Leave No Trace? Ecological and anthropogenic determinants of antibiotic resistant bacteria in a recreational alpine environment.

Antibiotic resistant bacteria (ARB) have been detected in remote environments, but the degree to which their presence is due to anthropogenic contamination remains unclear. Here, anthropogenic and ecological determinants of ARB were characterized in remote and highly visited areas of Rocky Mountain National Park in the United States. Soil and water samples were collected from 29 sites once a month for three months and measured for bacteria resistant to seven antibiotics with flow cytometry. A novel index of the likelihood of human presence (HPI) was generated for estimating human impact on ARB abundance. The HPI accounted for 44% of variation in ARB abundance in water samples (p < 0.0001) and 51% of variation in soil samples (p < 0.00001). Human presence index was illustrated as a reliable predictor of ARB abundance despite a tendency to underpredict at higher levels of human impact. Ecological determinants such as temperature, elevation, slope, and aspect were also found to be significantly associated with ARB abundance. These findings suggest that human presence drives the abundance of ARB in Rocky Mountain National Park, but ecological variables play a significant role in their presence and dispersal.

Characterization of Urinary Pesticide Metabolite Concentrations of Pregnant Women in Suriname.

Prenatal exposure to pesticides and the association with adverse health outcomes have been examined in several studies. However, the characterization of pesticide exposure among Surinamese women during pregnancy has not been assessed. As part of the Caribbean Consortium of Research in Environmental and Occupational Health research program, 214 urine samples were collected from pregnant women living in three regions in Suriname with different agricultural practices: capital Paramaribo, the rice producing district Nickerie, and the tropical rainforest, the Interior. We used isotope dilution tandem mass spectrometry to quantify urinary concentrations of biomarkers of three pesticide classes, including phenoxy acid herbicides and organophosphate and pyrethroid insecticides, all of which are commonly used in agricultural and residential settings in Suriname. We observed that participants residing in Nickerie had the highest urinary metabolite concentrations of 2,4-dichlorophenoxyacetic acid and pyrethroids compared to those from Paramaribo or the Interior. Paramaribo had the highest concentrations of organophosphate metabolites, specifically dialkyl phosphate metabolites. Para-nitrophenol was detected in samples from Paramaribo and the Interior. Samples from Nickerie had higher median urinary pesticide concentrations of 2,4-dichlorophenoxyacetic acid (1.06 µg/L), and the following metabolites, 3,5,6-trichloro-2-pyridinol (1.26 µg/L), 2-isopropyl-4-methyl-6-hydroxypyrimidine (0.60 µg/L), and 3-phenoxybenzoic acid (1.34 µg/L), possibly due to residential use and heavy rice production.

Assessing visitor use impact on antibiotic resistant bacteria and antibiotic resistance genes in soil and water environments of Rocky Mountain National Park.

Antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) have been detected in soil and water in close proximity to anthropogenic sources, but the extent to which human impact plays into ARB and ARGs entering the environment is not well described. This study aimed to determine the impact of visitor use on ARB and ARGs in a national park environment. Soil (n = 240) and water (n = 210) samples were collected across a gradient of human activity in Rocky Mountain National Park and analyzed for bacteria resistant to doxycycline, levofloxacin, and vancomycin. Amount of physical effort required to access a sampling site was used as a metric for the likelihood of human presence. A subset of samples was analyzed for the presence and abundance of six ARGs using quantitative polymerase chain reaction. Linear regression analysis demonstrated that anthropogenic factors including hiking effort and proximity to a toilet significantly contributed to the variance of the abundance of ARB for multiple antibiotics in soil and water. Additionally, ecological factors such as water movement, soil texture, and season may play a role in the detection of ARB and ARGs. Predictive analysis suggests that both human presence and human activities, such as waste elimination, significantly contributed to the abundance of ARB in soil and water. The results of this work evidence that the ecology of antibiotic resistance in remote environments is more complex than anthropogenic impact alone, necessitating further environmental characterization of ARB and ARGs.

Increased long-term health risks attributable to select volatile organic compounds in residential indoor air in southeast Louisiana.

