Miracle-dz/UniFAR-FTUs huggingface dataset:
β-Catenin Regulates Cardiac Energy Metabolism in Sedentary and Trained Mice

The role of canonical Wnt signaling in metabolic regulation and development of physiological cardiac hypertrophy remains largely unknown. To explore the function of β-catenin in the regulation of cardiac metabolism and physiological cardiac hypertrophy development, we used mice heterozygous for cardiac-specific β-catenin knockout that were subjected to a swimming training model. β-Catenin haploinsufficient mice subjected to endurance training displayed a decreased β-catenin transcriptional activity, attenuated cardiomyocytes hypertrophic growth, and enhanced activation of AMP-activated protein kinase (AMPK), phosphoinositide-3-kinase–Akt (Pi3K–Akt), and mitogen-activated protein kinase/extracellular signal-regulated kinases 1/2 (MAPK/Erk1/2) signaling pathways compared to trained wild type mice. We further observed an increased level of proteins involved in glucose aerobic metabolism and β-oxidation along with perturbed activity of mitochondrial oxidative phosphorylation complexes (OXPHOS) in trained β-catenin haploinsufficient mice. Taken together, Wnt/β-catenin signaling appears to govern metabolic regulatory programs, sustaining metabolic plasticity in adult hearts during the adaptation to endurance training.
Correlations between Basal Trace Minerals and Hormones in Middle and Long-Distance High-Level Male Runners

Several essential trace minerals play an important role in the endocrine system; however, toxic trace minerals have a disruptive effect. The aim of this research was to determine basal concentrations and the possible correlations between trace minerals in plasma and several plasma hormones in runners. Sixty high-level male endurance runners (21 ± 3 years; 1.77 ± 0.05 m; 64.97 ± 7.36 kg) participated in the present study. Plasma hormones were analyzed using an enzyme-linked immunosorbent assay (ELISA) and plasma trace minerals were analyzed with inductively coupled plasma mass spectrometry (ICP-MS). Correlations and simple linear regression were used to assess the association between trace minerals and hormones. Plasma testosterone concentrations were inversely correlated with manganese (r = −0.543; β = −0.410; p < 0.01), selenium (r = −0.292; β = −0.024; p < 0.05), vanadium (r = −0.406; β = −1.278; p < 0.01), arsenic (r = −0.336; β = −0.142; p < 0.05), and lead (r = −0.385; β = −0.418; p < 0.01). Plasma luteinizing hormone (LH) levels were positively correlated with arsenic (r = 0.298; β = 0.327; p < 0.05) and cesium (r = 0.305; β = 2.272; p < 0.05), and negatively correlated with vanadium (r = −0.303; β = −2.467; p < 0.05). Moreover, cortisol concentrations showed significant positive correlations with cadmium (r = 0.291; β = 209.01; p < 0.05). Finally, insulin concentrations were inversely related to vanadium (r = −0.359; β = −3.982; p < 0.05). In conclusion, endurance runners living in areas with high environmental levels of toxic minerals should check their concentrations of anabolic hormones.
Addition of Lymphatic Stimulating Self-Care Practices Reduces Acute Attacks among People Affected by Moderate and Severe Lower-Limb Lymphedema in Ethiopia, a Cluster Randomized Controlled Trial

Lymphedema causes disability and exacerbates poverty in many countries. The management of lymphatic filariasis (LF) and podoconiosis-related lymphedema involves daily hygiene to reduce secondary infections, but self-massage and deep-breathing, which have proven beneficial in cancer-related lymphedema, are not included. A cluster randomized trial in northern Ethiopia investigated the effects of lymphatic stimulation for people affected by moderate to severe lymphedema. Participants were allocated to either standard (control n = 59) or enhanced (intervention n = 67) self-care groups. Primary outcomes were lymphedema stage, mid-calf circumference, and tissue compressibility. Secondary outcomes were the frequency and duration of acute attacks. After 24 weeks, fewer patients were assessed as severe (control −37.8%, intervention −42.4%, p = 0.15) and there were clinically relevant changes in mid-calf tissue compressibility but not circumference. There was a significant between-group difference in patients who reported any acute attacks over the study period (control n = 22 (38%), intervention n = 7 (12%), p = 0.014). Daily lymphedema self-care resulted in meaningful benefits for all participants with a greater reduction in acute episodes among people performing lymphatic stimulation. Observations of a change in lymphedema status support earlier findings in Bangladesh and extend the demonstrated benefits of enhanced self-care to people affected by podoconiosis.
Oxidative DNA Damage, Inflammatory Signature, and Altered Erythrocytes Properties in Diamond-Blackfan Anemia

