Developing Integrated Approaches for Testing and Assessment (IATAs) in order to support nanomaterial safety.

Due to the unique characteristics of nanomaterials (NM) there has been an increase in their use in nanomedicines and innovative medical devices (MD). Although large numbers of NMs have now been developed, comprehensive safety investigations are still lacking. Current gaps in understanding the potential mechanisms of NM-induced toxicity can make it challenging to determine the safety testing necessary to support inclusion of NMs in MD applications. This article provides guidance for implementation of pre-clinical tailored safety assessment strategies with the aim to increase the translation of NMs from bench development to clinical use. Integrated Approaches to Testing and Assessment (IATAs) are a key tool in developing these strategies. IATAs follow an iterative approach to answer a defined question in a specific regulatory context to guide the gathering of relevant information for safety assessment, including existing experimental data, integrated with in silico model predictions where available and appropriate, and/or experimental procedures and protocols for generating new data to fill gaps. This allows NM developers to work toward current guidelines and regulations, while taking NM specific considerations into account. Here, an example IATA for NMs with potential for direct blood contact was developed for the assessment of haemocompatibility. This example IATA brings together the current guidelines for NM safety assessment within a framework that can be used to guide information and data gathering for the safety assessment of intravenously injected NMs. Additionally, the decision framework underpinning this IATA has the potential to be adapted to other testing needs and regulatory contexts.

Effects of MS bacteriophages, ultraviolet light, and organic acid applications on beef trim contaminated with STEC O157:H7 and the "Big Six" serotypes after a simulated High Event Period Scenario.

A high event period (HEP) occurs when beef processing facilities experience an elevated rate of STEC positive trim samples. In order to avoid contaminated vacuum-packaged beef entering into commerce, primals and subprimals associated to positive trim must be treated with antimicrobials, repackaged, and retested for STEC to ensure product wholesomeness. In this study, we evaluated the efficacy of Bacteriophages (P), Peroxiacetic Acid (PAA), Acidified Sodium Chlorite (ASC), and Ultraviolet light (UV) to reduce the O157:H7 and the Big Six STEC in beef after a simulated HEP scenario. In vacuum conditions and under aerobic conditions, phage applications and a combination of P + UV led to the greatest STEC reduction, respectively (P < 0.001). Overall, treatments including bacteriophage provided best reductions when compared to non-phage treatments (P < 0.001, for both vacuum and aerobic conditions). Bacteriophage solutions provided improved control of STEC O157:H7 and the Big Six serotypes when reworking beef after a simulated HEP scenario.

Effects of lipid and starch supplementation as water intake mitigation techniques on performance and efficiency of nursing Holstein calves.

Exploring alternative supplementation sources capable of maximizing feed and water efficiency in nursing Holstein calves is often ignored. The goals herein involve investigating the effects of two isoenergetic supplements on a nonmedicated milk replacer diet on total water intake, milk water intake, fresh water intake, feed intake parameters, and performance of Holstein nursing bull calves. Twenty-three animals (body weight [BW] = 94.67 ± 12.07 kg, age = 67 days old) were randomly assigned to one of three treatments for 68 days: control (CON; ad libitum milk replacer, n = 7), carbohydrate supplement (CHO; corn starch on top of ad libitum milk replacer-based diet, n = 8), or lipid supplement (FAT; menhaden fish oil on top of ad libitum milk replacer-based diet, n = 8). The isoenergetic supplementation consisted of 3% menhaden fish oil addition on DM basis for FAT. This was matched energetically with corn starch for the CHO group resulting in a 7% composition in DM basis. All animals were provided free access to mineral mix and 120 g daily dried microbrewer's spent grains (BG). Data were analyzed with the GLMMIX procedure of SAS in a completely randomized design with the diets as a fixed effect. Dry matter intake (DMI) adjusted by average daily gain (ADG; DMI/ADG) resulted in significantly lower values for supplemented groups with CON = 2.48, CHO = 2.38, and FAT = 2.27 kg/kg (ADG) (P = 0.033). Energy intake values were lower for CON when analyzing metabolizable energy intake (P < 0.0001), net energy intake for maintenance (P < 0.0001), and net energy intake for gain (P < 0.0001), followed by CHO, and then FAT. Total water intake (P < 0.0001), milk water intake (P < 0.0001), and fresh water intake (P < 0.0001) all resulted in CHO consuming 0.5 L or less water than the other two treatments. Energy requirements as digestible energy (P < 0.0001), metabolizable energy (P < 0.0001), net energy for maintenance (P < 0.0001), and net energy for gain (P < 0.0001) were lower for CHO, followed by CON, and then FAT having the highest requirements. Similar results were observed for residual feed (RFI; P = 0.006) and residual water intakes (RTWI; P = 0.902). Ultimately, no performance differences were detected with regards to BW (CON = 146.71, CHO = 146.25, and FAT = 150.48 kg; P > 0.1). These results indicate that lipid-based and starch-based supplementation can potentially increase feed efficiency and decrease voluntary water intake without adversely affecting performance.

