Configurable Artificial Spin Ice with Site-Specific Local Magnetic Fields.

We demonstrate ground state tunability for a hybrid artificial spin ice composed of Fe nanomagnets which are subject to site-specific exchange-bias fields, applied in integer multiples of the lattice along one sublattice of the classic square artificial spin ice. By varying this period, three distinct magnetic textures are identified: a striped ferromagnetic phase; an antiferromagnetic phase attainable through an external field protocol alone; and an unconventional ground state with magnetically charged pairs embedded in an antiferromagnetic matrix. Monte Carlo simulations support the results of field protocols and demonstrate that the pinning tunes relaxation timescales and their critical behavior.

Silica-Based Nanoparticles as Drug Delivery Vehicles for Prostate Cancer Treatment.

Prostate cancer (PCa) is one of the most commonly diagnosed cancers and is the fifth common cause of cancer-related mortality in men. Current methods for PCa treatment are insufficient owing to the challenges related to the non-specificity, instability and side effects caused by the drugs and therapy agents. These drawbacks can be mitigated by the design of a suitable drug delivery system that can ensure targeted delivery and minimise side effects. Silica based nanoparticles (SBNPs) have emerged as one of the most versatile materials for drug delivery due to their tunable porosities, high surface area and tremendous capacity to load various sizes and chemistry of drugs. This review gives a brief overview of the diagnosis and current treatment strategies for PCa outlining their existing challenges. It critically analyzes the design, development and application of pure, modified and hybrid SBNPs based drug delivery systems in the treatment of PCa, their advantages and limitations.

Anaerobic Microbial Degradation of Polycyclic Aromatic Hydrocarbons: A Comprehensive Review.

Polycyclic aromatic hydrocarbons (PAHs) are a class of hazardous organic contaminants that are widely distributed in nature, and many of them are potentially toxic to humans and other living organisms. Biodegradation is the major route of detoxification and removal of PAHs from the environment. Aerobic biodegradation of PAHs has been the subject of extensive research; however, reports on anaerobic biodegradation of PAHs are so far limited. Microbial degradation of PAHs under anaerobic conditions is difficult because of the slow growth rate of anaerobes and low energy yield in the metabolic processes. Despite the limitations, some anaerobic bacteria degrade PAHs under nitrate-reducing, sulfate-reducing, iron-reducing, and methanogenic conditions. Anaerobic biodegradation, though relatively slow, is a significant process of natural attenuation of PAHs from the impacted anoxic environments such as sediments, subsurface soils, and aquifers. This review is intended to provide comprehensive details on microbial degradation of PAHs under various reducing conditions, to describe the degradation mechanisms, and to identify the areas that should receive due attention in further investigations.

Improved HER Catalysis through Facile, Aqueous Electrochemical Activation of Nanoscale WSe2.

In the search for nonprecious metal catalysts for the hydrogen evolution reaction (HER), transition metal dichalcogenides (TMDCs) have been proposed as promising candidates. Here, we present a facile method for significantly decreasing the overpotential required for catalyzing the HER with colloidally synthesized WSe2. Solution phase deposition of 2H WSe2 nanoflowers (NFs) onto carbon fiber electrodes results in low catalytic activity in 0.5 M H2SO4 with an overpotential at -10 mA/cm2 of greater than 600 mV. However, two postdeposition electrode processing steps significantly reduce the overpotential. First, a room-temperature treatment of the prepared electrodes with a dilute solution of the alkylating agent Meerwein's salt ([Et3O][BF4]) results in a reduction in overpotential by approximately 130 mV at -10 mA/cm2. Second, we observe a decrease in overpotential of approximately 200-300 mV when the TMDC electrode is exposed to H+, Li+, Na+, or K+ ions under a reducing potential. The combined effect of ligand removal and electrochemical activation results in an improvement in overpotential by as much as 400 mV. Notably, the Li+ activated WSe2 NF deposited carbon fiber electrode requires an overpotential of only 243 mV to generate a current density of -10 mA/cm2. Measurement of changes in the material work function and charge transfer resistance ultimately provide rationale for the catalytic improvement.

Derivation of internal dose-based thresholds of toxicological concern for occupational inhalation exposure to systemically acting organic chemicals.

