(2+)/C-dots is more promising in the bioanalysis.

Graphenized pencil lead fiber: facile preparation and application in solid-phase microextraction.

Graphenized pencil lead fiber was facilely prepared by in situ chemical exfoliation of graphite in pencil lead fiber to few-layered graphene sheets via a one-pot, one-step pressurized oxidation reaction for the first time. This new fiber was characterized and demonstrated to be a highly efficient but low-cost solid-phase microextraction (SPME) fiber. The extraction performance of the fiber was evaluated with four bisphenol analogs [bisphenol A (BPA), bisphenol S (BPS), bisphenol AF (BPAF), and tetrabromobisphenol A (TBBPA)] as model analytes in direct SPME mode. Unlike commercially available fibers, the graphenized pencil lead fiber showed an excellent chemical stability in highly saline, acidic, alkaline and organic conditions due to its coating-free configuration. The fiber also showed a very long lifespan. Furthermore, high extraction efficiency and good selectivity for the analytes with a wide polarity range could be obtained due to the exceptional properties of graphene. The detection limits (LODs) for the analytes were in the range of 1.1-25ng/L. The fiber was successfully applied in the analysis of tap water and effluent samples from a waste water treatment plant with spike recoveries ranging from 68.5 to 105.1%. Therefore, the graphenized pencil lead fiber provides a high performance, cheap, robust, and reliable tool for SPME.

Electrochemical methods--important means for fabrication of fluorescent nanoparticles.

Fluorescent nanoparticles have attracted much attention over the last two decades. Due to the size- and composition-dependent optical and electrical properties, fluorescent nanoparticles have been emphasized in electronic, optical and biomedical applications. Till now, many kinds of methods have been developed to fabricate diverse fluorescent nanoparticles, which include pyrolysis, template synthesis, hydrothermal synthesis, microemulsion, electrochemical methods and so on. Among them, electrochemical methods are favored for relatively good controllability, ease of operation and mild reaction conditions. By adjusting the applied potential, current, components of the electrolyte and other relevant parameters, the fluorescent nanoparticles could be electrochemically manufactured with tunable sizes, compositions and surface structure, which allows for the modification of electronic and optical properties. Therefore, electrochemical methods are regarded as important means in preparing fluorescent nanoparticles. This review focuses on the recent progress in electrochemical fabrications of fluorescent nanoparticles (together with their optical properties and some applications in optoelectronics and biomedicine).

Lectin-modified trifunctional nanobiosensors for mapping cell surface glycoconjugates.

Nanomaterial-based nanobiosensors (nanobiodevices or nanobioprobes) are increasingly emphasized. Here, quantum dots and gamma-Fe(2)O(3) magnetic nanoparticles were co-embedded into single swelling poly(styrene/acrylamide) copolymer nanospheres to fabricate fluorescent-magnetic bifunctional nanospheres. Subsequently, fluorescent-magnetic-biotargeting trifunctional nanobiosensors (TFNS) modified with wheat germ agglutinin (WGA), peanut agglutinin (PNA) or Dolichos biflorus agglutinin (DBA) were conveniently produced so as to bind with A549 cells which are surface-expressed with N-acetylglucosamine, d-galactosamine and N-acetylgalactosamine residues. The values of WGA, PNA and DBA on each nanobiosensor were calculated to be 40, 14 and 60, respectively. These three kinds of lectin-modified trifunctional nanobiosensors (lectin-TFNS) can be used for qualitative and quantitative analysis of the glycoconjugates on A549 cell surface. The fluorescence intensity of WGA-modified nanobiosensors related to N-acetylglucosamine on A549 cell surface was much higher than that of PNA-modified nanobiosensors corresponding to d-galactosamine and that of N-acetylgalactosamine-related DBA-modified nanobiosensors, which is consistent with the results detected by flow cytometry. Lectin-modified trifunctional nanobiosensors not only can quantify the different glycoconjugates on A549 cell surface, but also can recognize and isolate A549 cells. 0.5mg of WGA-modified fluorescent-magnetic trifunctional nanobiosensors could capture 7.0 x 10(4) A549 cells. Therefore, the lectin-modified trifunctional nanobiosensors may be applied in mapping the glycoconjugates on cell surfaces and for recognition and isolation of targeted cells.

Wheat germ agglutinin-modified trifunctional nanospheres for cell recognition.

A simple and convenient strategy has been put forward to fabricate smart fluorescent magnetic wheat germ agglutinin-modified trifunctional nanospheres (WGA-TFNS) for recognition of human prostate carcinoma DU-145 cells which are surface-expressed with sialic acid and N-acetylglucosamine. These TFNS can be easily manipulated, tracked, and conveniently used to capture and separate target cells. The presence of wheat germ agglutinin on the surface of WGA-TFNS was confirmed by FTIR, biorecognition of carboxymethyl chitin-modified quantum dots (CM-CT-QDs), and bacterium Staphylococcus aureus. The success in recognizing DU-145 cells by the WGA-TFNS indicates that WGA-TFNS could be applicable.