Impact of Storage on In Vitro Permeation and Mucoadhesion Setup Experiments Using Swine Nasal Mucosa.

Intranasal topical administration offers a promising route for local and systemic drug delivery, with in vitro permeation and mucoadhesion studies often using porcine models. However, the impact of storage on mucosal integrity after the procedure remains unaddressed. This study aimed to standardize the preparation process and evaluated whether storage of porcine nasal mucosa impairs its integrity and permeability for experimental comparisons. Additionally, an optimized in vitro mucoadhesion experiment using texture analyzer equipment was investigated. Porcine nasal mucosa was subjected to different storage conditions ("fresh"; refrigerated at 4°C for 24 h and 48 h, and frozen at -20°C for two or three weeks) and assessed using optical and transmission electron microscopy. In vitro permeation assays were performed in a Franz-type vertical diffusion system with lidocaine hydrochloride (LDC). In vitro mucoadhesion assays were conducted using fresh nasal mucosa and a commercial nasal topical formulation using TA.XT. Plus texture analyzer. The variables involved (probe speed, contact time, and application force) in assessing mucoadhesive capacity (maximum mucoadhesive force Fmax and work of mucoadhesion Wmuc) were optimized using a Central Composite Design. Fresh tissues showed no alterations in histological arrangement or in the ultrastructure of adherence junctions. Stored tissues exhibited histological disorganization, reduced thickness, and loss of epithelial integrity. LDC permeability increased in storage tissues (p < 0.05). Contact force had a positive effect on Fmax and Wmuc (p < 0.0001), with a minimum required value of 0.48 N. Variations in contact time and probe speed did not affect the responses (p > 0.05). In conclusion, the preparation technique was adequate to maintain mucosa integrity for permeability studies. However, storing the mucosa at 4 or -20°C overestimated LDC permeation, which could mislead critical data for formulation development. Therefore, the use of fresh mucosa is recommended to ensure more reliable results. For in vitro mucoadhesion assays, a minimum contact force of 0.48N is required for optimal responses.

Development of active films with thymol-based hydrophobic eutectic solvents.

Thymol, known for its antimicrobial properties, was combined with acetic acid, betaine, and caprylic acid to form hydrophobic natural eutectic solvents (NAES), whose influence on the properties of bovine gelatin films was investigated. Films showed enhanced mechanical performance and a clear plasticizing effect provided by the natural eutectic solvents. At 300 wt% concentration, tensile strength and elongation at break reached 871 ± 78 kPa and 141 ± 10 % for acetic acid, 391 ± 41 kPa and 159 ± 10 % for betaine, and 1209 ± 52 kPa and 198 ± 15 % for caprylic acid. Water vapor permeability and total soluble matter were reduced, and swelling decreased to ~250 %, ~150 %, and ~ 200 % for films with 300 wt% of acetic acid, betaine, and caprylic acid, respectively. Pure thymol exhibited significant volatility, with 17.10 ± 1.50 % weight loss over one week, while the NADES demonstrated dramatically reduced losses (up to 1.15 ± 0.04 %). The films displayed exceptional antibacterial activity, achieving inhibition diameters of 34 mm against Gram-positive and Gram-negative bacteria, and films with caprylic or acetic NAES achieved undetectable CFU levels for major pathogens on chicken breast. These results highlight the antimicrobial potency and enhanced stability of NAES-based gelatin films for active packaging applications.

Petrographic and Petrophysical Characterization of Sandstones from Rio Bonito Formation, Paraná Basin (Southern Brazil).

This study focuses on the laboratory-scale petrophysical characterization of sandstones from the Rio Bonito Formation (Lower Permian), Paraná Basin, carried out from drill core samples from well PN-14-SC.02 obtained by CPRM-Brazilian Geological Service in the 1980s on the eastern edge of the Basin. This study includes integrating experimental data from routine petrophysics, sedimentary petrography, and nuclear magnetic resonance (NMR) obtained from 6 samples arranged in the normal direction of the stratification, present between 40 and 200 m deep. It was possible to conclude that the values of the permeability and porosity properties obtained from the NMR technique correlated in a very satisfactory way, with correlation coefficient R2 = 0.957 and Root Mean Squared Error (RMSE) = 0.208 about the porosity reference results offered by routine petrophysics, with lower values being less than a porosity unit (+/- 1 p.u.), in the range between 8 and 14%. The same was observed for the estimated permeability, R2 = 0.885 and RMSE = 0.152, by the Timur Coates method, with values in the range between 0.096 and 2.42 mD, which were well supported by the spectra information, as well as by petrographic analyses.

