Unsupervised learning of representative local atomic arrangements in molecular dynamics data.

Molecular dynamics (MD) simulations present a data-mining challenge, given that they can generate a considerable amount of data but often rely on limited or biased human interpretation to examine their information content. By not asking the right questions of MD data we may miss critical information hidden within it. We combine dimensionality reduction (UMAP) and unsupervised hierarchical clustering (HDBSCAN) to quantitatively characterize prevalent coordination environments of chemical species within MD data. By focusing on local coordination, we significantly reduce the amount of data to be analyzed by extracting all distinct molecular formulas within a given coordination sphere. We then efficiently combine UMAP and HDBSCAN with alignment or shape-matching algorithms to partition these formulas into structural isomer families indicating their relative populations. The method was employed to reveal details of cation coordination in electrolytes based on molecular liquids.

Enhanced and stabilized hydrogen production from methanol by ultrasmall Ni nanoclusters immobilized on defect-rich h-BN nanosheets.

Employing liquid organic hydrogen carriers (LOHCs) to transport hydrogen to where it can be utilized relies on methods of efficient chemical dehydrogenation to access this fuel. Therefore, developing effective strategies to optimize the catalytic performance of cheap transition metal-based catalysts in terms of activity and stability for dehydrogenation of LOHCs is a critical challenge. Here, we report the design and synthesis of ultrasmall nickel nanoclusters (∼1.5 nm) deposited on defect-rich boron nitride (BN) nanosheet (Ni/BN) catalysts with higher methanol dehydrogenation activity and selectivity, and greater stability than that of some other transition-metal based catalysts. The interface of the two-dimensional (2D) BN with the metal nanoparticles plays a strong role both in guiding the nucleation and growth of the catalytically active ultrasmall Ni nanoclusters, and further in stabilizing these nanoscale Ni catalysts against poisoning by interactions with the BN substrate. We provide detailed spectroscopy characterizations and density functional theory (DFT) calculations to reveal the origin of the high productivity, high selectivity, and high durability exhibited with the Ni/BN nanocatalyst and elucidate its correlation with nanocluster size and support-nanocluster interactions. This study provides insight into the role that the support material can have both regarding the size control of nanoclusters through immobilization during the nanocluster formation and also during the active catalytic process; this twofold set of insights is significant in advancing the understanding the bottom-up design of high-performance, durable catalytic systems for various catalysis needs.

Effect of Dietary Incorporation of Yellow Mealworm as a Partial Fishmeal Replacer on Growth, Metabolism, and Intestinal Histomorphology in Juvenile Meagre (Argyrosomus regius).

Efforts have been made to find alternatives to fish meal (FM), as the sustainability of aquaculture depends on it. Insect meal (IM) is a potential candidate to partially replace FM, being more sustainable and economically viable. In this experimental trial, three diets were tested with different yellow mealworm incorporation: a control diet with no IM, a diet with an inclusion of 10% IM (Ins10), and a diet with an incorporation of 20% IM (Ins20). The diets were tested on 10.5 g meagre for 47 days. The results showed that an IM inclusion higher than 10% affected both growth (2.6 vs. 2.2) and FCR (1.5 vs. 1.9) of meagre juveniles. However, this reduction in growth did not result from lower protein retention or changes in muscle fibre area or density. Little differences were observed in the activity of pancreatic and intestinal enzymes except for aminopeptidase total activity which was higher in the control and Ins10 compared to Ins20 (3847 vs. 3540 mU/mg protein), suggesting no limitations in protein synthesis. Also, the alkaline phosphatase intestinal maturation index was higher in the control group compared to the IM groups (437 vs. 296). On the contrary, several differences were also found in the proteolytic activity in the hepatic and muscle tissues of meagre juveniles fed the Ins10 diet. The inclusion of IM had no impact on intestine histomorphology but changes were detected in the enterocytes of fish from control and Ins10 which showed hypervacuolization and nucleus misplacement compared to the Ins20 treatment. Nevertheless, a higher percentage of Vibrionaceae was recorded for meagre fed on the Ins20 diet. Since no signs of inflammation were observed in the distal intestine, this suggests IM incorporation could have had an important impact on intestinal health due to its antimicrobial properties. This is supported by an increase in the haematocrit in the treatments where IM was added (20 to 25%). In conclusion, incorporations of IM at percentages up to 10% do not seem to have a negative impact on meagre performance at this age but can enhance the fish immune system and protection against intestinal inflammation.