This study aimed at deriving occupational thresholds of toxicological concern for inhalation exposure to systemically-acting organic chemicals using predicted internal doses. The latter were also used to evaluate the quantitative relationship between occupational exposure limit and internal dose. Three internal dose measures were identified for investigation: (i) the daily area under the venous blood concentration vs. time curve, (ii) the daily rate of the amount of parent chemical metabolized, and (iii) the maximum venous blood concentration at the end of an 8-hr work shift. A dataset of 276 organic chemicals with 8-hr threshold limit values-time-weighted average was compiled along with their molecular structure and Cramer classes (Class I: low toxicity, Class II: intermediate toxicity, Class III: suggestive of significant toxicity). Using a human physiologically-based pharmacokinetic model, the three identified dose metrics were predicted for an 8-hr occupational inhalation exposure to the threshold limit value for each chemical. Distributional analyses of the predicted dose metrics were performed to identify the percentile values corresponding to the occupational thresholds of toxicological concern. Also, simple linear regression analyses were performed to evaluate the relationship between the 8-hr threshold limit value and each of the predicted dose metrics, respectively. No threshold of toxicological concern could be derived for class II due to few chemicals. Based on the daily rate of the amount of parent chemical metabolized, the proposed internal dose-based occupational thresholds of toxicological concern were 5.61 × 10-2 and 9 × 10-4 mmol/d at the 10th percentile level for classes I and III, respectively, while they were 4.55 × 10-1 and 8.5 × 10-3 mmol/d at the 25th percentile level. Even though high and significant correlations were observed between the 8-hr threshold limit values and the predicted dose metrics, the one with the rate of the amount of chemical metabolized was remarkable regardless of the Cramer class (r2 = 0.81; n = 276). The proposed internal dose-based occupational thresholds of toxicological concern are potentially useful for screening-level assessments as well as prioritization within an integrated occupational risk assessment framework.

Magnetic Particle Imaging: A Novel in Vivo Imaging Platform for Cancer Detection.

Cancer remains one of the leading causes of death worldwide. Biomedical imaging plays a crucial role in all phases of cancer management. Physicians often need to choose the ideal diagnostic imaging modality for each clinical presentation based on complex trade-offs among spatial resolution, sensitivity, contrast, access, cost, and safety. Magnetic particle imaging (MPI) is an emerging tracer imaging modality that detects superparamagnetic iron oxide (SPIO) nanoparticle tracer with high image contrast (zero tissue background signal), high sensitivity (200 nM Fe) with linear quantitation, and zero signal depth attenuation. MPI is also safe in that it uses safe, in some cases even clinically approved, tracers and no ionizing radiation. The superb contrast, sensitivity, safety, and ability to image anywhere in the body lends MPI great promise for cancer imaging. In this study, we show for the first time the use of MPI for in vivo cancer imaging with systemic tracer administration. Here, long circulating MPI-tailored SPIOs were created and administered intravenously in tumor bearing rats. The tumor was highlighted with tumor-to-background ratio of up to 50. The nanoparticle dynamics in the tumor was also well-appreciated, with initial wash-in on the tumor rim, peak uptake at 6 h, and eventual clearance beyond 48 h. Lastly, we demonstrate the quantitative nature of MPI through compartmental fitting in vivo.

A decision tree approach to screen drinking water contaminants for multiroute exposure potential in developing guideline values.

The consideration of inhalation and dermal routes of exposures in developing guideline values for drinking water contaminants is important. However, there is no guidance for determining the eligibility of a drinking water contaminant for its multiroute exposure potential. The objective of the present study was to develop a 4-step framework to screen chemicals for their dermal and inhalation exposure potential in the process of developing guideline values. The proposed framework emphasizes the importance of considering basic physicochemical properties prior to detailed assessment of dermal and inhalation routes of exposure to drinking water contaminants in setting guideline values.

Mercury alters the bacterial community structure and diversity in soil even at concentrations lower than the guideline values.

This study evaluated the effect of inorganic mercury (Hg) on bacterial community and diversity in different soils. Three soils-neutral, alkaline and acidic-were spiked with six different concentrations of Hg ranging from 0 to 200 mg kg-1 and aged for 90 days. At the end of the ageing period, 18 samples from three different soils were investigated for bacterial community structure and soil physicochemical properties. Illumina MiSeq-based 16s ribosomal RNA (rRNA) amplicon sequencing revealed the alteration in the bacterial community between un-spiked control soils and Hg-spiked soils. Among the bacterial groups, Actinobacteria (22.65%) were the most abundant phyla in all samples followed by Proteobacteria (21.95%), Bacteroidetes (4.15%), Firmicutes (2.9%) and Acidobacteria (2.04%). However, the largest group showing increased abundance with higher Hg doses was the unclassified group (45.86%), followed by Proteobacteria. Mercury had a considerable negative impact on key soil functional bacteria such as ammonium oxidizers and nitrifiers. Canonical correspondence analysis (CCA) indicated that among the measured soil properties, Hg had a major influence on bacterial community structure. Furthermore, nonlinear regression analysis confirmed that Hg significantly decreased soil bacterial alpha diversity in lower organic carbon containing neutral and alkaline soils, whereas in acidic soil with higher organic carbon there was no significant correlation. EC20 values obtained by a nonlinear regression analysis indicated that Hg significantly decreased soil bacterial diversity in concentrations lower than several guideline values.