Measuring particle size distribution and mass concentration of nanoplastics and microplastics: addressing some analytical challenges in the sub-micron size range.

HYPOTHESIS: The implementation of the proposal from the European Chemical Agency (ECHA) to restrict the use of nanoplastics (NP) and microplastics (MP) in consumer products will require reliable methods to perform size and mass-based concentration measurements. Analytical challenges arise at the nanometre to micrometre interface, e.g., 800 nm-10 µm, where techniques applicable at the nanometre scale reach their upper limit of applicability and approaches applicable at the micrometre scale must be pushed to their lower limits of detection. EXPERIMENTS: Herein, we compared the performances of nine analytical techniques by measuring the particle size distribution and mass-based concentration of polystyrene mixtures containing both nano and microparticles, with the educational aim to underline applicability and limitations of each technique. FINDINGS: Light scattering-based measurements do not have the resolution to distinguish multiple populations in polydisperse samples. Nanoparticle tracking analysis (NTA), nano-flowcytometry (nFCM) and asymmetric flow field flow fractionation hyphenated with multiangle light scattering (AF4-MALS) cannot measure particles in the micrometre range. Static light scattering (SLS) is not able to accurately detect particles below 200 nm, and similarly to transmission electron microscopy (TEM) and flow cytometry (FCM), is not suitable for accurate mass-based concentration measurements. Alternatives for high-resolution sizing and concentration measurements in the size range between 60 nm and 5 µm are tunable resistive pulse sensing (TRPS) and centrifugal liquid sedimentation (CLS), that can bridge the gap between the nanometre and micrometre range.

Effects of bacteriophages and peroxyacetic acid applications on beef contaminated with Salmonella during different grinding stages.

Research has suggested that the incidence of Salmonella in ground beef may be associated with contaminated lymph nodes that are not removed from trimmings destined for grinding. In this study, we tested the application of bacteriophages and peroxyacetic acid solutions on trimmings and on coarse and fine ground beef to simulate different scenarios of contamination. Overall, peroxyacetic acid applications did not reduce Salmonella loads on ground beef when applied on trimmings or at any stage of grinding. When applied on contaminated trim, bacteriophage solutions at 1 × 108 PFU/g and 1 × 109 PFU/g reduced more than 1 log cfu/g of Salmonella. When applied directly on contaminated coarse or fine ground beef, bacteriophage solutions at 1 × 109 PFU/g reduced approximately 1.6 log cfu/g. Results of this study suggest that bacteriophage applications on contaminated, comminuted beef may be used as an aid to decrease Salmonella loads.

Asymmetric-flow field-flow fractionation for measuring particle size, drug loading and (in)stability of nanopharmaceuticals. The joint view of European Union Nanomedicine Characterization Laboratory and National Cancer Institute - Nanotechnology Characterization Laboratory.

Asymmetric-flow field-flow fractionation (AF4) has been recognized as an invaluable tool for the characterisation of particle size, polydispersity, drug loading and stability of nanopharmaceuticals. However, the application of robust and high quality standard operating procedures (SOPs) is critical for accurate measurements, especially as these complex drug nanoformulations are most often inherently polydisperse. In this review we describe a unique international collaboration that lead to the development of a robust SOP for the measurement of physical-chemical properties of nanopharmaceuticals by multi-detector AF4 (MD-AF4) involving two state of the art infrastructures in the field of nanomedicine, the European Union Nanomedicine Characterization Laboratory (EUNCL) and the National Cancer Institute-Nanotechnology Characterisation Laboratory (NCI-NCL). We present examples of how MD-AF4 has been used for the analysis of key quality attributes, such as particle size, shape, drug loading and stability of complex nanomedicine formulations. The results highlight that MD-AF4 is a very versatile analytical technique to obtain critical information on a material particle size distribution, polydispersity and qualitative information on drug loading. The ability to conduct analysis in complex physiological matrices is an additional very important advantage of MD-AF4 over many other analytical techniques used in the field for stability studies. Overall, the joint NCI-NCL/EUNCL experience demonstrates the ability to implement a powerful and highly complex analytical technique such as MD-AF4 to the demanding quality standards set by the regulatory authorities for the pre-clinical safety characterization of nanomedicines.

