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Open AccessReview
A Survey of Molecular Imaging of Opioid Receptors
Molecules 2019, 24(22), 4190; https://doi.org/10.3390/molecules24224190 (registering DOI) - 19 Nov 2019
Abstract
The discovery of endogenous peptide ligands for morphine binding sites occurred in parallel with the identification of three subclasses of opioid receptor (OR), traditionally designated as μ, δ, and κ, along with the more recently defined opioid-receptor-like (ORL1) receptor. Early efforts in opioid [...] Read more.
The discovery of endogenous peptide ligands for morphine binding sites occurred in parallel with the identification of three subclasses of opioid receptor (OR), traditionally designated as μ, δ, and κ, along with the more recently defined opioid-receptor-like (ORL1) receptor. Early efforts in opioid receptor radiochemistry focused on the structure of the prototype agonist ligand, morphine, although N-[methyl-11C]morphine, -codeine and -heroin did not show significant binding in vivo. [11C]Diprenorphine ([11C]DPN), an orvinol type, non-selective OR antagonist ligand, was among the first successful PET tracers for molecular brain imaging, but has been largely supplanted in research studies by the μ-preferring agonist [11C]carfentanil ([11C]Caf). These two tracers have the property of being displaceable by endogenous opioid peptides in living brain, thus potentially serving in a competition-binding model. Indeed, many clinical PET studies with [11C]DPN or [11C]Caf affirm the release of endogenous opioids in response to painful stimuli. Numerous other PET studies implicate μ-OR signaling in aspects of human personality and vulnerability to drug dependence, but there have been very few clinical PET studies of μORs in neurological disorders. Tracers based on naltrindole, a non-peptide antagonist of the δ-preferring endogenous opioid enkephalin, have been used in PET studies of δORs, and [11C]GR103545 is validated for studies of κORs. Structures such as [11C]NOP-1A show selective binding at ORL-1 receptors in living brain. However, there is scant documentation of δ-, κ-, or ORL1 receptors in healthy human brain or in neurological and psychiatric disorders; here, clinical PET research must catch up with recent progress in radiopharmaceutical chemistry. Full article
(This article belongs to the Special Issue Radiolabelled Molecules for Brain Imaging with PET and SPECT)
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Open AccessArticle
Exercise Mitigates the Loss of Muscle Mass by Attenuating the Activation of Autophagy during Severe Energy Deficit
Nutrients 2019, 11(11), 2824; https://doi.org/10.3390/nu11112824 (registering DOI) - 19 Nov 2019
Abstract
The loss of skeletal muscle mass with energy deficit is thought to be due to protein breakdown by the autophagy-lysosome and the ubiquitin-proteasome systems. We studied the main signaling pathways through which exercise can attenuate the loss of muscle mass during severe energy [...] Read more.
The loss of skeletal muscle mass with energy deficit is thought to be due to protein breakdown by the autophagy-lysosome and the ubiquitin-proteasome systems. We studied the main signaling pathways through which exercise can attenuate the loss of muscle mass during severe energy deficit (5500 kcal/day). Overweight men followed four days of caloric restriction (3.2 kcal/kg body weight day) and prolonged exercise (45 min of one-arm cranking and 8 h walking/day), and three days of control diet and restricted exercise, with an intra-subject design including biopsies from muscles submitted to distinct exercise volumes. Gene expression and signaling data indicate that the main catabolic pathway activated during severe energy deficit in skeletal muscle is the autophagy-lysosome pathway, without apparent activation of the ubiquitin-proteasome pathway. Markers of autophagy induction and flux were reduced by exercise primarily in the muscle submitted to an exceptional exercise volume. Changes in signaling are associated with those in circulating cortisol, testosterone, cortisol/testosterone ratio, insulin, BCAA, and leucine. We conclude that exercise mitigates the loss of muscle mass by attenuating autophagy activation, blunting the phosphorylation of AMPK/ULK1/Beclin1, and leading to p62/SQSTM1 accumulation. This includes the possibility of inhibiting autophagy as a mechanism to counteract muscle loss in humans under severe energy deficit. Full article
(This article belongs to the Special Issue Nutrition and Exercise Metabolism)
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Open AccessReview
The Role of MicroRNAs upon Epithelial-to-Mesenchymal Transition in Inflammatory Bowel Disease
Cells 2019, 8(11), 1461; https://doi.org/10.3390/cells8111461 (registering DOI) - 19 Nov 2019
Abstract
Increasing evidence suggest the significance of inflammation in the progression of cancer, for example the development of colorectal cancer in Inflammatory Bowel Disease (IBD) patients. Long-lasting inflammation in the gastrointestinal tract causes serious systemic complications and breaks the homeostasis of the intestine, where [...] Read more.