Bioremediation of mercury: not properly exploited in contaminated soils!

Contamination of land and water caused by heavy metal mercury (Hg) poses a serious threat to biota worldwide. The seriousness of toxicity of this neurotoxin is characterized by its ability to augment in food chains and bind to thiol groups in living tissue. Therefore, different remediation approaches have been implemented to rehabilitate Hg-contaminated sites. Bioremediation is considered as cheaper and greener technology than the conventional physico-chemical means. Large-scale use of Hg-volatilizing bacteria are used to clean up Hg-contaminated waters, but there is no such approach to remediate Hg-contaminated soils. This review focuses on recent uses of Hg-resistant bacteria in bioremediation of mercury-contaminated sites, limitation and advantages of this approach, and identifies the gaps in existing research.

Development of biomonitoring equivalents for barium in urine and plasma for interpreting human biomonitoring data.

The objectives of the present work were: (1) to assemble population-level biomonitoring data to identify the concentrations of urinary and plasma barium across the general population; and (2) to derive biomonitoring equivalents (BEs) for barium in urine and plasma in order to facilitate the interpretation of barium concentrations in the biological matrices. In population level biomonitoring studies, barium has been measured in urine in the U.S. (NHANES study), but no such data on plasma barium levels were identified. The BE values for plasma and urine were derived from U.S. EPA's reference dose (RfD) of 0.2 mg/kg bw/d, based on a lower confidence limit on the benchmark dose (BMDL05) of 63 mg/kg bw/d. The plasma BE (9 µg Ba/L) was derived by regression analysis of the near-steady-state plasma concentrations associated with the administered doses in animals exposed to barium chloride dihydrate in drinking water for 2-years in a NTP study. Using a human urinary excretion fraction of 0.023, a BE for urinary barium (0.19 mg/L or 0.25 mg/g creatinine) was derived for US EPA's RfD. The median and the 95th percentile barium urine concentrations of the general population in U.S. are below the BE determined in this study, indicating that the population exposure to inorganic barium is expected to be below the exposure guidance value of 0.2 mg/kg bw/d.

Arsenic resistance genes of As-resistant purple nonsulfur bacteria isolated from As-contaminated sites for bioremediation application.

This study aimed to identify arsenic resistant mechanisms in As-resistant purple nonsulfur bacteria (PNSB) by screening them for presence of As-resistance genes and related enzymes. Resistance to As(III) and As(V) of four As-resistant PNSB determined in terms of median inhibition concentration (IC50 values) were in the order of strains Rhodopseudomonas palustris C1 > R. palustris AB3 > Rubrivivax benzoatilyticus C31 > R. palustris L28 which corresponded to the presence of As-resistance genes in these bacteria. The strain C1 showed all As-marker genes; arsC, arsM, aioA, and acr3, while aioA was not detected in strain AB3. Strains C31 and L28 had only Arsenite-transporter gene, acr3. Translation of all these detected gene sequences of strain C1 to amino acid sequences showed that these proteins have vicinal cysteine; Cys126, Cys105, and Cys178 of Acr3, ArsC, AioA, respectively. Tertiary structure of proteins Acr3, ArsC, AioA, and ArsM showed strain C1 exhibits the high activities of arsenite oxidase and arsenate reductase enzymes that are encoded by aioA and arsC genes, respectively. Moreover, strain C1 with arsM gene produced volatile-methylated As-compounds; monomethylarsonic acid (MMA), dimethylarsenic acid (DMA), and arsenobetaine (AsB) in the presence of either As(III) or As(V). In conclusion, the strain C1 has great potential for its application in bioremediation of As-contaminated sites.

Detection of Cancer-Specific Proteases Using Magnetic Relaxation of Peptide-Conjugated Nanoparticles in Biological Environment.

