Miracle-dz/UniFAR-FTUs huggingface dataset:
Exercise Fat Oxidation Is Positively Associated with Body Fatness in Men with Obesity: Defying the Metabolic Flexibility Paradigm

Obesity is thought to be associated with a reduced capacity to increase fat oxidation in response to physical exercise; however, scientific evidence supporting this paradigm remains scarce. This study aimed to determine the interrelationship of different submaximal exercise metabolic flexibility (Metflex) markers and define its association with body fatness on subjects with obesity. Twenty-one male subjects with obesity performed a graded-intensity exercise protocol (Test 1) during which cardiorespiratory fitness (CRF), maximal fat oxidation (MFO) and its corresponding exercise intensity (FATmax) were recorded. A week afterward, each subject performed a 60-min walk (treadmill) at FATmax (Test 2), and the resulting fat oxidation area under the curve (TFO) and maximum respiratory exchange ratio (RERpeak) were recorded. Blood lactate (LAb) levels was measured during both exercise protocols. Linear regression analysis was used to study the interrelationship of exercise Metflex markers. Pearson’s correlation was used to evaluate all possible linear relationships between Metflex and anthropometric measurement, controlling for CRF). The MFO explained 38% and 46% of RERpeak and TFO’s associated variance (p < 0.01) while TFO and RERpeak were inversely related (R2 = 0.54, p < 0.01). Body fatness positively correlated with MFO (r = 0.64, p < 0.01) and TFO (r = 0.63, p < 0.01) but inversely related with RERpeak (r = −0.67, p < 0.01). This study shows that MFO and RERpeak are valid indicators of TFO during steady-state exercise at FATmax. The fat oxidation capacity is directly associated with body fatness in males with obesity.
ANALYTICAL RP-HPLC METHOD FOR DEVELOPMENT AND VALIDATION OF PREGABALIN AND METHYLCOBALAMINE IN COMBINED CAPSULE FORMULATION

Introduction PRE [2] chemically known as (S)-2(aminomethyl)-5-methylhexanoic acid is used as anticonvulsant, neurotransmitter. It binds with high affinity and specificity to voltage-gated calcium channel alpha (2)-delta proteins [5,6]. It is freely soluble in water both in acid and basic aqueous solution. It is well absorbed after oral administration and largely excreted by renal excretion. Abstract This work is concerned with application of simple, accurate, precise and highly selective reverse phase high performance liquid chromatographic (RP-HPLC) method for determination of pregabalin and methylcobalamine combined in capsule dosage form. Chromatographic separation was achieved isocratically using Waters allaiance 2695 seperation module,C18 column (250 х 4.6 mm,5 mcg/ml) at temperature 40°C. Flow rate selected was 1ml/min using UV visible PDA detector at 210nm. Mobile phase was prepared using ammonium dihydrogen-o-phosphate (buffer 6.0), acetonitrile and methanol in the ratio of 75:15:10 which gave better resolution and sensitivity. Developed method was validated in terms of linearity, range, specificity, precession, accuracy, robustness and ruggedness. The limit of detection was found to be 47.93mcg/ml for pregabalin and 1.33 mcg/ml for methycobalamine respectively. The limit of quantitation was found to be 145 mcg/ml and 4.05 mcg/ml for pregabalin and methycobalamine respectively. The method was found to be linear in the range of 3200-4800 mcg/ml and 16-24 mcg/ml for pregabalin and methylcobalamine respectively with correlation coefficients of 0.9938 and 0.9959. Content of pregabalin and methycobalamine was found to be 99.17 and 100.15% respectively. The validation of proposed method was verified by recovery studies and was found to be satisfactory.
Mitochondrial Sirtuins in Reproduction

