Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Caloric Intake and Aerobic Activity in Individuals with Prehypertension and Hypertension on Levels of Inflammatory, Adhesion and Prothrombotic Biomarkers—Secondary Analysis of a Randomized Controlled Trial

Background: Cardiopulmonary fitness and low calorie diets have been shown to reduce inflammation but few studies have been conducted in individuals with elevated blood pressure (BP) in a randomized intervention setting. Thereby, adhesion biomarkers, e.g., soluble intercellular adhesion molecule (sICAM)-3, have not been examined so far. Methods: Sixty-eight sedentary prehypertensive and mildly hypertensive individuals (mean age ± SEM: 45 ± 1 years; mean BP: 141/84 ± 1/1 mmHg) were randomized to one of three 12-week intervention groups: cardio training and caloric reduction, cardio training alone, or wait-list control group. Plasma levels of inflammatory, adhesion and prothrombotic biomarkers were assessed. In a second step, intervention groups were combined to one sample and multivariate regression analyses were applied in order to account for exercise and diet behavior changes. Results: There were no significant differences among the intervention groups. In the combined sample, greater caloric reduction was associated with a larger increase of sICAM-3 (p = 0.026) and decrease of C-reactive protein (p = 0.018) as a result of the interventions. More cardio training was associated with increases of sICAM-3 (p = 0.046) as well as interleukin-6 (p = 0.004) and a decrease of tumor necrosis factor-α (p = 0.017) levels. Higher BP predicted higher plasminogen activator inhibitor (PAI)-1 (p = 0.001), and greater fitness predicted lower PAI-1 levels (p = 0.006) after the intervention. Conclusions: In prehypertensive and hypertensive patients, plasma levels of the adhesion molecule sICAM-3 and inflammatory biomarkers have different response patterns to cardio training with and without caloric reduction. Such anti-inflammatory and anti-thrombotic effects may have implications for the prevention of atherothrombotic cardiovascular disease among individuals at increased risk.
Mitochondrial Structure and Function in the Metabolic Myopathy Accompanying Patients with Critical Limb Ischemia

Mitochondrial dysfunction has been implicated as a central mechanism in the metabolic myopathy accompanying critical limb ischemia (CLI). However, whether mitochondrial dysfunction is directly related to lower extremity ischemia and the structural and molecular mechanisms underpinning mitochondrial dysfunction in CLI patients is not understood. Here, we aimed to study whether mitochondrial dysfunction is a distinctive characteristic of CLI myopathy by assessing mitochondrial respiration in gastrocnemius muscle from 14 CLI patients (65.3 ± 7.8 y) and 15 matched control patients (CON) with a similar comorbidity risk profile and medication regimen but without peripheral ischemia (67.4 ± 7.4 y). Furthermore, we studied potential structural and molecular mechanisms of mitochondrial dysfunction by measuring total, sub-population, and fiber-type-specific mitochondrial volumetric content and cristae density with transmission electron microscopy and by assessing mitophagy and fission/fusion-related protein expression. Finally, we asked whether commonly used biomarkers of mitochondrial content are valid in patients with cardiovascular disease. CLI patients exhibited inferior mitochondrial respiration compared to CON. This respiratory deficit was not related to lower whole-muscle mitochondrial content or cristae density. However, stratification for fiber types revealed ultrastructural mitochondrial alterations in CLI patients compared to CON. CLI patients exhibited an altered expression of mitophagy-related proteins but not fission/fusion-related proteins compared to CON. Citrate synthase, cytochrome c oxidase subunit IV (COXIV), and 3-hydroxyacyl-CoA dehydrogenase (β-HAD) could not predict mitochondrial content. Mitochondrial dysfunction is a distinctive characteristic of CLI myopathy and is not related to altered organelle content or cristae density. Our results link this intrinsic mitochondrial deficit to dysregulation of the mitochondrial quality control system, which has implications for the development of therapeutic strategies.
Multivariate network meta‐analysis of survival function parameters

Network meta‐analysis (NMA) of survival data with a multidimensional treatment effect has been introduced as an alternative to NMA based on the proportional hazards assumption. However, these flexible models have some limitations, such as the use of an approximate likelihood based on discrete hazards, rather than a likelihood for individual event times. The aim of this article is to overcome the limitations and present an alternative implementation of these flexible NMA models for time‐to‐event outcomes with a two‐step approach.
Ancient Plant Genomics in Archaeology, Herbaria, and the Environment.