Application of MS bacteriophages on contaminated trimmings reduces Escherichia coli O157 and non-O157 in ground beef.

According to the United States Food and Drug Administration (FDA) agency, bacteriophage solutions targeting the serotype O157:H7 are Generally Recognized as Safe (GRAS) to control STEC during beef processing. However, outbreaks involving the "Big Six" STEC increased the industry concern about those serotypes. The objective of this study was to test the efficacy of MS bacteriophages to reduce the "Big Six" non-O157 STEC in beef. The lysing efficacy of phages isolated for each specific serotype varied from 96.2% to 99.9% in vitro. When applied to contaminated trim, reductions ranging from 0.7 to 1.3 Log of all STEC were observed in ground beef. Bacteriophages may provide an additional barrier against the "Big Six" STEC in ground beef. Results of this research provide support documentation to the FDA to extend GRAS status for bacteriophages as processing aids against all adulterant STEC.

Efficacy of bacteriophage and organic acids in decreasing STEC O157:H7 populations in beef kept under vacuum and aerobic conditions: A simulated High Event Period scenario.

After High Event Periods, beef subprimals are usually removed from vacuum and treated with antimicrobials. After re-packaging, subprimals are tested to verify the presence of STEC. In this study, bacteriophage and organic acids were applied on beef contaminated with STEC O157:H7 to evaluate the efficiency of industry practices. Beef samples inoculated with STEC were treated with bacteriophage, lactic acid, and peroxyacetic acid and kept under vacuum or aerobic conditions. STEC loads were evaluated 30 min and 6 h after antimicrobial applications. Under aerobic conditions for 30 min and 6 h, phage reduced STEC in beef by approximately 1.4 log whereas organic acids led to a 0.5 log reduction. Under vacuum for 30 min, bacteriophage significantly reduced STEC by 1 log. No effects were observed when samples were treated with organic acids. Under vacuum after 6 h, bacteriophage reduced STEC loads by 1.4 log, lactic acid reduced by 0.6 log, and no effects were observed when peroxyacetic acid was applied.

Multiplex profiling identifies clinically relevant signalling proteins in an isogenic prostate cancer model of radioresistance.

The exact biological mechanism governing the radioresistant phenotype of prostate tumours at a high risk of recurrence despite the delivery of advanced radiotherapy protocols remains unclear. This study analysed the protein expression profiles of a previously generated isogenic 22Rv1 prostate cancer model of radioresistance using DigiWest multiplex protein profiling for a selection of 90 signalling proteins. Comparative analysis of the profiles identified a substantial change in the expression of 43 proteins. Differential PARP-1, AR, p53, Notch-3 and YB-1 protein levels were independently validated using Western Blotting. Pharmacological targeting of these proteins was associated with a mild but significant radiosensitisation effect at 4Gy. This study supports the clinical relevance of isogenic in vitro models of radioresistance and clarifies the molecular radiation response of prostate cancer cells.

Effects of different antioxidants on quality of beef patties from steers fed low-moisture distillers grains.

This research evaluated the effects of different antioxidants on overall quality of beef patties from steers fed distillers grains. Crossbred steers (n = 24) were fed corn, 40% Dry distillers grains plus solubles, or 40% modified distillers grains plus solubles - Dry Matter basis). Patties were made from ground chuck of individual animals and 4 antioxidant treatments were evaluated (CONTROL - no antioxidant, 0.3% ROSEMARY, 0.25% ACEROLA, and 0.6% CITRUS). Diets minimally affected quality attributes. Patties treated with ROSEMARY were shown significant lighter in color than other treatments on day 6. Patties treated with CITRUS were the reddest on days 5 and 6 of display. ACEROLA and CITRUS provided better lipid stability during display when compared to CONTROL and ROSEMARY. Treatment CITRUS reduced APC growth by 2 log when compared to all other treatments (P < 0.01). Although patties treated with CITRUS had higher off-flavor intensity, no effect was observed for overall desirability. Patties treated with 0.6% of CITRUS provided optimal overall quality.

Measuring particle size distribution of nanoparticle enabled medicinal products, the joint view of EUNCL and NCI-NCL. A step by step approach combining orthogonal measurements with increasing complexity.

