Miracle-dz/UniFAR-FTUs huggingface dataset:
Which Milk during the Second Year of Life: A Personalized Choice for a Healthy Future?

Nutrition in early life is a crucial element to provide all essential substrates for growth. Although this statement may appear obvious, several studies have shown how the intake of micro and macronutrients in toddlers differs a lot from the recommendations of scientific societies. Protein intake often exceeds the recommended amount, while the intake of iron and zinc is frequently insufficient, as well as Vitamin D. Nutritional errors in the first years of life can negatively impact the health of the child in the long term. To date, no clear evidence on which milk is suggested during the second year of life is yet to be established. In this study, we compare the nutrient profiles of cow’s milk and specific formulas as well as nutritional risks in toddlers linked to growth and childhood obesity development. The purpose of this review is to resume the latest clinical studies on toddlers fed with cow’s milk or young children formula (YCF), and the potential risks or benefits in the short and long term.
Mechano-Immunomodulation in Space: Mechanisms Involving Microgravity-Induced Changes in T Cells

Of the most prevalent issues surrounding long-term spaceflight, the sustainability of human life and the maintenance of homeostasis in an extreme environment are of utmost concern. It has been observed that the human immune system is dysregulated in space as a result of gravitational unloading at the cellular level, leading to potential complications in astronaut health. A plethora of studies demonstrate intracellular changes that occur due to microgravity; however, these ultimately fall short of identifying the underlying mechanisms and dysfunctions that cause such changes. This comprehensive review covers the changes in human adaptive immunity due to microgravity. Specifically, there is a focus on uncovering the gravisensitive steps in T cell signaling pathways. Changes in gravitational force may lead to interrupted immune signaling cascades at specific junctions, particularly membrane and surface receptor-proximal molecules. Holistically studying the interplay of signaling with morphological changes in cytoskeleton and other cell components may yield answers to what in the T cell specifically experiences the consequences of microgravity. Fully understanding the nature of this problem is essential in order to develop proper countermeasures before long-term space flight is conducted.
Advances Achieved by Ionic-Liquid-Based Materials as Alternative Supports and Purification Platforms for Proteins and Enzymes

Ionic liquids (ILs) have been applied in several fields in which enzymes and proteins play a noteworthy role, for instance in biorefinery, biotechnology, and pharmaceutical sciences, among others. Despite their use as solvents and co-solvents, their combination with materials for protein- and enzyme-based applications has raised significant attention in the past few years. Among them, significant advances were brought by supported ionic liquids (SILs), in which ILs are introduced to modify the surface and properties of materials, e.g., as ligands when covalently bond or when physiosorbed. SILs have been mainly investigated as alternative supports for enzymes in biocatalysis and as new supports in preparative liquid chromatography for the purification of high-value proteins and enzymes. In this manuscript, we provide an overview on the most relevant advances by using SILs as supports for enzymes and as purification platforms for a variety of proteins and enzymes. The interaction mechanisms occurring between proteins and SILs/ILs are highlighted, allowing the design of efficient processes involving SILs. The work developed is discussed in light of the respective development phase and innovation level of the applied technologies. Advantages and disadvantages are identified, as well as the missing links to pave their use in relevant applications.
Real-Life Impact of Glucocorticoid Treatment in COVID-19 Mortality: A Multicenter Retrospective Study

We aimed to determine the impact of steroid use in COVID-19 in-hospital mortality, in a retrospective cohort study of the SEMICOVID19 database of admitted patients with SARS-CoV-2 laboratory-confirmed pneumonia from 131 Spanish hospitals. Patients treated with corticosteroids were compared to patients not treated with corticosteroids; and adjusted using a propensity-score for steroid treatment. From March–July 2020, 5.262 (35.26%) were treated with corticosteroids and 9.659 (64.73%) were not. In-hospital mortality overall was 20.50%; it was higher in patients treated with corticosteroids than in controls (28.5% versus 16.2%, OR 2.068 [95% confidence interval; 1.908 to 2.242]; p = 0.0001); however, when adjusting by occurrence of ARDS, mortality was significantly lower in the steroid group (43.4% versus 57.6%; OR 0.564 [95% confidence interval; 0.503 to 0.633]; p = 0.0001). Moreover, the greater the respiratory failure, the greater the impact on mortality of the steroid treatment. When adjusting these results including the propensity score as a covariate, in-hospital mortality remained significantly lower in the steroid group (OR 0.774 [0.660 to 0.907], p = 0.002). Steroid treatment reduced mortality by 24% relative to no steroid treatment (RRR 0.24). These results support the use of glucocorticoids in COVID-19 in this subgroup of patients.
Coronary Artery Disease in Women: A Comprehensive Appraisal

