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An abstract of the article "A Proteomic Study Investigating the Effect of Natural and Natural-like Compounds on Fusarium graminearum" by G. Pani and colleagues is presented.

An abstract of the article "Genomic and Proteomic Studies on the Pathogenic Grape Flora in Luxembourg" by M. Behr and colleagues is presented.

Nanomaterials (NMs) are increasingly used in medical treatments, electronics, and food additives. However, nanosafety-the possible adverse effects of NMs on human health-is an area of active research. This review provides an overview of the influence of biomolecular coronas on NM transformation following various exposure routes. We discuss potential exposure pathways, including inhalation and ingestion, describing the physiology of exposure routes and emphasising the relevance of coronas in these environments. Additionally, we review other routes to NM exposure, such as synovial fluid, blood (translocation and injection), dermal and ocular exposure, as well as the dose and medium impact on NM interactions. We emphasize the need for an in-depth characterisation of coronas in different biological media, highlighting the need and opportunity to study lung and gastric fluids to understand NM behaviour and potential toxicity. Future research aims to predict better in vivo outcomes and address the complexities of NM interactions with biological systems., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Making research data findable, accessible, interoperable and reusable (FAIR) is typically hampered by a lack of skills in technical aspects of data management by data generators and a lack of resources. We developed a Template Wizard for researchers to easily create templates suitable for consistently capturing data and metadata from their experiments. The templates are easy to use and enable the compilation of machine-readable metadata to accompany data generation and align them to existing community standards and databases, such as eNanoMapper, streamlining the adoption of the FAIR principles. These templates are citable objects and are available as online tools. The Template Wizard is designed to be user friendly and facilitates using and reusing existing templates for new projects or project extensions. The wizard is accompanied by an online template validator, which allows self-evaluation of the template (to ensure mapping to the data schema and machine readability of the captured data) and transformation by an open-source parser into machine-readable formats, compliant with the FAIR principles. The templates are based on extensive collective experience in nanosafety data collection and include over 60 harmonized data entry templates for physicochemical characterization and hazard assessment (cell viability, genotoxicity, environmental organism dose-response tests, omics), as well as exposure and release studies. The templates are generalizable across fields and have already been extended and adapted for microplastics and advanced materials research. The harmonized templates improve the reliability of interlaboratory comparisons, data reuse and meta-analyses and can facilitate the safety evaluation and regulation process for (nano) materials., (© 2024. Springer Nature Limited.)

The past few decades of managing the uncertain risks associated with nanomaterials have provided valuable insights (knowledge gaps, tools, methods, etc.) that are equally important to promote safe and sustainable development and use of advanced materials. Based on these insights, the current paper proposes several actions to optimize the risk and sustainability governance of advanced materials. We emphasise the importance of establishing a European approach for risk and sustainability governance of advanced materials as soon as possible to keep up with the pace of innovation and to manage uncertainty among regulators, industry, SMEs and the public, regarding potential risks and impacts of advanced materials. Coordination of safe and sustainable advanced material research efforts, and data management according to the Findable, Accessible, Interoperable and Reusable (FAIR) principles will enhance the generation of regulatory-relevant knowledge. This knowledge is crucial to identify whether current regulatory standardised and harmonised test methods are adequate to assess advanced materials. At the same time, there is urgent need for responsible innovation beyond regulatory compliance which can be promoted through the Safe and Sustainable Innovation Approach. that combines the Safe and Sustainable by Design concept with Regulatory Preparedness, supported