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Cultural proximity has been considered as a crucial determinant of bilateral trade flows. Scant emphasis has, instead, been devoted to the investigation of the opposite direction of causality. International trade eases contacts and increases trust among contracting parties and may, then, promote the spread of cultural beliefs across borders. By using World and European Values Surveys data, we provide evidence on the role of trade flows in favoring countries’ cultural convergence for a large sample of countries over the period 1989–2014. Results confirm that international trade narrows differences in cultural beliefs and attitudes, but just when trade partners share some culture-related traits. Common ancestry, religion and legal system as well as high historical bilateral migration flows are necessary conditions for trade reducing cultural distance. Also, the convergence effect turns to be completely driven by trade flows of differentiated goods which entail relationship-specific investments and a deeper commitment between contracting parties.

The research for alternative administration methods for anticancer drugs, towards enhanced effectiveness and selectivity, represents a major challenge for the scientific community. In the last decade, polymeric nanostructured delivery systems represented a promising alternative to conventional drug administration since they ensure secure transport to the selected target, providing active compounds protection against elimination, while minimizing drug toxicity to non-target cells. In the present research, poly(glycerol sebacate), a biocompatible polymer, was synthesized and then nanostructured to allow curcumin encapsulation, a naturally occurring polyphenolic phytochemical isolated from the powdered rhizome of Curcuma longa L. Curcumin was selected as an anticancer agent in virtue of its strong chemotherapeutic activity against different cancer types combined with good cytocompatibility within healthy cells. Despite its strong and fascinating biological activity, its possible exploitation as a novel chemotherapeutic has been hampered by its low water solubility, which results in poor absorption and low bioavailability upon oral administration. Hence, its encapsulation within nanoparticles may overcome such issues. Nanoparticles obtained through nanoprecipitation, an easy and scalable technique, were characterized in terms of size and stability over time using dynamic light scattering and transmission electron microscopy, confirming their nanosized dimensions and spherical shape. Finally, biological investigation demonstrated an enhanced cytotoxic effect of curcumin-loaded PGS-NPs on human cervical cancer cells compared to free curcumin.

We study the impact of immigration on the product mix of the receiving economy by combining information on the local presence of immigrants with a highly detailed definition of the set of goods produced by Italian provinces. For the period 2002–2011, we find that an increase in the share of migrants shifts the manufacturing output composition of host provinces in favour of less capital intensive products. This evidence is based on an IV strategy resting on the settlement of immigrants in the pre-sample period and is robust to several sensitivity checks. We shed light on two mechanisms potentially driving our result. On the one hand, we show that immigration reduces provinces’ dependence on imports of low capital intensity intermediate goods. On the other hand, immigration fosters relatively more the creation of new firms in local low capital intensity industries.

Strategies for endosomal escape and access to the cell nucleus are highly sought for nanocarriers to deliver their load efficiently following endocytosis. In this work, we have studied the uptake and intracellular trafficking of a polycationic polyamidoamine (PAA) endowed with a luminescent Ru complex, Ru-PhenAN, that shows unique trafficking to the cell nucleus. Live cell imaging confirmed the capacity of this polymer to access the nucleus, excluding artifacts due to cell fixation, and clarified that the mechanism of escape is light-triggered and relies on the presence of the Ru complexes and their capacity to absorb light and act as photosensitizers for singlet oxygen production. These results open up the possibility to use PAA-ruthenium complexes for targeted light-triggered delivery of genetic material or drugs to the cytosol and nucleus.

The exploitation of self-assembled systems to improve the solubility of drugs is getting more and more attention. Among the different types of self-assembled biomaterials, peptides and in particular peptides containing non-coded amino acids (NCAPs) are promising because their use opens the door to more stable materials inducing increased stability to proteolysis. New classes of NCAP, Ac-Ala-X-Ala-Aib- AlaCONH2 (X ¼ alpha-aminoisobutyric acid (Aib) or X ¼ cyclopentane amino acid (Ac5c)) have been prepared and the correlation between the different secondary peptide structure and solvent (i.e. CD3CN, CD3OH, H2O/D2O) verified by NMR. Furthermore, the formation of a nanocolloidal system in water was deeply studied by DLS and the morphology of the obtained spherical aggregates with nanometric dimensions was assessed by TEM. Aib containing pentapeptide was selected for greater ease of synthesis. Its ability to encapsulate curcumin, as a model insoluble drug molecule, was investigated using fluorescence emission and confocal microscopy analyses. Two different approaches were used to study the interaction between curcumin and peptide aggregates. In the first approach peptide aggregates were formed in the presence of curcumin, while in the second approach curcumin was added to the already formed peptide aggregates. We succeeded in our challenge by using the second approach and 53.8% of added curcumin had been encapsulated.

Self-assembly of biomolecules such as peptides, nucleic acids or their analogues affords supramolecular objects, exhibiting structures and physical properties dependent on the amino-acid or nucleobase composition. Conjugation of the peptide diphenylalanine (FF) to peptide nucleic acids triggers formation of self-assembled structures, mainly stabilized by interactions between FF. In this work we report formation of homogeneous chiral fibers upon self-assembly of the hybrid composed of the tetraphenylalanine peptide (4F) conjugated to the PNA dimer adenine-thymine (at). In this case nucleobases seem to play a key role in determining the morphology and chirality of the fibers. When the PNA "at" is replaced by guanine-cytosine dimer "gc", disordered structures are observed. Spectroscopic characterization of the self-assembled hybrids, along with AFM and SEM studies is reported. Finally, a structural model consistent with the experimental evidence has also been obtained, showing how the building blocks of 4Fat arrange to give helical fibers.

In this paper we investigate the labour content of complex products. By exploiting O*NET information on the skill and knowledge required by occupations, we find that the product complexity measure suggested by Hausmann and Hidalgo (2009) is highly intensive in STEM knowledge and in Science, Mathematics and Critical Thinking skill requirements. We then propose a new measure of occupational complexity based on these occupational features. Among other advantages, this indicator has the merit to measure complexity for service industries that, so far, has never been measured. In an empirical model of the growth of USA Metropolitan Areas (MSAs), we find that MSAs whose initial industrial structure embeds a higher level of occupational complexity experience higher real per capita GDP growth over the 2001–2017 period. The occupational complexity measure is a stronger predictor of growth than other metrics of industries’ occupational and task content as well as compared to indicators of local occupational and industrial composition. When we separately compute occupational complexity of service and manufacturing industries and delve into their specific role for long run growth, we find a prominent role of the occupation complexity embedded in local services with respect to the one embedded in local manufacturing. Our baseline evidence is corroborated in the context of the NUTS3 regions of France over the period 2010–2017.

