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Epidermal integrin α3β1 is a regulator of the macrophage stimulating factor, CSF-1, and of crosstalk from keratinocytes to macrophages during cutaneous wound healing
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The development of integrin-targeted wound therapy is hindered by incomplete understanding of integrin function in cutaneous wound healing and the wound microenvironment. Following cutaneous injury, keratinocytes migrate to restore the skin barrier, and macrophages aid in debris clearance. Thus, both keratinocytes and macrophages are critical to the coordination of tissue repair. Keratinocyte integrins have been shown to participate in this coordinated effort by regulating secreted factors, some of which crosstalk to distinct cells in the wound microenvironment. Our earlier findings have identified integrin α3β1 as a key regulator of the keratinocyte secretome and of the skin tumor microenvironment. Previous mass spectrometric analysis of conditioned medium from immortalized keratinocytes indicated that α3β1 positively regulates colony-stimulating factor 1 (CSF-1), a secreted cytokine that is a primary regulator of macrophage differentiation, proliferation, and survival. In our current work, we use an in vivo murine model to show that cutaneous wounds deficient in epidermal integrin α3β1 express less epidermal-derived CSF-1. α3β1-deficient wounds also have fewer wound-proximal macrophages, suggesting that keratinocyte α3β1 may stimulate wound macrophages through the regulation of CSF-1. Indeed, using a panel of immortalized keratinocytes, we demonstrate that keratinocyte-derived CSF-1 supports macrophage growth, and that α3β1 regulates Csf1 expression through YAP-TEAD-mediated transcription. Consistently, α3β1-deficient wounds in vivo display a substantially reduced number of keratinocytes with YAP-positive nuclei. Overall, our findings identify a novel role for epidermal integrin α3β1 in regulating the cutaneous wound microenvironment by mediating paracrine crosstalk from keratinocytes to wound macrophages, implicating α3β1 as a potential target of wound therapy.

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Exploring the Influence of V2O5 Content on the Mechanism of Electrical Transport in the Na2O-V2O5-Nb2O5-P2O5 Glass System: A Perspective through Model-Free Scaling Procedures

Sodium-vanadium-phosphate-based materials have garnered significant interest as cathodes for high-rate sodium-ion batteries, owing to their stable framework, minimal volume change, thermodynamic stability, and excellent sodium storage capacity with fast ion transport kinetics1. Furthermore, as these materials consist of both alkali and transition metal (TM) ions, which can exist in various oxidation states (V4+, V5+), these systems can exhibit the mixed ionic-polaronic conduction mechanism. Such feature has proven to be highly effective in facilitating the intercalation and deintercalation of alkali ions2. Another crucial property of cathode materials is thermal stability which can be significantly enhanced by incorporating metal oxides such as Nb2O53. Based on this premise, the current study focuses on investigating the electrical properties of glasses within the Na2O-V2O5-Nb2O5-P2O5 system. The P2O5 component is gradually replaced by Nb2O5 while maintaining constant Na2O and V2O5 content. By varying the concentration of V2O5 (10 and 25 mol%), the influence of its content on the electrical transport mechanism is examined, enabling the evaluation of its possible polaronic contribution. Solid-state impedance spectroscopy (SS-IS) is employed to examine electrical transport across a wide frequency (0.01 Hz to 1 MHz) and temperature (–90 °C to 240 °C) range and the conductivity spectra are studied in detail using two model-free scaling procedures, namely Summerfield and Sidebottom scaling. The successful construction of conductivity master curves for all glasses with lower V2O5 content (10 mol%) validates the time-temperature superposition (TTS) and confirms a purely ionic conduction mechanism, indicating that V2O5 does not contribute to electrical conductivity via a polaronic mechanism. However, master curves cannot be obtained for glasses with higher V2O5 (25 mol%) and low Nb2O5 content (0 and 5 mol%), suggesting the presence of mixed ionic-polaronic conductivity with a dominant polaronic contribution. Furthermore, with the addition of Nb2O5 above 10 mol%, the ionic conductivity mechanism prevails. The findings of this study provide valuable insights into the mixed-conductive glass system and role of V2O5 and/or Nb2O5, and demonstrate the ability to tune the mechanism of electrical conductivity by adjusting the content of oxide glass and its ratio.