The ancient DNA revolution of the past 35 years has driven an explosion in the breadth, nuance, and diversity of questions that are approachable using ancient biomolecules, and plant research has been a constant, indispensable facet of these developments. Using archaeological, paleontological, and herbarium plant tissues, researchers have probed plant domestication and dispersal, plant evolution and ecology, paleoenvironmental composition and dynamics, and other topics across related disciplines. Here, we review the development of the ancient DNA discipline and the role of plant research in its progress and refinement. We summarize our understanding of long-term plant DNA preservation and the characteristics of degraded DNA. In addition, we discuss challenges in ancient DNA recovery and analysis and the laboratory and bioinformatic strategies used to mitigate them. Finally, we review recent applications of ancient plant genomic research. Expected final online publication date for the Annual Review of Plant Biology, Volume 71 is April 29, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Clitopilus, Clitocella, and Clitopilopsis in China

ABSTRACT Within the family Entolomataceae, many reports of Entoloma and Rhodocybe have been published, but few reports on Clitopilus and allied genera are available. In this study, Clitopilus, Clitocella, and Clitopilopsis from China were studied by morphological and phylogenetic methods. Portions of nuc 28S rDNA (28S), RNA polymerase II second largest subunit (rpb2), translation elongation factor 1-alpha (tef1), and ATPase subunit 6 (atp6), were employed to elucidate the relationships of Clitopilus and allies. Results indicate that Clitopilus should be divided into three sections, namely, sect. Clitopilus, sect. Scyphoides, and sect. Crispi, the last of which is newly described. In total, 17 species of Clitopilus, Clitocella, and Clitopilopsis are found in China; 14 species belong to Clitopilus, of which 5 are new: C. yunnanensis, C. brunniceps, C. rugosiceps, C. sinoapalus, and C. umbilicatus. Two species of Clitocella, including one new species, Clitocella orientalis, are described. One new species of Clitopilopsis, namely, Clitopilopsis albida, is proposed.
Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value

Breast cancer metastasis is the leading cause of cancer deaths in women and is difficult to combat due to the long periods in which disseminated cells retain a potential to be re-activated and start the relapse. Assessing the number and molecular profile of circulating tumor cells (CTCs) in breast cancer patients, especially in early breast cancer, should help in identifying the possibility of relapse in time for therapeutic intervention to prevent or delay recurrence. While metastatic breast cancer is considered incurable, molecular analysis of CTCs still have a potential to define particular susceptibilities of the cells representing the current tumor burden, which may differ considerably from the cells of the primary tumor, and offer more tailored therapy to the patients. In this review we inspect the routes to metastasis and how they can be linked to specific features of CTCs, how CTC analysis may be used in therapy, and what is the current status of the research and efforts to include CTC analysis in clinical practice.
Ginseng Gintonin Contains Ligands for GPR40 and GPR55

Gintonin, a novel ginseng-derived glycolipoprotein complex, has an exogenous ligand for lysophosphatidic acid (LPA) receptors. However, recent lipid analysis of gintonin has shown that gintonin also contains other bioactive lipids besides LPAs, including linoleic acid and lysophosphatidylinositol (LPI). Linoleic acid, a free fatty acid, and LPI are known as ligands for the G-protein coupled receptors (GPCR), GPR40, and GPR55, respectively. We, herein, investigated whether gintonin could serve as a ligand for GPR40 and GPR55, using the insulin-secreting beta cell-derived cell line INS-1 and the human prostate cancer cell line PC-3, respectively. Gintonin dose-dependently enhanced insulin secretion from INS-1 cells. Gintonin-stimulated insulin secretion was partially inhibited by a GPR40 receptor antagonist but not an LPA1/3 receptor antagonist and was down-regulated by small interfering RNA (siRNA) against GPR40. Gintonin dose-dependently induced [Ca2+]i transients and Ca2+-dependent cell migration in PC-3 cells. Gintonin actions in PC-3 cells were attenuated by pretreatment with a GPR55 antagonist and an LPA1/3 receptor antagonist or by down-regulating GPR55 with siRNA. Taken together, these results demonstrated that gintonin-mediated insulin secretion by INS-1 cells and PC-3 cell migration were regulated by the respective activation of GPR40 and GPR55 receptors. These findings indicated that gintonin could function as a ligand for both receptors. Finally, we demonstrated that gintonin contained two more GPCR ligands, in addition to that for LPA receptors. Gintonin, with its multiple GPCR ligands, might provide the molecular basis for the multiple pharmacological actions of ginseng.
Evolutionary Analysis of the Zinc Finger and Homeoboxes Family of Proteins Identifies Multiple Conserved Domains and a Common Early Chordate Ancestor