Membrane tension-dependent conformational change of Isoleucine 106 of loop B diminishes water permeability in FaPIP2;1.

Aquaporins (AQPs) are membrane proteins specialized in facilitating water transport across membranes. Mechanical stress is one of the various stimuli that regulate AQPs. Briefly, there are several studies that report a decrease in permeability upon an increase in membrane tension. However, the molecular details of this mechanosensitive (MS) response are still a matter of debate. Our work attempts to close that gap in knowledge by providing evidence of a conformational change that occurs inside the pore of the strawberry aquaporin FaPIP2;1. Via osmotic shock experiments and molecular dynamics (MD) simulations, we found that a residue of loop B, I106, is key to the blocking of the permeation pathway and such a change is almost exclusively found under membrane tensile stress. In detail, osmotic shock experiments exhibited a nonlinear increment in water fluxes for increasing osmolarities, evidencing a decrease in the FaPIP2;1 permeability. MD simulations under membrane tension showed the same trend, with a significant increase in states with a low water permeability. The latter was correlated with a conformational change in I106 that generates a permeation barrier of around 18 kJ mol-1, effectively closing the pore. This work constitutes the first report of a PIP type aquaporin reacting to tensile stress in the membrane. Our findings could pave the way to test whether this conformational change is also responsible for mechanical gating in the other MS aquaporins, both those already reported and those still waiting to be found.

Permeability and Toxicity of Cryoprotective Agents in Silkworm Embryos: Impact on Cryopreservation.

The permeation of cryoprotectants into insect embryos is critical for successful cryopreservation. However, the permeability of silkworm embryos to cryoprotectants and the effects of cryopreservation remain poorly studied. In this study, we evaluated the permeability and toxicity of four cryoprotective agents (CPAs) as well as the vitrification effect on the viability of silkworm embryos. Among the four CPAs, propylene glycol (PG) showed the best permeability. Ethylene glycol (EG) and PG were the least toxic CPAs, but glycerol (GLY) and dimethyl sulfoxide (DMSO) were more toxic. Moreover, we examined several factors including the kind and the concentration of CPAs, exposure time, embryonic stage, and silkworm strains. Embryos at the earlier phases of stage 25 were more tolerant to vitrification using EG. We found that over 21% of embryos treated with EG at the early 2 phase of stage 25: 163 h after egg laying (AEL) developed and progressed to serosa ingestion after vitrification and rewarming. The result was the same in other strains as well. Our results are valuable for the development of new cryopreservation protocols of silkworm embryos.

Substituting corn starch with wolf's fruit and butterfly lily starches in thermopressed films: Physicochemical, mechanical, and biodegradation properties.

The industrial use of corn starch competes with food supplies, encouraging the investigation of native starches as an alternative for its partial replacement. This study aimed to analyze the effects of replacing corn starch (CS) with wolf's fruit (WFS) and butterfly lily (BLS) starches on the physicochemical, mechanical, and biodegradation properties of starch-based films. Plasticized (with glycerin and citric acid) and unplasticized films were prepared with a microwave (10 s) and by thermopressing (1.5 t/120 °C/2 min) and were analyzed for amylose, scanning electron microscopy, X-ray diffraction, and paste properties. Furthermore, the biodegradability of films was tested in two soils over 42 days. Our results show that BLS is not a suitable raw material to replace corn starch. WFS with 27.5 % apparent amylose content and granule size of 12.5 µm produced films with thickness, permeability, tensile strength, and elongation of ~110 µm, ~4.8 g (m.s.Pa)-1, ~2.5 MPa, and ~2.9 %, respectively, similar to CS. The biodegradability of WFS film showed greater resistance (≤61.4 %), increasing with the addition of plasticizers (89-93 % for WFS302) or partial replacement of CS (73-91 % for CSWFS303). These findings indicate that WFS can partially or fully replace CS in thermopressed films.