Increasing evidence suggest the significance of inflammation in the progression of cancer, for example the development of colorectal cancer in Inflammatory Bowel Disease (IBD) patients. Long-lasting inflammation in the gastrointestinal tract causes serious systemic complications and breaks the homeostasis of the intestine, where the altered expression of regulatory genes and miRNAs trigger malignant transformations. Several steps lead from acute inflammation to malignancies: epithelial-to-mesenchymal transition (EMT) and inhibitory microRNAs (miRNAs) are known factors during multistage carcinogenesis and IBD pathogenesis. In this review, we outline the interactions between EMT components and miRNAs that may affect cancer development during IBD. Full article
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Open AccessReview
NAD Analogs in Aid of Chemical Biology and Medicinal Chemistry
Molecules 2019, 24(22), 4187; https://doi.org/10.3390/molecules24224187 (registering DOI) - 19 Nov 2019
Abstract
Nicotinamide adenine dinucleotide (NAD) serves as an essential redox co-factor and mediator of multiple biological processes. Besides its well-established role in electron transfer reactions, NAD serves as a substrate for other biotransformations, which, at the molecular level, can be classified as protein post-translational [...] Read more.
Nicotinamide adenine dinucleotide (NAD) serves as an essential redox co-factor and mediator of multiple biological processes. Besides its well-established role in electron transfer reactions, NAD serves as a substrate for other biotransformations, which, at the molecular level, can be classified as protein post-translational modifications (protein deacylation, mono-, and polyADP-ribosylation) and formation of signaling molecules (e.g., cyclic ADP ribose). These biochemical reactions control many crucial biological processes, such as cellular signaling and recognition, DNA repair and epigenetic modifications, stress response, immune response, aging and senescence, and many others. However, the links between the biological effects and underlying molecular processes are often poorly understood. Moreover, NAD has recently been found to tag the 5′-ends of some cellular RNAs, but the function of these NAD-capped RNAs remains largely unrevealed. Synthetic NAD analogs are invaluable molecular tools to detect, monitor, structurally investigate, and modulate activity of NAD-related enzymes and biological processes in order to aid their deeper understanding. Here, we review the recent advances in the design and development of NAD analogs as probes for various cellular NAD-related enzymes, enzymatic inhibitors with anticancer or antimicrobial therapeutic potential, and other NAD-related chemical biology tools. We focus on research papers published within the last 10 years. Full article
(This article belongs to the Special Issue Design and Synthesis of Bioactive Compounds)
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Open AccessArticle
Electric Mobility and Smart Mobility Concepts—Restrained Uptake in German Cities
World Electr. Veh. J. 2019, 10(4), 81; https://doi.org/10.3390/wevj10040081 (registering DOI) - 19 Nov 2019
Abstract
Ninety German cities exceeded the European threshold on NO2 in 2016, 65 of those cities developed countermeasures and strategies that were published in Green City Plans (GCP). In the scope of this study, 55 publicly available GCPs were evaluated in order to [...] Read more.