by a trusted environment. We further recommend consolidating all efforts and networks related to the risk and sustainability governance of advanced materials in a single, easy-to-use digital portal. Given the anticipated complexity and tremendous efforts required, we identified the need of establishing an organisational structure dedicated to aligning the fast technological developments in advanced materials with proper risk and sustainability governance. Involvement of multiple stakeholders in a trusted environment ensures a coordinated effort towards the safe and sustainable development, production, and use of advanced materials. The existing infrastructures and network of experts involved in the governance of nanomaterials would form a solid foundation for such an organisational structure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

A substantial increase in engineered nanoparticles in consumer products has been observed, heightening human and environmental exposure. Inhalation represents the primary route of human exposure, necessitating a focus on lung toxicity studies. However, to avoid ethical concerns the use of in vitro models is an efficient alternative to in vivo models. This study utilized an in vitro human alveolar barrier model at air-liquid-interface with four cell lines, for evaluating the biological effects of different gold nanoparticles. Exposure to PEGylated gold nanospheres, nanorods, and nanostars did not significantly impact viability after 24 h, yet all AuNPs induced cytotoxicity in the form of membrane integrity impairment. Gold quantification revealed cellular uptake and transport. Transcriptomic analysis identified gene expression changes, particularly related to the enhancement of immune cells. Despite limited impact, distinct effects were observed, emphasizing the influence of nanoparticles physicochemical parameters while demonstrating the model's efficacy in investigating particle biological effects., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The rapid development of engineered nanomaterials (ENMs) causes humans to become increasingly exposed to them. Therefore, a better understanding of the health impact of ENMs is highly demanded. Considering the 3Rs (Replacement, Reduction, and Refinement) principle, in vitro and computational methods are excellent alternatives for testing on animals. Among computational methods, nano-quantitative structure-activity relationship (nano-QSAR), which links the physicochemical and structural properties of EMNs with biological activities, is one of the leading method. The nature of toxicological experiments has evolved over the last decades; currently, one experiment can provide thousands of measurements of the organism's functioning at the molecular level. At the same time, the capacity of the in vitro systems to mimic the human organism is also improving significantly. Hence, the authors would like to discuss whether the nano-QSAR approach follows modern toxicological studies and takes full advantage of the opportunities offered by modern toxicological platforms. Challenges and possibilities for improving data integration are underlined narratively, including the need for a consensus built between the in vitro and the QSAR domains., (© 2023 Wiley-VCH GmbH.)

Background: The establishment of reliable and robust in vitro models for hazard assessment, a prerequisite for moving away from animal testing, requires the evaluation of model transferability and reproducibility. Lung models that can be exposed via the air, by means of an air-liquid interface (ALI) are promising in vitro models for evaluating the safety of nanomaterials (NMs) after inhalation exposure. We performed an inter-laboratory comparison study to evaluate the transferability and reproducibility of a lung model consisting of the human bronchial cell line Calu-3 as a monoculture and, to increase the physiologic relevance of the model, also as a co-culture with macrophages (either derived from the THP-1 monocyte cell line or from human blood monocytes). The lung model was exposed to NMs using the VITROCELL® Cloud12 system at physiologically relevant dose levels., Results: Overall, the results of the 7 participating laboratories are quite similar. After exposing Calu-3 alone and Calu-3 co-cultures with macrophages, no effects of lipopolysaccharide (LPS), quartz (DQ12) or titanium dioxide (TiO 2 ) NM-105 particles on the cell viability and barrier integrity were detected. LPS exposure induced moderate cytokine release in the Calu-3 monoculture, albeit not statistically significant in most labs. In the co-culture models, most