Protease expression is closely linked to malignant phenotypes of different solid tumors; as such, their detection is promising for diagnosis and treatment of cancers, Alzheimer's, and vascular diseases. Here, we describe a new method for detecting proteases by sensitively monitoring the magnetic relaxation of monodisperse iron oxide nanoparticles (IONPs) using magnetic particle spectrometer (MPS). In this assay, tailored peptides functioning as activatable nanosensors link magnetic nanoparticles and possess selective sites that are recognizeable and cleaveable by specific proteases. When these linker peptides, labeled with biotin at N- and C-terminals, are added to the neutravidin functionalized IONPs, nanoparticles aggregate, resulting in well-defined changes in the MPS signal. However, as designed, in the presence of proteases these peptides are cleaved at predetermined sites, redispersing IONPs, and returning the MPS signal(s) close to its preaggregation state. These changes observed in all aspects of the MPS signal (peak intensity, its position as a function of field amplitude, and full width at half-maximum-when combined, these three also eliminate false positives), help to detect specific proteases, relying only on the magnetic relaxation characteristics of the functionalized nanoparticles. We demonstrate the general utility of this assay by detecting one each from the two general classes of proteases: trypsin (digestive serine protease, involved in various cancers, promoting proliferation, invasion, and metastasis) and matrix metalloproteinase (MMP-2, observed through metastasis and tumor angiogenesis). This MPS based protease-assay is rapid, reproducible, and highly sensitive and can form the basis of a feasible, high-throughput method for detection of various other proteases.

Toxicity of Inorganic Mercury to Native Australian Grass Grown in Three Different Soils.

In this study, three native Australian grasses namely Iseilema membranaceum (Barcoo), Dichanthium sericeum (Queensland Blue) and Sporobolus africanus (Tussock) were grown in three different soils spiked with different concentrations of inorganic mercury and the root elongation was monitored up to 28 days following the germination. Results showed that mercury at certain concentrations significantly inhibited the root growth of all three tested native grasses grown in three soils, however, the toxicity was less in the soil with high organic carbon content and acidic pH. The calculated EC50 values ranged from 10 to 224 mg/kg total Hg in soil. However, the EC10 values indicated that existing guideline values for mercury may be of protective to the native Australian vegetation. Considering their tolerance to soil mercury, these grass species have the potential for their use in rehabilitation of mercury contaminated sites.

Mercury remediation potential of a mercury resistant strain Sphingopyxis sp. SE2 isolated from contaminated soil.

A mercury resistant bacterial strain SE2 was isolated from contaminated soil. The 16s rRNA gene sequencing confirms the strain as Sphingopyxis belongs to the Sphingomonadaceae family of the α-Proteobacteria group. The isolate showed high resistance to mercury with estimated concentrations of Hg that caused 50% reduction in growth (EC50) of 5.97 and 6.22mg/L and minimum inhibitory concentrations (MICs) of 32.19 and 34.95mg/L in minimal and rich media, respectively. The qualitative detection of volatilized mercury and the presence of mercuric reductase enzyme proved that the strain SE2 can potentially remediate mercury. ICP-QQQ-MS analysis of the remaining mercury in experimental broths indicated that a maximum of 44% mercury was volatilized within 6hr by live SE2 culture. Furthermore a small quantity (23%) of mercury was accumulated in live cell pellets. While no volatilization was caused by dead cells, sorption of mercury was confirmed. The mercuric reductase gene merA was amplified and sequenced. Homology was observed among the amino acid sequences of mercuric reductase enzyme of different organisms from α-Proteobacteria and ascomycota groups.

Derivation of biomonitoring equivalent for inorganic tin for interpreting population-level urinary biomonitoring data.

Population-level biomonitoring of tin in urine has been conducted by the U.S. National Health and Nutrition Examination Survey (NHANES) and the National Nutrition and Health Study (ENNS - Étude nationale nutrition santé) in France. The general population is predominantly exposed to inorganic tin from the consumption of canned food and beverages. The National Institute for Public Health and the Environment of the Netherlands (RIVM) has established a tolerable daily intake (TDI) for chronic exposure to inorganic tin based on a NOAEL of 20 mg/kg bw per day from a 2-year feeding study in rats. Using a urinary excretion fraction (0.25%) from a controlled human study along with a TDI value of 0.2 mg/kg bw per day, a Biomonitoring Equivalent (BE) was derived for urinary tin (26 µg/g creatinine or 20 µg/L urine). The geometric mean and the 95th percentile tin urine concentrations of the general population in U.S. (0.705 and 4.5 µg/g creatinine) and France (0.51 and 2.28 µg/g creatinine) are below the BE associated with the TDI, indicating that the population exposure to inorganic tin is below the exposure guidance value of 0.2 mg/kg bw per day. Overall, the robustness of pharmacokinetic data forming the basis of the urinary BE development is medium. The availability of internal dose and kinetic data in the animal species forming the basis of the assessment could improve the overall confidence in the present assessment.