Ninety German cities exceeded the European threshold on NO2 in 2016, 65 of those cities developed countermeasures and strategies that were published in Green City Plans (GCP). In the scope of this study, 55 publicly available GCPs were evaluated in order to assess their potential for traffic turnaround at a municipal level. All GCPs were analyzed to determine in which of the mentioned five to seven fields of action the respective city had planned measures and which fields of action were prioritized. A more in-depth qualitative analysis of the main topics: Electric mobility, public transport, and mobility concepts was carried out. To get a better understanding of the potential impact of the measures elaborated in the GCPs, complementary information on municipal fleet vehicle stocks, requirements of charging infrastructure for public buses and results of the European roadmap on mobility concepts are given. The evaluation of the GCPs showed that to this day, city administrations mainly optimize the current system by measures of electrification and digitization. Electrification of municipal fleets, car-sharing fleets, and public transport buses is in the focus of the strategies. Instruments to increase non-motorised transport, sustainable commercial transport, and/or mobility concepts are mentioned, but play a minor role. However, there still has been no system change in Germany. Therefore, a substantial turnaround of the transport system (“Verkehrswende”) is necessary. This applies to integrated urban and transport planning, flexible, strong, fast PT, non-motorised and flexible operating systems. Full article
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Open AccessArticle
Temporal Trends in Maternal Food Intake Frequencies and Associations with Gestational Diabetes: The Cambridge Baby Growth Study
Nutrients 2019, 11(11), 2822; https://doi.org/10.3390/nu11112822 (registering DOI) - 19 Nov 2019
Abstract
Previous studies have suggested that in the first decade of this century the incidence of gestational diabetes (GDM) in pregnancy rose worldwide. In the Cambridge Baby Growth Study cohort we observed that this temporal trend was associated with an index of multiple deprivation [...] Read more.
Previous studies have suggested that in the first decade of this century the incidence of gestational diabetes (GDM) in pregnancy rose worldwide. In the Cambridge Baby Growth Study cohort we observed that this temporal trend was associated with an index of multiple deprivation and reductions in indices of insulin secretion. Deprivation level was not directly associated with GDM, suggesting that the temporal trend may relate more to other factors linked to it, such as dietary composition. In this study we investigated temporal trends in perceived food intake frequencies, derived from a qualitative, short questionnaire, in 865 pregnant Cambridge Baby Growth Study (CBGS) recruits. A number of food frequency ranks showed both temporal trends and associations with GDM, but of note is the frequency of egg consumption (negative temporal trend p = 0.03, slope = −6.2 ranks/year; negative association with GDM p = 3.0 × 10−8, slope = −0.002 increased risk/rank) as it was also positively associated with the insulin disposition index (p = 1.17 × 10−3, slope = 0.42 ranks. L/mmoL). These results are consistent with a potential protective effect of factors related to the frequency of egg consumption in pregnancy. Such factors may have contributed to the observed temporal trend in GDM risk but the overall detectable effect appears to have been small. Full article
(This article belongs to the Special Issue Nutrition for Gestational Diabetes)
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Open AccessArticle
Plasma versus Erythrocyte Vitamin E in Renal Transplant Recipients, and Duality of Tocopherol Species
Nutrients 2019, 11(11), 2821; https://doi.org/10.3390/nu11112821 (registering DOI) - 19 Nov 2019
Abstract
Redox imbalance is an adverse on-going phenomenon in renal transplant recipients (RTR). Vitamin E has important antioxidant properties that counterbalance its deleterious effects. However, plasma vitamin E affinity with lipids challenges interpretation of its levels. To test the hypothesis that erythrocyte membranes represent [...] Read more.
Redox imbalance is an adverse on-going phenomenon in renal transplant recipients (RTR). Vitamin E has important antioxidant properties that counterbalance its deleterious effects. However, plasma vitamin E affinity with lipids challenges interpretation of its levels. To test the hypothesis that erythrocyte membranes represent a lipids-independent specimen to estimate vitamin E status, we performed a cross-sectional study in a cohort of adult RTR (n = 113) recruited in a university setting (2015–2018). We compared crude and total lipids-standardized linear regression-derived coefficients of plasma and erythrocyte tocopherol species in relation to clinical and laboratory parameters. Strongly positive associations of fasting lipids with plasma tocopherol became inverse, rather than absent, in total lipids-standardized analyses, indicating potential overadjustment. Whilst, no variables from the lipids domain were associated with the tocopherol species measured from erythrocyte specimens. In relation to inflammatory status and clinical parameters with antioxidant activity, we found associations in directions that are consistent with either beneficial or adverse effects concerning α- or γ-tocopherol, respectively. In conclusion, erythrocytes offer a lipids-independent alternative to estimate vitamin E status and investigate its relationship with parameters over other biological domains. In RTR, α- and γ-tocopherol may serve as biomarkers of relatively lower or higher vulnerability to oxidative stress and inflammation, noticeably in opposite directions. Full article
(This article belongs to the Special Issue Vitamin E: Uses, Benefits, Emerging Aspects, and RDA)
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Open AccessArticle
High-Resolution Image Inpainting Based on Multi-Scale Neural Network
Electronics 2019, 8(11), 1370; https://doi.org/10.3390/electronics8111370 (registering DOI) - 19 Nov 2019
Abstract
Although image inpainting based on the generated adversarial network (GAN) has made great breakthroughs in accuracy and speed in recent years, they can only process low-resolution images because of memory limitations and difficulty in training. For high-resolution images, the inpainted regions become blurred [...] Read more.