N,N-Dimethyl 3β-hydroxychol-5-en-24-amide (DMHCA, 3) is the prototype of cholenamides, a class of steroidal LXR modulators characterized by the nucleus of Δ5-cholen-3β-ol and the presence of an amide moiety at C-24. DMHCA (3) has been reported to act as a gene-selective modulator able to fully induce ABCA1 expression whilst poorly up-regulate the expression of FASN and SREBP-1α genes. With the aim to widen the limited structure-activity relationships of DMHCA (3), herein we describe the synthesis and the biological evaluation of nine novel derivatives, resulting from a) the homologation of DMHCA's side-chain to give N,N-dimethyl 3β-hydroxy-24a-homochol-5-en-24a-amide (4); b) the distal branching of the side-chain of 3 and 4 by introducing an ethyl group at C-23 and C-24, respectively; c) the replacement of the dimethyl amide moiety of all the derivatives with a carboxylic acid function. While broadening the structure-activity relationships of the class of cholenamides, we were successful in the discovery of (24R)-N,N-dimethyl-24-ethyl-3β-hydroxy-24a-homochol-5-en-24a-amide (6) as a novel LXR agonist with improved profile in term of selective gene modulation respect to the prototype DMHCA (3); indeed, 6 was able to up-regulate the expression of ABCA1 more than DMHCA (3), without to induce SREBP-1c, differently from DMHCA (3). Moreover, 6 induced the expression of FASN less than 3 and interestingly was a negative modulator towards SCD1 in contrast to DMHCA (3), which instead weakly induced the expression of this gene.

Visual stress is defined as a neuronal-based dysfunction of visual processing, with a deficit in the magnocellular system and in the primary visual cortex. It is characterized by visual-perceptual distortions and progressive visual discomfort in reading. The present study verified the prevalence of visual stress among students from 3rd and 4th grades of elementary school (7 to 10 years old) with reading difficulties, as well as investigated the effect of the use of overlays on reading ability. All eligible participants (n = 58) had reading difficulties and adequate binocular visual acuity. Overlays were selected and distributed to students for use for three months. The Visual Reading Perception Scale, the Reading Rate Test and the Reading Test - Comprehension and Sentence characterized the pre- and post-intervention conditions. The results indicated a 12% prevalence of visual stress (severe symptoms). After the intervention, it was verified that the use of spectral slides promoted an increase in sentence comprehension and reading rate. Thus, it is concluded that visual stress is a very prevalent disorder among children with reading difficulties and that overlays are an effective method of intervention to reduce visual stress in reading. El estrés visual se define como una disfunción neuronal del procesamiento visual, con un déficit en el sistema magnocelular y en la corteza visual primaria. Se caracteriza por distorsiones visual-perceptivas y malestar visual progresivo en la lectura. El presente estudio verificó la prevalencia de estrés visual en estudiantes de 3º y 4º grados de la escuela primaria (7 a 10 años) con dificultades lectoras, además de investigar el efecto del uso de diapositivas espectrales sobre la capacidad lectora. Todos los participantes elegibles (n = 58) tenían dificultades para leer y una agudeza visual binocular adecuada. Se seleccionaron diapositivas espectrales y se distribuyeron a los estudiantes para su uso durante tres meses. La Escala de Percepción de Lectura Visual, la Prueba de Tasa de Lectura y la Prueba de Lectura - Comprensión y Oración caracterizaron las condiciones previas y posteriores a la intervención. Los resultados indicaron una prevalencia del 12% de estrés visual (síntomas graves). Luego de la intervención, se verificó que el uso de diapositivas espectrales promovió un aumento en la comprensión de oraciones y la tasa de lectura. Así, se concluye que el estrés visual es un trastorno muy prevalente entre los niños con dificultades lectoras y que los deslizamientos espectrales son un método eficaz de intervención para reducir el estrés visual en la lectura. O estresse visual é definido como uma disfunção do processamento visual, de base neuronal, com um déficit do sistema magnocelular e no córtex visual primário. Ele é caracterizado por distorções visuoperceptuais e desconforto visual progressivo na leitura. O presente estudo verificou a prevalência do estresse visual entre escolares do 3º e 4º ano do ensino fundamental (7 a 10 anos) com dificuldade de leitura, assim como investigou o efeito do uso de lâminas espectrais na habilidade de leitura. Todos os participantes elegíveis (n = 58) apresentavam dificuldade de leitura e adequada acuidade visual binocular. As lâminas espectrais foram selecionadas e distribuídas aos alunos para uso por três meses. A Escala de Percepção Visual de Leitura, o Teste de Taxa de Leitura e o Teste de Leitura - Compreensão e Sentença caracterizaram as condições pré e pós-intervenção. Os resultados indicaram prevalência de 12% de estresse visual (sintomas severos). Após a intervenção, foi verificado que o uso das lâminas espectrais promoveu incremento da compreensão de sentenças e da taxa de leitura. Assim, conclui-se que o estresse visual é uma disfunção muito prevalente entre crianças com dificuldade de leitura e que as lâminas espectrais são um método eficaz de intervenção para reduzir o estresse visual na leitura.

Halloysite nanotubes (HNT) are aluminosilicates bearing an Al-OH terminated inner lumen and a Si-O-Si exposing outer surface, which hold promise in several research fields due to their intrinsic surface duality. Functionalization with octylphophonic acid (OPA) was here investigated as a means to achieve selective functionalization of the HNT lumen and pH-triggered release. Model oxides were adopted to investigate the role of chemical nature and surface charge on the adsorption mode and reversibility of the OPA bond to the surface. Beside silica and aluminium (oxo)hydroxide used to mimic respectively the outer and inner HNT surfaces, titanium dioxide was also studied due to its intermediate isoelectric point and surface acidity. The effect of the functionalization pH and OPA content, along with the pH-dependent adsorption reversibility, were investigated using both spectroscopic characterization and wetting determinations. Results on both model oxides and HNT support a preferential adsorption of OPA on the Al-OH exposing surface. Functionalized HNT retained their inner lumen porosity and water dispersibility, which are desired properties in terms of application. The specific character of the OPA-HNT interaction is discussed with respect to (oxo)hydroxides, particularly in terms of the pH-dependent adsorption reversibility.