The particle size distribution (PSD) and the stability of nanoparticles enabled medicinal products (NEP) in complex biological environments are key attributes to assess their quality, safety and efficacy. Despite its low resolution, dynamic light scattering (DLS) is the most common sizing technique since the onset of NEP in pharmaceutical technologies. Considering the limitations of the existing sizing measurements and the challenges posed by complex NEPs both scientists and regulators encourage the combination of multiple orthogonal high-resolution approaches to shed light in the NEP sizing space (e.g. dynamic light scattering, electron microscopy, field flow fractionation coupled to online sizing detectors, centrifugal techniques, particle tracking analysis and tunable resistive pulse sensing). The pharmaceutical and biotechnology developers are now challenged to find their own pragmatic characterisation approaches, which should be fit for purpose and minimize costs at the same time, in a complicated landscape where only a few standards exist. In order to support the community, the European Nanomedicine Characterisation Laboratory (EUNCL) and the US National Cancer Institute Nanotechnology Characterization Laboratory (NCI-NCL) have jointly developed multiple standard operating procedures (SOPs) for NEP assessment, including the measurements of particle size distribution, and are offering wide access to their 'state of the art' characterisation platforms, in addition to making SOPs publicly available. This joint perspective article would like to present the NCI-NCL and EUNCL multi-step approach of incremental complexity to measure particle size distribution and size stability of NEPs, consisting of a quick preliminary step to assess sample integrity and stability by low resolution techniques (pre-screening), followed by the combination of complementary high resolution sizing measurements performed both in simple buffers and in complex biological media. Test cases are presented to demonstrate: i) the need for employing at least one high-resolution sizing technique, ii) the importance of selecting the correct sizing techniques for the purpose, and iii) the robustness of utilizing orthogonal sizing techniques to study the physical properties of complex NEP samples.

Growth performance and carcass traits of steers finished on three different systems including legume-grass pasture and grain diets.

Inclusion of legume in grass pastures optimizes protein values of the forage and promotes improved digestibility. Therefore, we hypothesized that finishing steers on a novel combination of legumes and grass pasture would produce carcasses with acceptable traits when compared to carcasses from steers finished in feedlot systems. In this study, we evaluated the effects of finishing steers on three systems including: grazing legume-grass pasture containing oats, ryegrass, white and red clover (PAST), grazing PAST plus supplementation with whole corn grain (14 g/kg BW (SUPP)), and on a feedlot-confined system with concentrate only (28 g/kg BW, consisting of 850 g/kg of whole corn grain and 150 g/kg of protein-mineral-vitamin supplement (GRAIN)) on growth performance of steers, carcass traits and digestive disorders. Eighteen steers were randomly assigned to one of three dietary treatments and finished for 91 days. Data regarding pasture and growth performance were collected during three different periods (0 to 28, 29 to 56 and 57 to 91 days). Subsequently, steers were harvested to evaluate carcass traits, presence of rumenitis, abomasitis and liver abscesses. The legume-grass pasture provided more than 19% dry matter of protein. In addition, pasture of paddocks where steers were assigned to SUPP and PAST treatments showed similar nutritional quality. When compared to PAST, finishing on SUPP increased total weight gain per hectare, stocking rate, daily and total weight gains. The increase of weight gain was high to GRAIN than SUPP and PAST. Steers finished on GRAIN had high hot carcass weight, fat thickness and marbling score when compared to PAST. However, these attributes did not differ between GRAIN and SUPP. Abomasum lesions were more prevalent in steers finished on GRAIN when compared to PAST. Results of this research showed that it is possible to produce carcasses with desirable market weight and fat thickness by finishing steers on legume-grass pasture containing oats, ryegrass, white and red clover. Moreover, supplementing steers with corn when grazing on legume-grass pasture produced similar carcass traits when compared to beef fed corn only.

Oxidative stability of beef from steers finished exclusively with concentrate, supplemented, or on legume-grass pasture.

The objective of this study was to evaluate the effects of three finishing systems based on concentrate and legume-grass pasture on beef. Steers were finished for 91 days with an exclusively whole corn grain-based (GRAIN) diet, grazed on legume-grass pasture plus 1.4% of body weight of whole corn grain supplementation (SUPP), or grazed on legume-grass pasture (PAST) only. Lipid and myoglobin oxidation, pH, objective color, and α-tocopherol concentrations were evaluated on M. longissimus thoracis steaks. Dietary treatments did not affect pH and minimally affected protein carbonylation. Steaks from steers fed GRAIN were less red, showed higher lipid oxidation during retail display, and higher metmyoglobin formation from day 7 to 13 when compared to PAST. Levels of α-tocopherol were higher in steaks from steers fed diets containing legume and grass. Inclusion of roughage in finishing diets is essential to maintain retail color and prevent lipid and myoglobin oxidation.