Although image inpainting based on the generated adversarial network (GAN) has made great breakthroughs in accuracy and speed in recent years, they can only process low-resolution images because of memory limitations and difficulty in training. For high-resolution images, the inpainted regions become blurred and the unpleasant boundaries become visible. Based on the current advanced image generation network, we proposed a novel high-resolution image inpainting method based on multi-scale neural network. This method is a two-stage network including content reconstruction and texture detail restoration. After holding the visually believable fuzzy texture, we further restore the finer details to produce a smoother, clearer, and more coherent inpainting result. Then we propose a special application scene of image inpainting, that is, to delete the redundant pedestrians in the image and ensure the reality of background restoration. It involves pedestrian detection, identifying redundant pedestrians and filling in them with the seemingly correct content. To improve the accuracy of image inpainting in the application scene, we proposed a new mask dataset, which collected the characters in COCO dataset as a mask. Finally, we evaluated our method on COCO and VOC dataset. the experimental results show that our method can produce clearer and more coherent inpainting results, especially for high-resolution images, and the proposed mask dataset can produce better inpainting results in the special application scene. Full article
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Open AccessArticle
The Role of Environmental Tax in Alleviating the Impact of Environmental Pollution on Residents’ Happiness in China
Int. J. Environ. Res. Public Health 2019, 16(22), 4574; https://doi.org/10.3390/ijerph16224574 (registering DOI) - 19 Nov 2019
Abstract
Background: Environmental tax has been implemented by the government in response to the demands of the residents to control environmental pollution. However, a tax has a wide effect on many interacting aspects of the society. It remains unknown whether enacting an environmental [...] Read more.
Background: Environmental tax has been implemented by the government in response to the demands of the residents to control environmental pollution. However, a tax has a wide effect on many interacting aspects of the society. It remains unknown whether enacting an environmental tax for the government can improve the residents’ happiness. This study aimed to examine the impact of air and water pollution on residents’ happiness and evaluate whether an environmental tax can alleviate the impact of air and water pollution on residents’ happiness. Methods: Based on the 2015 Chinese General Social Survey Data, 28 provinces in China were divided into two categories according to their environmental tax rates: baseline-tax areas (n = 13) and high-tax areas (n = 15). The ordered probit model was used to analyze the impact of air and water pollution on the residents’ happiness in baseline-tax areas and high-tax areas, respectively. The Chow Test was used to test whether the impact of environmental pollution on happiness was different between baseline-tax areas and high-tax areas. Results: The impact of air pollution on residents’ happiness was statistically significant in the baseline-tax areas (coefficient −0.162, 95% confidence interval (CI) −0.239, −0.086, p < 0.001), but the significance was weakened in the high-tax areas (coefficient −0.030, 95% CI −0.060, 0.000, p = 0.051). The Chow Test showed that the absolute value of the regression coefficient in the baseline-tax areas was significantly higher than the value in the high-tax areas (F = 12.712, p < 0.001). Similarly, the impact of water pollution on residents’ happiness was statistically significant (coefficient −0.264, 95% CI −0.353, −0.174, p < 0.001) in the baseline-tax areas and in the high-tax areas (coefficient −0.063, 95% CI −0.091, −0.035, p < 0.001), but the Chow Test showed that the absolute value of the regression coefficient in the baseline-tax areas was significantly higher than the value in the high-tax areas (F = 13.758, p < 0.001). Conclusions: Both air and water pollution impair residents’ happiness. The present study shows for the first time that enacting an environmental tax significantly alleviates the negative effect of air and water pollution on residents’ happiness. The findings of the present study provide empirical evidence for the government to levy environmental tax. Full article
Open AccessFeature PaperArticle
Looking for Energy Losses of a Rotary Permanent Magnet Magnetic Refrigerator to Optimize Its Performances
Energies 2019, 12(22), 4388; https://doi.org/10.3390/en12224388 (registering DOI) - 19 Nov 2019
Abstract
In this paper, an extensive study on the energy losses of a magnetic refrigerator prototype developed at University of Salerno, named ‘8MAG’, is carried out with the aim to improve the performance of such a system. The design details of ‘8MAG’ evidences both [...] Read more.