Valorization of okara by-product for obtaining soluble dietary fibers and their use in biodegradable carboxymethyl cellulose-based film.

In the face of mounting environmental concerns and the need for sustainable innovation, the use of agro-industrial wastes as raw materials offers a promising pathway. In this context, this study investigated the okara, a by-product of soy processing, as a novel source of soluble dietary fiber for the enrichment of carboxymethyl cellulose (CMC) biodegradable films based on environmental benefits of waste reduction with the creation of renewable packaging alternatives. Okara soluble dietary fiber (OSDF)-enriched CMC film was compared with films made from traditional and innovative soluble dietary fibers, such as pectin, inulin, and ß-glucan. OSDF was obtained through acid hydrolysis at 121 °C, achieving a yield of 5.31 % relative to its initial dry weight. All the produced films exhibited a maximum crystallinity of 5 %, as revealed by X-ray diffraction (XRD), indicative of their largely amorphous structure, while scanning electron microscopy (SEM) ensured their uniformity and flawlessness. The CMC film enriched with okara soluble dietary fiber exhibited key properties, such as thickness, water vapor permeability, and thermal stability, comparable to other soluble fibers studied. These characteristics are essential for effective packaging applications. A notable distinction of the OSDF-enriched film was its capacity to block UV light, offering protection for light-sensitive items. The solubility tests showed that okara and ß-glucan contributed to films with a higher solubility percentage. Mechanical testing underscored the influence of fiber on tensile strength, with the film enriched with ß-glucan outperforming others at 27.5 MPa. All films showed rapid biodegradation within one week, emphasizing their eco-friendliness and the study alignment with sustainable development objectives in packaging.

The potential of nanofibrillated cellulose from Hevea brasiliensis to produce films for bio-based packaging.

Cellulose micro/nanofibril (MNFC) films are an interesting alternative to plastic-based films for application in biodegradable packaging. In this study, we aimed to produce and characterize MNFC films obtained from alkaline-pretreated rubberwood (Hevea brasiliensis) waste and Eucalyptus sp. commercial pulp. MNFC and films were evaluated regarding microstructure; crystallinity; stability; and physical, optical, mechanical, and barrier properties. A combined quality index (QI) was also calculated. Eucalyptus MNFC suspensions were more stable than H. brasiliensis. Both films had a hydrophobic surface (>90°) and high grease resistance (oil kit 12). H. brasiliensis films had lower transparency (26.4 %) and high crystallinity (∼89 %), while Eucalyptus films had lower permeability and higher mechanical strength. The QI of MNFC was 51 ± 5 for H. brasiliensis and 55 ± 4 for Eucalyptus, showing that both types of raw material have potential for application in the packaging industry and in the reinforcement of composites, as well as for high value-added applications in products made from special materials.

Microstructural, Fluid Dynamic, and Mechanical Characterization of Zinc Oxide and Magnesium Chloride-Modified Hydrogel Scaffolds.

Scaffolds for the filling and regeneration of osteochondral defects are a current challenge in the biomaterials field, and solutions with greater functionality are still being sought. The novel approach of this work was to obtain scaffolds with biologically active additives possessing microstructural, permeability, and mechanical properties, mimicking the complexity of natural cartilage. Four types of scaffolds with a gelatin/alginate matrix modified with hydroxyapatite were obtained, and the relationship between the modifiers and substrate properties was evaluated. They differed in the type of second modifier used, which was hydrated MgCl2 in two proportions, ZnO, and nanohydroxyapatite. The samples were obtained by freeze-drying by using two-stage freezing. Based on microstructural observations combined with X-ray microanalysis, the microstructure of the samples and the elemental content were assessed. Permeability and mechanical tests were also performed. The scaffolds exhibited a network of interconnected pores and complex microarchitecture, with lower porosity at the surface (15 ± 7 to 29 ± 6%) and higher porosity at the center (67 ± 8 to 75 ± 8%). The additives had varying effects on the pore sizes and permeabilities of the samples. ZnO yielded the most permeable scaffolds (5.92 × 10-11 m2), whereas nanohydroxyapatite yielded the scaffold with the lowest permeability (1.18 × 10-11 m2), values within the range reported for trabecular bone. The magnesium content had no statistically significant effect on the permeability. The best mechanical parameters were obtained for ZnO samples and those containing hydrated MgCl2. The scaffold's properties meet the criteria for filling osteochondral defects. The developed scaffolds follow a biomimetic approach in terms of hierarchical microarchitecture and mechanical parameters as well as chemical composition. The obtained composite materials have the potential as biomimetic scaffolds for the regeneration of osteochondral defects.

