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International audience; Reaching the corneal endothelium through the topical administration of therapeutic drugs remains a challenge in ophthalmology. Besides, endothelial cells are not able to regenerate, and diseases at this site can lead to corneal blindness. Targeting the corneal endothelium implies efficient penetration through the three corneal layers, which still remains difficult for small molecules. Carbon quantum dots (CQDs) have demonstrated great potential for ocular nanomedicine. This study focuses on the corneal penetration abilities of differently charged CQDs and their use as permeation enhancers for drugs. Excised whole bovine eyes were used as an ex vivo model to investigate corneal penetration of CQDs derived from glucosamine using β-alanine, ethylenediamine, or spermidine as a passivation agent. It was found that negatively charged CQDs have limited corneal penetration ability, while positively charged CQDs derived from glucosamine hydrochloride and spermidine (CQD-S) penetrate the entire corneal epithelium all the way down to the endothelium. CQD-S were shown to enhance the penetration of FITC-dextran 150 kDa, suggesting that they could be used as efficient penetration enhancers for therapeutic delivery to the corneal endothelium.

International audience; Rationally designed structures and elements are important for the construction of effective electrocatalysts for water splitting. Herein, we developed an ultrathin hierarchical P-doped MoS2/Ni3S2 heterostructure on nickel foam (NF) by a one-pot synthesis. Owing to its optimized electronic structure configuration and hierarchical structure with plenty of active sites, the optimized catalyst P1.0-doped MoS2/Ni3S2/NF showed promising activity for both hydrogen evolution reaction and oxygen evolution reaction in an alkaline medium requiring an overpotential of, respectively, 0.449 and 0.239 V at 100 mA cm–2. Furthermore, the P1.0–MoS2/Ni3S2/NF electrode was applied for overall water splitting using a two-electrode system. The electrolyzer achieved low cell voltages of 1.50 and 1.65 V at current densities of, respectively, 20 and 40 mA cm–2 with excellent stability over 60 h when compared with previously reported Ni3S2-based materials. The results obtained in this work highlight the prime combination of doping and interface engineering for the design of advanced materials in electrocatalysis.

International audience; This work describes the preparation of ternary bismuth ferrite oxide nanoparticles (Bi2Fe4O9 NPs) with an enzyme mimetic activity for dopamine (DA) qualitative and quantitative detection. Bi2Fe4O9 NPs were prepared using a facile, low cost, and one-pot hydrothermal treatment. The chemical composition, morphology, and optical properties of Bi2Fe4O9 nanozyme were characterized using different techniques such as Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction pattern (XRD), X-ray photoelectron spectroscopy (XPS), thermo-gravimetric analysis (TGA), dynamic light scattering (DLS), field-emission scanning electron microscopy (FESEM) imaging, FESEM-energy dispersive X-ray spectroscopy (EDS), UV–vis absorption, and fluorescence emission spectroscopy. Bi2Fe4O9 NPs were utilized to catalyze the oxidation of a typical chromogenic peroxidase substrate, 3,3′,5,5′-tetramethylbenzidine (TMB), to form the blue-colored oxidized product (oxTMB), in the presence of hydrogen peroxide (H2O2). All reactions occurred in acetate buffer solution (pH 3.5) to generate hydroxyl radicals (•OH) and the kinetics were followed by UV–vis absorbance at 654 nm. The steady-state kinetic parameters were obtained from the Michaelis-Menten equation and exhibited a good catalytic efficiency of Bi2Fe4O9 NPs as enzyme mimetics. Michaelis–Menten constant (Km) values were estimated as 0.07 and 0.73 mM for TMB and H2O2, respectively. The presented method is efficient, rapid, cost-effective, and sensitive for the colorimetric detection of dopamine with a linear range (LR) from 0.15 to 50 μM and a detection limit (LOD) of 51 nM. The proposed colorimetric sensor was successfully applied for the detection of different concentrations of dopamine in spiked fetal bovine serum (FBS) and horse serum (HS) samples. It is anticipated that Bi2Fe4O9 nanozyme holds great potential in biomedical analysis and diagnostic applications of dopamine-related diseases.