In this paper, an extensive study on the energy losses of a magnetic refrigerator prototype developed at University of Salerno, named ‘8MAG’, is carried out with the aim to improve the performance of such a system. The design details of ‘8MAG’ evidences both mechanical and thermal losses, which are mainly attributed to the eddy currents generation into the support of the regenerators (magnetocaloric wheel) and the parasitic heat load of the rotary valve. The latter component is fundamental since it imparts the direction of the heat transfer fluid distribution through the regenerators and it serves as a drive shaft for the magnetic assembly. The energy losses concerning eddy currents and parasitic heat load are evaluated by two uncoupled models, which are validated by experimental data obtained with different operating conditions. Then, the achievable coefficient of performance (COP) improvements of ‘8MAG’ are estimated, showing that reducing eddy currents generation (by changing the material of the magnetocaloric wheel) and the parasitic heat load (enhancing the insulation of the rotary valve) can lead to increase the COP from 2.5 to 2.8 (+12.0%) and 3.0 (+20%), respectively, and to 3.3 (+32%), combining both improvements, with an hot source temperature of 22 °C and 2 K of temperature span. Full article
(This article belongs to the Special Issue Refrigeration Systems and Applications)
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Open AccessReview
Nucleocytoplasmic Shuttling of STATs. A Target for Intervention?
Cancers 2019, 11(11), 1815; https://doi.org/10.3390/cancers11111815 (registering DOI) - 19 Nov 2019
Abstract
Signal transducer and activator of transcription (STAT) proteins are transcription factors that in the latent state are located predominantly in the cytoplasm. Activation of STATs through phosphorylation of a single tyrosine residue results in nuclear translocation. The requirement of tyrosine phosphorylation for nuclear [...] Read more.
Signal transducer and activator of transcription (STAT) proteins are transcription factors that in the latent state are located predominantly in the cytoplasm. Activation of STATs through phosphorylation of a single tyrosine residue results in nuclear translocation. The requirement of tyrosine phosphorylation for nuclear accumulation is shared by all STAT family members but mechanisms of nuclear translocation vary between different STATs. These differences offer opportunities for specific intervention. To achieve this, the molecular mechanisms of nucleocytoplasmic shuttling of STATs need to be understood in more detail. In this review we will give an overview on the various aspects of nucleocytoplasmic shuttling of latent and activated STATs with a special focus on STAT3 and STAT5. Potential targets for cancer treatment will be identified and discussed. Full article
(This article belongs to the Special Issue Targeting STAT3 and STAT5 in Cancer)
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Open AccessArticle
The Optimization of Gel Preparations Using the Active Compounds of Arabica Coffee Ground Nanoparticles
Sci. Pharm. 2019, 87(4), 32; https://doi.org/10.3390/scipharm87040032 (registering DOI) - 19 Nov 2019
Abstract
Arabica coffee (Coffea arabica L.) ground nanoparticles contain phenolics compounds that have anti-inflammatory effects, so they can be used as sources of active compounds in anti-inflammatory gel preparations. This study aims to determine the optimum formulation of anti-inflammatory gel preparations using Arabica [...] Read more.