Volatile organic compounds (VOCs) represent a broad class of chemicals, many of which can be found in indoor air including residential indoor air. VOCs derive from a variety of sources including cleaning products, cooking practices, fragrances and fresheners, hobbies and at-home work behaviors. This study examined residential indoor air in homes (n = 99) in southeast Louisiana using passive organic vapor monitors and gas chromatography/mass spectrometry to determine if select VOCs were present, at what concentrations, and if those posed any potential long-term health risks. Twenty-nine VOCs were targeted in cross-sectional analyses using a 48-h sampling period. Twelve VOCs were detected in most of the homes sampled including xylenes, pinenes, benzene, toluene, ethylbenzene, hexane, pentane, chloroform, and carbon tetrachloride. Concentrations of alkanes and BTEX compounds were highly correlated (Spearman's r > 0.63, p < 0.0001). Using health risk measures (i.e. reference concentrations [RfCs] and inhalation unit risks [IURs]) available from the USEPA non-cancer risk assessments and cancer risk assessments were developed for some of these VOCs. Alkanes and BTEX compounds likely come from the same indoor source(s). Using existing health standards published by the USEPA, no unacceptable non-cancer risks were evident except under extremely high concentrations. Lifetime cancer risks, on the other hand, may well be considered unacceptable for chloroform and benzene (upper IUR) and for the combination of chloroform, benzene, and carbon tetrachloride. These exceeded a 1 in 10,000 cancer risk threshold in 35-50% of our simulations. Further study of residential indoor air in low-income women's homes in this area is needed. Including a larger number of VOCs may reveal yet more potential health risks.

Inhibition of progesterone biosynthesis induced by deca-brominated diphenyl ether (BDE-209) in mouse Leydig tumor cell (MLTC-1).

Polybrominated Diphenyl Ethers (PBDEs) have been extensively applied as flame retardants in different polymeric materials since the 1970s, which have become a group of long-lasting environmental pollutants. They have been reported from previous studies to accumulate and then disrupt the endocrine system in humans. However, the mechanisms are still little known. In the present study, mouse Leydig tumor cells were utilized to investigate steroidogenic activity influenced by deca-brominated diphenyl ether (BDE-209). Our data showed that BDE-209 did not change intracellular cAMP level in the presence of human Chorionic Gonadotropin (hCG), cholera toxin (CT), and forskolin, which indicated that reduction of progesterone may not be related to the hCG-cAMP signal pathway in MLTC-1 cells. Furthermore, the reduction of progesterone generation was not shifted by 8-Br-cAMP, an analog of cAMP, indicating that BDE-209 may inhibit post-cAMP sites. In addition, mRNA expression levels of P450 side-chain cleavage enzyme (P450scc) and 3ß-hydroxysteroid dehydrogenase (3ß-HSD) presented a concentration-dependent decrease. In conclusion, this study suggested that BDE-209 may attenuate the progesterone secretion mainly through lowering the expression of these two enzymes.

Aryl hydrocarbon receptor signaling, toxicity, and gene expression responses to mono-methylchrysenes.

Polycyclic aromatic hydrocarbons (PAHs) comprise a large family of toxic compounds that come from natural and anthropogenic sources. Chrysene is a PAH with multiple effects, but the toxic potentials of mono-methylchrysenes are less characterized. A comparison of chrysene and six mono-methylchrysenes was performed using assays for cytotoxicity, human aryl hydrocarbon receptor (AhR) reporter gene signaling, and AhR-regulated target gene and protein expression. Sulforhodamine B and trypan blue dye binding assays revealed these chrysenes to be similar in their cytotoxic effects on HepG2 cells. A yeast-based reporter assay detecting human AhR-mediated gene expression identified 4-methylchrysene as being six times more potent and 5-methylchrysene about one-third as potent as chrysene. Other methylchrysenes were more similar to chrysene in the ability to act as AhR ligands. The mono-methylchrysenes all strongly induced CYP1A1 mRNA and protein and moderately induced CYP1B1 expression in HepG2 cells. Levels of CYP1A2 mRNA were induced at higher concentrations of the chrysenes, but protein expression was not significantly altered. The PCR-based gene expression and immunoblotting analyses indicated induced expression differences across the chrysene members were similar to each other. Overall, the effects of methylated chrysenes were comparable to unsubstituted chrysene, suggesting members of this group may be considered approximately equivalent in their effects. © 2019 Wiley Periodicals, Inc.