Brazil Nut (Bertholletia excelsa H.B.K.) Consumption in Energy-Restricted Intervention Decreases Proinflammatory Markers and Intestinal Permeability of Women with Overweight/Obesity: A Controlled Trial (Brazilian Nuts Study).

BACKGROUND: Obesity is associated with low-grade inflammation and increased intestinal permeability (IP). The Brazil nut (BN) (Bertholletia excelsa H.B.K.) appears to be a promising dietary intervention to control inflammation by enhancing antioxidant defenses. OBJECTIVES: We aimed to assess the effect of daily BN consumption on inflammatory biomarkers and IP in the context of an energy-restricted intervention. Furthermore, we evaluated the correlation between the changes in these inflammatory markers and the changes in serum selenium and IP. METHODS: In this 8-wk nonrandomized controlled trial, 56 women with overweight or obesity were allocated into 2 groups, both following an energy-restricted diet (-500 kcal/d). The control group (CO) consumed a nut-free diet, while the BN group consumed 8 g BN/d, providing 347.2 µg selenium (Se). Inflammatory cytokines were analyzed in plasma and Se in serum. IP was assessed using the lactulose/mannitol test (LM ratio). RESULTS: Forty-six women completed the intervention. Both groups achieved similar energy restriction (CO Δ= -253.7 ± 169.4 kcal/d; BN Δ= -265.8 ± 141.8 kcal/d) and weight loss (CO Δ= -2.5 ± 0.5 kg; BN Δ= -3.5 ± 0.5 kg). The BN group showed lower values of C-reactive protein, tumor necrosis factor, interleukin (IL)1-ß, IL-8, percentage lactulose excretion, and LM ratio than the CO group. Additionally, changes in serum Se concentration were predictive of changes in IL-8 concentration (ß: -0.054; adjusted R2: 0.100; 95% confidence interval [CI]: -0.100; -0.007; P = 0.025), and changes in IL-8 were predictive of changes in the LM ratio (ß: 0.006; adjusted R2: 0.101; 95% CI: 0.001, 0.011; P = 0.024). CONCLUSIONS: Regular intake of BNs can be a promising complementary dietary strategy for controlling low-grade inflammation and improving IP in women with overweight/obesity undergoing energy-restricted treatment. However, the effects of BNs seem to be Se status-dependent. This trial was registered at the Brazilian Registry of Clinical Trials (ReBEC: https://ensaiosclinicos.gov.br/rg/RBR-3ntxrm/.

Preparation and characterization of sustainable active packaging based on myofibrillar proteins and protein hydrolysates from the cutting by-product of Scomberomorus brasiliensis filleting on the band saw machine.

Protein hydrolysates derived from aquaculture by-products hold significant promise as key components in the formulation of active films. In our study, we investigated the impact of different protein hydrolysates levels (0.4%, 0.8%, and 1.2%) obtained from the cutting by-product of Serra Spanish mackerel on the mechanical (PHSSM), morphological, optical, thermal, and antioxidant properties, as well as the degradability of biodegradable films. Four treatments were produced, varying the concentrations of PHSSM: C (control, without PHSSM), T4 (with 0.4% PHSSM), T8 (with 0.8% PHSSM), and T12 (with 1.2% PHSSM). These films were based on myofibrillar proteins from fish by-products and pectin extracted from yellow passion fruit. The incorporation of PHSSM led to enhanced barrier properties, resulting in a proportional reduction in water vapor permeability compared to the control film. However, high PHSSM levels (>0.8%) compromised film homogeneity and increased fracture susceptibility. Tensile strength remained unaffected (p > 0.05). PHSSM-enriched films exhibited reduced transparency and lightness, regardless of PHSSM concentration. The addition of PHSSM imparted a darker, reddish-yellow hue to the films, indicative of heightened visible light barrier properties. Moreover, increased PHSSM content (0.8% and 1.2%) appeared to accelerate film degradation in soil. Fourier transform infrared spectroscopy confirmed the presence of pectin-protein complexes in the films, with no discernible differences among the treated samples in the spectra. Incorporating PHSSM also enhanced film crystallinity and thermal resistance. Furthermore, an improvement in the antioxidant activity of the films was observed with PHSSM addition, dependent on concentration. The T8 emerged as the promising candidate for developing active primary packaging suitable for oxidation-sensitive foods.