laboratories showed that LPS can significantly induce cytokine release (IL-6, IL-8 and TNF-α). The exposure to quartz and TiO 2 particles did not induce a statistically significant increase in cytokine release in both cell models probably due to our relatively low deposited doses, which were inspired by in vivo dose levels. The intra- and inter-laboratory comparison study indicated acceptable interlaboratory variation for cell viability/toxicity (WST-1, LDH) and transepithelial electrical resistance, and relatively high inter-laboratory variation for cytokine production., Conclusion: The transferability and reproducibility of a lung co-culture model and its exposure to aerosolized particles at the ALI were evaluated and recommendations were provided for performing inter-laboratory comparison studies. Although the results are promising, optimizations of the lung model (including more sensitive read-outs) and/or selection of higher deposited doses are needed to enhance its predictive value before it may be taken further towards a possible OECD guideline., Competing Interests: Declaration of Competing Interest Barbara Birk, Andreas Verlohner and Robert Landsiedel are employees of BASF. This model might be used in the future for the registration of BASF products. Otmar Schmid and Pramod Kumar are employees of the Helmholtz Center Munich, which receives license fees for the VITROCELL Cloud technology. Otmar Schmid, a co-patent holder of the underlying ALICE Cloud technology, receives a share of these license fees. All other authors declare no competing financial interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Air-liquid interface (ALI) lung cell models cultured on permeable transwell inserts are increasingly used for respiratory hazard assessment requiring controlled aerosolization and deposition of any material on ALI cells. The approach presented herein aimed to assess the transwell insert-delivered dose of aerosolized materials using the VITROCELL® Cloud12 system, a commercially available aerosol-cell exposure system. An inter-laboratory comparison study was conducted with seven European partners having different levels of experience with the VITROCELL® Cloud12. A standard operating procedure (SOP) was developed and applied by all partners for aerosolized delivery of materials, i.e., a water-soluble molecular substance (fluorescence-spiked salt) and two poorly soluble particles, crystalline silica quartz (DQ 12 ) and titanium dioxide nanoparticles (TiO 2 NM-105). The material dose delivered to transwell inserts was quantified with spectrofluorometry (fluorescein) and with the quartz crystal microbalance (QCM) integrated in the VITROCELL® Cloud12 system. The shape and agglomeration state of the deposited particles were confirmed with transmission electron microscopy (TEM). Inter-laboratory comparison of the device-specific performance was conducted in two steps, first for molecular substances (fluorescein-spiked salt), and then for particles. Device- and/or handling-specific differences in aerosol deposition of VITROCELL® Cloud12 systems were characterized in terms of the so-called deposition factor (DF), which allows for prediction of the transwell insert-deposited particle dose from the particle concentration in the aerosolized suspension. Albeit DF varied between the different labs from 0.39 to 0.87 (mean (coefficient of variation (CV)): 0.64 (28%)), the QCM of each VITROCELL® Cloud 12 system accurately measured the respective transwell insert-deposited dose. Aerosolized delivery of DQ 12 and TiO 2 NM-105 particles showed good linearity (R 2  > 0.95) between particle concentration of the aerosolized suspension and QCM-determined insert-delivered particle dose. The VITROCELL® Cloud 12 performance for DQ 12 particles was identical to that for fluorescein-spiked salt, i.e., the ratio of measured and salt-predicted dose was 1.0 (29%). On the other hand, a ca. 2-fold reduced dose was observed for TiO 2 NM-105 (0.54 (41%)), which was likely due to partial retention of TiO 2 NM-105 agglomerates in the vibrating mesh nebulizer of the VITROCELL® Cloud12. This inter-laboratory comparison demonstrates that the QCM integrated in the VITROCELL® Cloud 12 is a reliable tool for dosimetry, which accounts for potential variations of the transwell insert-delivered dose due to device-, handling- and/or material-specific effects. With the detailed protocol presented herein, all seven partner laboratories were able to demonstrate dose-controlled aerosolization of material suspensions using the VITROCELL® Cloud12 exposure system at dose levels relevant for observing in vitro hazard responses. This