We investigate the role of local labor standards on MNEs’ location decisions across different sectors and sub-national regions within a developing country. We suggest that foreign investors adopt selective location strategies in connection with specific labor standards as a result of reputational and operating considerations. Foreign firms in more hazardous sectors prefer locations with higher occupational health and safety standards because they are more exposed to reputational risks. Those in sectors with less reversible investments prefer locations with lower degrees of unionization because their lower bargaining power increases their sensitivity to operating costs. We test our arguments across 26 sub-national Turkish regions over the period 2005–2011.

The intrauterine system (IUS) is an effective and reversible contraceptive method, very popular in emerging countries. However, in some cases, aggravating factors may occur, such as displacement of the IUS, which is a rare complication. The migration of the IUS may cause uterine perforation, either during or after insertion, which can be asymptomatic or present clinical symptoms ranging from abnormal bleeding to fistula formation. We report a case of a 31-year-old patient, IUS user, who complained of moderate pain in the hypogastric region. During a hysterectomy, it was found that the IUS was in extrauterine location. El sistema intrauterino (SIU) es un método anticonceptivo eficaz, reversible y muy popular en los países emergentes. Sin embargo, en algunos casos, pueden aparecer factores agravantes, como el desplazamiento del SIU, que es una complicación poco común. La migración del SIU puede ocasionar perforación uterina, ya sea durante o después de la inserción, que puede ser asintomática o presentar síntomas clínicos que van desde sangrado anormal hasta formación de fístula. Presentamos el caso de una paciente de 31 años, usuario de SIU, que consultaba por dolor moderado en la región hipogástrica. Durante una histerectomía, se encontró que el SIU estaba en una localización extrauterina. O sistema intrauterino (SIU) é um método contraceptivo eficaz, reversível e muito popular em países emergentes. Entretanto, em alguns casos, podem ocorrer alguns agravantes, como o deslocamento do SIU que é uma rara complicação. A migração do SIU pode causar a perfuração uterina, tanto durante como depois da inserção, que pode ser assintomática ou apresentar sintomas clínicos que variam de sangramento anormal até formação de fístula. Relatamos o caso de uma paciente de 31 anos que possuía SIU e se queixava de dor de intensidade moderada em região hipogástrica. Durante uma histerectomia, foi constatado que o SIU estava em localização extrauterina.

The adsorption of biomacromolecules is a fundamental process that can alter the behaviour and adverse effects of nanoparticles (NPs) in natural systems. While the interaction of NPs with natural molecules present in the environment has been described, their biological impacts are largely unknown. Therefore, this study aims to provide a first evidence of the influence of biomolecules sorption on the toxicity of cerium oxide nanoparticles (CeO2NPs) towards the freshwater bivalve Dreissena polymorpha. To this aim, we compared naked CeO2NPs and coated with alginate and chitosan, two polysaccharides abundant in aquatic environments. Mussels were exposed to the three CeO2NPs (naked, chitosan- and alginate-coated) up to 14 days at 100 μg L−1, which is a concentration higher than the environmental one predicted for this type of NP. A suite of biomarkers related to oxidative stress and energy metabolism was applied, and metabolomics was also carried out to identify metabolic pathways potentially targeted by CeO2NPs. Results showed that the coating with chitosan reduced NP aggregation and increased the stability in water. Nonetheless, the Ce accumulation in mussels was similar in all treatments. As for biological effects, all three types of CeO2NPs reduced significantly the level of reactive oxygen species and the activity of superoxide dismutase, glutathione peroxidase and glutathione-S-transferase. The effect was more pronounced in individuals exposed to CeO2NPs coated with alginate, which also significantly induced the activity of the electron transport system. Metabolomics analysis of amino acid metabolism showed modulation only in mussels treated with CeO2NPs coated with alginate. In this group, 25 metabolites belonging to nucleotides, lipids/sterols and organic osmolytes were also modulated, suggesting that the nanoparticles affect energetic metabolism and osmoregulation of mussels. This study highlights the key role of the interaction between nanoparticles and natural molecules as a driver of nanoparticle ecotoxicity.

It is known that, for marine coastal ecosystems, pollution and global warming are among the most threatening factors. Among emerging pollutants, nanoparticles (NPs) deserve particular attention as their possible adverse effects are significantly influenced by environmental factors such as salinity, pH and temperature, as well as by their ability to interact with other contaminants. In this framework, the present study aimed to evaluate the potential interactions between CeO2 NPs and the toxic classic metal mercury (Hg), under current and warming conditions. The marine bivalve Mytilus galloprovincialis was used as biological model and exposed to CeO2 NPs and Hg, either alone or in combination, for 28 day at 17 °C and 22 °C. A suite of biomarkers related to energetic metabolism, oxidative stress/damage, redox balance, and neurotoxicity was applied in exposed and non-exposed (control) mussels. The Hg and Ce accumulation was also assessed. Results showed that the exposure to CeO2 NPs alone did not induce toxic effects in M. galloprovincialis. On the contrary, Hg exposure determined a significant loss of energetic metabolism and a general impairment in biochemical performances. Hg accumulation in mussels was not modified by the presence of CeO2 NPs, while the biochemical alterations induced by Hg alone were partially canceled upon co-exposure with CeO2 NPs. The temperature increase induced loss of metabolic and biochemical functions and the effects of temperature prevailed on mussels exposed to pollutants acting alone or combined.

Polyamide 6 (PA6) suffers from fast degradation in humid conditions due to hydrolysis of amide bonds, which limits its durability. The addition of nanotubular fillers represents a viable strategy for overcoming this issue, although the additive/polymer interface at high filler content can become privileged site for moisture accumulation. As a cost-effective and versatile material, halloysite nanotubes (HNT) were investigated to prepare PA6 nanocomposites with very low loadings (1&ndash, 45% w/w). The roles of the physicochemical properties of two differently sourced HNT, of filler functionalization with (3-aminopropyl)triethoxysilane and of dispersion techniques (in situ polymerization vs. melt blending) were investigated. The aspect ratio (5 vs. 15) and surface charge (&minus, 31 vs. &minus, 59 mV) of the two HNT proved crucial in determining their distribution within the polymer matrix. In situ polymerization of functionalized HNT leads to enclosed and well-penetrated filler within the polymer matrix. PA6 nanocomposites crystal growth and nucleation type were studied according to Avrami theory, as well as the formation of different crystalline structures (&alpha, and &gamma, forms). After 1680 h of ageing, functionalized HNT reduced the diffusion of water into polymer, lowering water uptake after 600 h up to 90%, increasing the materials durability also regarding molecular weights and rheological behavior.