Effects of feeding legume-grass pasture and different concentrate levels on fatty acid profile, volatile compounds, and off-flavor of the M. longissimus thoracis.

Pasture-finished beef is becoming more popular among consumers due to concerns related to fatty acid content and sustainable practices. The effects of finishing crossbred steers on legume-grass pasture comprised of oats, ryegrass, and clover (PAST), legume-grass pasture plus whole corn grain (WCG) supplementation (SUPP), and only with WCG (GRAIN) on fatty acids profile, volatile compounds, sensory, and texture attributes were studied. Pasture diets (PAST and SUPP) led to lower n-6/n-3 ratio (P < 0.001), and highest deposition of C18:2 cis-9 trans-11 (P < 0.001) in the lean. Beef from steers fed GRAIN had the highest values of volatile compounds associated with lipid oxidation. Off-flavor intensity was significantly greater on beef from steers fed GRAIN when compared to PAST. Overall, muscles from steers finished on PAST and SUPP showed similar attributes but differ when compared to GRAIN. The presence of forage is essential to improve fatty acid profile, decrease volatile compounds associated with lipid oxidation, and minimize off-flavor.

Effect of ultraviolet light, organic acids, and bacteriophage on Salmonella populations in ground beef.

This study investigated individual and combined effects of organic acids, bacteriophages, and ultraviolet light interventions on Salmonella populations in ground beef. Beef trim was inoculated with four Salmonella strains to result in a contamination level of 3.5 log CFU/g after grinding. Lactic (LA) and peroxyacetic (PAA) acids, bacteriophages (S16 and FO1a) (BA), and ultraviolet light (UV) were applied on fresh trim prior to grinding. Applications of individual or combined organic acids did not significantly decrease Salmonella populations in ground beef. Individual applications of BA and UV light decreased approximately 1 log CFU/g (P<0.05). Combined applications of BA and UV provided an optimal decrease of 2 log CFU/g (P<0.05). Organic acid applications do not reduce Salmonella populations in ground beef when applied on trim prior to grinding. Combined applications of UV and BA may be used in industry settings to improve Salmonella control in ground beef.

Effects of finishing diets containing wet distillers grains plus solubles on beef quality attributes and fatty acid profile.

The objective of this study was to evaluate the effects of feeding wet distillers grains plus solubles (WDGS) on quality attributes of three beef muscles (longissimus lumborum, psoas major, and infraspinatus). Ninety-six, yearlings crossbred steers were randomly assigned to one of three dietary treatments (Corn, 15%, or 30% WDGS - DM basis) and fed for 133 d. No significant differences were observed in marbling score (P=0.89), marbling texture (P=0.70), and marbling distribution (P=0.36). Greater concentrations of PUFA and lower levels of 18:1(n-7) were observed in beef from steers fed 30% WDGS when compared to other treatments. Lipid oxidation was also greater in beef from steers fed 30% WDGS (P≤0.05). No significant differences were observed in sensorial attributes and Warner-Bratzler shear force (WBSF) for all muscles (P>0.05). Feeding WDGS increased PUFA and lipid oxidation, which may lead to shorter shelf life.

Evaluation of palatability and muscle composition of novel value-added beef cuts.

The aim of this study was to evaluate the muscle profile of novel added-value beef cuts including the caudal tip of the M. infraspinatus (Bonanza Cut; TIP) and M. subscapularis (SUB) and two traditional sirloin steak cuts, M. gluteus medius (top sirloin; GLM) and M. rectus femoris (sirloin tip; REC). Samples were subjected to Warner-Braztler Shear Force (WBSF), sensory, cooking loss, and proximate analysis. The muscle TIP had superior values of subjective tenderness, juiciness, and slight off-flavor intensity when compared to all other muscles. The TIP and SUB were similar in WBSF. Cooking loss and moisture values of raw samples were lowest for TIP. Results suggest that TIP can provide enhanced eating experience for consumers and improved marketability for the meat industry.

Low toxicity superparamagnetic magnetite nanoparticles: One-pot facile green synthesis for biological applications.