Abstract The Zinc Fingers and Homeoboxes (Zhx) proteins, Zhx1, Zhx2, and Zhx3, comprise a small family of proteins containing two amino-terminal C2–H2 zinc fingers and four or five carboxy-terminal homeodomains. These multiple homeodomains make Zhx proteins unusual because the majority of homeodomain-containing proteins contain a single homeodomain. Studies in cultured cells and mice suggest that Zhx proteins can function as positive or negative transcriptional regulators. Zhx2 regulates numerous hepatic genes, and all three Zhx proteins have been implicated in different cancers. Because Zhx proteins contain multiple predicted homeodomains, are associated with interesting physiological traits, and seem to be only present in the vertebrate lineage, we investigated the evolutionary history of this small family by comparing Zhx homologs from a wide range of chordates. This analysis indicates that the zinc finger motifs and homeodomains are highly similar among all Zhx proteins and also identifies additional Zhx-specific conserved regions, including a 13 amino acid amino-terminal motif that is nearly identical among all gnathostome Zhx proteins. We found single Zhx proteins in the sea lamprey (Petromyzon marinus) and in the nonvertebrate chordates sea squirt (Ciona intestinalis) and lancelet (Branchiostoma floridae); these Zhx proteins are most similar to gnathostome Zhx3. Based on our analyses, we propose that a duplication of the primordial Zhx gene gave rise to Zhx3 and the precursor to Zhx1 and Zhx2. A subsequent tandem duplication of this precursor generated Zhx1 and Zhx2 found in gnathostomes.
Brain-derived neurotrophic factor as biomarker

The publication on “Prognostic significance of brain-derived neurotrophic factor (BDNF) levels in patients with heart failure and reduced left ventricular ejection fraction” is very interesting (1). Barman et al. (1) concluded that decreased serum BDNF levels were associated with death and rehospitalization in patients with HF, suggesting their usefulness as prognostic biomarkers. As commented in the editorial, concurrent medical disorders can alter the clinical significance of BDNF (2). Nevertheless, there are other concerning factors regarding the usefulness of BDNF as a biomarker. For example, in laboratory medicine, poor reproducibility of the BDNF assay is common, which limits its usefulness as a biomarker (3). In addition, the conditions of blood sample collection and processing can significantly affect the BDNF levels (4). As reported by Tsuchimine et al. (5), anticoagulant compounds as well as the storage time and temperature during blood sampling can affect the measurements of plasma BDNF levels.
In Silico and In Vitro Studies of Mycotoxins and Their Cocktails; Their Toxicity and Its Mitigation by Silibinin Pre-Treatment

Mycotoxins found in randomly selected commercial milk thistle dietary supplement were evaluated for their toxicity in silico and in vitro. Using in silico methods, the basic physicochemical, pharmacological, and toxicological properties of the mycotoxins were predicted using ACD/Percepta. The in vitro cytotoxicity of individual mycotoxins was determined in mouse macrophage (RAW 264.7), human hepatoblastoma (HepG2), and human embryonic kidney (HEK 293T) cells. In addition, we studied the bioavailability potential of mycotoxins and silibinin utilizing an in vitro transwell system with differentiated human colon adenocarcinoma cells (Caco-2) simulating mycotoxin transfer through the intestinal epithelial barrier. The IC50 values for individual mycotoxins in studied cells were in the biologically relevant ranges as follows: 3.57–13.37 nM (T-2 toxin), 5.07–47.44 nM (HT-2 toxin), 3.66–17.74 nM (diacetoxyscirpenol). Furthermore, no acute toxicity was obtained for deoxynivalenol, beauvericin, zearalenone, enniatinENN-A, enniatin-A1, enniatin-B, enniatin-B1, alternariol, alternariol-9-methyl ether, tentoxin, and mycophenolic acid up to the 50 nM concentration. The acute toxicity of these mycotoxins in binary combinations exhibited antagonistic effects in the combinations of T-2 with DON, ENN-A1, or ENN-B, while the rest showed synergistic or additive effects. Silibinin had a significant protective effect against both the cytotoxicity of three mycotoxins (T-2 toxin, HT-2 toxin, DAS) and genotoxicity of AME, AOH, DON, and ENNs on HEK 293T. The bioavailability results confirmed that AME, DAS, ENN-B, TEN, T-2, and silibinin are transported through the epithelial cell layer and further metabolized. The bioavailability of silibinin is very similar to mycotoxins poor penetration.
The Histone Marks Signature in Exonic and Intronic Regions Is Relevant in Early Response of Tomato Genes to Botrytis cinerea and in miRNA Regulation