We present for the first time a method for the preparation of magnetic halloysite nanotubes (HNT) by loading of preformed superparamagnetic magnetite nanoparticles (SPION) of diameter size ∼6 nm with a hydrodynamic diameter of ∼10 nm into HNT. We found that the most effective route to reach this goal relies on the modification of the inner lumen of HNT by tetradecylphosphonic acid (TDP) to give HNT–TDP, followed by the loading with preformed oleic acid (OA)-stabilized SPION. Transmission electron microscopy evidenced the presence of highly crystalline magnetic nanoparticles only in the lumen, partially ordered in chainlike structures. Conversely, attempts to obtain the same result by exploiting either the positive charge of the HNT inner lumen employing SPIONs covered with negatively charged capping agents or the in situ synthesis of SPION by thermal decomposition were not effective. HNT–TDP were characterized by infrared spectroscopy (ATR-FTIR), thermogravimetric analysis (TGA), and ζ-potential, and all of the techniques confirmed the presence of TDP onto the HNT. Moreover, the inner localization of TDP was ascertained by the use of Nile Red, a molecule whose luminescence is very sensitive to the polarity of the environment. The free SPION@OA (as a colloidal suspension and as a powder) and SPION-in-HNT powder were magnetically characterized by measuring the ZFC-FC magnetization curves as well as the hysteresis cycles at 300 and 2.5 K, confirming that the super-paramagnetic behavior and the main magnetic properties of the free SPION were preserved once embedded in SPION-in-HNT., SPION nanoparticles are selectively loaded into halloysite lumen, keeping their superparamagnetic character.

[Re3(μ-H)3(μ3-CH3)(CO)9]- (1) reacts with CO at 273 K to quantitatively give the [Re3(μ-H)3(μ-CH3)(CO)10]- derivative (2) through the conversion of the methyl group from triply to doubly-bridging coordination. An NMR isotopic perturbation experiment demonstrates the unsymmetrical bridging of the methyl group on the Re-Re bond, and a fast exchange, in solution, between one agostic and two terminal C H bonds. This is in agreement with X-Ray diffraction analysis performed on single crystals of 2. In solution at room temperature 2 decomposes with CH4 elimination, which is also observed when 2 is treated with CO affording the [Re3(μ-H)2(CO)12]- anion. The opening of the triple bridging methyl coordination in 1 occurs also with other different L ligands, yielding to the syn and anti isomers of unsymmetrically bridged methyl complexes of general formula [Re3(μ-H)3(μ-CH3)(CO)9(L)]- (L = MeCN, PMePh2, THF). The kinetic and thermodynamic stabilities of these isomers vary with the nucleophilicity of the ligand and the polarity of the solvent. In particular, the strong nucleophile PMePh2 affords the quantitative conversion of anion 1 into the thermodynamic syn isomer, which is stable in THF at room temperature for several days. On the contrary, weak nucleophiles, such as MeCN or THF, give equilibrium mixtures containing residual amounts of anion 1. The adducts with MeCN are stable in solution at room temperature for several hours, while decompose fastly in neat MeCN affording mainly the cluster anion [Re3(μ-H)4(CO)9(MeCN)]-. This suggests that cluster stabilization after methane evolution follows a different path with respect to that observed in the reaction of 1 with CO.

Using a rich firm level data set for Turkish manufacturing, we test whether sharing similar religious beliefs with potential contracting parties drives a firm’s first time entry into export markets. We exploit variation in the practice of Islam across Turkish NUTS3 regions and we find that firms located in regions characterised by stronger religiousness are more likely to enter export destinations with a higher share of Muslims among their population. This result is robust to the control for past trade, common language, cultural and migration ties as well as for selective trade policy in favour of politically connected religious business groups. In particular, religious proximity eases export entry for producers of “trust intensive” goods, it favours subsequent foreign market entries and reduces the export exit probability. All in all, our evidence supports an export enhancing effect of religious proximity working through export sunk costs reduction rather than through similarity in preferences.

This study aimed to assess the toxicological consequences related to the interaction of fullerene nanoparticles (C60) and Benzo(α)pyrene (B(α)P) on zebrafish embryos, which were exposed to C60 and B(α)P alone and to C60 doped with B(α)P. The uptake of pollutants into their tissues and intra-cellular localization were investigated by immunofluorescence and electron microscopy. A set of biomarkers of genotoxicity and oxidative stress, as well as functional proteomics analysis were applied to assess the toxic effects due to C60 interaction with B(α)P. The carrier role of C60 for B(α)P was observed, however adsorption on C60 did not affect the accumulation and localization of B(α)P in the embryos. Instead, C60 doped with B(α)P resulted more prone to sedimentation and less bioavailable for the embryos compared to C60 alone. As for toxicity, our results suggested that C60 alone elicited oxidative stress in embryos and a down-regulation of proteins involved in energetic metabolism. The C60 + B(α)P induced cellular response mechanisms similar to B(α)P alone, but generating greater cellular damages in the exposed embryos. Once C60 nanoparticles and B(α)P meet in water, they reciprocally affect their bioavailability and, by consequence, their toxicity to organisms.

Phytosterols are stucturally correlated to the endogenous ligands of Liver X Receptor (LXR), a ligand-activated nuclear receptor that has emerged as an attractive drug target due to its ability to integrate metabolic and inflammatory signaling. Natural and semi-synthetic phytosterol derivatives characterized by the presence of side-chain oxygenated functions have shown to be able to modulate LXR activity. Here, we describe the efficient synthesis of four stigmastane derivatives, endowed with a hydroxyl group at C24 position, namely (24R)- and (24S)-stigmasta-5,28-diene-3β,24-ols (also referred to as saringosterols, 10a and 10b) and (24R)- and (24S)-stigmasta-5-ene-3β,24-ols (11a and 11b), starting from the readily available stigmasterol. Thanks to X-ray crystallography the absolute configuration of the newly created chiral centers was definitively assigned for all the four compounds. The subsequent luciferase assays with GAL-4 chimeric receptors evidenced the ability of the two 24(S)-epimers, 10b and 11b, to interact with LXRs, showing the same degree of affinity as (22R)-hydroxycholesterol (1). With regard to the isoform selectivity both the derivatives 10b and 11b showed a preference for LXRβ, up to 4-fold in terms of efficacy for 11b. The gene expression profiling of (24S)-stigmasta-5,28-diene-3β,24-ol (10a) and (24S)-stigmasta-5-ene-3β,24-ol (11a) demonstrated the capability of both the compounds to induce the expression of four well-known LXR target genes, such as ABCA1, SREBP1c, FASN, and SCD1 in U937 monocytic cell line, thus supporting the hypothesis they were LXR positive modulators.