International audience; Over the last years, we observed a significant increase in the number of published studies that focus on the synthesis and characterization of deep eutectic solvents (DESs). These materials are of particular interest mainly due to their physical and chemical stability, low vapor pressure, ease of synthesis, and the possibility of tailoring their properties through dilution or change of the ratio of parent substances (PS). DESs, considered as one of the greenest families of solvents, are used in many fields, such as organic synthesis, (bio)catalysis, electrochemistry, and (bio)medicine. DESs applications have already been reported in various review articles. However, these reports mainly described these components’ basics and general properties without focusing on the particular, PS-wise, group of DESs. Many DESs investigated for potential (bio)medical applications comprise organic acids. However, due to the different aims of the reported studies, many of these substances have not yet been investigated thoroughly, which makes it challenging for the field to move forward. Herein, we propose distinguishing DESs comprising organic acids (OA-DESs) as a specific group derived from natural deep eutectic solvents (NADESs). This review aims to highlight and compare the applications of OA-DESs as antimicrobial agents and drug delivery enhancers—two essential fields in (bio)medical studies where DESs have already been implemented and proven their potential. From the survey of the literature data, it is evident that OA-DESs represent an excellent type of DESs for specific biomedical applications, owing to their negligible cytotoxicity, fulfilling the rules of green chemistry and being generally effective as drug delivery enhancers and antimicrobial agents. The main focus is on the most intriguing examples and (where possible) application-based comparison of particular groups of OA-DESs. This should highlight the importance of OA-DESs and give valuable clues on the direction the field can take.

International audience; The development of high-performance and cost-effective hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) electrocatalysts is highly required for electrochemical water splitting. The sluggish reaction kinetics, poor stability, and complicated processing restrict the practical application of most electrocatalysts. Herein, we report a facile oxygen corrosion strategy for the fabrication of Pt nanoparticles loaded on cobalt-iron layer double hydroxide (Pt-Co/Fe LDH) on iron foam using an oxygen corrosion method regulated by sodium chloride (NaCl). The as-prepared Pt-Co/Fe LDH electrodes feature overpotentials as low as 126 and 285 mV to deliver 100 mA cm–2 for HER and OER, respectively. Moreover, the Pt-Co/Fe LDH was applied as anode and cathode in an electrochemical electrolyzer and recorded a current density of 50 mA cm–2 at a small voltage of 1.66 V, which is superior to that of the Pt/C-FF || RuO2-FF system (1.89 V) and those of most previously reported electrocatalysts. The excellent electrocatalytic activity of Pt-Co/Fe LDH could be assigned to its specific structure, consisting of three-dimensional (3D) nanoflower-shaped nanosheets, favorable for promoting fast mass transport and ion diffusion and generating more active sites for the OER process. In addition, the synergistic effect between Pt and the Co/Fe LDH heterojunction structure effectively improves the electronic conductivity and H adsorption for HER performance. The oxygen corrosion method regulated by NaCl and interface engineering of the LDH structure is simple to implement and can be easily extended for the preparation of a plethora of other bifunctional and cost-effective electrocatalysts for various electrochemical processes.

International audience; This report describes, for the first time, the coupling of UV–visible spectroscopy with multivariate curve resolution-alternative least-squares (MCR-ALS) algorithm to study peroxidase-like catalytic reaction of polyethylene glycol-functionalized poly (N-phenyl glycine) (PNPG-PEG) as an efficient and intrinsic peroxidase mimic activity (PMA) class of conducting organic polymer for selective detection of dopamine (DA) in the PNPG-PEG + TMB + H2O2 reaction system. PNPG-PEG was produced by means of a chemical route using ammonium persulphate (APS) as an oxidant agent of N-phenyl glycine monomer. The chemical composition, morphology, and thermal behavior of PNPG-PEG were examined by various instrumental techniques. PNPG-PEG exhibited significant peroxidase-mimic activity to catalyze the oxidation 3,3′,5,5′- tetramethylbenzidine (TMB) substrate to oxidized TMB (oxTMB). The qualitative and quantitative determination of the oxidized TMB can easily be detected by the naked-eye and the recorded UV–vis absorbance spectra at 652 nm, respectively. Owing to the superior peroxidase-mimic activity of PNPG-PEG, the colorimetric detection of dopamine was successfully achieved at pH 4.0. Under optimal conditions, acceptable linear dependency was recorded in the concentration range of 5.1–125.0 μM, with a limit of detection (LOD) and limit of quantification (LOQ) equal to 4.6 μM and 13.8 μM (S/N = 3), respectively. Furthermore, this colorimetric assay was successfully used for quantitative analysis of dopamine in fetal bovine serum (FBS) and horse serum (HS) samples with recoveries in the range of 97–105% and 100–122%, respectively. After resolving the bilinear data matrix using MCR-ALS, three chemical components were found for different concentrations and pure spectral profiles. Based on the resolved profiles, the presence of free, slightly penetrated, and majorly penetrated TMB molecules entering the polymeric structure can be easily detected using MCR-ALS as an available statical method without any complex separation instruments. This peroxidase mimetic nanozyme as a visual, simple, low-cost, sensitive, and reproducible colorimetric platform can provide great potential applications in the monitoring and diagnosis of dopamine-related diseases.