Research into the relationship between epigenetic regulation and resistance to biotic stresses provides alternatives for plant protection and crop improvement. To unravel the mechanisms underlying tomato responses to Botrytis cinerea, we performed a chromatin immunoprecipitation (ChIP) analysis showing the increase in H3K9ac mark along the early induced genes SlyDES, SlyDOX1, and SlyLoxD encoding oxylipin-pathway enzymes, and SlyWRKY75 coding for a transcriptional regulator of hormonal signaling. This histone mark showed a more distinct distribution than the previously studied H3K4me3. The RNAPol-ChIP analysis reflected the actual gene transcription associated with increased histone modifications. A different pattern of marks in the oxylipin-related genes against P. syringae supported a pathogen-specific profile, while no significant differences occurred in SlyWRKY75. The epigenetic regulation of SlyWRKY75 by the intron-binding miR1127-3p was supported by the presence of SlyWRKY75 pre-mRNA in control plants. Interestingly, mRNA was found to be accumulated in response to B. cinerea and P. syringae, while reduction in miRNA only occurred against B. cinerea. The intronic region presented a similar pattern of marks than the rest of the gene in both pathosystems, except for H3K4me3 in the miRNA binding site upon B. cinerea. We located the gene encoding Sly-miR1127-3p, which presented reduced H3K4me3 on its promoter against B. cinerea.
Precision Cutting of the Molds of an Optical Functional Texture Film with a Triangular Pyramid Texture

Based on an analysis of the precision and preparation technology of an optical texture film with a triangular pyramid texture, the technical requirements of the original mold were determined, and precision shaping planning technology was adopted to process the original mold. The shape error of the optical texture mold of the triangular pyramid was assessed by defining the area ratio of the retro-reflection. The influence of the tool nose radius and exit burr on the area ratio of the retro-reflection were analyzed. By optimizing the cutting tools, cutting materials and cutting boundaries, a five-axis ultra-precision machining system was used to plan the triangular pyramid structure with a base length of 115 µm and an included angle between two sides of 70.5°. The experimental results indicate that the dimension error of the triangular pyramid element is less than 1 µm, the angle error of the included angle between two sides is less than 0.05°, and the average roughness of the side of the triangular pyramid can reach 9.2 nm, which satisfies the processing quality requirements of the triangular pyramid texture mold.
Genome-wide interaction study reveals age-dependent determinants of responsiveness to inhaled corticosteroids in individuals with asthma

While genome-wide association studies have identified genes involved in differential treatment responses to inhaled corticosteroids (ICS) in asthma, few studies have evaluated the potential effects of age in this context. A significant proportion of asthmatics experience exacerbations (hospitalizations and emergency department visits) during ICS treatment. We evaluated the interaction of genetic variation and age on ICS response (measured by the occurrence of exacerbations) through a genome-wide interaction study (GWIS) of 1,321 adult and child asthmatic patients of European ancestry. We identified 107 genome-wide suggestive (P<10−05) age-by-genotype interactions, two of which also met genome-wide significance (P<5x10-08) (rs34631960 [OR 2.3±1.6–3.3] in thrombospondin type 1 domain-containing protein 4 (THSD4) and rs2328386 [OR 0.5±0.3–0.7] in human immunodeficiency virus type I enhancer binding protein 2 (HIVEP2)) by joint analysis of GWIS results from discovery and replication populations. In addition to THSD4 and HIVEP2, age-by-genotype interactions also prioritized genes previously identified as asthma candidate genes, including DPP10, HDAC9, TBXAS1, FBXL7, and GSDMB/ORMDL3, as pharmacogenomic loci as well. This study is the first to link these genes to a pharmacogenetic trait for asthma.
An In-Line Fiber Optic Fabry–Perot Sensor for High-Temperature Vibration Measurement