Coronary artery disease (CAD) is a significant cause of illness and death amongst women. The pathophysiology, manifestations, and outcomes of CVD and CAD differ between sexes. These sex differences remain under-recognized. The aim of this review is to highlight and raise awareness of the burden and unique aspects of CAD in women. It details the unique pathophysiology of CAD in women, cardiovascular risk factors in women (both traditional and sex-specific), the clinical presentation of CAD in women, and the range of disease in obstructive and non-obstructive CAD in women.
3D Printing of Macro Porous Sol-Gel Derived Bioactive Glass Scaffolds and Assessment of Biological Response

3D printing emerged as a potential game-changer in the field of biomedical engineering. Robocasting in particular has shown excellent capability to produce custom-sized porous scaffolds from pastes with suitable viscoelastic properties. The materials and respective processing methods developed so far still need further improvements in order to obtain completely satisfactory scaffolds capable of providing both the biological and mechanical properties required for successful and comprehensive bone tissue regeneration. This work reports on the sol-gel synthesis of an alkali-free bioactive glass and on its characterization and processing ability towards the fabrication of porous scaffolds by robocasting. A two-fold increase in milling efficiency was achieved by suitably adjusting the milling procedures. The heat treatment temperature exerted a profound effect on the surface area of mesoporous powders. Robocasting inks containing 35 vol.% solids were prepared, and their flow properties were characterized by rheological tests. A script capable of preparing customizable CAD scaffold geometries was developed. The printing process was adjusted to increase the technique’s resolution. The mechanical properties of the scaffolds were assessed through compressive strength tests. The biomineralization ability and the biological performance were assessed by immersing the samples in simulated body fluid (SBF) and through MTT assays, respectively. The overall results demonstrated that scaffolds with macro porous features suitable for bone ingrowth (pore sizes of ~340 μm after sintering, and a porosity fraction of ~70%) in non-load-bearing applications could be successfully fabricated by 3D printing from the bioactive glass inks. Moreover, the scaffolds exhibited good biomineralization activity and good biocompatibility with human keratinocytes, suggesting they are safe and thus suited for the intended biomedical applications.
Properties of Particleboard from Oil Palm Biomasses Bonded with Citric Acid and Tapioca Starch

The study investigated the effects of the addition of starch on the properties of oil palm biomass particleboard bonded with citric acid. Three kinds of oil palm biomasses were used in this study for the fabrication of particleboard, namely, oil palm frond (OPF), oil palm trunk (OPT), and empty fruit bunch (EFB) particles. Citric acid and tapioca starch at the mixing ratios of 100:0, 87.5:12.5, and 75:25 were prepared at a 60% solid content. A 30% resin content based on the oven-dried weight of the oil palm biomass particles was used. The sprayed particles were pre-dried at 80 °C for 12 h before being hot-pressed at 180 °C and 4 MPa pressure for 10 min. The physical and mechanical properties of the particleboard were evaluated. The mixtures of citric acid and tapioca starch were characterized by thermogravimetric analysis (TGA). Thermal stability of citric acid was reduced after the addition of tapioca starch. The addition of 12.5% tapioca starch improved the bending strength of the particleboard but increased the thickness swelling slightly. All UF-bonded particleboard exhibited significantly inferior performance than that of citric-acid-bonded particleboard. Citric-acid-bonded particleboard maintained its original shape after being subjected to a cyclic-aging treatment, while the UF-bonded particleboard disintegrated half way through the treatment. The performance of EFB particleboard was significantly inferior to its OPT and OPF counterparts.
Assessing Fast Structure Formation Processes in Isotactic Polypropylene with a Combination of Nanofocus X-ray Diffraction and In Situ Nanocalorimetry

