Miracle-dz/UniFAR-FTUs huggingface dataset:
Seasonal Changes in the Distinct Taxonomy and Function of the Gut Microbiota in the Wild Ground Squirrel (Spermophilus dauricus)

Simple Summary Gut microbiota is a large number of microbes colonized in the gut tract, and it plays a certain role in regulating the host’s immunity, metabolism, and nervous system. Recent studies have shown that the gut microbiota also has a close relationship with reproduction. The wild ground squirrel (Spermophilus dauricus) is a typical seasonal breeding animal. The purpose of this study was to explore the distinct taxonomy and function of the gut microbiota in the breeding and non-breeding seasons of the wild ground squirrel using 16S rRNA gene sequencing technology. The results show that the taxonomy of gut microbiota was different between the breeding season and non-breeding season. Functional prediction of the gut microbiota indicated that the relative abundance of metabolic pathways was differentially enriched between the breeding season and non-breeding season. This study further revealed the potential relationship between gut microbiota and reproduction and expanded our understanding of the function of gut microbiota. At the same time, it provided a new direction for research on the breeding strategy of seasonal breeding animals. Abstract Seasonal breeding is a normal phenomenon in which animals adapt to natural selection and reproduce only in specific seasons. Large studies have reported that the gut microbiota is closely related to reproduction. The purpose of this study was to explore the distinct taxonomy and function of the gut microbiota in the breeding and non-breeding seasons of the wild ground squirrel (Spermophilus dauricus). The 16S rRNA gene sequencing technology was utilized to sequence the gut microbiota of the wild ground squirrel. PICRUSt analysis was also applied to predict the function of the gut microbiota. The results suggested that the main components of the gut microbiota in all samples were Firmicutes (61.8%), Bacteroidetes (32.4%), and Proteobacteria (3.7%). Microbial community composition analyses revealed significant differences between the breeding and non-breeding seasons. At the genus level, Alistipes, Mycoplasma, Anaerotruncus, and Odoribacter were more abundant in the non-breeding season, while Blautia and Streptococcus were more abundant in the breeding season. The results of a functional prediction suggested that the relative abundance of functional categories that were related to lipid metabolism, carbohydrate metabolism, and nucleotide metabolism increased in the breeding season. The relative abundance of energy metabolism, transcription, and signal transduction increased in the non-breeding season. Overall, this study found differences in the taxonomy and function of the gut microbiota of the wild ground squirrel between the breeding and non-breeding seasons, and laid the foundation for further studies on the relationship between the gut microbiota and seasonal breeding.
Kinetic, Thermodynamic, Physicochemical, and Economical Characterization of Pectin from Mangifera indica L. cv. Haden Residues

The effect of temperature (60, 70, 80, and 90 °C) and time (30, 45, 60, 75, and 90 min) on citric acid extraction of Haden mango (Mangifera indica L. cv. Haden) peel pectin was evaluated in the present study. In order to obtain a better understanding of both the extraction process and the characteristics of the pectin (obtained from an agro-industrial waste) for a future scaling process, the following characterizations were performed: (1) Kinetic, with the maximum extraction times and yields at all evaluated temperatures; (2) thermodynamic, obtaining activation energies, enthalpies, entropies, and Gibbs free energies for each stage of the process; (3) physicochemical (chemical analysis, monosaccharide composition, degree of esterification, galacturonic acid content, free acidity, Fourier-transform infrared spectroscopy, thermogravimetric and derivative thermogravimetric analyses); and (4) economical, of the pectin with the highest yield. The Haden mango peel pectin was found to be characterized by a high-esterified degree (81.81 ± 0.00%), regular galacturonic acid content (71.57 ± 1.26%), low protein (0.83 ± 0.05%) and high ash (3.53 ± 0.02%) content, low mean viscometric molecular weight (55.91 kDa), and high equivalent weight (3657.55 ± 8.41), which makes it potentially useful for food applications.
Utility of suPAR and NGAL for AKI Risk Stratification and Early Optimization of Renal Risk Medications among Older Patients in the Emergency Department