Superparamagnetic magnetite nanoparticles have been synthesized by a highly reproducible polyvinyl alcohol (PVA)-based modified sol-gel process using water as the only solvent. The synthesis method has proven to be effective, time and cost saving and environmental friendly, resulting in PVA-coated magnetite nanoparticles as direct product from the synthesis, without any special atmosphere or further thermal treatment. X-ray diffraction and transmission electron microscopy revealed that the biocompatible PVA-coating prevents the nanoparticle agglomeration, giving rise to spherical crystals with sizes of 6.8nm (as-cast) and 9.5nm (heat treated) with great control over size and shape with narrow size distribution. Complementary compositional and magnetic characterizations were employed in order to study the surface chemistry and magnetic behavior of the samples, respectively. Cytotoxicity endpoints including no observed adverse effect concentration (NOAEC), 50% lethal concentration (LC50) and total lethal concentration (TLC) of the tested materials on cell viability were determined after 3, 24 and 48h of exposure. The PVA coating improved the biocompatibility of the synthesized magnetite nanoparticles showing good cell viability and low cytotoxicity effects on the MTT assay performed on BHK cells. Preliminary assessment of nanoparticles in vivo effects, performed after 48h on Balb/c mice, exposed to a range of different sub-lethal doses, showed their capacity to penetrate in liver and kidneys with no significant morphological alterations in both organs.

Transcriptional and cellular effects of paracetamol in the oyster Crassostrea gigas.

Acetaminophen (paracetamol) (PAR) is one of the most popular non-steroidal anti-inflammatory drugs (NSAIDs) with analgesic and antipyretic properties consumed worldwide and often detected in the aquatic environment. Due to the fact that PAR induces oxidative stress in mammals, the aim of this study was to evaluate if similar effects were observed in oysters Crassostrea gigas, given their economic and ecological importance and worldwide distribution. Oysters were exposed for 1, 4 and 7 days to two different sublethal PAR concentrations (0, 1 and 100µgL-1). Cell viability, DNA damage in hemocytes and enzymatic activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidases (GPx), glutathione reductase (GR), glucose 6-phosphate dehydrogenase (G6PDH) and glutathione S-transferases (GST) were evaluated in oyster gills. In addition, changes at transcriptional level of Cu/Zn superoxide dismutase (SOD), catalase-like (CAT-like), cytochrome P450 genes (CYP30C1, CYP2AU2, CYP3071A1, CYP356A1), glutathione S-transferase isoforms (GST-ω and GST-π-like), cyclooxygenase (COX), fatty acid binding proteins-like (FABP-like), and caspase genes were evaluated in oyster gills and digestive gland. No changes in cell viability and DNA damage were observed in oysters exposed to both PAR concentrations. Similarly, no significant changes were detected in the major antioxidant enzymes (except for auxiliary enzyme GR) in oyster gills, suggesting that changes in GR activity are enough to counteract a potential oxidative stress in C. gigas gills under these experimental conditions. Furthermore, changes at transcriptional level are concentration and tissue dependent. PAR elicited an inhibition of CYP30C1, CYP3071A1 and FABP-like transcripts highlighting their role in drug metabolism, transport and detoxification of PAR in the gills. GST transcript levels were type, tissue and concentration-dependent. GST-π-like was down-regulated in oyster gills exposed to the lowest PAR concentration and up-regulated in the digestive gland of oysters exposed to the highest PAR concentration. However, GST-ω transcript levels were lower only in oysters digestive gland exposed to the lowest PAR concentration. Therefore, changes at transcriptional level were more sensitive to assess the exposure to PAR at environmental relevant concentrations.

Enantioselective cytotoxicity of ZnS:Mn quantum dots in A549 cells.

Chirality strongly influences many biological properties of materials, such as cell accumulation, enzymatic activity, and toxicity. In the past decade, it has been shown that quantum dots (QDs), fluorescent semiconductor nanoparticles with unique optical properties, can demonstrate optical activity due to chiral ligands bound on their surface. Optically active QDs could find potential applications in biomedical research, therapy, and diagnostics. Consequently, it is very important to investigate the interaction of QDs capped with chiral ligands with living cells. The aim of our study was to investigate the influence of the induced chirality of Mn-doped ZnS QDs on the viability of A549 cells. These QDs were stabilized with D- and L-cysteine using a ligand exchange technique. The optical properties of QDs were studied using UV-Vis, photoluminescence (PL), and circular dichroism (CD) spectroscopy. The cytotoxicity of QDs was investigated by high content screening analysis. It was found that QDs stabilized by opposite ligand enantiomers, had identical PL and UV-Vis spectra and mirror-imaged CD spectra, but displayed different cytotoxicity: QDs capped with D-cysteine had greater cytotoxicity than L-cysteine capped QDs.