Formulations based on pullulan and a derivative as coating material for the food sector.

Carboxymethylated derivatives of pullulan (PU) were synthesized and evaluated as coating for the postharvest preservation of blueberries. Carboxymethylpullulan was obtained by etherification reaction with the substitution degrees of 0.52, 0.34, and 0.26 for CMP1, CMP2, and CMP3 respectively. Infrared spectroscopy and nuclear magnetic resonance results showed characteristic signals of the carbonyl group belonging to the carboxymethyl group. Thermal analysis showed that CMP1, CMP2, and CMP3 derivatives presented thermal stability values of 209.91 C, 214.73 C, and 225.52 °C, respectively, and were lower with respect to PU with Td of 238.84 °C. Furthermore, an increase in the glass transition temperature due to carboxymethylation was determined. The chemical modification decreased the contact angle with respect to PU (71.34°) with values for CMP1, CMP2, and CMP3 of 39.89°, 53.72° and 60.61°, respectively. The carboxymethylation also increased the water vapor permeability and mechanical properties of the films. In addition, it was found that the CMP molecules affected the optical properties. The application of CMP-based coatings reduced the mass loss and ripening rate of blueberries compared to native pullulan, therefore, packaging from CMP molecules could be used as a coating capable of delaying ripening and extending the shelf life of fruits.

Can Diet Alter the Intestinal Barrier Permeability in Healthy People? A Systematic Review.

Dietary factors can modify the function of the intestinal barrier, causing permeability changes. This systematic review analyzed evidence on the link between diet or dietary interventions and changes in intestinal barrier permeability (IBP) in healthy individuals. A systematic search for primary studies was conducted using the virtual databases EMBASE, PubMed, Web of Science, CINAHL, and Scopus. This review adhered to PRISMA 2020 guidelines, assessing the methodological quality using the Newcastle-Ottawa scale for observational studies and ROB 2.0 for randomized clinical trials. Out of 3725 studies recovered, 12 were eligible for review. Chicory inulin and probiotics reduced IBP in adults with a moderate GRADE level of evidence. The opposite result was obtained with fructose, which increased IBP in adults, with a very low GRADE level of evidence. Only intervention studies with different dietary components were found, and few studies evaluated the effect of specific diets on the IBP. Thus, there was no strong evidence that diet or dietary interventions increase or decrease IBP in healthy individuals. Studies on this topic are necessary, with a low risk of bias and good quality of evidence generated, as there is still little knowledge on healthy populations.

Development of biopolymer films loaded with fluconazole and thymol for resistant vaginal candidiasis.

Vulvovaginal candidiasis (VVC) is an opportunistic infection caused by a fungus of the Candida genus, affecting approximately 75 % of women during their lifetime. Fungal resistance cases and adverse effects have been the main challenges of oral therapies. In this study, the topical application of thin films containing fluconazole (FLU) and thymol (THY) was proposed to overcome these problems. Vaginal films based only on chitosan (CH) or combining this biopolymer with pectin (PEC) or hydroxypropylmethylcellulose acetate succinate (HPMCAS) were developed by the solvent casting method. In addition to a higher swelling index, CH/HPMCAS films showed to be more plastic and flexible than systems prepared with CH/PEC or only chitosan. Biopolymers and FLU were found in an amorphous state, contributing to explaining the rapid gel formation after contact with vaginal fluid. High permeability rates of FLU were also found after its immobilization into thin films. The presence of THY in polymer films increased the distribution of FLU in vaginal tissues and resulted in improved anti-Candida activity. A significant activity against the resistant C. glabrata was achieved, reducing the required FLU dose by 50 %. These results suggest that the developed polymer films represent a promising alternative for the treatment of resistant vulvovaginal candidiasis, encouraging further studies in this context.