is an important step towards regulatory approved implementation of ALI lung cell cultures for in vitro hazard assessment of aerosolized materials., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Barbara Birk, Manuel Rissel, Robert Landsiedel are employees of BASF. BASF produces some of the test material. In the future this set-up (Cloud12) might be used also for toxicological testing of BASF products. Otmar Schmid is employee of the Helmholtz Zentrum Munich, which receives license fees for the VITROCELL Cloud technology. Otmar Schmid as co-patent holder of the underlying ALICE Cloud technology receives a share of these license fees. All other authors declare no competing financial interests., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The aim of the present study was the assessment of the sub-chronic effects of silver (AgNPs) and gold nanoparticles (AuNPs) of 40 nm primary size either stabilised with citrate (CIT) or coated with polyethylene glycol (PEG) on the freshwater invertebrate Gammarus fossarum. Silver nitrate (AgNO 3 ) was used as a positive control in order to study the contribution of silver ions potentially released from AgNPs on the observed effects. A multibiomarker approach was used to assess the long-term effects of AgNPs and AuNPs 40 nm on molecular, cellular, physiological and behavioural responses of G. fossarum. Specimen of G. fossarum were exposed for 15 days to 0.5 and 5 µgL -1 of CIT and PEG AgNPs and AuNPs 40 nm in the presence of food. A significant uptake of both Ag and Au was observed in exposed animals but was under the toxic threshold leading to mortality of G. fossarum. Silver nanoparticles (CIT-AgNPs and PEG-AgNPs 40 nm) led to an up-regulation of Na + K + ATPase gene expression. An up-regulation of Catalse and Chitinase gene expressions due to exposure to PEG-AgNPs 40 nm was also observed. Gold nanoparticles (CIT and PEG-AuNPs 40 nm) led to an increase of CuZnSOD gene expression. Furthermore, both AgNPs and AuNPs led to a more developed digestive lysosomal system indicating a general stress response in G. fossarum. Both AgNPs and AuNPs 40 nm significantly affected locomotor activity of G. fossarum while no effects were observed on haemolymphatic ions and ventilation., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Exposure to aerosol from electronic vapor (e-vapor) products has been suggested to result in less risk of harm to smokers than cigarette smoke (CS) exposure. Although many studies on e-vapor products have tested the effects of liquid formulations on cell cultures, few have evaluated the effects of aerosolized formulations. We examined the effects of acute exposure to the aerosol of an e-vapor device that uses the MESH® technology (IQOS® MESH, Philip Morris International) and to CS from the 3R4F reference cigarette on human organotypic bronchial epithelial culture and alveolar triculture models. In contrast to 3R4F CS exposure, exposure to the IQOS MESH aerosol (Classic Tobacco flavor) did not cause cytotoxicity in bronchial epithelial cultures or alveolar tricultures despite its greater concentrations of deposited nicotine (3- and 4-fold, respectively). CS exposure caused a marked decrease in the frequency and active area of ciliary beating in bronchial cultures, whereas IQOS MESH aerosol exposure did not. Global mRNA expression and secreted protein profiles revealed a significantly lower impact of IQOS MESH aerosol exposure than 3R4F CS exposure. Overall, our whole aerosol exposure study shows a clearly reduced impact of IQOS MESH aerosol relative to CS in bronchial and alveolar cultures, even at greater nicotine doses., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

Nanotechnologies have reached maturity and market penetration that require nano-specific changes in legislation and harmonization among legislation domains, such as the amendments to REACH for nanomaterials (NMs) which came into force in 2020. Thus, an assessment of the components and regulatory boundaries of NMs risk governance is timely, alongside related methods and tools, as part of the global efforts to optimise nanosafety and integrate it into product design processes, via Safe(r)-by-Design (SbD) concepts. This paper provides an overview of the state-of-the-art regarding risk governance of NMs and lays out the theoretical basis for the development and implementation of an effective, trustworthy and transparent risk governance framework for NMs. The proposed framework enables continuous integration of the evolving state of the science, leverages best practice from contiguous disciplines and facilitates responsive re-thinking of nanosafety