Diagnosis of acute kidney injury (AKI) based on plasma creatinine often lags behind actual changes in renal function. Here, we investigated early detection of AKI using the plasma soluble urokinase plasminogen activator receptor (suPAR) and neutrophil gelatinase-sssociated lipocalin (NGAL) and observed the impact of early detection on prescribing recommendations for renally-eliminated medications. This study is a secondary analysis of data from the DISABLMENT cohort on acutely admitted older (≥65 years) medical patients (n = 339). Presence of AKI according to kidney disease: improving global outcomes (KDIGO) criteria was identified from inclusion to 48 h after inclusion. Discriminatory power of suPAR and NGAL was determined by receiver-operating characteristic (ROC). Selected medications that are contraindicated in AKI were identified in Renbase®. A total of 33 (9.7%) patients developed AKI. Discriminatory power for suPAR and NGAL was 0.69 and 0.78, respectively, at a cutoff of 4.26 ng/mL and 139.5 ng/mL, respectively. The interaction of suPAR and NGAL yielded a discriminatory power of 0.80, which was significantly higher than for suPAR alone (p = 0.0059). Among patients with AKI, 22 (60.6%) used at least one medication that should be avoided in AKI. Overall, suPAR and NGAL levels were independently associated with incident AKI and their combination yielded excellent discriminatory power for risk determination of AKI.
The Effects of a Macronutrient-Based Diet and Time-Restricted Feeding (16:8) on Body Composition in Physically Active Individuals—A 14-Week Randomised Controlled Trial

The number of people suffering from being overweight or obese has risen steadily in recent years. Consequently, new forms of nutrition and diets were developed as potential solutions. In the last years, the time-restricted feeding and continuous energy restriction via macronutrient-based diets were increasingly popular. Both diets were exclusively studied separately. A comparison of the two diets for people with a high body mass index despite regular physical activity has not yet been studied in detail. Therefore, this study aimed to compare the effects of these two diets on body composition and adherence. For this study, a total of 42 subjects (m = 21, f = 21) with a BMI above 25 were recruited from a local fitness gym. After a two-week familiarisation period, one of the two diets was followed over 14 weeks. Dietary behaviour was monitored throughout the period with a food diary. The primary measurement parameters were body weight, lean body mass, fat mass, body mass index, and waist and hip circumference. In addition, adherence was assessed and calculated by food diary and questionnaire. In total, the data of 35 participants (m = 14, f = 21) were analysed. Significant reductions in body weight, fat mass, body mass index, and waist and hip circumference were observed in both groups (p < 0.05). No significant change could be observed in lean body mass in either category. No group and gender differences were detected in any of the primary parameters. For the secondary parameters, a significantly higher adherence was observed in the time-restricted feeding group (p < 0.05). In addition, it can be assumed that an adherence of 60–70% cannot lead to positive changes in body composition. In conclusion, there were no differences between the two diets on the primary parameters. However, it seemed that time-restricted feeding can be better implemented in everyday life, and an adherence of more than 70% is required for both diets to prove effective.
Mechanisms of DNA Methylation in Virus-Host Interaction in Hepatitis B Infection: Pathogenesis and Oncogenetic Properties