Multifactorial evaluation of an ultra-fast process for electrospinning of recycled expanded polystyrene to manufacture high-efficiency membranes for nanoparticle air filtration.

The increased production of polystyrene waste has led to the need to find efficient ways to dispose of it. One possibility is the use of solid waste to produce filter media by the electrospinning technique. The aim of this work was to develop an ultra-fast electrospinning process applied to recycled polystyrene, with statistical evaluation of the influence of polymeric solution parameters (polymer concentration and percentage of DL-limonene) and process variables (flow rate, voltage, and type of support) on nanoparticle collection efficiency, air permeability, and fiber diameter. An extensive characterization of the materials and evaluation of the morphology of the fibers was also carried out. It was found that recycled expanded polystyrene could be used in electrospinning to produce polymeric membranes. The optimized condition that resulted in the highest nanoparticle collection efficiency was a polymer concentration of 13.5%, percentage of DL-limonene of 50%, voltage of 25 kV, and flow rate of 1.2 mL/h, resulting in values of 99.97 ± 0.01%, 2.6 ± 0.5 × 10-13 m2, 0.19 Pa-1, and 708 ± 176 nm for the collection efficiency of nanoparticles in the range from 6.38 to 232.9 nm, permeability, quality factor, and mean fiber diameter, respectively. All the parameters were found to influence collection efficiency and fiber diameter. The use of DL-limonene, a natural solvent, provided benefits including increased collection efficiency and decreased fiber size. In addition, the electrostatic filtration mechanism was evaluated using the presence of a copper grid as a support for the nanofibers. The findings demonstrated that an electrospinning time of only 5 min was sufficient to obtain filters with high collection efficiencies and low pressure drops, opening perspectives for the application of polystyrene waste in the development of materials with excellent characteristics for application in the area of atmospheric pollution mitigation.

Development and validation of a stability-indicating method, structural elucidation of new degradation products from misoprostol by LC-MS time-of-flight, and an ex vivo study of vaginal permeation.

Misoprostol (MSP) is commonly prescribed in obstetrics and gynecology clinical practice for labor induction, cervical ripening, first-trimester pregnancy termination, and the treatment of postpartum hemorrhage. Furthermore, there is a lack of comprehensive discussion evaluating how different commercially available formulations influence the overall efficacy of MSP, even though reports indicate issues with the quality of these formulations, particularly regarding stability and vaginal absorption processes. This study investigates the stability of MSP under acidic conditions and its in vitro permeation using swine vaginal mucosa. A forced degradation study was conducted using 0.2 M HCl, and a high-efficiency LC method was developed. Three degradation products were identified and characterized using electrospray ionization-high-resolution quadrupole-time-of-flight-MS, with respective m/z values of 391.2508, 405.2705, and 387.2259, respectively. These results suggest that the degradation mechanism involves dehydration of the ß-hydroxy ketone moiety, followed by isomerization to its most resonance-stable form and de-esterification. Finally, the in vitro permeation study revealed that the esterified form of MSP was unable to permeate the mucosa and required prior degradation for any component to be detected in the receptor fluid.

Starch-based films affected by the addition of collagen from Prochilodus magdalenae residues and HPMC: Application in Andean blackberry (Rubus glaucus Benth) coatings.

Starch-based films offer the advantages of biodegradability, edibility, barrier properties, flexibility, and adaptability. This study compared the physicochemical properties of starch-based films by adding raw fish collagen and hydroxypropylmethylcellulose (HPMC). The tensile properties were evaluated, and the interaction with water was analyzed. Barrier properties, such as water vapor and oxygen permeability, were examined, and optical properties, such as gloss and good internal transmittance, were evaluated. The films were evaluated as coatings on Andean blackberries (Rubus glaucus Benth) for 2 weeks at 85% RH and 25°C. The results showed that the inclusion of collagen caused a reduction in the tensile strength and elastic modulus of the films. Also, the formulation with the highest collagen concentration (F7) exhibited the lowest weight loss and water vapor permeability, also it had the highest collagen concentration and showed the highest reduction in Xw and WAC, with values of 0.048 and 0.65 g water/g dry film, respectively. According to analyzing the optical properties, F1 presented the highest bright-ness and transmittance values, with 18GU and 82 nm values, respectively. In general, the films and coatings are alternatives to traditional packaging materials to prolong the shelf life of these fruits.