The acute toxicity of three differently shaped carbon nanomaterials (CNMs) was studied on Daphnia magna, comparing the induced effects and looking for the toxic mechanisms. We used carbon nano-powder (CNP), with almost spherical primary particle morphology, multi-walled carbon nanotubes (CNTs), tubes of multi-graphitic sheets, and cubic-shaped carbon nanoparticles (CNCs), for which no ecotoxicological data are available so far. Daphnids were exposed to six suspensions (1, 2, 5, 10, 20 and 50 mg L−1) of each CNM, and then microscopically analyzed. Ultrastructural analyses evidenced cellular uptake of nanoparticle in CNP and CNT exposed groups, but not in samples exposed to CNCs. Despite this difference, very similar effects were observed in tissues exposed to the three used CNMs: empty spaces between cells, cell detachment from the basal lamina, many lamellar bodies and autophagy vacuoles. These pathological figures were qualitatively similar among the three groups, but they differed in frequency a...

This study focused on the effects of surface coating, acquired through the interaction with natural biomolecules, on the behavior and ecotoxicity of nanoparticles (NPs). To this aim, the effects of Cerium Oxide Nanoparticles (CeO2NPs) naked and coated with chitosan and alginate on the marine mussel Mytilus galloprovincialis were compared. Mussels were exposed for 7 days to 100 μg L−1 of CeO2NPs and for 28 days to 1 μg L−1 of CeO2NPs. In both experiments CeO2NPs were used naked and coated with the two polysaccharides. The lowest tested concentration allowed to understand the environmental relevance of this biological process. A set of biomarkers related to oxidative stress/damage and energy metabolism was applied to assess the ecotoxicity of CeO2NPs. The aggregation and stability in water of CeO2NPs were measured through dynamic light scattering analysis and the levels of Ce in the exposure media and in mussels soft tissues were determined by inductively coupled plasma-mass spectrometry. Results showed a different hydrodynamic behavior and stability of CeO2NPs in saltwater related to the different coatings. Despite this, no differences in the bioaccumulation of CeO2NPs were observed among the experimental groups. Different coatings affected also CeO2NPs toxicological outcomes in both 7- and 28-days exposures. Coating with chitosan enhanced antioxidant enzyme activities while coating with alginate triggered oxidative damage. Although the oxidant pathways did not differ that much among the exposures, biomarkers of energetic supplies suggested a different strategy of defense in response to CeO2NP exposure at a lower concentration and for a longer period of time. The obtained results are in line with findings of a previous study on freshwater mussels, suggesting that the coating with biomolecules, which impart negative charge to the NPs, might enhance their biological effects. This study highlighted that interactions of NPs with natural biomolecules largely present in the aquatic environment could affect NPs toxicity altering the interaction towards organisms.

O estresse visual é definido como uma disfunção do processamento visual, de base neuronal, com um déficit do sistema magnocelular e no córtex visual primário. Ele é caracterizado por distorções visuoperceptuais e desconforto visual progressivo na leitura. O presente estudo verificou a prevalência do estresse visual entre escolares do 3º e 4º ano do ensino fundamental (7 a 10 anos) com dificuldade de leitura, assim como investigou o efeito do uso de lâminas espectrais na habilidade de leitura. Todos os participantes elegíveis (n = 58) apresentavam dificuldade de leitura e adequada acuidade visual binocular. As lâminas espectrais foram selecionadas e distribuídas aos alunos para uso por três meses. A Escala de Percepção Visual de Leitura, o Teste de Taxa de Leitura e o Teste de Leitura - Compreensão e Sentença caracterizaram as condições pré e pós-intervenção. Os resultados indicaram prevalência de 12% de estresse visual (sintomas severos). Após a intervenção, foi verificado que o uso das lâminas espectrais promoveu incremento da compreensão de sentenças e da taxa de leitura. Assim, conclui-se que o estresse visual é uma disfunção muito prevalente entre crianças com dificuldade de leitura e que as lâminas espectrais são um método eficaz de intervenção para reduzir o estresse visual na leitura.

We add to the debate on the determinants of firms' green investment strategies (GIS) by looking at societal stakeholders and explicitly testing the role of local environmental non-profit organizations (ENPOs) in GIS engagement by family and non-family firms. We argue that ENPOs favor GIS engagement only by family firms, which, due to their resource constraints, risk aversion and local embeddedness, are more sensitive to ENPOs normative pressure. We also suggest that the role of ENPOs is especially important for family firms' GIS in those sectors with less stringent regulations, where ENPOs may act as a substitute for the coercive pressure of regulation, and promote firms' self-regulatory behaviors. We test and find support for our arguments on a sample of about 2000 Italian manufacturing firms over the period 2001–2003. Our results are robust to the control of observable omitted variables, reverse causality and to alternative model specifications.

The increasing use of nanomaterials raises several concerns regarding their potential risk for the environment and human health. In particular, the aquatic ecosystems appear highly susceptible. In this context, we investigated the interplay between carbon nanopowder (CNPW) and the common pollutant benzo(α)pyrene (B(α)P) in zebrafish embryos. CNPW was contaminated with B(α)P, and showed significant adsorption towards the hydrocarbon. Embryos were then exposed to CNPW (50 mg L−1) or B(α)P (0.2, 6, 20 μg L−1) alone, or to the CNPW doped with the three B(α)P concentrations. We demonstrated that CNPW helps B(α)P uptake by zebrafish embryos and we also demonstrated that the interaction between CNPW and the hydrocarbon affects the stress response pathways of the organism, so eliciting the toxic effect. In particular, the modulation of genes related to the cellular stress response (cyp1a, hsp70, sod1, sod2) and the measurement of oxidative stress enzyme activities allowed us to identify critical molecular events modulated by the pollutants alone and in co-exposure. Finally, to evaluate the toxic effects due to CNPW interactions with B(α)P, we analyzed biomarkers of cyto-genotoxicity. No significant genotoxicity was induced by B(α)P and CNPW alone, but the co-exposure led to an increase of cytotoxicity, and a higher incidence of necrotic and apoptotic cells. Altogether our data show that nanomaterials, even if they are not toxic per se, could help to enhance the toxicity of common pollutants.