X-ray absorption spectroscopy insights on the structure anisotropy and charge transfer in Chevrel Phase chalcogenides.

The electronic structure and local coordination of binary (Mo6T8) and ternary Chevrel Phases (MxMo6T8) are investigated for a range of metal intercalant and chalcogen compositions. We evaluate differences in the Mo L3-edge and K-edge X-ray absorption near edge structure across the suite of chalcogenides MxMo6T8 (M = Cu, Ni, x = 1-2, T = S, Se, Te), quantifying the effect of compositional and structural modification on electronic structure. Furthermore, we highlight the expansion, contraction, and anisotropy of Mo6 clusters within these Chevrel Phase frameworks through extended X-ray absorption fine structure analysis. Our results show that metal-to-cluster charge transfer upon intercalation is dominated by the chalcogen acceptors, evidenced by significant changes in their respective X-ray absorption spectra in comparison to relatively unaffected Mo cations. These results explain the effects of metal intercalation on the electronic and local structure of Chevrel Phases across various chalcogen compositions, and aid in rationalizing electron distribution within the structure.

Lactic Acid-Based Natural Deep Eutectic Solvents to Extract Bioactives from Marine By-Products.

Natural deep eutectic solvents (NaDES) were used to extract bioactive compounds from marine by-products: codfish bones, mussel meat, and tuna vitreous humor. NaDES were prepared using natural compounds, including lactic acid (Lac), fructose (Fru), and urea (Ur), and were characterized to define their physicochemical properties, including the viscosity, density, surface tension, and refractive index. FTIR and NMR analysis confirmed the presence of intermolecular hydrogen bonding in NaDES. The extracts obtained using these NaDES were characterized to define their composition. Results demonstrated that the extract's composition differed highly, depending not only on the DES used, but also on the structure and composition of the raw material. Proteins and lipids were mainly present in extracts obtained from mussels, while ash content was highest in the extracts obtained from codfish bones. The biocompatibility of NaDES and the soluble fractions (SF) of the raw materials in NaDES was evaluated, and it was possible to conclude that the soluble ingredients obtained from the raw materials improved the biocompatibility of NaDES.

Alternative Extraction and Downstream Purification Processes for Anthocyanins.

Anthocyanins are natural pigments displaying different attractive colors ranging from red, violet, to blue. These pigments present health benefits that increased their use in food, nutraceuticals, and the cosmetic industry. However, anthocyanins are mainly extracted through conventional methods that are time-consuming and involve the use of organic solvents. Moreover, the chemical diversity of the obtained complex extracts make the downstream purification step challenging. Therefore, the growing demand of these high-value pigments has stimulated the interest in designing new, safe, cost-effective, and tunable strategies for their extraction and purification. The current review focuses on the potential application of compressed fluid-based (such as subcritical and supercritical fluid extraction and pressurized liquid extraction) and deep eutectic solvents-based extraction methods for the recovery of anthocyanins. In addition, an updated review of the application of counter-current chromatography for anthocyanins purification is provided as a faster and cost-effective alternative to preparative-scale HPLC.

Key factor cutoffs and interval reference values for stratified fall risk assessment in community-dwelling older adults: the role of physical fitness, body composition, physical activity, health condition, and environmental hazards.