Mitochondria act as hubs of numerous metabolic pathways. Mitochondrial dysfunctions contribute to altering the redox balance and predispose to aging and metabolic alterations. The sirtuin family is composed of seven members and three of them, SIRT3-5, are housed in mitochondria. They catalyze NAD+-dependent deacylation and the ADP-ribosylation of mitochondrial proteins, thereby modulating gene expression and activities of enzymes involved in oxidative metabolism and stress responses. In this context, mitochondrial sirtuins (mtSIRTs) act in synergistic or antagonistic manners to protect from aging and aging-related metabolic abnormalities. In this review, we focus on the role of mtSIRTs in the biological competence of reproductive cells, organs, and embryos. Most studies are focused on SIRT3 in female reproduction, providing evidence that SIRT3 improves the competence of oocytes in humans and animal models. Moreover, SIRT3 protects oocytes, early embryos, and ovaries against stress conditions. The relationship between derangement of SIRT3 signaling and the imbalance of ROS and antioxidant defenses in testes has also been demonstrated. Very little is known about SIRT4 and SIRT5 functions in the reproductive system. The final goal of this work is to understand whether sirtuin-based signaling may be taken into account as potential targets for therapeutic applications in female and male infertility.
Emerging Evidence for Pleiotropism of Eosinophils

Eosinophils are complex granulocytes with the capacity to react upon diverse stimuli due to their numerous and variable surface receptors, which allows them to respond in very different manners. Traditionally believed to be only part of parasitic and allergic/asthmatic immune responses, as scientific studies arise, the paradigm about these cells is continuously changing, adding layers of complexity to their roles in homeostasis and disease. Developing principally in the bone marrow by the action of IL-5 and granulocyte macrophage colony-stimulating factor GM-CSF, eosinophils migrate from the blood to very different organs, performing multiple functions in tissue homeostasis as in the gastrointestinal tract, thymus, uterus, mammary glands, liver, and skeletal muscle. In organs such as the lungs and gastrointestinal tract, eosinophils are able to act as immune regulatory cells and also to perform direct actions against parasites, and bacteria, where novel mechanisms of immune defense as extracellular DNA traps are key factors. Besides, eosinophils, are of importance in an effective response against viral pathogens by their nuclease enzymatic activity and have been lately described as involved in severe acute respiratory syndrome coronavirus SARS-CoV-2 immunity. The pleiotropic role of eosinophils is sustained because eosinophils can be also detrimental to human physiology, for example, in diseases like allergies, asthma, and eosinophilic esophagitis, where exosomes can be significant pathophysiologic units. These eosinophilic pathologies, require specific treatments by eosinophils control, such as new monoclonal antibodies like mepolizumab, reslizumab, and benralizumab. In this review, we describe the roles of eosinophils as effectors and regulatory cells and their involvement in pathological disorders and treatment.
Investigating the Effects of a Phytobiotics-Based Product on the Fecal Bacterial Microbiome of Weaned Pigs

Simple Summary Maintaining gut health during the weaning period remains a major challenge for swine producers. Phytobiotics, which are plant-derived bioactive products for use as supplements in food animals, have shown great promise in helping to stabilize the gut environment of weaned pigs, but their mechanisms of action remain unclear. To determine if the positive impact of phytobiotics on gut health may be by influencing the symbiotic bacteria that inhabit the gut of young pigs, this report describes a comparison between fecal bacterial populations of weaned pigs supplemented with a commercial phytobiotic product for seven days to those of untreated pigs. Together, the results indicate that phytobiotic supplementation may provide a favorable environment for both lactate-producing and lactate-utilizing bacteria. Abstract The transition to a solid diet, as well as environmental and social stress, have a direct impact on swine gut physiology during weaning, affecting host gastrointestinal functions, as well as resident symbiotic microbial communities. While plant-derived bioactive products, such as phytobiotics, have shown great potential to mitigate these challenges, providing benefits such as antimicrobial, antioxidant, and anti-inflammatory activities, their mechanisms of action remain largely unexplored. To gain more insight, a 21 day trial is conducted to investigate the effects of LiveXtract, a commercial plant-based product, using fecal samples as a proxy for gut bacteria in weaned pigs. High-throughput sequencing of amplicons targeting the V1–V3 region of the 16S rRNA gene is used to determine bacterial composition at days 1 (pre-treatment), 4, 10, and 21 postweaning. Our results show that Lactobacillaceae and Peptostreptococcaceae are both higher in the supplemented group at D4 (p < 0.05), while Streptococcaceae are significantly lower in the treated group at D10 and D21. At D10, Erysipelotrichaceae are lower, and Veillonellaceae are higher in the treated samples than the control group (p < 0.05). Of the thirteen abundant Operational Taxonomic Units (OTUs) that have different representation between treated and control pigs (p < 0.05), six are predicted to be lactate producers (affiliation to Lactobacillus or Streptococcus), and one is predicted to be a lactate utilizer, based on its high identity to Megasphaera elsdenii. Together, these data suggest that phytobiotics may provide a favorable metabolic equilibrium between lactate production and utilization. Lactate is considered a critical microbial end product in gut environments, as it can inhibit pathogens or be metabolized to propionate for utilization by host cells.
Evaluation of Implementing TOM: A Group-Based Fall Prevention Programme among Community-Dwelling Older Adults in The Netherlands