ACKNOWLEDGMENTS
This work is supported by the CSF under the projects IP-2018-01-5425 and DOK-2021-02-9665.

1. Wang, C. et al. A multiphase sodium vanadium phosphate cathode material for high-rate sodium-ion batteries. J. Mater. Sci. Technol. 66, 121–127 (2021).
2. Wang, C. & Hong, J. Ionic/electronic conducting characteristics of LiFePO4 cathode materials. Electrochem. Solid-State Lett. 10, A65 (2007).
3. Getachew, B., Ramesh, K. P. & Honnavar, G. V. Nickel ferrite doped lithium substituted zinc and niobo vanadate glasses: thermal, physical, and electrical characterization. Mater. Res. Express 7, 095202 (2020).

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    Anti-mycotoxigenic efficacy of redox-active natural compounds and derivatives
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    Contamination of the food supply by natural sources such as mycotoxins is problematic, with outbreaks of commodity-specific food products directly affecting the public health. This study addresses developing control measures to reduce or eliminate mycotoxin contamination by Aspergillus species by using natural products or their structural derivatives. The natural, redox‐active chemicals, such as benzoic compounds, can be potent redox cyclers that inhibit normal fungal physiology by disrupting cellular redox homeostasis, thus interfere with mycotoxin biosynthesis. Thirteen compounds, generally recognized as safe, were examined at concentrations maintaining fungal growth but inhibiting mycotoxin production in Aspergillus flavus and Aspergillus parasiticus. Our data indicated that 4-isopropyl-3-methylphenol, structural analog of the natural compound thymol, exhibited a potent anti-mycotoxigenic activity while salicylic acid was less effective. Structure-activity relationship existed for the differential efficacy of test compounds on the inhibition of mycotoxin production. We concluded that selected natural products can be used for preventing mycotoxin contamination, which could be applicable to safe production of foods.

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    First-principles study on optoelectronic properties for caswellsilverite mixed metal oxide MgZnO
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    In this work, we investigated the optoelectronic properties of MgZnO using density functional theory based on linear augmented plane wave (FP-LAPW) method. To deal with the exchange-correlation potential for total energy calculations, the LDA and GGA approximations were used. In addition, the modified Becke Johnson (TB-mBJ) approach, which successfully corrects the band gap problem, was used for the band structure calculations. The calculated lattice constants and band gap values for this compound are in good agreement with available theoretical data. As well as the dielectric function and the absorption coefficient are calculated to get the optical parameters. The achieved results indicate that this material is particularly interesting for photovoltaic conversion applications.

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    Incorporation of Actinidia arguta extract in mucoadhesive films – A new oral mucositis prevention/treatment approach

    Actinidia arguta is a perennial vine that mostly grows in Asian countries, being described as a traditional herbal medicine in Korea [1]. The fruit, commonly known as kiwiberry, has been associated with different therapeutic properties and pro-healthy benefits for consumers, particularly antioxidant, anti-inflammatory and anticancer effects [2-4]. These bioactive properties are due to the outstanding content in phenolic compounds, vitamins, and organic acids [4], which attracted the researcher’s attention for potential application in nutraceutical and pharmaceutical industries. This is the case of oral mucositis (OM), a common side effect of cancer treatments that causes oral inflammation and pain [5]. OM can take advantageous of these natural bioactive compounds to alleviate symptoms and promote healing [6, 7]. Therefore, the aim of this work is to formulate mucoadhesive films to prevent/treat OM symptoms through incorporation of A. arguta extract. The films were prepared by solvent casting method employing 1% of HPMC K100 LV EP solution with 2.5% glycerin, and A. arguta extract as solvent. Different parameters were assessed on films, namely physical features (weight: 194.8 mg; thickness: 0.37 mm; disintegration time: 15.05 min; superficial pH: 4.20; moisture content: 10.53%; swelling capacity: 55.95 %) as well as mechanical properties (resistance to extension: 10.11 N; percent elongation: 33.64%; Young’s modulus: 0.0034 MPa). The in vitro cell assays revealed that films did not affect the viability of HSC-3 and TR146 oral cell lines. Additionally, the compounds release profile is being performed by in vitro and ex vivo permeation assays coupled to LC-MS quantification.