BACKGROUND: Fall risk assessment and determination of older adults' individual risk profiles are crucial elements in fall prevention. As such, it is essential to establish cutoffs and reference values for high and low risk according to key risk factor outcomes. This study main objective was to determine the key physical fitness, body composition, physical activity, health condition and environmental hazard risk outcome cutoffs and interval reference values for stratified fall risk assessment in community-dwelling older adults. METHODS: Five-hundred community-dwelling Portuguese older adults (72.2 ± 5.4 years) were assessed for falls, physical fitness, body composition, physical (in) activity, number of health conditions and environmental hazards, and sociodemographic characteristics. RESULTS: The established key outcomes and respective cutoffs and reference values used for fall risk stratification were multidimensional balance (low risk: score > 33, moderate risk: score 32-33, high risk: score 30-31, and very high: score < 30); lean body mass (low risk: > 44 kg, moderate risk: 42-44 kg, high risk: 39-41 kg, and very high: < 39 kg); fat body mass (low risk: < 37%, moderate risk: 37-38%, high risk: 39-42%, and very high: > 42%); total physical activity (low risk: > 2800 Met-min/wk., moderate risk: 2300-2800 Met-min/wk., high risk: 1900-2300 Met-min/wk., and very high: < 1900 Met-min/wk); rest period weekdays (low risk: < 4 h/day, moderate risk: 4-4.4 h/day, high risk: 4.5-5 h/day, and very high: > 5 h/day); health conditions (low risk: n < 3, moderate risk: n = 3, high risk: n = 4-5, and very high: n > 5); and environmental hazards (low risk: n < 5, moderate risk: n = 5, high risk: n = 6-8, and very high: n > 8). CONCLUSIONS: Assessment of community-dwelling older adults' fall risk should focus on the above outcomes to establish individual older adults' fall risk profiles. Moreover, the design of fall prevention interventions should manage a person's identified risks and take into account the determined cutoffs and respective interval values for fall risk stratification.

Physicochemical Characterization and Simulation of the Solid-Liquid Equilibrium Phase Diagram of Terpene-Based Eutectic Solvent Systems.

The characterization of terpene-based eutectic solvent systems is performed to describe their solid-liquid phase transitions. Physical properties are measured experimentally and compared to computed correlations for deep eutectic solvents (DES) and the percentage relative error er for the density, surface tension, and refractive index is obtained. The thermodynamic parameters, including the degradation, glass transition and crystallization temperatures, are measured using DSC and TGA. Based on these data, the solid-liquid equilibrium phase diagrams are calculated for the ideal case and predictions are made using the semi-predictive UNIFAC and the predictive COSMO RS models, the latter with two different parametrization levels. For each system, the ideal, experimental, and predicted eutectic points are obtained. The deviation from ideality is observed experimentally and using the thermodynamic models for Thymol:Borneol and Thymol:Camphor. In contrast, a negative deviation is observed only experimentally for Menthol:Borneol and Menthol:Camphor. Moreover, the chemical interactions are analyzed using FTIR and 1H-NMR to study the intermolecular hydrogen bonding in the systems.

Supercritical CO2 Extraction as a Tool to Isolate Anti-Inflammatory Sesquiterpene Lactones from Cichorium intybus L. Roots.

Cichorium intybus L. or chicory plants are a natural source of health-promoting compounds in the form of supplements such as inulin, as well as other bioactive compounds such as sesquiterpene lactones (SLs). After inulin extraction, chicory roots are considered waste, with most SLs not being harnessed. We developed and optimized a new strategy for SL extraction that can contribute to the conversion of chicory root waste into valuable products to be used in human health-promoting applications. In our work, rich fractions of SLs were recovered from chicory roots using supercritical CO2. A response surface methodology was used to optimize the process parameters (pressure, temperature, flow rate, and co-solvent percentage) for the extraction performance. The best operating conditions were achieved at 350 bar, 40 °C, and 10% EtOH as a co-solvent in a 15 g/min flow rate for 120 min. The extraction with supercritical CO2 revealed to be more selective for the SLs than the conventional solid-liquid extraction with ethyl acetate. In our work, 1.68% mass and a 0.09% sesquiterpenes yield extraction were obtained, including the recovery of two sesquiterpene lactones (8-deoxylactucin and 11ß,13-dihydro-8-deoxylactucin), which, to the best of our knowledge, are not commercially available. A mixture of the abovementioned compounds were tested at different concentrations for their toxic profile and anti-inflammatory potential towards a human calcineurin/NFAT orthologue pathway in a yeast model, the calcineurin/Crz1 pathway. The SFE extract obtained, rich in SLs, yielded results of inhibition of 61.74 ± 6.87% with 50 µg/mL, and the purified fraction containing 8-deoxylactucin and 11ß,13-dihydro-8-deoxylactucin inhibited the activation of the reporter gene up to 53.38 ± 3.9% at 10 µg/mL. The potential activity of the purified fraction was also validated by the ability to inhibit Crz1 nuclear translocation and accumulation. These results reveal a possible exploitable green technology to recover potential anti-inflammatory compounds from chicory roots waste after inulin extraction.