There is strong evidence that effective fall prevention elements exist, but the implementation into society remains difficult. The aim of the current study is to describe and evaluate the implementation of the fall prevention programme “Thuis Onbezorgd Mobiel” (TOM). This novel approach combines effective components into a multidisciplinary group-based programme for adults aged 65 years or older with an increased risk of falling. To investigate the impact on several health-related outcomes such as subjective health, quality of life, physical functioning, and falls, we applied a quasi-experimental pre–post design including a follow-up period. A total of 164 older adults subscribed to the programme: 80 were eligible to start and 73 completed it. The impact analysis revealed a significant improvement in subjective health, physical functioning, and quality of life directly after participating in the programme. The impact on subjective health and quality of life persisted six months after the programme. Important facilitators for the implementation of the programme were social contact and clear communication. Lack of a concrete follow-up was seen as an important barrier. The results of the current research help guide further implementation of effective fall prevention interventions in practice.
Fecal Microbial Transplantation versus Mesalamine Enema for Treatment of Active Left-Sided Ulcerative Colitis—Results of a Randomized Controlled Trial

Background and Aims: Ulcerative colitis (UC) is a chronic inflammatory disease. Fecal microbial transplantation (FMT) is a promising alternative treatment. Methods: This multicenter, open-label, noninferiority trial randomized patients with active left-sided UC (Mayo score 4–10) equally to FMT or 5-aminosalicylic acid (5-ASA) enemas. FMT enemas were administered five times in the first week and then once weekly for 5 weeks. 5-ASA enemas were administered daily for 2 weeks and then every other day. The primary study endpoint was clinical remission, with a total Mayo score ≤2 at week 12 with no subscore >1. Results: Sixty-one patients were screened; 45 were enrolled and randomized to FMT (n = 23) or 5-ASA (n = 22). Twenty-one FMT and 22 5-ASA patients completed at least the week 4 study visit and were included in the mITT analysis. Twelve FMT (57%) and eight 5-ASA patients achieved the primary study endpoint. FMT noninferiority with 10% margin was confirmed (95% CI: −7.6%, 48.9%). Adverse events occurred in 12 FMT (57%) and 13 5-ASA (59%) patients. Increased microbial diversity persisted 3 months after FMT. Conclusion: FMT is an effective treatment for left-sided UC and increased recipient microbiome diversity. Targeted microbiome modification may improve FMT efficacy. Further investigation is needed to guide donor and patient selection.
Life-On-Hold: Lanthanoids Rapidly Induce a Reversible Ametabolic State in Mammalian Cells

Simple Summary We found that incubation with a solution containing ~50 mM neodymium (one of the rare-earth elements, REE) induces a rapid of active metabolism in mammalian cells. We have named this state REEbernation and found that the process involves a rapid replacement of calcium with neodymium in membranes and organelles of a cell, allowing it to maintain its shape and membrane integrity under extreme conditions, including vacuum. Furthermore, phosphate exchange is blocked because of non-dissolvable neodymium salts formation, which “discharged” the cell. We also showed that REEbernation is characterized by instant shutting down RNA transcriptional activity in the cells, providing an intriguing opportunity to study a snapshot of gene expression at a given time point. Finally, we found that the REEbernation state is reversible, and we could restore the metabolism and proliferation capacity of the cells. The REEbernation provides a new method to reversibly place a cell into “on-hold” mode, opening opportunities to develop protocols for biological samples fixation with a minimum effect on the omics profile for biomedical needs. Abstract Until now, the ability to reversibly halt cellular processes has been limited to cryopreservation and several forms of anabiosis observed in living organisms. In this paper we show that incubation of living cells with a solution containing ~50 mM neodymium induces a rapid shutdown of intracellular organelle movement and all other evidence of active metabolism. We have named this state REEbernation (derived from the terms REE (rare earth elements) and hibernation) and found that the process involves a rapid replacement of calcium with neodymium in membranes and organelles of a cell, allowing it to maintain its shape and membrane integrity under extreme conditions, such as low pressure. Furthermore, phosphate exchange is blocked as a result of non-dissolvable neodymium salts formation, which “discharged” the cell. We further showed that REEbernation is characterized by an immediate cessation of transcriptional activity in observed cells, providing an intriguing opportunity to study a snapshot of gene expression at a given time point. Finally, we found that the REEbernation state is reversible, and we could restore the metabolism and proliferation capacity of the cells. The REEbernation, in addition to being an attractive model to further investigate the basic mechanisms of cell metabolism control, also provides a new method to reversibly place a cell into “on-hold” mode, opening opportunities to develop protocols for biological samples fixation with a minimum effect on the omics profile for biomedical needs.
Characteristics of Chimeric West Nile Virus Based on the Japanese Encephalitis Virus SA14-14-2 Backbone