Num período onde a transição digital é evidente em várias áreas do conhecimento, é imprescindível que o ensino acompanhe esta evolução e que implemente, num ambiente controlado, as ferramentas tecnológicas que contribuam para aumentar o interesse dos alunos e também a consolidação das suas aprendizagens. Uma dessas ferramentas é justamente a gamificação. A implementação de gamificação em sala de aula encontra-se numa fase de pleno desenvolvimento, mas é alvo de muita resistência devido ao seu carácter lúdico e por vezes exigente a nível técnico. No entanto, são vários os exemplos onde o seu uso resulta num maior interesse e motivação por parte dos alunos. Apesar de existirem exemplos de aplicabilidade, especialmente no caso da matemática, são ainda raros ou pouco estruturados os exemplos na disciplina de geografia. Este trabalho, através da metodologia adotada na Prática de Ensino Supervisionada pretende demonstrar que a implementação de jogos digitais pode constituir um recurso útil na aprendizagem dos alunos e na sua motivação, através de uma solução harmoniosa enquadrando a componente didática com os conteúdos programáticos. Para além do desenvolvimento de jogos, foi implementado um questionário aos alunos onde eram encorajados a avaliar e a providenciar feedback quanto à utilização de gamificação ao longo do ano letivo como também a sugerir metodologias e aplicações passíveis de serem aplicadas. In a period where the digital transition is clear in several areas of knowledge, it is essential that teaching keeps up with this evolution and implements, in a controlled environment, technological tools that contribute to increase student interest and the consolidation of their learning. One of these tools is precisely gamification. The implementation of gamification in the classroom is in a stage of full development but is subject to much resistance due to its playful and sometimes technically demanding nature. However, there are several examples where its use results in increased student interest and motivation. Although there are examples of applicability, especially in the case of mathematics, examples in geography are still rare or poorly structured. This work, through the methodology adopted in the Supervised Teaching Practice, aims to demonstrate that the implementation of digital games can be a useful resource in student learning and motivation, through a harmonious solution framing the didactic component with the syllabus. In addition to the development of games, a questionnaire was given to students to encourage them to evaluate and provide feedback on the use of gamification throughout the school year, and to suggest methodologies and applications that could be applied.

International audience; Pancreatic islet amyloid deposition is a pathological hallmark of Type 2 diabetes (T2D), contributing to reduced functional β-cell mass. Islet amyloids result not only from the aggregation and fibrillation of human islet amyloid polypeptide (hIAPP), but also from beta-amyloid 42 (Aβ42), the key amyloidogenic peptide linked to Alzheimer's disease. Importantly, Aβ42 and hIAPP aggregates (IAPP:Aβ42) can interact with each other and form some harmful heterocomplex fibrils. While it is well-documented that hIAPP aggregation occurs only when islets are exposed to a diabetic environment, including hyperglycemia and/or elevated concentrations of saturated fatty acids (SFAs), it remains unclear if hIAPP and IAPP:Aβ42 heteromer fibrillations are directly or indirectly triggered by this environment. In this study, we show the interplay between high glucose concentrations and palmitate as the SFA in the aggregation of hIAPP. In addition, we outline that the interaction of hIAPP and Aβ42 leads to the formation of complex protein aggregates, which are toxic to β-cells. Carbon nanocolloids in the form of positively charged carbon quantum dots (CQD-pos) efficiently prevent single amyloid aggregation and the formation of IAPP:Aβ42 heterocomplexes. We provide clear evidence with this study that the diabetogenic environment of islets could directly contribute to the formation of homomeric and heteromeric amyloid aggregates and fibrils in T2D. We also propose carbon nanocolloids as biocompatible nanomaterials for developing innovative therapeutic strategies that prevent the decline of functional β-cell mass.