A combination of in situ nanocalorimetry with simultaneous nanofocus 2D Wide-Angle X-ray Scattering (WAXS) was used to study polymorphic behaviour and structure formation in a single micro-drop of isotactic polypropylene (iPP) with defined thermal history. We were able to generate, detect, and characterize a number of different iPP morphologies using our custom-built ultrafast chip-based nanocalorimetry instrument designed for use with the European Synchrotron Radiation Facility (ESRF) high intensity nanofocus X-ray beamline facility. The detected iPP morphologies included monoclinic alpha-phase crystals, mesophase, and mixed morphologies with different mesophase/crystalline compositional ratios. Monoclinic crystals formed from the mesophase became unstable at heating rates above 40 K s−1 and showed melting temperatures as low as ~30 K below those measured for iPP crystals formed by slow cooling. We also studied the real-time melt crystallization of nanogram-sized iPP samples. Our analysis revealed a mesophase nucleation time of around 1 s and the co-existence of mesophase and growing disordered crystals at high supercooling ≤328 K. The further increase of the iPP crystallization temperature to 338 K changed nucleation from homogeneous to heterogeneous. No mesophase was detected above 348 K. Low supercooling (≥378 K) led to the continuous growth of the alpha-phase crystals. In conclusion, we have, for the first time, measured the mesophase nucleation time of supercooled iPP melted under isothermal crystallization conditions using a dedicated experimental setup designed to allow simultaneous ultrafast chip-based nanocalorimetry and nanofocus X-ray diffraction analyses. We also provided experimental evidence that upon heating, the mesophase converts directly into thermodynamically stable monoclinic alpha-phase crystals via perfection and reorganization and not via partial melting. The complex phase behaviour of iPP and its dependence on both crystallization temperature and time is presented here using a time–temperature–transformation (TTT) diagram.
Withdrawal from cocaine conditioning progressively alters AMPA receptor‐mediated transmission in the ventral hippocampus

Drugs of abuse, such as cocaine, produce aberrant changes in synaptic transmission and plasticity that emerge throughout withdrawal. One region of the brain that displays a high degree of synaptic plasticity, as well as connectivity with mesolimbic structures such as the nucleus accumbens, is the ventral hippocampus (vH). Here, we investigated the effects of an escalating cocaine dosing schedule on vH CA1 excitatory transmission by measuring place preference and recording excitatory postsynaptic currents (EPSCs) at three different withdrawal time points: withdrawal day (WD) 2, 9 or 28. Behaviourally, this escalating cocaine‐conditioning protocol was capable of producing conditioned place preference that persisted through WD28. Physiologically, cocaine conditioning produced an increase in vH excitatory transmission on WD2 that appeared to be the result of an increase in calcium‐impermeable (CI)‐AMPA receptor density. Excitatory transmission was still enhanced in cocaine‐treated animals on WD9; however, a significant increase in the contribution of calcium‐permeable (CP)‐AMPA receptors to EPSCs was detected as compared with WD2. By WD28, these CP‐AMPA receptors provided a major contribution to vH CA1 excitatory transmission, resulting in synaptic responses distinct from WD2 and WD9. Taken together, these results highlight progressive changes in vH synaptic transmission during withdrawal that may enhance cocaine contextual associations.
Serum and Amniotic Fluid Metabolic Profile Changes in Response to Gestational Diabetes Mellitus and the Association with Maternal–Fetal Outcomes

This study was designed to identify serum and amniotic fluid (AF) metabolic profile changes in response to gestational diabetes mellitus (GDM) and explore the association with maternal–fetal outcomes. We established the GDM rat models by combining a high-fat diet (HFD) with an injection of low-dose streptozotocin (STZ), detected the fasting plasma glucose (FPG) of pregnant rats in the second and third trimester, and collected AF and fetal rats by cesarean section on gestational day 19 (GD19), as well as measuring the weight and crown–rump length (CRL) of fetal rats. We applied liquid chromatography–tandem mass spectrometry (LC-MS/MS) for the untargeted metabolomics analyses of serum and AF samples and then explored their correlation with maternal–fetal outcomes via the co-occurrence network. The results showed that 91 and 68 metabolites were upregulated and 125 and 78 metabolites were downregulated in serum and AF samples exposed to GDM, respectively. In maternal serum, the obvious alterations emerged in lipids and lipid-like molecules, while there were great changes in carbohydrate and carbohydrate conjugates, followed by amino acids, peptides, and analogs in amniotic fluid. The altered pathways both in serum and AF samples were amino acid, lipid, nucleotide, and vitamin metabolism pathways. In response to GDM, changes in the steroid hormone metabolic pathway occurred in serum, and an altered carbohydrate metabolism pathway was found in AF samples. Among differential metabolites in two kinds of samples, there were 34 common biochemicals shared by serum and AF samples, and a mutual significant association existed. These shared differential metabolites were implicated in several metabolism pathways, including choline, tryptophan, histidine, and nicotinate and nicotinamide metabolism, and among them, N1-methyl-4-pyridone-3-carboxamide, 5’-methylthioadenosine, and kynurenic acid were significantly associated with both maternal FPG and fetal growth. In conclusion, serum and AF metabolic profiles were remarkably altered in response to GDM. N1-Methyl-4-pyridone-3-carboxamide, 5’-methylthioadenosine, and kynurenic acid have the potential to be taken as biomarkers for maternal–fetal health status of GDM. The common and inter-related differential metabolites both in the serum and AF implied the feasibility of predicting fetal health outcomes via detecting the metabolites in maternal serum exposed to GDM.
SLITRK2, an X-linked modifier of the age at onset in C9orf72 frontotemporal lobar degeneration.