    Acknowledgments:
    This work received financial support from project EXPL/BAA-GR/0663/2021 – Kiwi4Health – Exploring the Eco-Innovative Re-Use of Kiwiberry, supported by national funds by FCT/MCTES and by the projects UIDB/50006/2020 and UIDP/50006/2020 through national funds. This work was also financed by national funds from FCT - Fundação para a Ciência e a Tecnologia, I.P., in the scope of the project UIDP/04378/2020, UIDB/04378/2020 and the project LA/P/0140/2020.Filipa Teixeira is thankful for the scholarship from project EXPL/BAA-GR/0663/2021. Ana Margarida Silva is thankful for the Ph.D. grant (SFRH/BD/144994/2019) financed by POPH-QREN and subsidized by the European Science Foundation and Ministério da Ciência, Tecnologia e Ensino Superior. Francisca Rodrigues (CEECIND/01886/2020) is thankful for contract financed by FCT/MCTES—CEEC Individual Program Contract.

    References:
    [1] Kwon, D., et al., Pinoresinol diglucoside is screened as a putative α-glucosidase inhibiting compound in Actinidia arguta leaves. Journal of the Korean Society for Applied Biological Chemistry, 2014. 57(4): p. 473-479.
    [2] Silva, A.M., et al., Influence of temperature on the subcritical water extraction of Actinidia arguta leaves: A screening of pro-healthy compounds. Sustainable Chemistry and Pharmacy, 2022. 25: p. 100593.
    [3] Zhang, J., et al., Phenolics Profile and Antioxidant Activity Analysis of Kiwi Berry (Actinidia arguta) Flesh and Peel Extracts From Four Regions in China. Frontiers in Plant Science, 2021. 12.
    [4] Macedo, C., et al., Insights into the polyphenols extraction from Actinidia arguta fruit (kiwiberry): A source of pro-healthy compounds. Scientia Horticulturae, 2023. 313: p. 111910.
    [5] Ferreira, A.S., et al., Natural Products for the Prevention and Treatment of Oral Mucositis—A Review. International Journal of Molecular Sciences, 2022. 23(8): p. 4385.
    [6] Landová, H., et al., Evaluation of the Influence of Formulation and Process Variables on Mechanical Properties of Oral Mucoadhesive Films Using Multivariate Data Analysis. BioMed Research International, 2014. 2014: p. 179568.
    [7] Nair, A.B., et al., In vitro techniques to evaluate buccal films. Journal of Controlled Release, 2013. 166(1): p. 10-21.

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    Assessment of nutraceutical potential of a chestnut by-product towards circular economy – In-vitro versus in-vivo studies

    The increasing demand for nutraceuticals has pressured the industry to seek new pro-healthy compounds. Agro-industrial residues generated across the food supply chain have been explored as sources of added-value molecules, reducing their environmental impacts, and creating additional economic revenue towards the implementation of circular economy [1]. Chestnut (Castanea sativa) shells (CS) are an exceptional source of antioxidants [2,3]. Although the European legislation on nutraceuticals’ validation remains vague, an in-depth assessment of in-vitro and in-vivo bioactivity should be accomplished, with metabolomics arising as a valuable tool. This study explores the nutraceutical potential of CS extract prepared by Subcritical Water Extraction (SWE) after in-vitro simulated digestion and in-vivo bioavailability assays on rats (50 and 100 mg/kg body weight, per os administered once daily for 7 days) using metabolomic techniques by LC-ESI-LTQ-Orbitrap-MS and LC/DAD-ESI-MS. Antioxidant activity was evaluated by spectrophotometric assays, while hypoglycemic and neuroprotective properties were assessed using commercial kits. The extract optimization and safety on intestinal cells were attested in our previous work [2]. The relationship between metabolomic fingerprinting and potential oxidative stress biomarkers was ascertained by multivariate analysis.

    The results unveiled higher phenolic concentrations retained after intestinal digestion, reaching 40% of bioaccessibility. The metabolomic profiling sustained the antioxidant, hypoglycemic, and neuroprotective effects observed before and after in-vitro digestion probably ascribed to phenolic acids and hydrolyzable tannins metabolites. Considering animal studies, metabolites from phase I and II reactions were identified in rat tissues, mainly derived from phenolic acids, flavonoids, and lignans. The multivariate analysis predicted the outstanding contribution of phenolic metabolites to the in-vivo antioxidant responses. This study supports the use of CS extract as potential anti-aging ingredient for prevention of oxidative stress-triggered diseases in nutraceuticals.