Consumption of Fish and Shrimp from Southeast Louisiana Poses No Unacceptable Lifetime Cancer Risks Attributable to High-Priority Polycyclic Aromatic Hydrocarbons.

Following oil spills such as the Deepwater Horizon accident (DWH), contamination of seafood resources and possible increased health risks attributable to consumption of seafood in spill areas are major concerns. In this study, locally harvested finfish and shrimp were collected from research participants in southeast Louisiana and analyzed for polycyclic aromatic hydrocarbons (PAHs). PAHs are some of the most important chemicals of concern regarding oil-spill-contaminated seafood resources during and following oil spills. Some PAHs are considered carcinogens for risk assessment purposes, and currently, seven of these can be combined in lifetime cancer risk assessments using EPA approaches. Most PAHs were not detected in these samples (minimum detection limits ranged from 1.2 to 2.1 PPB) and of those that were detected, they were generally below 10 PPB. The pattern of detected PAHs suggested that the source of these chemicals in these seafood samples was not a result of direct contact with crude oil. Lifetime cancer risks were assessed using conservative assumptions and models in a probabilistic framework for the seven carcinogenic PAHs. Lifetime health risks modeled using this framework did not exceed a 1/10,000 cancer risk threshold. Conservative, health-protective deterministic estimates of the levels of concern for PAH chemical concentration and seafood intake rates were above the concentrations and intake rates modeled under this probabilistic framework. Taken together, consumption of finfish and shrimp harvested from southeast Louisiana following the DWH does not pose unacceptable lifetime cancer risks from these seven carcinogenic PAHs even for the heaviest possible consumers.

compMS2Miner: An Automatable Metabolite Identification, Visualization, and Data-Sharing R Package for High-Resolution LC-MS Data Sets.

A long-standing challenge of untargeted metabolomic profiling by ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) is efficient transition from unknown mass spectral features to confident metabolite annotations. The compMS2Miner (Comprehensive MS2 Miner) package was developed in the R language to facilitate rapid, comprehensive feature annotation using a peak-picker-output and MS2 data files as inputs. The number of MS2 spectra that can be collected during a metabolomic profiling experiment far outweigh the amount of time required for pain-staking manual interpretation; therefore, a degree of software workflow autonomy is required for broad-scale metabolite annotation. CompMS2Miner integrates many useful tools in a single workflow for metabolite annotation and also provides a means to overview the MS2 data with a Web application GUI compMS2Explorer (Comprehensive MS2 Explorer) that also facilitates data-sharing and transparency. The automatable compMS2Miner workflow consists of the following steps: (i) matching unknown MS1 features to precursor MS2 scans, (ii) filtration of spectral noise (dynamic noise filter), (iii) generation of composite mass spectra by multiple similar spectrum signal summation and redundant/contaminant spectra removal, (iv) interpretation of possible fragment ion substructure using an internal database, (v) annotation of unknowns with chemical and spectral databases with prediction of mammalian biotransformation metabolites, wrapper functions for in silico fragmentation software, nearest neighbor chemical similarity scoring, random forest based retention time prediction, text-mining based false positive removal/true positive ranking, chemical taxonomic prediction and differential evolution based global annotation score optimization, and (vi) network graph visualizations, data curation, and sharing are made possible via the compMS2Explorer application. Metabolite identities and comments can also be recorded using an interactive table within compMS2Explorer. The utility of the package is illustrated with a data set of blood serum samples from 7 diet induced obese (DIO) and 7 nonobese (NO) C57BL/6J mice, which were also treated with an antibiotic (streptomycin) to knockdown the gut microbiota. The results of fully autonomous and objective usage of compMS2Miner are presented here. All automatically annotated spectra output by the workflow are provided in the Supporting Information and can alternatively be explored as publically available compMS2Explorer applications for both positive and negative modes ( https://wmbedmands.shinyapps.io/compMS2_mouseSera_POS and https://wmbedmands.shinyapps.io/compMS2_mouseSera_NEG ). The workflow provided rapid annotation of a diversity of endogenous and gut microbially derived metabolites affected by both diet and antibiotic treatment, which conformed to previously published reports. Composite spectra (n = 173) were autonomously matched to entries of the Massbank of North America (MoNA) spectral repository. These experimental and virtual (lipidBlast) spectra corresponded to 29 common endogenous compound classes (e.g., 51 lysophosphatidylcholines spectra) and were then used to calculate the ranking capability of 7 individual scoring metrics. It was found that an average of the 7 individual scoring metrics provided the most effective weighted average ranking ability of 3 for the MoNA matched spectra in spite of potential risk of false positive annotations emerging from automation. Minor structural differences such as relative carbon-carbon double bond positions were found in several cases to affect the correct rank of the MoNA annotated metabolite. The latest release and an example workflow is available in the package vignette ( https://github.com/WMBEdmands/compMS2Miner ) and a version of the published application is available on the shinyapps.io site ( https://wmbedmands.shinyapps.io/compMS2Example ).