The G4C2-repeat expansion in C9orf72 is the most common cause of frontotemporal dementia and of amyotrophic lateral sclerosis. The variability of age at onset and phenotypic presentations is a hallmark of C9orf72 disease. In this study, we aimed to identify modifying factors of disease onset in C9orf72 carriers using a family-based approach, in pairs of C9orf72 carrier relatives with concordant or discordant age at onset. Linkage and association analyses provided converging evidence for a locus on chromosome Xq27.3. The minor allele A of rs1009776 was associated with an earlier onset (P = 1 × 10-5). The association with onset of dementia was replicated in an independent cohort of unrelated C9orf72 patients (P = 0.009). The protective major allele delayed the onset of dementia from 5 to 13 years on average depending on the cohort considered. The same trend was observed in an independent cohort of C9orf72 patients with extreme deviation of the age at onset (P = 0.055). No association of rs1009776 was detected in GRN patients, suggesting that the effect of rs1009776 was restricted to the onset of dementia due to C9orf72. The minor allele A is associated with a higher SLITRK2 expression based on both expression quantitative trait loci (eQTL) databases and in-house expression studies performed on C9orf72 brain tissues. SLITRK2 encodes for a post-synaptic adhesion protein. We further show that synaptic vesicle glycoprotein 2 and synaptophysin, two synaptic vesicle proteins, were decreased in frontal cortex of C9orf72 patients carrying the minor allele. Upregulation of SLITRK2 might be associated with synaptic dysfunctions and drives adverse effects in C9orf72 patients that could be modulated in those carrying the protective allele. How the modulation of SLITRK2 expression affects synaptic functions and influences the disease onset of dementia in C9orf72 carriers will require further investigations. In summary, this study describes an original approach to detect modifier genes in rare diseases and reinforces rising links between C9orf72 and synaptic dysfunctions that might directly influence the occurrence of first symptoms.
Reactive Oxygen Species Detection Using Fluorescence in Enchytraeus crypticus—Method Implementation through Ag NM300K Case Study

An imbalance between reactive oxygen species (ROS) and antioxidants in a living organism results in oxidative stress. Measures of such imbalance can be used as a biomarker of stress in ecotoxicology. In this study, we implemented the ROS detection method based on the oxidant-sensing probe dichloro-dihydro-fluorescein diacetate (DCFH-DA), detected by fluorescence microscopy, in Enchytraeus crypticus adults and cocoons, i.e., also covering the embryo stage. Hydrogen peroxide (H2O2), a well-known ROS inducer, was used both to optimize the method and as positive control. Implementation was successful, and the method was used to assess ROS formation in E. crypticus cocoons and adults when exposed to the reference silver nanomaterial Ag NM300K, at two effect concentrations (EC20 and EC50) for both hatching and reproduction over 3 and 7 days. The measured ROS levels varied with time, concentration, and developmental stage, with higher levels detected in adults compared with cocoons. In cocoons, ROS levels were higher at the EC20 than the EC50, which could be explained by non-monotonic concentration-response curve for hatching and reproduction, as previously observed. The increase in ROS levels at day 3 preceded the oxidative damage, as reported to occur later (day 7) in adults. The DCFH-DA method was successfully implemented here and can be further used as a new tool to detect ROS formation in E. crypticus, especially after short-term exposure to chemicals, including nanomaterials. We recommend the use of 3 and 7 days in the exposure design for this assessment.
BolTLP1, a Thaumatin-like Protein Gene, Confers Tolerance to Salt and Drought Stresses in Broccoli (Brassica oleracea L. var. Italica)