Arabica coffee (Coffea arabica L.) ground nanoparticles contain phenolics compounds that have anti-inflammatory effects, so they can be used as sources of active compounds in anti-inflammatory gel preparations. This study aims to determine the optimum formulation of anti-inflammatory gel preparations using Arabica coffee ground nanoparticles as active compounds. Treatment optimization was performed using a Response Surface Methodology according to the Box-Behnken Design with a quadratic model in the Design Expert Version 10.0.3.0 software. In this study we used three factors (x): carbopol 940, triethanolamine (TEA), and nanoparticles, each of which consists of three levels, the response (y) observed including the acidity degree (pH), spreadability, viscosity and total phenolic content. ANOVA analysis results show that the quadratic model is very appropriate since it produces a high R2 value and a low PRESS value for all responses, as well as significant p-values (<0.0500) and an insignificant lack of Fit values (p-value> 5%). The optimum formulations for the gel preparations of the Arabica coffee ground nanoparticles obtained in this study are carbopol 940 (0.569%), TEA (0.468%), and nanoparticles (3.000%), which have values w/o an interval (0.994) and a desirable (0.981) response to acidity (5.212), spreadability (5.850 cm), viscosity (3734.244 cps) and total phenolic content (669.227 µgGAE/g). Full article
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Open AccessArticle
Direct Observation of Monolayer MoS2 Prepared by CVD Using In-Situ Differential Reflectance Spectroscopy
Nanomaterials 2019, 9(11), 1640; https://doi.org/10.3390/nano9111640 (registering DOI) - 19 Nov 2019
Abstract
The in-situ observation is of great significance to the study of the growth mechanism and controllability of two-dimensional transition metal dichalcogenides (TMDCs). Here, the differential reflectance spectroscopy (DRS) was performed to monitor the growth of molybdenum disulfide (MoS2) on a SiO [...] Read more.
The in-situ observation is of great significance to the study of the growth mechanism and controllability of two-dimensional transition metal dichalcogenides (TMDCs). Here, the differential reflectance spectroscopy (DRS) was performed to monitor the growth of molybdenum disulfide (MoS2) on a SiO2/Si substrate prepared by chemical vapor deposition (CVD). A home-built in-situ DRS setup was applied to monitor the growth of MoS2 in-situ. The formation and evolution of monolayer MoS2 are revealed by differential reflectance (DR) spectra. The morphology, vibration mode, absorption characteristics and thickness of monolayer MoS2 have been confirmed by optical microscopy, Raman spectroscopy, ex-situ DR spectra, and atomic force microscopy (AFM) respectively. The results demonstrated that DRS was a powerful tool for in-situ observations and has great potential for growth mechanism and controllability of TMDCs prepared by CVD. To the best of the authors’ knowledge, it was the first report in which the CVD growth of two-dimensional TMDCs has been investigated in-situ by reflectance spectroscopy. Full article
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Open AccessCommunication
Impact of Vitamin D on Physical Efficiency and Exercise Performance—A Review
Nutrients 2019, 11(11), 2826; https://doi.org/10.3390/nu11112826 (registering DOI) - 19 Nov 2019
Abstract
Vitamin D deficiency amongst athletes and the general population seems to be a prominent problem. The most recognized role of vitamin D is its regulation of calcium homeostasis; there is a strong relationship between vitamin D and bone health. Moreover, its concentrations are [...] Read more.
Vitamin D deficiency amongst athletes and the general population seems to be a prominent problem. The most recognized role of vitamin D is its regulation of calcium homeostasis; there is a strong relationship between vitamin D and bone health. Moreover, its concentrations are associated with muscle function and immune response in both the general and athletic populations. Vitamin D level is strongly connected with the presence of VDRs (vitamin D receptors) in most human extraskeletal cells. Expression of multiple myogenic transcription factors enhancing muscle cell proliferation and differentiation is caused by an exposure of skeletal muscles to vitamin D. The aim of this review is to summarize current understanding of the significance of vitamin D on exercise performance and physical efficiency, as well to analyze the impact of vitamin D on multiple potential mechanisms. More high-quality research studies, considering free 25(OH)D as a better marker of vitamin D status, the baseline level of 25(OH)D and multiple pathways of vitamin D acting and usage in athletes are required. Full article
(This article belongs to the Special Issue Vitamin D and Sport Performance)

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