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    Evaluating the Effect of Asphalt Binder and Bio-Geopolymer Composite on the Permanent Deformation Resistance of Asphalt Concrete via Response Surface Method
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    This study evaluated the influence of asphalt binder and biochar-based geopolymer composites on the permanent deformation resistance (PDR) of asphalt concrete. The influence of three design variations: asphalt binder, biochar, and geopolymer content was evaluated by employing the response surface method (RSM) based on the Box Behnken approach. The asphalt binder content ranged between 4 and 6%, whereas the biochar and geopolymer content ranged between 0 and 4%. The average rut depth of Bio-Geopolymer Asphalt concrete (BGAC) was employed as the response variable. The synergetic influence of the design variable was examined using the RSM approach, and a model was developed to determine optimum contents for improving PDR. The model has very high R2 values and adequate precision, showing that there is a significant relationship between the experimental and predicted values. The study ANOVA revealed that the asphalt binder and a biochar-based geopolymer composite modifier showed a significant effect in enhancing the PDR of BGAC. Furthermore, the optimization shows that the optimal content for biochar, geopolymer, and asphalt binder are 3.22%, 1.81%, and 5.4% respectively. The generated model's percentage error was found to be 5%, showing a significant correlation between actual and predicted data. The results of this study show that using RSM to predict and optimize the PDR of BGAC is a very efficient and effective technique.

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    Assessment of natural radioactivity in raw and manufactured commonly used building materials in Morocco
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    In addition to the natural radiation we encounter from the Earth and outer space, it's important to consider the impact of building materials on indoor gamma radiation. These materials, such as cements, bricks, gypsums, and Marbles collected from various locations in Morocco, were carefully examined using HPGe spectrometry to determine the concentrations of naturally occurring radionuclides. Interestingly, we found significant variations in concentrations among different materials and even within the same material at different sites.

    To assess the potential external exposure to gamma rays, we calculated the Gamma Index using the specific activities of 226Ra, 238U, and 40K. Notably, all the values obtained for the analyzed samples were found to be below the reference level recommended in the European Directive 59/2013, indicating that they pose no significant risk.

    Our study is the first of its kind to provide valuable data on the radiological composition of commonly used building materials in Morocco. The aim of this work is to enhance our understanding of the potential impact on indoor radiation levels and contribute to informed decision-making in the construction industry.

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    Topological insulator, Bi2Se3, and carbon fiber reinforced polymer heterostructure for electromagnetic interference shielding applications.

    Electromagnetic interference (EMI) forms an important issue in the aerospace industry as aircraft are under constant exposure to EMI from space, communication systems, and pieces of equipment around. This work shows the design of an EMI shield with the help of topological insulator coating on the carbon-fiber-reinforced polymer (CFRP). The CFRP is well known for its great potential strength, lightweight, non-corrosion, and excellent fatigue resistance, making it an important candidate material for the aviation industry. Bi2Se3 is a topological insulator known for its absorbing properties in the microwave frequency range. The deposition of thin films of Bi2Se3 on CFRP by magnetron sputtering with an RF source makes the layered structure, a good EMI shield that incorporates the mechanism of both reflection and absorption for attenuation of the incoming electromagnetic waves. The process is also cost-effective. The designed heterostructure of 10nm Bi2Se3 deposited on CFRP gave a shielding effectiveness of – 64dB at a frequency of 27 GHz. The free-space focused beam method measured the shielding effectiveness in the frequency range of 26-40 GHz. The CFRP used were unidirectional and confirmed the anisotropic electrical behavior for the SE measurements when the incident signals were polarized along the direction of CFRP as well as perpendicular to it, giving a high degree of shielding effectiveness for signal polarized in the direction of CFRP’s fiber alignment.

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    Dynamics of Beddington De-Angelis type eco-epidemiological model with prey refuge, and prey harvesting

    Analysing the prey-predator model is the purpose of this paper. In interactions with the
    Beddington De-Angelis type, the predator consumes its prey. For the model, first, we analyse
    the existence and local stability of possible non-negative equilibrium points. In addition, we
    examine the Hopf-bifurcation analysis for the proposed model involving the prey refuge. To
    emphasise our key analytical conclusions, we show some numerical simulation results at the
    end.

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