Plant thaumatin-like proteins (TLPs) play pleiotropic roles in defending against biotic and abiotic stresses. However, the functions of TLPs in broccoli, which is one of the major vegetables among the B. oleracea varieties, remain largely unknown. In the present study, bolTLP1 was identified in broccoli, and displayed remarkably inducible expression patterns by abiotic stress. The ectopic overexpression of bolTLP1 conferred increased tolerance to high salt and drought conditions in Arabidopsis. Similarly, bolTLP1-overexpressing broccoli transgenic lines significantly improved tolerance to salt and drought stresses. These results demonstrated that bolTLP1 positively regulates drought and salt tolerance. Transcriptome data displayed that bolTLP1 may function by regulating phytohormone (ABA, ethylene and auxin)-mediated signaling pathways, hydrolase and oxidoreductase activity, sulfur compound synthesis, and the differential expression of histone variants. Further studies confirmed that RESPONSE TO DESICCATION 2 (RD2), RESPONSIVE TO DEHYDRATION 22 (RD22), VASCULAR PLANT ONE-ZINC FINGER 2 (VOZ2), SM-LIKE 1B (LSM1B) and MALATE DEHYDROGENASE (MDH) physically interacted with bolTLP1, which implied that bolTLP1 could directly interact with these proteins to confer abiotic stress tolerance in broccoli. These findings provide new insights into the function and regulation of bolTLP1, and suggest potential applications for bolTLP1 in breeding broccoli and other crops with increased tolerance to salt and drought stresses.
Alleviative Effects of Exopolysaccharide Produced by Lactobacillus helveticus KLDS1.8701 on Dextran Sulfate Sodium-Induced Colitis in Mice

Ulcerative colitis (UC) is a non-specific chronic inflammatory disease with lesions located in the colon and rectum. The aim of this study was to evaluate the anti-inflammatory effects of exopolysaccharide-1 (EPS-1) isolated by L. helveticus KLDS1.8701 on UC. The anti-inflammatory effects of EPS-1 were studied using dextran sulphate sodium (DSS)-induced UC model. In vivo results showed that EPS-1 administration significantly ameliorated weight loss, colon shortening, disease activity index (DAI) score, myeloperoxidase (MPO) activity, and colon tissue damage. In addition, EPS-1 administration significantly decreased the levels of pro-inflammatory cytokines and increased levels of anti-inflammatory cytokines. Meanwhile, EPS-1 administration significantly up-regulated the expression of tight junction proteins and mucin. Furthermore, EPS-1 administration modulated gut microbiota composition caused by DSS and increased the short-chain fatty acids (SCFAs) levels. Collectively, our study showed the alleviative effects of EPS- isolated by L. helveticus KLDS1.8701 on DSS-induced UC via alleviating intestinal inflammation, improving mucosal barrier function, and modulating gut microbiota composition.
The Timing and Effects of Low-Dose Ethanol Treatment on Acetaminophen-Induced Liver Injury

Acetaminophen (APAP) overdose is the major cause of drug-induced liver injury and acute liver failure. Approximately 10% of APAP is metabolized by cytochrome P450 (CYP2E1) into toxic N-acetyl-p-benzoquinone imine (NAPQI). CYP2E1 also contributes to ethanol metabolism, especially during conditions of high blood ethanol concentration. Acute and chronic ethanol consumption appears to have opposite effects on APAP-induced liver injury. We determined the effects of different doses, pre- and post-treatment, and various schedules of ethanol exposure in APAP-induced liver injury. Treatment with ethanol (0.5 g/kg) after 1 h of APAP (300 mg/kg) administration decreased serum ALT levels, histopathological features, and inflammatory cell infiltration. Moreover, ethanol treatment 1 h after APAP treatment reduced APAP-induced liver injury compared with later administration. Interestingly, ethanol pretreatment did not provide any protective effect. Furthermore, ethanol treatment was associated with a significant decrease in ERK and AKT phosphorylation during the acute injury phase. Ethanol exposure also increased CYP2E1 expression and decreased PCNA expression during the liver regeneration phase.