International audience; DNA-based aptamers are widely employed as bioreceptors, owing to their tuneable affinity and specificity towards their targets. The use of peptide nucleic acids (PNAs) has instead proven challenging for this purpose, due to the absence of selection methods for the independent discovery of suitable receptors and due to the difficult mimicry of established DNA-based ones. Despite that PNAs exceed homologous DNA or RNA in terms of complementary base pairing, they can fail to reproduce alternative modes of binding because of their different structural features. The remarkable stability and charge distribution of PNAs could be beneficial to produce sensing bioreceptors, especially in the development of electronic devices such as field-effect transistor-based (FET) biosensors. We hereby report for the first time a high-affinity PNA aptamer for cardiac Troponin I (cTnI), a biomarker of acute myocardial infarction, able to interact with this specific protein in the picomolar range. The PNA aptamer was immobilized onto a graphene-based FET (gFET) transducer, and its ability in the direct detection of cTnI was compared with that of a DNA-based one of the same sequence. Similar dissociation constants were recorded for both receptors in 0.01 × PBS, as well as comparable detection limits of 6.0 ± 1.0 pg mL-1 (PNA aptamer) and 3.3 ± 0.7 pg mL-1 (DNA aptamer). Apart from the non-trivial demonstration that a PNA can behave as an aptamer, the tested receptor proved to be more consistent upon working in more complex biological matrices.

International audience; In the fight against prostate cancer (PCa), TRPM8 is one of the most promising clinical targets. Indeed, several studies have highlighted that TRPM8 involvement is key in PCa progression because of its impact on cell proliferation, viability, and migration. However, data from the literature are somewhat contradictory regarding the precise role of TRPM8 in prostatic carcinogenesis and are mostly based on in vitro studies. The purpose of this study was to clarify the role played by TRPM8 in PCa progression. We used a prostate orthotopic xenograft mouse model to show that TRPM8 overexpression dramatically limited tumor growth and metastasis dissemination in vivo. Mechanistically, our in vitro data revealed that TRPM8 inhibited tumor growth by affecting the cell proliferation and clonogenic properties of PCa cells. Moreover, TRPM8 impacted metastatic dissemination mainly by impairing cytoskeleton dynamics and focal adhesion formation through the inhibition of the Cdc42, Rac1, ERK, and FAK pathways. Lastly, we proved the in vivo efficiency of a new tool based on lipid nanocapsules containing WS12 in limiting the TRPM8–positive cells’ dissemination at metastatic sites. Our work strongly supports the protective role of TRPM8 on PCa progression, providing new insights into the potential application of TRPM8 as a therapeutic target in PCa treatment.

International audience; Cardiovascular diseases result in millions of deaths around the globe, many of which could have been avoided if identified at an early stage. Preventive cardiovascular disease diagnostics plays a vital role reducing the critical fatality rate by allowing to take timely necessary precautions. Here, we demonstrate the exceptional properties of aptamer modified graphenebased FET (GFET) for cardiac troponin I (cTnI) specific sensing in different bodily fluids. Concentration-dependent measurements made with cardiac troponin I (cTnI) on an aptamer/polyethylene glycol (PEG) modified GFET exhibited real-time detection of cTnI from 1-400 pg mL-1 in 0.01× phosphate-buffered saline (PBS) solution. The sensor performance is within the clinical important window of 10 pg mL-1 to 500 pg mL-1 , allowing the differentiation between healthy, and people with low and high risk for myocardial infraction (AMI). Even more important is the very reproducible shift and neglectable leakage current of the individual IDSVGS-curves upon contact with cTnI solutions. To further evaluate the applicability of the developed point of care device for troponin I sensing in serum, samples of 15 patients with different troponin levels were analysed for their troponin I levels. The 15 patients were grouped