West Nile virus disease (WND) is an arthropod-borne zoonosis responsible for nonspecific fever or severe encephalitis. The pathogen is West Nile virus belonging to the genus Flavivirus, family Flaviviridae. Every year, thousands of cases were reported, which poses significant public health risk. Here, we constructed a West Nile virus chimera, ChiVax-WN01, by replacing the prMΔE gene of JEV SA14-14-2 with that of the West Nile virus NY99. The ChiVax-WN01 chimera showed clear, different characters compared with that of JEV SA14-14-2 and WNV NY99 strain. An animal study indicated that the ChiVax-WN01 chimera presented moderate safety and immunogenicity for 4-week female BALB/c mice.
Amino Acid Composition of Amniotic Fluid during the Perinatal Period Reflects Mother’s Fat and Carbohydrate Intake

Dietary content during pregnancy is important because it is necessary for the growth of the fetus. With the assumption that the nutritional status of the fetus can be monitored by measuring amino acid concentrations in the amniotic fluid, we investigated whether the habitual dietary intake of pregnant women affected the composition of the amniotic fluid and the significance of performing amniotic fluid analysis. The subjects were 34 mothers who delivered full-term babies by cesarean section. Three biological samples were collected from the mothers: blood, cord blood, and amniotic fluid. At the same time, the mothers’ prenatal nutritional intake information was also recorded. When the amino acid contents of the samples were compared with the mothers’ nutrient intake, many amino acids in the amniotic fluid were positively correlated with lipid intake, but not with protein intake. There was a negative correlation between lipid intake and carbohydrate intake, and the amino acid contents of the amniotic fluid were also negatively correlated with carbohydrate intake. The results of this study were consistent with those found in animal models, suggesting that the analysis of amniotic fluid may be a useful method to investigate the effects of habitual diet during human pregnancy on the fetus.
Crimean-Congo Hemorrhagic Fever Virus: Current Advances and Future Prospects of Antiviral Strategies

Crimean-Congo hemorrhagic fever virus (CCHFV) is a widespread, tick-borne pathogen that causes Crimean-Congo hemorrhagic fever (CCHF) with high morbidity and mortality. CCHFV is transmitted to humans through tick bites or direct contact with patients or infected animals with viremia. Currently, climate change and globalization have increased the transmission risk of this biosafety level (BSL)-4 virus. The treatment options of CCHFV infection remain limited and there is no FDA-approved vaccine or specific antivirals, which urges the identification of potential therapeutic targets and the design of CCHF therapies with greater effort. In this article, we discuss the current progress and some future directions in the development of antiviral strategies against CCHFV.
Serine-Threonine Kinase Receptor-Associated Protein (STRAP) Knockout Decreases the Malignant Phenotype in Neuroblastoma Cell Lines