Molecular pathophysiology of Diamond-Blackfan anemia (DBA) involves disrupted erythroid-lineage proliferation, differentiation and apoptosis; with the activation of p53 considered as a key component. Recently, oxidative stress was proposed to play an important role in DBA pathophysiology as well. CRISPR/Cas9-created Rpl5- and Rps19-deficient murine erythroleukemia (MEL) cells and DBA patients’ samples were used to evaluate proinflammatory cytokines, oxidative stress, DNA damage and DNA damage response. We demonstrated that the antioxidant defense capacity of Rp-mutant cells is insufficient to meet the greater reactive oxygen species (ROS) production which leads to oxidative DNA damage, cellular senescence and activation of DNA damage response signaling in the developing erythroblasts and altered characteristics of mature erythrocytes. We also showed that the disturbed balance between ROS formation and antioxidant defense is accompanied by the upregulation of proinflammatory cytokines. Finally, the alterations detected in the membrane of DBA erythrocytes may cause their enhanced recognition and destruction by reticuloendothelial macrophages, especially during infections. We propose that the extent of oxidative stress and the ability to activate antioxidant defense systems may contribute to high heterogeneity of clinical symptoms and response to therapy observed in DBA patients.
Impact of protein on the composition and metabolism of the human gut microbiota and health

The composition and metabolic activity of the bacteria that inhabit the large intestine can have a major impact on health. Despite considerable inter-individual variation across bacterial species, the dominant phyla are generally highly conserved. There are several exogenous and gut environmental factors that play a role in modulating the composition and activities of colonic bacteria including diet with intakes of different macronutrients, including protein, accounting for approximately 20% of the microbial variation. Certain bacterial species tend to be considered as generalists and can metabolise a broad range of substrates, including both carbohydrate- and protein-derived substrates, whilst other species are specialists with a rather limited metabolic capacity. Metabolism of peptides and amino acids by gut bacteria can result in the formation of a wide range of metabolites several of which are considered deleterious to health including nitrosamines, heterocyclic amines and hydrogen sulphide as some of these products are genotoxic and have been linked to colonic disease. Beneficial metabolites however include SCFA and certain species can use amino acids to form butyrate which is the major energy source for colonocytes. The impact on health may however depend on the source of these products. In this review, we consider the impact of diet, particularly protein diets, on modulating the composition of the gut microbiota and likely health consequences and the potential impact of climate change and food security.
Biochemical characterization of two chitinases from Bacillus cereus sensu lato B25 with antifungal activity against Fusarium verticillioides P03.

Bacterial chitinases are a subject of intense scientific research due to their biotechnological applications, particularly their use as biological pesticides against phytopathogenic fungi as a green alternative to avoid the use of synthetic pesticides. Bacillus cereus sensu lato B25 is a rhizospheric bacterium that is a proven antagonist of Fusarium verticillioides, a major fungal pathogen of maize. This bacterium produces two chitinases that degrade the fungal cell wall and inhibit its growth. In this work, we used a heterologous expression system to purify both enzymes to investigate their biochemical traits in terms of Km, Vmax, optimal pH and temperature. ChiA and ChiB work as exochitinases, but ChiB exhibited a dual substrate activity and it is also an endochitinase. In this work, the direct addition of these chitinases inhibited fungal conidial germination and therefore they may play a major role in the antagonism against F. verticillioides.
Infectious Bronchitis Virus in Egypt: Genetic Diversity and Vaccination Strategies