Antibody modified gold nanoparticles for fast colorimetric screening of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic joint inflammation and one of the main causes of chronic disability worldwide with high prevalence in the ageing population. RA is characterized by autoantibody production, synovial inflammation and bone destruction, and the most accepted biomarker is rheumatoid factor (RF) autoantibodies. In this work, we developed a low-cost approach for the detection and quantification of the RF marker. This colorimetric immunosensor is based on gold nanoprobe crosslinking that results in extensive aggregation in the presence of the pentameric IgM RF. Aggregation of the nanoconjugates yields a color change from red to purple that can be easily observed by the naked eye. The interaction between nanoconjugates and the specific target was confirmed via dynamic light scattering (DLS), Raman spectroscopy and atomic force microscopy (AFM) imaging. This conceptual system shows a LOD of 4.15 UA mL-1 IgM RF (clinical threshold is set for 20 IU mL-1). The one-step biosensor strategy herein proposed is much faster than conventional detection techniques, without the need for secondary antibodies, additional complex washing or signal amplification protocols. To the best of our knowledge this is the first report on target induced aggregation of gold nanoprobes for quantitative colorimetric autoantibody detection.

Smart and Assistive Walker - ASBGo: Rehabilitation Robotics: A Smart-Walker to Assist Ataxic Patients.

Locomotion is an important human faculty that affects an individual's life, bringing not only physical and psychosocial implications but also heavy social-economic consequences. Thus, it becomes paramount to find means (augmentative/assistive devices) to empower the user's residual capacities and promote functional recovery.In this context, a smart walker (SW) is explored for further clinical evaluation of ataxic patients during walker-assisted and to serve as a functional compensation and assist-as-needed personalized/customized rehabilitation tool, autonomously adapting assistance to the users' needs, through innovative combination of real-time multimodal sensory information from SW built-in sensors. To meet the users' needs, its design was weighed, considering to whom it is intended.Thereby, this paper presents the system overview, focusing on design considerations, mechanical structure (frame and main components), electronic and mechatronic components, followed by its functionalities. Lastly, it presents results regarding the main functionalities, addressing clinical evidence.

Ectopic expression of CITED2 prior to reprogramming, promotes and homogenises the conversion of somatic cells into induced pluripotent stem cells.

Cited2 plays crucial roles in mouse embryonic stem cells self-renewal, the initiation of the somatic reprogramming process into induced pluripotent stem cells (iPSC) and the suppression of cell senescence. Here, we investigated the potential of CITED2 expression in combination with the Oct4, Sox2, Klf4 and c-Myc factors for reprogramming of primary mouse embryonic fibroblasts (MEF) at passage 2 and 4. The ectopic CITED2 expression in primary MEF prior to the onset of the reprogramming process, generated iPSC with less variability in the expression of endogenous pluripotency-related genes. In contrast, part of the MEF reprogrammed without ectopic expression of CITED2 at passage 4 originated partially reprogrammed iPSC or pre-iPSC. However, the overexpression of CITED2 in the pre-iPSC was insufficient to complete the reprogramming process into iPSC. These results indicated that ectopic CITED2 expression at the onset of the reprogramming process in combination with the reprogramming factors promotes a complete and homogeneous conversion of somatic cells into iPSC.

Preliminary studies on haematological and plasmatic parameters in gilthead sea bream (Sparus aurata) held under day/night temperature variations.