An in-line fiber optic Fabry–Perot (FP) sensor for high-temperature vibration measurement is proposed and experimentally demonstrated in this paper. We constructed an FP cavity and a mass on single-mode fibers (SMFs) by fusion, and together they were inserted into a hollow silica glass tube (HST) to form a vibration sensor. The radial dimension of the sensor was less than 500 μm. With its all-silica structure, the sensor has the prospect of measuring vibration in high-temperature environments. In our test, the sensor had a resonance frequency of 165 Hz. The voltage sensitivity of the sensor system was about 11.57 mV/g and the nonlinearity was about 2.06%. The sensor could work normally when the temperature was below 500 °C, and the drift of the phase offset point with temperature was 0.84 pm/°C.
The German Basic Psychological Needs Satisfaction in Physical Education Scale: Adaption and Multilevel Validation in a Sample of Sixth-Grade Girls

(1) Background: Self-determination theory (SDT) claims that need supportive behavior is related to the satisfaction of the basic psychological needs: autonomy, relatedness and competence. The student–teacher relationship is of special interest to understand mechanisms of physical activity behavior change in physical education (PE). (2) Methods: In this cross-sectional study, 481 girls answered a German version of the Basic Psychological Need Satisfaction (BPNS) in PE Scale. Contrary to previous studies, the psychometric properties of this scale were examined by multilevel confirmatory factor analysis. (3) Results: A model with three latent factors on both levels showed acceptable fit and all items showed significant factor loadings. Although one item was excluded due to psychometric reasons, the scale showed good internal consistencies; α = 0.85 at the individual level and α = 0.84 at the class level. Subscales’ internal consistency at the individual levels was good, while at class level, the scores differed from poor to good. Small significant correlations of BPNS with moderate to vigorous physical activity support criterion validity. (4) Conclusion: The 11-item scale is a valid measurement tool to assess BPNS in PE and further application in the school setting would broaden the insights into the psychological impacts of SDT in PE.
Novel 2,4-Disubstituted-1,3-Thiazole Derivatives: Synthesis, Anti-Candida Activity Evaluation and Interaction with Bovine Serum Albumine

Herein we report the synthesis of two novel series of 1,3-thiazole derivatives having a lipophilic C4-substituent on account of the increasing need for novel and versatile antifungal drugs for the treatment of resistant Candida sp. -based infections. Following their structural characterization, the anti-Candida activity was evaluated in vitro while using the broth microdilution method. Three compounds exhibited lower Minimum Inhibitory Concentration (MIC) values when compared to fluconazole, being used as the reference antifungal drug. An in silico molecular docking study was subsequently carried out in order to gain more insight into the antifungal mechanism of action, while using lanosterol-C14α-demethylase as the target enzyme. Fluorescence microscopy was employed to further investigate the cellular target of the most promising molecule, with the obtained results confirming its damaging effect towards the fungal cell membrane integrity. Finally, the distribution and the pharmacological potential in vivo of the novel thiazole derivatives was investigated through the study of their binding interaction with bovine serum albumin, while using fluorescence spectroscopy.
Use of cellulose acetate butyrate as a carrier for preparation of alcohol-resistant matrix tablet

Abstract The objective of this study was to investigate cellulose acetate butyrate (CAB) as a carrier for extended-release alcohol-resistant matrix tablet. Powder blends were either directly compressed or granulated before compression. The drug release from CAB matrix tablet was robust to formulation/process parameters such as compression force (10−20 kN), granular size (0.15−1.40 mm), and drug content (50–70%). In addition, release medium variables such as ionic strength, pH, and agitation rate had no effect on the drug release. CAB matrix tablet was more robust than ethylcellulose matrix tablet; the release from CAB matrix tablet was not affected by ethanol content (up to 20% v/v) in the release medium irrespective of agitation. CAB is a promising polymer for formulating of alcohol-resistant extended-release matrix tablet.