Infectious bronchitis virus (IBV) is a highly evolving avian pathogen that has increasingly imposed a negative impact on poultry industry worldwide. In the last 20 years, IBV has been continuously circulating among chicken flocks in Egypt causing huge economic losses to poultry production. Multiple IBV genotypes, namely, GI-1, GI-13, GI-16, and GI-23 have been reported in Egypt possessing different genetic and pathogenic features. Different vaccine programs are being used to control the spread of the disease in Egypt. However, the virus continues to spread and evolve where multiple IBV variants and several recombination evidence have been described. In this review, we highlight the current knowledge concerning IBV circulation, genesis, and vaccination strategies in Egypt. In addition, we analyze representative Egyptian IBV strains from an evolutionary perspective based on available data of their S1 gene. We also provide insight into the importance of surveillance programs and share our perspectives for better control of IBV circulating in Egypt.
Intravenous Hydrogen Therapy With Intracisternal Magnesium Sulfate Infusion in Severe Aneurysmal Subarachnoid Hemorrhage

Background and Purpose: Poor-grade subarachnoid hemorrhage still has a poor prognosis. This randomized controlled clinical trial evaluated intracisternal magnesium sulfate infusion combined with intravenous hydrogen therapy in patients with poor-grade subarachnoid hemorrhage. Methods: Thirty-seven patients with poor-grade subarachnoid hemorrhage were randomized to Mg+H2, Mg, and control groups. Mg and Mg+H2 groups received intracisternal magnesium sulfate infusion (2.5 mmol/L) at 20 mL/h for 14 days. Mg+H2 group also received intravenous hydrogen-rich solution infusion for 14 days. Primary outcome measures were occurrence of delayed cerebral ischemia and cerebral vasospasm. Secondary outcome measures were modified Rankin Scale and Karnofsky performance status at 3 and 12 months, Barthel index at 12 months, and serum and cerebrospinal fluid malondialdehyde and neuron-specific enolase. Results: Serum neuron-specific enolase levels were significantly lower in the Mg+H2 group from days 3 to 14 than in the control group. Cerebrospinal fluid neuron-specific enolase levels were also significantly lower in the Mg+H2 group from days 3 to 7 than in the control group. Incidences of cerebral vasospasm and delayed cerebral ischemia were significantly higher in the control group than in other groups. Modified Rankin Scale and Karnofsky performance status did not significantly differ between the three groups at 3 months. Modified Rankin Scale scores 0 to 2 were more common in the Mg and Mg+H2 groups at 1 year. Barthel index was higher in the Mg+H2 group than in the control group. Conclusions: Intracisternal magnesium sulfate infusion started immediately after surgery reduces the incidence of cerebral vasospasm and delayed cerebral ischemia and improves clinical outcomes without complications in patients with poor-grade subarachnoid hemorrhage. Intracisternal magnesium sulfate infusion combined with intravenous hydrogen therapy decreases serum malondialdehyde and neuron-specific enolase and improves Barthel index, indicating hydrogen has additional effects. Registration: URL: https://www.umin. ac.jp/ctr/index.htm. Unique identifier: UMIN000014696.
Hidden Granzyme B-Mediated Injury in Chronic Active Antibody-Mediated Rejection.

OBJECTIVES Antibody-mediated injury in chronic active antibody-mediated rejection, possibly with other effector T cells, may play a role in graft injury. The role of inflammatory cells in the inflammation and fibrosis and tubular atrophy region has been recently advocated in the progression of injury. Cytotoxic T cells play a prominent role in T-cell-mediated rejection; however, the possible role of cytotoxic T cells in circulation and the intragraft compartment in chronic active antibody-mediated rejection, a common immunological cause of long-term graft failure, has not been well-studied. MATERIALS AND METHODS We measured the frequency of circulating cytotoxic T cells with flow cytometry, serum granzyme B level by enzyme-linked immunosorbent assay and intragraft granzyme B+ cell, and mRNA by immunohistochemistry and real-time polymerase chain reaction in biopsy tissue from living donor renal allograft recipients with stable graft function and chronic active antibody-mediated rejection. RESULTS The frequency of CD3+ and CD3+CD8+ T cells was similar in both stable graft function patients and chronic active antibody-mediated rejection patients. The frequency of CD3+CD8+granzyme B+ cytotoxic T cells was significantly lower in peripheral blood. Serum granzyme B level and intragraft number of granzyme B+ cells (counts/mm²) were also significantly higher in the chronic active antibody-mediated rejection group compared with that of patients with stable graft function. The intragraft granzyme B+ T cell count was positively correlated with serum creatinine and 24-hour urine proteinuria but negatively correlated with estimated glomerular filtration rate. CONCLUSIONS Granzyme B mediates covert graft injury in patients with chronic active antibody-mediated rejection in addition to antibody-mediated injury.
A meta-analysis of the association between obesity and COVID-19