Cultural influences on the management of environmental health risks among low-income pregnant women.

Following environmental health disasters such as Hurricane Katrina and the Gulf Oil Spill, U.S. Gulf residents expressed concern regarding air quality. Women with children make many decisions that mitigate household air quality risks; however, research examining culture's influence in their risk perception and the influence which this has on their behaviour is limited. In this article we examine the cultural connection between low-income women with children along the U.S. Gulf concerning the local threat of air quality. We used cultural consensus analysis to examine the perceptions of low-income, first-time pregnant women. We undertook an interview survey of 112 women living in Southeast Louisiana, USA between May 2014 and March 2015. In this article we examine if there was a shared (cultural) understanding among these women on how to manage air quality threats, to evaluate what determined cultural sharing in the group, and to explore what role cultural beliefs played in their intended household strategies. We found that although air quality was rarely discussed by the women in our study, we were able to identify two multi-centric cultural models of how these women sought to make sense of air quality issues. In one model they relied on their immediate social network of family and friends while in the other model they were willing to make use of official sources of information. These two models helped explain what measures these women planned to take to address air quality issues in an around their household. Our findings show that cultural norms permeate the assessment of risk in a community and that programmes designed to improve public health need to take into account the cultural context of the population.

Diet-induced obesity increases the frequency of Pig-a mutant erythrocytes in male C57BL/6J mice.

Obesity increases the risk of a number of chronic diseases in humans including several cancers. Biological mechanisms responsible for such increased risks are not well understood at present. Increases in systemic inflammation and oxidative stress, endogenous production of mutagenic metabolites, altered signaling in proliferative pathways, and increased sensitivity to exogenous mutagens and carcinogens are some of the potential contributing factors. We hypothesize that obesity creates an endogenously mutagenic environment in addition to increasing the sensitivity to environmental mutagens. To test this hypothesis, we examined two in vivo genotoxicity endpoints. Pig-a mutant frequencies and micronucleus frequencies were determined in blood cells in two independent experiments in 30-week old male mice reared on either a high-fat diet (60% calories from fat) that exhibit an obese phenotype or a normal-fat diet (10% calories from fat) that do not exhibit an obese phenotype. Mice were assayed again at 52 weeks of age in one of the experiments. N-ethyl-N-nitrosourea (ENU) was used as a positive mutation control in one experiment. ENU induced a robust Pig-a mutant and micronucleus response in both phenotypes. Obese, otherwise untreated mice, did not differ from non-obese mice with respect to Pig-a mutant frequencies in reticulocytes or micronucleus frequencies. However, such mice, had significantly higher and sustained Pig-a mutant frequencies (increased 2.5-3.7-fold, p < 0.02) in erythrocytes as compared to non-obese mice (based on measurements collected at 30 weeks or 30 and 52 weeks of age). This suggests that obesity, in the absence of exposure to an exogenous mutagen, is itself mutagenic. Environ. Mol. Mutagen. 57:668-677, 2016. © 2016 Wiley Periodicals, Inc.

Louisiana residents' self-reported lack of information following the Deepwater Horizon oil spill: Effects on seafood consumption and risk perception.