governance to meet future needs. To achieve and operationalise such framework, a science-based Risk Governance Council (RGC) for NMs is being developed. The framework will provide a toolkit for independent NMs' risk governance and integrates needs and views of stakeholders. An extension of this framework to relevant advanced materials and emerging technologies is also envisaged, in view of future foundations of risk research in Europe and globally., (© 2020 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Silica nanoparticles (SiNPs) are among the most widely manufactured and used nanoparticles. Concerns about potential health effects of SiNPs have therefore risen. Using a 3D tri-culture model of the alveolar lung barrier we examined effects of exposure to SiNPs (Si10) and crystalline silica (quartz; Min-U-Sil) in the apical compartment consisting of human alveolar epithelial A549 cells and THP-1-derived macrophages, as well as in the basolateral compartment with Ea.hy926 endothelial cells. Inflammation-related responses were measured by ELISA and gene expression., Results: Exposure to both Si10 and Min-U-Sil induced gene expression and release of CXCL8, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α) and interleukin-1β (IL-1β) in a concentration-dependent manner. Cytokine/chemokine expression and protein levels were highest in the apical compartment. Si10 and Min-U-Sil also induced expression of adhesion molecules ICAM-1 and E-selectin in the apical compartment. In the basolateral endothelial compartment we observed marked, but postponed effects on expression of all these genes, but only at the highest particle concentrations. Geneexpressions of heme oxygenase-1 (HO-1) and the metalloproteases (MMP-1 and MMP-9) were less affected. The IL-1 receptor antagonist (IL-1RA), markedly reduced effects of Si10 and Min-U-Sil exposures on gene expression of cytokines and adhesion molecules, as well as cytokine-release in both compartments., Conclusions: Si10 and Min-U-Sil induced gene expression and release of pro-inflammatory cytokines/adhesion molecules at both the epithelial/macrophage and endothelial side of a 3D tri-culture. Responses in the basolateral endothelial cells were only induced at high concentrations, and seemed to be mediated by IL-1α/β released from the apical epithelial cells and macrophages.

Background: The present study aimed to evaluate the potential differences in the biological effects of two types of spherical silver particles of 20 and 200 nm (Ag20 and Ag200), and of PVP-coated silver nanowires (AgNWs) with a diameter of 50 nm and length up to 50 μm, using a complex 3D model representative for the alveolar barrier cultured at air-liquid interface (ALI). The alveolar model was exposed to 0.05, 0.5 and 5 μg/cm 2 of test compounds at ALI using a state-of-the-art exposure system (Vitrocell™Cloud System). Endpoints related to the oxidative stress induction, anti-oxidant defence mechanisms, pro-inflammatory responses and cellular death were selected to evaluate the biocompatibility of silver particles and nanowires (AgNMs) and to further ascribe particular biological effects to the different morphologic properties between the three types of AgNMs evaluated., Results: Significant cytotoxic effect was observed for all three types of AgNMs at the highest tested doses. The increased mRNA levels of the pro-apoptotic gene CASP7 suggests that apoptosis may occur after exposure to AgNWs. All three types of AgNMs increased the mRNA level of the anti-oxidant enzyme HMOX-1 and of the metal-binding anti-oxidant metallothioneins (MTs), with AgNWs being the most potent inducer. Even though all types of AgNMs induced the nuclear translocation of NF-kB, only AgNWs increased the mRNA level of pro-inflammatory mediators. The pro-inflammatory response elicited by AgNWs was further confirmed by the increased secretion of the 10 evaluated interleukins., Conclusion: In the current study, we demonstrated that the direct exposure of a complex tetra-culture alveolar model to different types of AgNMs at ALI induces shape- and size-specific biological responses. From the three AgNMs tested, AgNWs were the most potent in inducing biological alterations. Starting from 50 ng/cm 2 , a dose representative for an acute exposure in a high exposure occupational setting, AgNWs induced prominent changes indicative for a pro-inflammatory response. Even though the acute responses towards a dose representative for a full-lifetime exposure were also evaluated, chronic exposure scenarios at low dose are still unquestionably needed to reveal the human health impact of AgNMs during realistic conditions.