Gene expression profile changes in Eisenia fetida chronically exposed to PFOA.

Eisenia fetida is a terrestrial organism, which can be used to diagnose sub-lethal concentrations of PFOA by using molecular biomarkers. In order to identify potential molecular biomarkers, we have exposed E. fetida to 10 mg/kg of PFOA in soil for 8 months. The mRNA isolation, sequencing, transcriptome assembly followed by differential gene expression studies have revealed that genes that are involved in apoptotic process, reproduction, calcium signalling, neuronal development and lipid metabolism are predominantly affected. Highly specific genes that are altered by PFOA can be further validated and used as biomarker to detect sub-lethal concentrations of PFOA in the soil.

In vivo delivery, pharmacokinetics, biodistribution and toxicity of iron oxide nanoparticles.

Iron oxide nanoparticles (IONPs) have been extensively used during the last two decades, either as effective bio-imaging contrast agents or as carriers of biomolecules such as drugs, nucleic acids and peptides for controlled delivery to specific organs and tissues. Most of these novel applications require elaborate tuning of the physiochemical and surface properties of the IONPs. As new IONPs designs are envisioned, synergistic consideration of the body's innate biological barriers against the administered nanoparticles and the short and long-term side effects of the IONPs become even more essential. There are several important criteria (e.g. size and size-distribution, charge, coating molecules, and plasma protein adsorption) that can be effectively tuned to control the in vivo pharmacokinetics and biodistribution of the IONPs. This paper reviews these crucial parameters, in light of biological barriers in the body, and the latest IONPs design strategies used to overcome them. A careful review of the long-term biodistribution and side effects of the IONPs in relation to nanoparticle design is also given. While the discussions presented in this review are specific to IONPs, some of the information can be readily applied to other nanoparticle systems, such as gold, silver, silica, calcium phosphates and various polymers.

Mercury Inhibits Soil Enzyme Activity in a Lower Concentration than the Guideline Value.

Three soil types - neutral, alkaline and acidic were experimentally contaminated with nine different concentrations of inorganic mercury (0, 5, 10, 50, 100, 150, 200, 250, 300 mg/kg) to derive effective concentrations of mercury that exert toxicity on soil quality. Bioavailability of mercury in terms of water solubility was lower in acidic soil with higher organic carbon. Dehydrogenase enzyme activity and nitrification rate were chosen as indicators to assess soil quality. Inorganic mercury significantly inhibited (p < 0.001) microbial activities in the soils. The critical mercury contents (EC10) were found to be less than the available safe limits for inorganic mercury which demonstrated inadequacy of existing guideline values.

Tuning surface coatings of optimized magnetite nanoparticle tracers for in vivo Magnetic Particle Imaging.

Surface coatings are important components of Magnetic Particle Imaging (MPI) tracers - they preserve their key properties responsible for optimum tracer performance in physiological environments. In vivo, surface coatings form a physical barrier between the hydrophobic SPION cores and the physiological environment, and their design dictates the blood half-life and biodistribution of MPI tracers. Here we show the effect of tuning poly(ethylene glycol) (PEG)-based surface coatings on both in vitro and in vivo (mouse model) MPI performance of SPIONs. Our results showed that varying PEG molecular weight had a profound impact on colloidal stability, characterized using Dynamic Light Scattering (DLS), and the m'(H) response of SPIONs, measured in a 25 kHz/20 mTµ0-1max Magnetic Particle Spectrometer (MPS). Increasing PEG molecular weight from 5 kDa to 20 kDa preserved colloidal stability and m'(H) response of ~25 nm SPIONs - the optimum core diameter for MPI - in serum-rich cell culture medium for up to 24 hours. Furthermore, we compared the in vivo circulation time of SPIONs as a function of hydrodynamic diameter and showed that clustered SPIONs can adversely affect blood half-life; critically, SPIONs with clusters had 5 times shorter blood half-life than individually coated SPIONs. We anticipate that the development of MPI SPION tracers with long blood half-lives have potential not only in vascular imaging applications, but also enable opportunities in molecular targeting and imaging - a critical step towards early cancer detection using the new MPI modality.