Identifying Substructures That Facilitate Compounds to Penetrate the Blood-Brain Barrier via Passive Transport Using Machine Learning Explainer Models.

The local interpretable model-agnostic explanation (LIME) method was used to interpret two machine learning models of compounds penetrating the blood-brain barrier. The classification models, Random Forest, ExtraTrees, and Deep Residual Network, were trained and validated using the blood-brain barrier penetration dataset, which shows the penetrability of compounds in the blood-brain barrier. LIME was able to create explanations for such penetrability, highlighting the most important substructures of molecules that affect drug penetration in the barrier. The simple and intuitive outputs prove the applicability of this explainable model to interpreting the permeability of compounds across the blood-brain barrier in terms of molecular features. LIME explanations were filtered with a weight equal to or greater than 0.1 to obtain only the most relevant explanations. The results showed several structures that are important for blood-brain barrier penetration. In general, it was found that some compounds with nitrogenous substructures are more likely to permeate the blood-brain barrier. The application of these structural explanations may help the pharmaceutical industry and potential drug synthesis research groups to synthesize active molecules more rationally.

Amphibian tolerance to arsenic: microbiome-mediated insights.

Amphibians are often recognized as bioindicators of healthy ecosystems. The persistence of amphibian populations in heavily contaminated environments provides an excellent opportunity to investigate rapid vertebrate adaptations to harmful contaminants. Using a combination of culture-based challenge assays and a skin permeability assay, we tested whether the skin-associated microbiota may confer adaptive tolerance to tropical amphibians in regions heavily contaminated with arsenic, thus supporting the adaptive microbiome principle and immune interactions of the amphibian mucus. At lower arsenic concentrations (1 and 5 mM As3+), we found a significantly higher number of bacterial isolates tolerant to arsenic from amphibians sampled at an arsenic contaminated region (TES) than from amphibians sampled at an arsenic free region (JN). Strikingly, none of the bacterial isolates from our arsenic free region tolerated high concentrations of arsenic. In our skin permeability experiment, where we tested whether a subset of arsenic-tolerant bacterial isolates could reduce skin permeability to arsenic, we found that isolates known to tolerate high concentrations of arsenic significantly reduced amphibian skin permeability to this metalloid. This pattern did not hold true for bacterial isolates with low arsenic tolerance. Our results describe a pattern of environmental selection of arsenic-tolerant skin bacteria capable of protecting amphibians from intoxication, which helps explain the persistence of amphibian populations in water bodies heavily contaminated with arsenic.

Magnetic carbon nanotubes modified with proteins and hydrophilic monomers: Cytocompatibility, in-vitro toxicity assays and permeation across biological interfaces.

Carbon nanotubes are promising materials for biomedical applications like delivery systems and tissue scaffolds. In this paper, magnetic carbon nanotubes (M-CNTs) covered with bovine serum albumin (M-CNTs-BSA) or functionalized with hydrophilic monomers (M-CNTs-HL) were synthesized, characterized, and evaluated concerning their interaction with Caco-2 cells. There is no comparison between these two types of functionalization, and this study aimed to verify their influence on the material's interaction with the cells. Different concentrations of the nanotubes were applied to investigate cytotoxicity, cell metabolism, oxidative stress, apoptosis, and capability to cross biomimetic barriers. The materials showed cytocompatibility up to 100 µg mL-1 and a hemolysis rate below 2 %. Nanotubes' suspensions were allowed to permeate Caco-2 monolayers for up to 8 h under the effect of the magnetic field. Magnetic nanoparticles associated with the nanotubes allowed estimation of permeation through the monolayers, with values ranging from 0.50 to 7.19 and 0.27 to 9.30 × 10-3 µg (equivalent to 0.43 to 6.22 and 0.23 to 9.54 × 10-2 % of the initially estimated mass of magnetic nanoparticles) for cells exposed and non-exposed to the magnets, respectively. Together, these results support that the developed materials are promising for applications in biomedical and biotechnological fields.