This study aimed to evaluate to what extent diel water temperature oscillations over a short period of time (41 h) affected haematologic and plasmatic parameters of gilthead sea bream. Sea bream juveniles (160 fish; 177.2 ± 20.9 g) were divided in two homogenous groups, experimental and control. The experimental group was exposed to water at 22.3 ± 0.6 °C between 5 a.m. and 5 p.m. and to colder water from 5 p.m. to 5 a.m. (temperature variation of 8.6 ± 0.3 °C) during 41h period, whereas for the control group, water temperature was maintained constant (22.4 ± 0.7 °C) for the same period. Fish were fed three times per day (10:30 a.m., 2 p.m., 4 p.m.). Blood was collected from fish caudal veins (n = 6) at different time points (10 a.m., 1 p.m., 5 p.m., 6:30 p.m., 8 p.m. and 10 a.m. of the following day) from each group, for haematologic (haematocrit and haemoglobin) and plasmatic (glucose, cortisol, triglycerides and total protein) determinations. All parameters studied tended to vary throughout the study period, both for experimental and control groups. Significant differences were observed between the two groups for all the studied parameters at different sampling points. These differences were observed near the influence of the cold-water period or during the cooling-water period. Results suggested that colder water temperature cycles depressed fish metabolic activity and affected the levels of the analysed blood-circulating metabolites. Overall, results suggested that stress response was similar for experimental and control groups and that gilthead sea bream were able to cope with diel water temperature variations.

Acute loss of Cited2 impairs Nanog expression and decreases self-renewal of mouse embryonic stem cells.

Identifying novel players of the pluripotency gene regulatory network centered on Oct4, Sox2, and Nanog as well as delineating the interactions within the complex network is key to understanding self-renewal and early cell fate commitment of embryonic stem cells (ESC). While overexpression of the transcriptional regulator Cited2 sustains ESC pluripotency, its role in ESC functions remains unclear. Here, we show that Cited2 is important for proliferation, survival, and self-renewal of mouse ESC. We position Cited2 within the pluripotency gene regulatory network by defining Nanog, Tbx3, and Klf4 as its direct targets. We also demonstrate that the defects caused by Cited2 depletion are, at least in part, rescued by Nanog constitutive expression. Finally, we demonstrate that Cited2 is required for and enhances reprogramming of mouse embryonic fibroblasts to induced pluripotent stem cells.

Is C50 a superaromat? Evidence from electronic structure and ring current calculations.

The fullerene-50 is a 'magic number' cage according to the 2(N + 1)(2) rule. For the three lowest isomers of C50 with trigonal and pentagonal symmetries, we calculate the sphericity index, the spherical parentage of the occupied π-orbitals, and the current density in an applied magnetic field. The minimal energy isomer, with D3 symmetry, comes closest to a spherical aromat or a superaromat. In the D5h bond-stretch isomers the electronic structure shows larger deviations from the ideal spherical shells, with hybridisation or even reversal of spherical parentages. It is shown that relative stabilities of fullerene cages do not correlate well with aromaticity, unlike the magnetic properties which are very sensitive indicators of spherical aromaticity. Superaromatic diamagnetism in the D3 cage is characterized by global diatropic currents, which encircle the whole cage. The breakdown of sphericity in the D5h cages gives rise to local paratropic countercurrents.

Protective Effect of a (Poly)phenol-Rich Extract Derived from Sweet Cherries Culls against Oxidative Cell Damage.

Oxidative stress is one of the key phenomena behind the most common types of chronic diseases. Therefore, the modulation of oxidative stress is an interesting target for acting either through prevention or as a therapeutic approach. In this work, a Portuguese variety of cherry (Saco Cherry) was processed in order to obtain a potent in vitro antioxidant phenolic-rich extract (Ch-PRE), which was further explored to evaluate its potential application as nutraceutical agent against cellular oxidative stress damage. Ch-PRE was mainly composed of anthocyanins, particularly cyanidin-3-rutinoside, cyanidin-3-glucoside, peonidin-3-glucoside and neochlorogenic acid, and exhibited a potent chemical antioxidant activity expressed by its oxygen radical absorbance capacity (ORAC) and hydroxyl radical averting capacity (HORAC) values. Ch-PRE also displayed effective intracellular radical scavenging properties in intestinal epithelial and neuronal cells challenged with oxidative stress but showed a different order of effectiveness regarding the modulation of endogenous antioxidant system. Ch-PRE could be an attractive candidate to formulate an agent for the prevention of oxidative stress-induced disorders such as intestinal inflammation disorders or with an appropriated delivery system for neurodegenerative diseases.

FBXL5 modulates HIF-1α transcriptional activity by degradation of CITED2.