The synthesis of a series of neutral dinuclear rhenium complexes of the general formula [Re2(μ-ER)2(CO)6(μ-pydz)] (pydz = pyridazine; E = S, Se or Te; R = methyl or phenyl; the TeMe is not included) has been carried out via new, either one-pot or two-step, procedures. The one-pot synthesis consists of the oxidative addition of RE–ER across the Re–Re bond of [Re2(CO)10], in the presence of 1 equivalent of pyridazine, and affords the corresponding dinuclear complexes in high yields (ca. 85%). Furthermore, a general two-step procedure has been carried out, which involves the synthesis of heterocubane-like [Re4(μ3-ER)4(CO)12] molecules and their reaction with pyridazine, quantitatively affording the corresponding dinuclear species through a symmetric [2+2] fragmentation pathway. The molecular structure of the complexes has been elucidated by single crystal XRD analysis, and TD-DFT calculations predicted the existence of conformers differing in the orientation of the chalcogen substituents with respect to the pyridazine ligand. The relative stabilities and the activation barriers for the interconversion have been calculated, observing a regular trend that has been rationalized depending on the hybridization of the chalcogen atom. Variable temperature NMR studies experimentally confirmed the theoretical prediction, showing, in solution, two conformers with different relative amounts and different interconversion rates between them, depending on the chalcogen nature. From the electrochemical point of view the S, Se and Te complexes display a bi-electronic reversible oxidation peak, differently from the two mono-electronic irreversible oxidation peaks previously observed for the O derivatives. Moreover, a progressive narrowing of the HOMO–LUMO gap on going from O to Te, arising from the increase of the HOMO level, has been observed. This is in line with the decreasing electron-withdrawing strength of the chalcogenide bridging ligand, so that the energy gap for the telluride derivative is 1.64 eV, the smallest value in the whole family of the di-rhenium pyridazine complexes. The spectroscopic HOMO–LUMO gap parallels this trend, with a significant red-shift of the metal-to-ligand charge transfer absorption, making the telluride complex highly promising as a photosensitizer in the field of solar energy conversion. In agreement with the narrow HOMO–LUMO gap, no photoluminescence has been observed upon optical excitation.

In this work, we report the synthesis of [Ru(phen)3 2+]-based complexes and their use as photosensitizers for photodynamic therapy (PDT), a treatment of pathological conditions based on the photoactivation of bioactive compounds, which are not harmful in the absence of light irradiation. Of these complexes, Ru-PhenISA and Ru-PhenAN are polymer conjugates containing less than 5%, (on a molar basis), photoactive units. Their performance is compared with that of a small [Ru(phen)3 2+] compound, [Ru(phen)2BAP](OTf)2 (BAP = 4-(4′-aminobutyl)-1,10-phenanthroline, OTf = triflate anion), used as a model of the photoactive units. The polymer ligands, PhenISA and PhenAN, are polyamidoamines with different acid-base properties. At physiological pH, the former is zwitterionic, the latter moderately cationic, and both intrinsically cytocompatible. The photophysical characterizations show that the complexation to macromolecules does not hamper the Ru(phen)3 2+ ability to generate toxic singlet oxygen upon irradiation, and phosphorescence lifetimes and quantum yields are similar in all cases. All three compounds are internalized by HeLa cells and can induce cell death upon visible light irradiation. However, their relative PDT efficiency is different: the zwitterionic PhenISA endowed with the Ru-complex lowers the PDT efficiency of the free complex, while conversely, the cationic PhenAN boosts it. Flow cytometry demonstrates that the uptake efficiency of the three agents reflects the observed differences in PDT efficacy. Additionally, intracellular localization studies show that while [Ru(phen)2BAP](OTf)2 remains confined in vesicular structures, Ru-PhenISA localization is hard to determine due to the very low uptake efficiency. Very interestingly, instead, the cationic Ru-PhenAN accumulates inside the nucleus in all treated cells. Overall, the results indicate that the complexation of [Ru(phen)2BAP](OTf)2 with a cationic polyamidoamine to give the Ru-PhenAN complex is an excellent strategy to increase the Ru-complex cell uptake and, additionally, to achieve accumulation at the nuclear level. These unique features together make this compound an excellent photosensitizer with very high PDT efficiency.

Postsynthesis ligand exchange has been employed extensively on lead halide perovskite (LHP) nanocrystals (NCs), but the complex ligand shell composition of the starting NCs prevented a clear understanding of the exchange process, and the surface chemistry of the final NCs remained poorly characterized. Here, we describe a ligand exchange strategy involving the displacement of both cationic and anionic ligands on native model systems of CsPbBr 3 NCs, which are exclusively coated with Cs-oleate. These ligands are exchanged with various quaternary ammonium bromides (R 4 NBr), and complete exchange is confirmed by nuclear magnetic resonance (NMR) spectroscopy analysis. The displacement of the native Cs-oleate ligands with proton-free R 4 NBr delivers NCs with excellent colloidal stability and near-unity PLQY, which is preserved after washing with polar solvents, over 3 weeks of storage in air, and after heating a solution of NCs to 80 °C, as confirmed by NMR analysis. The results, together with density functional theory calculations, suggest that the higher stability of quaternary ammonium capped NCs is not due to a stronger binding interaction to the surface but rather to weaker solvent-ligand interactions of R 4 NBr compared to Cs-oleate, driving the former to the surface of the NCs.

O sistema intrauterino (SIU) é um método contraceptivo eficaz, reversível e muito popular em países emergentes. Entretanto, em alguns casos, podem ocorrer alguns agravantes, como o deslocamento do SIU que é uma rara complicação. A migração do SIU pode causar a perfuração uterina, tanto durante como depois da inserção, que pode ser assintomática ou apresentar sintomas clínicos que variam de sangramento anormal até formação de fístula. Relatamos o caso de uma paciente de 31 anos que possuía SIU e se queixava de dor de intensidade moderada em região hipogástrica. Durante uma histerectomia, foi constatado que o SIU estava em localização extrauterina.