International audience; In this work, we report on enhanced adsorption of anionic dyes, Reactive blue 49 (RB 49) and Direct Blue 199 (DB 199), using a phytic acid-doped poly-N-phenylglycine@potato peel (PA-PPG@PP) nanocomposite material. The PA-PPG@PP was prepared using a radical polymerization process by varying the amount of potato peel powder (PP) in the composite material. The surface structure and composition were examined by zeta potential, scanning electron microscopy (SEM), Fourier-transform infrared (FTIR), Raman spectroscopy, X-ray photoelectron spectroscopy (XPS) and Brunauer–Emmett–Teller (BET) analysis. The influence of different operating conditions such as adsorbent dose, initial dye concentration, contact time, pH and ionic strength on the removal efficiency of PA-PPG@PP2 was assessed to achieve the optimum conditions for RB 49 dye adsorption. Adsorption equilibrium data were well-described by the Langmuir model and the maximum adsorption capacities of PA-PPG@PP2 for RB 49 and DB 199 at 298 K and pH = 6.5 were 216 and 1148 mg g−1, respectively. The maximum adsorption capacity of RB 49 dye on the PA-PPG@PP2 surface was achieved at 318 K (285 mg g−1). The adsorption process was described by the pseudo-second-order kinetics model (R2 > 0.999). The thermodynamic study proved that the adsorption processes were endothermic and favorable. The dye molecules were adsorbed on the composite material surface mainly through hydrophobic and electrostatic interactions, as well as hydrogen bonding. Additionally, our experimental results suggested that the hydrophobic interactions increased upon increasing ionic strength, while the electrostatic interactions decreased upon elevating the ionic strength of the solution. The findings in this work revealed the potential of biomass powder, potato peels, in adsorption processes upon hybridization with a biocompatible organic polymer, poly-N-phenylglycine.

International audience; This study investigated, for the first time, the antimicrobial properties of polyethylene glycol-functionalized poly(N-phenylglycine) nanoparticles (PNPG-PEG NPs). PNPG-PEG NPs exhibit high extinction coefficient in the near-infrared (NIR) region; they can convert light energy into heat energy with high thermal transformation efficiency. Additionally, they can generate cytotoxic reactive oxygen species (ROS) upon light irradiation. Also, PNPG-PEG NPs are not cytotoxic. All these properties make them appropriate for combined dual-modal photothermal and photodynamic therapies. The antibacterial activity of PNPG-PEG NPs was assessed using Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) pathogenic strains. The results revealed that NIR light (810 nm) irradiation for 10 min could kill effectively the planktonic bacteria and destroy Escherichia coli and Staphylococcus aureus biofilms. The results demonstrated that PNPG-PEG NPs represent a very effective nanoplatform for killing of pathogenic bacteria.

Electrospun fiber mats loaded with therapeutics have gained considerable attention as a versatile tool in the biomedical field. While these bandages are largely based on fast-dissolving polymers to release the cargo, stimuli-responsive fiber mats have the advantages of providing a timely and spatially controlled drug delivery platform, which can be refilled and reused several times. These benefits make electrospun fiber patches original platforms for painless and convenient on-demand hormone release. Because of the high need of more convenient and non-invasive methods for delivering insulin, a hormone that is currently used to treat hundred million people with diabetes worldwide, we have investigated the tremendous potential of reduced graphene oxide modified poly(acrylic acid) based fiber mats as an original platform for buccal and corneal insulin delivery on-demand. The PAA@rGO hydrogel-like fibers rendered water-insoluble by incorporating β-cyclodextrin, followed by thermal cross-linking, which showed adequate tensile strength along with high adsorption capacity of insulin at pH 7 and good recyclability. The fiber mats maintained good fibrous morphology and high loading efficiency even after five loading-release cycles. The mucoadhesive nature of the fibers allowed their application for insulin delivery via the eye cornea and the buccal mouth lining, as evidenced in ex vivo studies. Insulin loaded PAA@rGO hydrogel-like fibers showed an insulin flux via buccal lining of pigs of 16.6 ± 2.9 μg cm-2 h-1 and 24.3 ± 3.1 μg cm-2 h-1 for porcine cornea. Testing on healthy adult volunteers confirmed the excellent, mucoadhesive nature of the bandage, with three out of six volunteers feeling completely comfortable (note 8.3) while wearing the patches in the buccal cavity., The Centre National de la Recherche Scientifique (CNRS), the University of Lille, the Hauts-de-France region, and the CPER “Photonics for Society” are acknowledged for financial support. This work was partly supported by the French Renatech network. A.V. thanks the i-SITE foundation of the University of Lille for a PhD fellowship. This project has received funding from the European Union’s Horizon 2020 Research and Innovation Staff Exchange (RISE) Marie Skłodowska-Curie Actions under grant agreement No 690836.