In 2010, the Deepwater Horizon (DWH) oil spill adversely impacted many communities along the Gulf of Mexico. Effects on Gulf waters, marshes, aquatic life, and fisheries were evident in the following days, months, and years. Through studying affected communities' perceptions regarding the DWH accident, we aim to identify behavioral changes, understand public information sources, and inform dissemination strategies that improve communications from regulatory agencies. Over a three-year period (2012-2015), residents (n = 192) from 7 coastal parishes in southeast Louisiana were surveyed about their perceptions and behaviors before, during, and after the DWH accident. Self-reported consumption of local seafood decreased significantly (50%) during the DWH oil spill but returned to pre-event reported levels by 2015. However, negative seafood quality perceptions remain and have not returned to what were generally positive pre-event levels. Over 30% of study participants trust relatives, friends, and neighbors more than government officials or scientists as information sources regarding locally harvested seafood. Importantly, nearly 50% of participants report that they lack the information needed to make informed decisions regarding the safety of consuming local seafood. We conclude that a lack of information and trust in government agencies exacerbated negative perceptions of oil spill-related dangers. In some cases, overestimation of perceived dangers likely led to behavioral modifications that persist today. Efforts should be made to improve relationships between public health agencies and communities in order to properly inform all citizens of risks following environmental disasters.

The RPTEC/TERT1 Cell Line as an Improved Tool for In Vitro Nephrotoxicity Assessments.

In earlier studies, we have characterized a newly developed cell line derived from the renal proximal tubule epithelial cells (RPTEC) of a healthy human male donor in order to provide an improved in vitro model with which to investigate human diseases, such as cancer, that may be promoted by toxicant exposure. The RPTEC/TERT1 cell line has been immortalized using the human telomerase reverse transcriptase (hTERT) catalytic subunit and does not exhibit chromosomal abnormalities (Evercyte Laboratories). We have previously conducted single-compound and binary mixture experiments with the common environmental carcinogens, cadmium (Cd), and benzo[a]pyrene (B[a]P). Cells exhibited cytotoxic and compound-specific responses to low concentrations of B[a]P and Cd. We detected responses after exposure consistent with what is known regarding these cells in a normal, healthy kidney including significant gene expression changes, BPDE-DNA adducts in the presence of B[a]P, and indications of oxidative stress in the presence of Cd. The RPTEC/TERT1 cell line was also amenable to co-exposure studies due to its sensitivity and compound-specific properties. Here, we review our earlier work, compare our findings with commonly used renal cell lines, and suggest directions for future experiments. We conclude that the RPTEC/TERT1 cell line can provide a useful tool for future toxicological and mixture studies.

A targeted health risk assessment following the Deepwater Horizon oil spill: polycyclic aromatic hydrocarbon exposure in Vietnamese-American shrimp consumers.

BACKGROUND: The Deepwater Horizon oil spill of 2010 prompted concern about health risks among seafood consumers exposed to polycyclic aromatic hydrocarbons (PAHs) via consumption of contaminated seafood. OBJECTIVE: The objective of this study was to conduct population-specific probabilistic health risk assessments based on consumption of locally harvested white shrimp (Litopenaeus setiferus) among Vietnamese Americans in southeast Louisiana. METHODS: We conducted a survey of Vietnamese Americans in southeast Louisiana to evaluate shrimp consumption, preparation methods, and body weight among shrimp consumers in the disaster-impacted region. We also collected and chemically analyzed locally harvested white shrimp for 81 individual PAHs. We combined the PAH levels (with accepted reference doses) found in the shrimp with the survey data to conduct Monte Carlo simulations for probabilistic noncancer health risk assessments. We also conducted probabilistic cancer risk assessments using relative potency factors (RPFs) to estimate cancer risks from the intake of PAHs from white shrimp. RESULTS: Monte Carlo simulations were used to generate hazard quotient distributions for noncancer health risks, reported as mean ± SD, for naphthalene (1.8 × 10-4 ± 3.3 × 10-4), fluorene (2.4 × 10-5 ± 3.3 × 10-5), anthracene (3.9 × 10-6 ± 5.4 × 10-6), pyrene (3.2 × 10-5 ± 4.3 × 10-5), and fluoranthene (1.8 × 10-4 ± 3.3 × 10-4). A cancer risk distribution, based on RPF-adjusted PAH intake, was also generated (2.4 × 10-7 ± 3.9 × 10-7). CONCLUSIONS: The risk assessment results show no acute health risks or excess cancer risk associated with consumption of shrimp containing the levels of PAHs detected in our study, even among frequent shrimp consumers.

Activation of aryl hydrocarbon receptor signaling by extracts of teak and other wood dusts.