Tumor-derived metabolites dampen tumor-infiltrating immune cells and antitumor immune responses. Among the various metabolites produced by tumors, we recently showed that cholesterol oxidized products, namely oxysterols, favor tumor growth through the inhibition of DC migration toward lymphoid organs and by promoting the recruitment of pro-tumor neutrophils within the tumor microenvironment. Here, we tested different drugs capable of blocking cholesterol/oxysterol formation. In particular, we tested efficacy and safety of different administration schedules, and of immunotherapy-based combination of a class of compounds, namely zaragozic acids, which inhibit cholesterol pathway downstream of mevalonate formation, thus leaving intact the formation of the isoprenoids, which are required for the maturation of proteins involved in the immune cell function. We show that zaragozic acids inhibit the in vivo growth of the RMA lymphoma and the Lewis lung carcinoma (LLC) without inducing side effects. Tumor growth inhibition requires an intact immune system, as immunodeficient tumor-bearing mice do not respond to zaragozic acid treatment. Of note, the effect of zaragozic acids is accompanied by a marked reduction in the LXR target genes Abcg1, Mertk, Scd1 and Srebp-1c in the tumor microenvironment. On the other hand, zoledronate, which blocks also isoprenoid formation, did not control the LLC tumor growth. Finally, we show that zaragozic acids potentiate the antitumor effects of active and adoptive immunotherapy, significantly prolonging the overall survival of tumor-bearing mice treated with the combo zaragozic acids and TAA-loaded DCs. This study identifies zaragozic acids as new antitumor compounds exploitable for the treatment of cancer patients.

The improper release of plastic items and wastes is nowadays one of the main environmental and social problems, whose solution or mitigation represents a great challenge worldwide. In this context, the growing use of the so-called biodegradable plastics could represent a possible solution in the short to medium term. The few information known about the ecological impact of these materials on freshwater organisms, especially the ones relative to the micro-debris derived from their aging, prompted us to study the comparison of the sub-lethal effects eventually caused by plastic and biodegradable plastic micro-debris on the mussel Dreissena polymorpha, which represents an excellent biological model for the freshwater ecosystems. We selected two powders of polyvinylchloride (PVC) and Mater-Bi® administered at 1 mg/L to D. polymorpha specimens in semi-static conditions for 14 days. The presence of micro-debris was evaluated on mussel tissues and pseudo-faeces using advanced microscopy techniques. The sub-lethal effects were investigated on exposed mussels at 6 and 14 days using a suite of biomarkers of cellular stress, oxidative damage, and genotoxicity. Lastly, we compared the ecotoxicity of these two materials integrating each endpoint in the Biomarker Response Index. Microscopy observations highlighted the surprising absence of micro-debris in the gut lumen and tissues of exposed mussels, but the presence of both PVC and Mater-Bi® micro-debris in the pseudo-faeces, suggesting a possible efficient elimination mechanism adopted by mussels to avoid the micro-debris gulping. Consequently, we did not observe significant sub-lethal effects, except for the glutathione-S-transferase activity modulation after 6 days of exposure.

The ongoing development of nanotechnology has raised concerns regarding the potential risk of nanoparticles (NPs) to the environment, particularly aquatic ecosystems. A relevant aspect that drives NP toxicity is represented by the abiotic and biotic processes occurring in natural matrices that modify NP properties, ultimately affecting their interactions with biological targets. Therefore, the objective of this study was to perform an ecotoxicological evaluation of CeO2NPs with different surface modifications representative of NP bio-interactions with molecules naturally occurring in the water environment, to identify the role of biomolecule coatings on nanoceria toxicity to aquatic organisms. Ad hoc synthesis of CeO2NPs with different coating agents, such as Alginate and Chitosan, was performed. The ecotoxicity of the coated CeO2NPs was assessed on the marine bacteria Aliivibrio fischeri, through the Microtox® assay, and with the freshwater crustacean Daphnia magna. Daphnids at the age of 8 days were exposed for 48 h, and several toxicity endpoints were evaluated, from the molecular level to the entire organism. Specifically, we applied a suite of biomarkers of oxidative stress and neurotoxicity and assessed the effects on behaviour through the evaluation of swimming performance. The different coatings affected the hydrodynamic behaviour and colloidal stability of the CeO2NPs in exposure media. In tap water, NPs coated with Chitosan derivative were more stable, while the coating with Alginate enhanced the aggregation and sedimentation rate. The coatings also significantly influenced the toxic effects of CeO2NPs. Specifically, in D. magna the CeO2NPs coated with Alginate triggered oxidative stress, while behavioural assays showed that CeO2NPs coated with Chitosan induced hyperactivity. Our findings emphasize the role of environmental modification in determining the NP effects on aquatic organisms. Interactions with environmental molecules influence the fate and ecotoxicity of NPs.

Dendritic cells (DCs) initiate adaptive immune responses after their migration to secondary lymphoid organs. The LXR ligands/oxysterols and the RXR ligand 9-cis Retinoic Acid (9-cis RA) were shown to dampen DC migration to lymphoid organs through the inhibition of CCR7 expression. We performed transcriptomics of DCs undergoing maturation in the presence of the LXR ligand 22R-Hydroxycholesterol (22R-HC). The analysis highlighted more than 1500 genes modulated by 22R-HC treatment, including the triggering receptor expressed on myeloid cells (TREM)-1, which was found markedly up-regulated. We tested the effect of other nuclear receptor ligands (NRL) and we reported the induction of TREM-1 following RXR, RAR and VDR activation. From a functional point of view, triggering of TREM-1 induced by retinoids increased TNFα and IL-1β release, suggesting an active role of NRL-activated TREM-1(+) DCs in inflammation-driven diseases, including cancer. Consistently with this hypothesis we detected DCs expressing TREM-1 in pleural effusions and ascites of cancer patients, an observation validated by the induction of TREM-1, LXR and RAR target genes when monocyte-DCs were activated in the presence of tumor-conditioned fluids. Finally, we observed a better control of LLC tumor growth in Trem-1(−/-) bone marrow chimera mice as compared to wild type chimera mice. Future studies will be necessary to shed light on the mechanism of TREM-1 induction by distinct NRL, and to characterize the role of TREM-1(+) DCs in tumor growth.