Abstract Owing to limited data, we conducted a meta-analysis to re-evaluate the relationship between obesity and coronavirus-2019 (COVID-19). Literature published between 1 January 2020 and 22 August 2020 was comprehensively analysed, and RevMan3.5 was used for data analysis. A total of 50 studies, including data on 18 260 378 patients, were available. Obesity was associated with a higher risk of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) infection (odds ratio (OR): 1.39, 95% confidence interval (CI) 1.25–1.54; P < 0.00001) and increased severity of COVID-19 (hospitalisation rate: OR: 2.45, 95% CI 1.78–3.39; P < 0.00001; severe cases: OR: 3.74, 95% CI 1.18–11.87; P: 0.02; need for intensive care unit admission: OR: 1.30, 95% CI 1.21–1.40; P < 0.00001; need for invasive mechanical ventilation: OR: 1.59, 95% CI 1.35–1.88; P < 0.00001 and mortality: OR: 1.65, 95% CI 1.21–2.25; P: 0.001). However, we found a non-linear association between BMI and the severity of COVID-19. In conclusion, we found that obesity could increase the risk of SARS-CoV2 infection and aggregate the severity of COVID-19. Further studies are needed to explore the possible mechanisms behind this association.
Fancy-Shaped Gold–Platinum Nanocauliflowers for Improved Proton Irradiation Effect on Colon Cancer Cells

Enhancing the effectiveness of colorectal cancer treatment is highly desirable. Radiation-based anticancer therapy—such as proton therapy (PT)—can be used to shrink tumors before subsequent surgical intervention; therefore, improving the effectiveness of this treatment is crucial. The addition of noble metal nanoparticles (NPs), acting as radiosensitizers, increases the PT therapeutic effect. Thus, in this paper, the effect of novel, gold–platinum nanocauliflowers (AuPt NCs) on PT efficiency is determined. For this purpose, crystalline, 66-nm fancy shaped, bimetallic AuPt NCs were synthesized using green chemistry method. Then, physicochemical characterization of the obtained AuPt NCs by transmission electron microscopy (TEM), selected area electron diffraction (SAED), energy dispersive X-ray spectroscopy (EDS), and UV-Vis spectra measurements was carried out. Fully characterized AuPt NCs were placed into a cell culture of colon cancer cell lines (HCT116, SW480, and SW620) and a normal colon cell line (FHC) and subsequently subjected to proton irradiation with a total dose of 15 Gy. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) test, performed after 18-h incubation of the irradiated cell culture with AuPt NCs, showed a significant reduction in cancer cell viability compared to normal cells. Thus, the radio-enhancing features of AuPt NCs indicate their potential application for the improvement in effectiveness of anticancer proton therapy.
Formation of retromer transport carriers is disrupted by the Parkinson disease‐linked Vps35 D620N variant

Retromer core complex is an endosomal scaffold that plays a critical role in orchestrating protein trafficking within the endosomal system. Here we characterized the effect of the Parkinson's disease‐linked Vps35 D620N in the endo‐lysosomal system using Vps35 D620N rescue cell models. Vps35 D620N fully rescues the lysosomal and autophagy defects caused by retromer knock‐out. Analogous to Vps35 knock out cells, the endosome‐to‐trans‐Golgi network transport of cation‐independent mannose 6‐phosphate receptor (CI‐M6PR) is impaired in Vps35 D620N rescue cells because of a reduced capacity to form endosome transport carriers. Cells expressing the Vps35 D620N variant have altered endosomal morphology, resulting in smaller, rounder structures with less tubule‐like branches. At the molecular level retromer incorporating Vps35 D620N variant has a decreased binding to retromer associated proteins wiskott–aldrich syndrome protein and SCAR homologue (WASH) and SNX3 which are known to associate with retromer to form the endosome transport carriers. Hence, the partial defects on retrograde protein trafficking carriers in the presence of Vps35 D620N represents an altered cellular state able to cause Parkinson's disease.
Clinical characteristics of COVID‐19 patients with hepatitis B virus infection — a retrospective study