Wood dusts, as a group, are categorized as known human carcinogens, but the risks of exposure to specific types of wood dusts and the carcinogenic chemicals they contain are not well studied. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that is linked to the carcinogenic action of specific classes of chemicals. Here we examined whether chemicals in various wood dusts had the potential to activate AhR signaling as a potential toxic mechanism of action. We found that methanol extracts of teak, walnut, mahogany, and poplar dusts contained a wide range of AhR ligand activity, whereas extracts of oak, pine, and other softwoods did not contain appreciable activity. Teak dust extract, being particularly potent, was subjected to chemical analysis. The 2-methylanthraquinone (2-MAQ) accounted for the AhR ligand activity and was present at an average concentration of 0.27 parts per hundred in teak dust. Pure 2-MAQ potently induced AhR signaling (EC50 115 nM), confirming that this was the active ligand. Aqueous extracts of teak dust made using yeast or mammalian cell culture medium also contained robust AhR activity, suggesting the 2-MAQ ligand is soluble at bioactive concentrations in physiologically relevant fluids. The high concentration and potency of 2-MAQ in teak wood suggest it may mediate toxic effects through activation of AhR signaling in exposed wood workers.

Cadmium alters the formation of benzo[a]pyrene DNA adducts in the RPTEC/TERT1 human renal proximal tubule epithelial cell line.

Previously, we demonstrated the sensitivity of RPTEC/TERT1 cells, an immortalized human renal proximal tubule epithelial cell line, to two common environmental carcinogens, cadmium (Cd) and benzo[a]pyrene (B[a]P). Here, we measured BPDE-DNA adducts using a competitive ELISA method after cells were exposed to 0.01, 0.1, and 1 µM B[a]P to determine if these cells, which appear metabolically competent, produce BPDE metabolites that react with DNA. BPDE-DNA adducts were most significantly elevated at 1 µM B[a]P after 18 and 24 hours with 36.34 +/- 9.14 (n = 3) and 59.75 +/- 17.03 (n = 3) adducts/108 nucleotides respectively. For mixture studies, cells were exposed to a non-cytotoxic concentration of Cd, 1 µM, for 24 hours and subsequently exposed to concentrations of B[a]P for 24 hours. Under these conditions, adducts detected at 1 µM B[a]P after 24 hours were significantly reduced, 17.28 +/- 1.30 (n = 3) adducts/108 nucleotides, in comparison to the same concentration at previous time points without Cd pre-treatment. We explored the NRF2 antioxidant pathway and total glutathione levels in cells as possible mechanisms reducing adduct formation under co-exposure. Results showed a significant increase in the expression of NRF2-responsive genes, GCLC, HMOX1, NQO1, after 1 µM Cd × 1 µM B[a]P co-exposure. Additionally, total glutathione levels were significantly increased in cells exposed to 1 µM Cd alone and 1 µM Cd × 1 µM B[a]P. Together, these results suggest that Cd may antagonize the formation of BPDE-DNA adducts in the RPTEC/TERT1 cell line under these conditions. We hypothesize that this occurs through priming of the antioxidant response pathway resulting in an increased capacity to detoxify BPDE prior to BPDE-DNA adduct formation.

TEM-induced structural evolution in amorphous Fe oxide nanoparticles.

Exposure to the high energy electron beam of a TEM changes the morphology of amorphous Fe oxide nanoparticles from solid spheres to hollow shells. Amorphous Fe oxide nanoparticles prepared via high-temperature methods using hexadecylamine and trioctylphosphine oxide surfactants were compared to crystalline gamma-Fe2O3 particles of similar size. Both sets of particles are fully characterized via SQUID magnetometry, X-ray powder diffraction, BET surface analysis, EPR spectroscopy, high-resolution transmission electron microscopy (TEM), and electron energy loss spectroscopy (EELS). Time-resolved TEM images reveal that the amorphous Fe oxide particles evolve from solid spheres into hollow shells in <2 min, whereas crystalline gamma-Fe2O3 are unaffected by the electron beam. The resulting nanocrystalline Fe oxide shells bear striking resemblance to core-shell nanocrystals, but are a result of a morphology change attributed to restructuring of particle voids and defects induced by quasi-melting in the TEM. These results thus imply that caution is necessary when using TEM to analyze nanoparticle core-shell and heterostructured nanoparticles.