Simple Summary Neuroblastoma is the most common extra-cranial tumor in children and despite medical advancements in cancer treatment, five-year survival for high-risk neuroblastoma remains less than 50%. Investigation of the mechanisms responsible for aggressive disease is necessary to identify novel therapeutic targets and improve survival. Serine-threonine kinase receptor associated protein (STRAP) is upregulated in several malignancies and plays an important role in tumor growth and metastasis. The role of STRAP in pediatric malignancies and specifically in neuroblastoma has not been explored. We sought to determine whether STRAP functions assisted to promote the malignant phenotype in neuroblastoma and could provide a potential target for future therapies. Abstract Background: Serine-threonine kinase receptor-associated protein (STRAP) plays an important role in neural development but also in tumor growth. Neuroblastoma, a tumor of neural crest origin, is the most common extracranial solid malignancy of childhood and it continues to carry a poor prognosis. The recent discovery of the role of STRAP in another pediatric solid tumor, osteosarcoma, and the known function of STRAP in neural development, led us to investigate the role of STRAP in neuroblastoma tumorigenesis. Methods: STRAP protein expression was abrogated in two human neuroblastoma cell lines, SK-N-AS and SK-N-BE(2), using transient knockdown with siRNA, stable knockdown with shRNA lentiviral transfection, and CRISPR-Cas9 genetic knockout. STRAP knockdown and knockout cells were examined for phenotypic alterations in vitro and tumor growth in vivo. Results: Cell proliferation, motility, and growth were significantly decreased in STRAP knockout compared to wild-type cells. Indicators of stemness, including mRNA abundance of common stem cell markers Oct4, Nanog, and Nestin, the percentage of cells expressing CD133 on their surface, and the ability to form tumorspheres were significantly decreased in the STRAP KO cells. In vivo, STRAP knockout cells formed tumors less readily than wild-type tumor cells. Conclusion: These novel findings demonstrated that STRAP plays a role in tumorigenesis and maintenance of neuroblastoma stemness.
Aquatic Training after Joint Immobilization in Rats Promotes Adaptations in Myotendinous Junctions

The myotendinous junction (MTJ) is the muscle-tendon interface and constitutes an integrated mechanical unit to force transmission. Joint immobilization promotes muscle atrophy via disuse, while physical exercise can be used as an adaptative stimulus. In this study, we aimed to investigate the components of the MTJ and their adaptations and the associated elements triggered with aquatic training after joint immobilization. Forty-four male Wistar rats were divided into sedentary (SD), aquatic training (AT), immobilization (IM), and immobilization/aquatic training (IMAT) groups. The samples were processed to measure fiber area, nuclear fractal dimension, MTJ nuclear density, identification of telocytes, sarcomeres, and MTJ perimeter length. In the AT group, the maintenance of ultrastructure and elements in the MTJ region were observed; the IM group presented muscle atrophy effects with reduced MTJ perimeter; the IMAT group demonstrated that aquatic training after joint immobilization promotes benefits in the muscle fiber area and fractal dimension, in the MTJ region shows longer sarcomeres and MTJ perimeter. We identified the presence of telocytes in the MTJ region in all experimental groups. We concluded that aquatic training is an effective rehabilitation method after joint immobilization due to reduced muscle atrophy and regeneration effects on MTJ in rats.
Theoretical design of organic-inorganic hybrids based on hexamolybdate toward high performance dye-sensitized solar cells

Abstract The electronic structures, absorption spectra and photovoltaic (PV) performance of four dyes based on triphenylamine and polyoxometalate (POM) organic–inorganic hybrids for p-type dye-sensitised solar cells have been discussed by density functional theory (DFT) and time-dependent DFT calculations. In the four designed dyes, the triarylamine and carbazole take the role of the electron donor and the POMs act as the electron acceptor. It was found that introduction of electron donating groups (diphenylamine group and carbazole) into the triarylamine unit enabled better PV performance. This work is expected to be helpful for designing triarylamine–POM hybrid dyes with target properties.
Mapping and Analysis of Swi5 and Sfr1 Phosphorylation Sites

The evolutionarily conserved Swi5-Sfr1 complex plays an important role in homologous recombination, a process crucial for the maintenance of genomic integrity. Here, we purified Schizosaccharomyces pombe Swi5-Sfr1 complex from meiotic cells and analyzed it by mass spectrometry. Our analysis revealed new phosphorylation sites on Swi5 and Sfr1. We found that mutations that prevent phosphorylation of Swi5 and Sfr1 do not impair their function but swi5 and sfr1 mutants encoding phosphomimetic aspartate at the identified phosphorylation sites are only partially functional. We conclude that during meiosis, Swi5 associates with Sfr1 and both Swi5 and Sfr1 proteins are phosphorylated. However, the functional relevance of Swi5 and Sfr1 phosphorylation remains to be determined.