The outbreak of coronavirus disease 2019 (COVID‐19) has been declared a pandemic. Although COVID‐19 is caused by infection in the respiratory tract, extrapulmonary manifestations including dysregulation of the immune system and hepatic injury have been observed. Given the high prevalence of hepatitis B virus (HBV) infection in China, we sought to study the impact of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and HBV coinfection in patients.
Supercooling of Water to -92�C Under Pressure

The temperature at which "clean" supercooled water freezes has been determined as a function of pressure up to 3 kilobars, using a differential thermal analysis technique on subdivided water samples. The supercooling limit of such samples, -38�C at normal pressure, is lowered by initial increase of pressure, reaching a minimum value of -92�C at 2.00 kilobars.
The Diffusive Gradients in Thin Films Technique Predicts Sediment Nickel Toxicity to the Amphipod Melita plumulosa

The geographical shift of nickel mining to small island countries of the Southeast Asia and Melanesia region has produced a need to assess the environmental risk associated with increased sediment nickel exposure to benthic estuarine/marine biota. Chemical measurements of nickel concentration and potential bioavailability, including the use of diffusive gradients in thin films (DGT), were compared to effects on 10‐d reproduction of the epibenthic estuarine/marine amphipod Melita plumulosa in nickel‐spiked sediments and field‐contaminated sediments with different characteristics. The 10% effect concentrations (EC10s) for amphipod reproduction ranged from 280 to 690 mg/kg total recoverable nickel, from 110 to 380 mg/kg dilute acid–extractable nickel, and from 34 to 87 μg Ni/m2/h DGT‐labile nickel flux. Nickel bioavailability was lower in sediments with greater total organic carbon, clay content, and percentage of fine particles. Measurements of DGT‐labile nickel flux at the sediment–water interface integrated exposure to nickel from porewater, overlying water, and ingested sediment exposure pathways and were found to have the strongest relationship with the biological response. At most, there was a 29% reduction in 10‐d M. plumulosa reproduction relative to the control when exposed to nickel from field‐contaminated sediments collected from nickel laterite mining regions of New Caledonia. The DGT technique can be used as a complementary tool to measure the bioavailability of nickel in estuarine/marine sediments, especially sediments that are in nickel laterite mining regions where there are no or few toxicity data available for determining biological effects on local species. Based on the combined data set of the 3 nickel‐spiked sediments a DGT‐labile nickel EC10 threshold of 50 (30–69) μg Ni/m2/h was determined. Environ Toxicol Chem 2021;40:1266–1278. © 2020 SETAC
Identification of Markers Predicting Clinical Course in Patients with IgG4-Related Ophthalmic Disease by Unbiased Clustering Analysis

Purpose: To describe the clinical features of patients with immunoglobulin G4 (IgG4)-related ophthalmic disease (IgG4-ROD) grouped by unbiased cluster analysis using peripheral blood test data and to find novel biomarkers for predicting clinical features. Methods: One hundred and seven patients diagnosed with IgG4-ROD were divided into four groups by unsupervised hierarchical cluster analysis using peripheral blood test data. The clinical features of the four groups were compared and novel markers for prediction of clinical course were explored. Results: Unbiased cluster analysis divided patients into four groups. Group B had a significantly higher frequency of extraocular muscle enlargement (p < 0.001). The frequency of patients with decreased best corrected visual acuity (BCVA) was significantly higher in group D (p = 0.002). Receiver operating characteristic (ROC) curves for the prediction of extraocular muscle enlargement and worsened BCVA using a panel consisting of important blood test data identified by machine learning yielded areas under the curve of 0.78 and 0.86, respectively. Clinical features were compared between patients divided into two groups by the cutoff serum IgE or IgG4 level obtained from ROC curves. Patients with serum IgE above 425 IU/mL had a higher frequency of extraocular muscle enlargement (25% versus 6%, p = 0.004). Patients with serum IgG4 above 712 mg/dL had a higher frequency of decreased BCVA (37% versus 5%, p ≤ 0.001). Conclusion: Unsupervised hierarchical clustering analysis using routine blood test data differentiates four distinct clinical phenotypes of IgG4-ROD, which suggest differences in pathophysiologic mechanisms. High serum IgG4 is a potential predictor of worsened BCVA, and high serum IgE is a potential predictor of extraocular muscle enlargement in IgG4-ROD patients.