CITED2 is a ubiquitously expressed nuclear protein exhibiting a high affinity for the cysteine-histidine-rich domain 1 (CH1) of the transcriptional co-activators CBP/p300. CITED2 is particularly efficient in the inhibition of the hypoxia-inducible factor-1α (HIF-1α) dependent transcription by competing with it for the interaction with the CH1 domain. Here we report a direct and specific interaction between CITED2 and the F-box and leucine rich repeat protein 5 (FBXL5), a substrate adaptor protein which is part of E3 ubiquitin ligase complexes mediating protein degradation by the proteasome. We demonstrated that depletion of FBXL5 by RNA interference led to an increase of CITED2 protein levels. Conversely, overexpression of FBXL5 caused the decrease of CITED2 protein levels in a proteasome-dependent manner, and impaired the interaction between CITED2 and the CH1 domain of p300 in living cells. In undifferentiated mouse embryonic stem cells, the overexpression of FBXL5 also reduced Cited2 protein levels. Finally, we evidenced that FBXL5 overexpression and the consequent degradation of CITED2 enabled the transcriptional activity of the N-terminal transactivation domain of HIF-1α. Collectively, our results highlighted a novel molecular interaction between CITED2 and FBXL5, which might regulate the steady state CITED2 protein levels and contribute to the modulation of gene expression by HIF-1α.

Comparison of in vitro methods for carboxylesterase activity determination in immortalized cells representative of the intestine, liver and kidney.

Herein we compare the fluorimetric determination of total and specific carboxylesterase activity in immortalized human derived living cells and in cell lysates. The cell lines chosen are representative of metabolism occurring in the intestine (Caco-2 and HT-29), kidney (HEK-293T) and liver (Hep G2). Caco-2 and HT-29, as cells prone to differentiation, were tested along the differentiation time. For evaluation of both methods when distinguishing activity of different carboxylesterases, HEK-293T transfected with the human carboxylestarase-2 (hCES2) were also tested. Application to Caco-2 or HT-29 cells demonstrated higher activity detected in cell lysates than in cell monolayers. The difference is most striking when comparing the methods at different stages of Caco-2 and HT-29 cell maturation, highlighting substrate accessibility as a limiting step in the in vivo hydrolysis rates (possibly limited by plasma and Endoplasmic Reticulum membrane permeability) with increasing relevance as the cells differentiate. Application to Hep G2 or to hCES2 transfected and non-transfected HEK-293T cells, demonstrated a tendency for higher sensitivity in living cell suspensions than that obtained with the cell lysates which indicates the importance of cell environment in the maintenance of enzyme activity. However, quantification of hCES2 activity relative to total esterase, or to total carboxylesterase activity, was not significantly different in any case. The results herein presented help to clarify which method is best suited for evaluation of carboxylesterase activity in vitro depending on the final goal of the study.

Skin colour, skin redness and melanin biometric measurements: comparison study between Antera(®) 3D, Mexameter(®) and Colorimeter(®).

BACKGROUND: The actual skin colorimeters analyse reflect values from a limited number of broad spectral bands and consequently present limited reproducibility and specificity when measuring skin colour. Here, Antera 3D(®) , a new device which uses reflectance mapping of seven different light wavelengths spanning the entire visible spectrum, has been compared with Mexameter(®) MX-18, an established narrow-band reflectance spectrophotometer and with Colorimeter(®) CL-400, an established tristimulus colorimetric instrument. METHODS: Thirty volunteers were exposed to a controlled ultra-violet B light. Measurements with Antera 3D(®) , Mexameter(®) MX-18 and Colorimeter(®) CL-400 were done before treatment and after 2, 7 and 14 days. RESULTS: Antera 3D(®) showed to have a better sensitivity and specificity than Mexameter(®) MX-18 regarding the melanin parameter. A similar sensitivity between Antera 3D(®) and Mexameter(®) MX-18 was found for erythema determination and also for the Commission Internationale de l'Eclairage L*, a* and b* parameters between Antera 3D(®) and Colorimeter(®) CL-400. Good correlations were observed for all the parameters analysed. Repeatability of Mexameter(®) MX-18 and Colorimeter(®) CL-400 values were lower than that of Antera 3D(®) for all the parameters analysed. CONCLUSION: Antera 3D(®) , such as Mexameter(®) MX-18 and Colorimeter(®) CL-400, are robust, sensitive and precise equipment for the skin colour analysis.