A synthetic strategy was established for decorating and stabilizing superparamagnetic iron oxide nanoparticles (SPIONs) with a zwitterionic linear polyamidoamine (PAA). The strategy was successfully tested with a PAA coded ISA23 previously found endowed with interesting biological properties, such as biocompatibility, degradability in aqueous media and stealth-like properties when injected in test animals. A post-synthetic functionalization with catechol-bearing moieties of a preformed PAA was successfully carried out. ISA23 was obtained by polyaddition reactions of methyl-piperazine and 2,2-bis(acrylamidoacetic) acid. It was functionalized using nitrodopamine and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide as coupling agent, to randomly form amide bonds with 17% of ISA23 carboxylic groups (ISA23-ND). SPIONs were prepared by a thermal decomposition synthesis in 1-octadecene with oleic acid, and then transferred in water by two distinct ligand exchange procedures: i) the direct displacement of oleate molecules from SPION surface by ISA23 in a biphasic (n-hexane/water) environment; ii) the two-step method involving an intermediate small molecule, tetramethylammonium hydroxide, used as a transient transfer agent, which was in turn exchanged with ISA23-ND in a second exchange step occurring in water. The two-step procedure provided a SPION@PAA nanocomposite more stable than that obtained by the one-step procedure in the presence of an applied external magnetic field. ATR-FTIR spectroscopy, ζ-potential and thermogravimetric analysis (TGA) showed the presence of the ISA23 on the SPION surface. In particular, TGA showed that the ISA23-ND amount on the NPs accounted for 26% of the overall nanocomposite mass. The nanocomposite size was determined by both TEM (21.1±2.9 nm) and DLS measurements (hydrodynamic size 100±28 nm). SPION@ISA23-ND were re-suspended after lyophilization reverting to their pristine dimensions. The SPION@ISA23-ND adsorption of BSA in water, considered as the first stage of phagocytosis, was very low, suggesting that ISA23 could impart stealthiness to SPION@ISA23-ND. 1H-NMR relaxivity measurements showed an r2 value of 158 s-1 mmol-1 L (vs 100 s-1 mmol-1L for Endorem®) at relevant clinical fields for magnetic resonance imaging (from 0.2 to 1.5 T). SPION@ISA23-ND was tested on HeLa cells and their internalization was visualized by reflectance microscopy. Finally, with the aim of prepare a new dual magneto-optical system, a synthetic procedure to decorate SPION@ISA23-ND with a fluorescent dye was devised, even though the emission intensity of the resultant conjugate was lower than expected, possibly due to luminescence quenching caused by the closeness of emitting moieties to the SPION surface.

A Síndrome de Meares-Irlen (SMI) é um distúrbio visuoperceptivo decorrente de um déficit no córtex visual primário e/ou na via Magnocelular. A SMI é caracterizada como uma sensibilidade do sistema visual a certos comprimentos de onda espectrais, que podem provocar distorções no processamento pós-retiniano, comprometendo não só a habilidade de leitura e escrita, como a qualidade de vida dos indivíduos. Desta forma, o objetivo desta pesquisa foi identificar, por meio da metodologia desenvolvida por Irlen (1987), o Irlen Reading Perceptual Scale (IRPS), os alunos com SMI em escolas municipais de Alfenas/MG e implementar ações que visem melhorar a leitura e assim a qualidade de vida destas crianças. Das 58 crianças avaliadas ao final do processo de seleção, a maioria apresentou dificuldade moderada (62%) e desconforto leve (43%) para as atividades de leitura. Destas crianças, 42 (72,4%) foram diagnosticadas com SMI moderado a severo, integrando o grupo de intervenção (GI), e as 16 (27,6%) restantes não apresentaram ou relataram sintoma muito leves de SMI, integrando o grupo placebo ativo (GP). As overlays foram selecionadas e distribuídas aos alunos para uso por um período de três meses, ao final do qual as crianças foram reavaliadas. Com base nos resultados obtidos, identificamos uma prevalência da SMI de 18%, com prevalência maior de meninas em nossa amostra. A pesquisa também mostrou um claro benefício do uso das overlays nas crianças do grupo GI, as quais apresentaram média de desempenho maior do que 10% na velocidade de leitura. Dentre as crianças com dificuldade de leitura, 17,2% aumentaram a velocidade de leitura em mais de 15%. Interessantemente, este efeito benéfico não foi observado no grupo GP, indicando a alta especificidade do diagnóstico e da intervenção proposta. Assim, nosso estudo confirma o uso das overlays como método de intervenção de alta eficiência, baixo custo e simples manejo para tratamento da SMI. Contribuiu-se para a difusão do conhecimento sobre esta síndrome entre pais, profissionais de saúde e de educação, além de resgatar a autoestima e valorizar a capacidade de aprendizado das crianças diagnosticadas com SMI. Meares-Irlen Syndrome (MIS) is a visuoperceptive disorder due to a deficit in the primary visual cortex and / or the Magnocellular pathway. The MIS is characterized as a sensitivity of the visual system to certain spectral wavelengths, which can cause distortions in the postretinal processing, compromising not only the ability to read and write, but also the quality of life of individuals. The objective of this research was to identify, through the methodology developed by Irlen (1987), the Irlen Reading Perceptual Scale (IRPS), students with SMI in municipal schools of Alfenas / MG and implement actions aimed at improving reading and the quality of life of these children. Of the 58 children evaluated at the end of the selection process, the majority presented moderate difficulty (62%) and mild discomfort (43%) for reading activities. Of these children, 42 (72.4%) were diagnosed with moderate to severe MCH, and the remaining 16 (27.6%) did not present or reported a very mild MCH symptom, integrating the intervention group placebo (GP). Overlays were selected and distributed to students for use for a period of three months, at the end of which the children were reevaluated. Based on the results, we identified a prevalence of MIS of 18%, with a higher prevalence of girls in our sample. The research also showed a clear benefit of the use of overlays in the children of the GI group, who presented a performance average greater than 10% in reading speed. Among children with reading difficulties, 17.2% increased reading speed by more than 15%. Interestingly, this beneficial effect was not observed in the GP group, indicating the high specificity of the diagnosis and the proposed intervention. Thus, our study confirms the use of overlays as an intervention method of high efficiency, low cost and simple management for MIS treatment. It contributed to the diffusion of knowledge about this syndrome among parents, health professionals and education, as well as to rescue the selfesteem and to value the learning capacity of the children diagnosed with MIS.