Hepatitis B virus (HBV), the well-studied oncovirus that contributes to the majority of hepatocellular carcinomas (HCC) worldwide, can cause a severe inflammatory microenvironment leading to genetic and epigenetic changes in hepatocyte clones. HBV replication contributes to the regulation of DNA methyltransferase gene expression, particularly by X protein (HBx), and subsequent methylation changes may lead to abnormal transcription activation of adjacent genes and genomic instability. Undoubtedly, the altered expression of these genes has been known to cause diverse aspects of infected hepatocytes, including apoptosis, proliferation, reactive oxygen species (ROS) accumulation, and immune responses. Additionally, pollutant-induced DNA methylation changes and aberrant methylation of imprinted genes in hepatocytes also complicate the process of tumorigenesis. Meanwhile, hepatocytes also contribute to epigenetic modification of the viral genome to affect HBV replication or viral protein production. Meanwhile, methylation levels of HBV integrants and surrounding host regions also play crucial roles in their ability to produce viral proteins in affected hepatocytes. Both host and viral changes can provide novel insights into tumorigenesis, individualized responses to therapeutic intervention, disease progress, and early diagnosis. As such, DNA methylation-mediated epigenetic silencing of cancer-related genes and viral replication is a compelling therapeutic goal to reduce morbidity and mortality from liver cancer caused by chronic HBV infection. In this review, we summarize the most recent research on aberrant DNA methylation associated with HBV infection, which is involved in HCC development, and provide an outlook on the future direction of the research.
Mulberry (Morus alba L.) Fruit Extract Ameliorates Inflammation via Regulating MicroRNA-21/132/143 Expression and Increases the Skeletal Muscle Mitochondrial Content and AMPK/SIRT Activities

The Mulberry (Morus alba L.) fruit is a rich source of polyphenolic compounds; most of these are anthocyanins. Obesity is intimately related to low-grade inflammation, with increased pro-inflammatory cytokine secretion and macrophage infiltration in white adipose tissue (WAT). This study investigated whether mulberry fruit extract (ME) has beneficial effects on obesity-induced inflammation and skeletal muscle mitochondrial dysfunction. Sprague-Dawley rats were divided into four groups and fed either a low-fat diet (LFD), high-fat diet (HFD), HFD + 5 g/kg of ME (ME-L), or HFD + 10 g/kg of ME (ME-H) for 14 weeks. ME alleviated dyslipidemia and lipid accumulation, as well as pro-inflammatory cytokine production such as tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and monocyte chemoattractant protein 1 (MCP1) in the WAT. ME mitigated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) phosphorylation and macrophage infiltration in WAT. Notably, microRNA (miR)-21, miR-132, and miR-43 expressions were downregulated in the WAT of the ME groups compared to the HFD group. Moreover, ME increased the mitochondrial size and mitochondrial DNA (mtDNA) content, as well as key genes’ expression related to mitochondrial function, including sirtuin (SIRT)1, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), carnitine palmitoyltransferase 1β (CPT-1β), and uncoupling protein 3 (UCP3), and adenosine monophosphate-activated protein kinase (AMPK)/SIRT activities in skeletal muscle. These results suggested that ME might alleviate obesity-induced inflammation and mitochondrial dysfunction by regulating miR-21, miR-132, and miR-43 expression in WAT, and by activating the PGC-1α/SIRT1 pathway in muscle.
D-2-Hydroxyglutarate in Glioma Biology

Isocitrate dehydrogenase (IDH) mutations are common genetic abnormalities in glioma, which result in the accumulation of an “oncometabolite”, D-2-hydroxyglutarate (D-2-HG). Abnormally elevated D-2-HG levels result in a distinctive pattern in cancer biology, through competitively inhibiting α-ketoglutarate (α-KG)/Fe(II)-dependent dioxgenases (α-KGDDs). Recent studies have revealed that D-2-HG affects DNA/histone methylation, hypoxia signaling, DNA repair, and redox homeostasis, which impacts the oncogenesis of IDH-mutated cancers. In this review, we will discuss the current understanding of D-2-HG in cancer biology, as well as the emerging opportunities in therapeutics in IDH-mutated glioma.
Lactobacillus reuteri FYNLJ109L1 Attenuating Metabolic Syndrome in Mice via Gut Microbiota Modulation and Alleviating Inflammation

Metabolic syndrome is caused by an excessive energy intake in a long-term, high-fat and/or high-sugar diet, resulting in obesity and a series of related complications, which has become a global health concern. Probiotics intervention can regulate the gut microbiota and relieve the systemic and chronic low-grade inflammation, which is an alternative to relieving metabolic syndrome. The aim of this work was to explore the alleviation of two different Lactobacillus reuteri strains on metabolic syndrome. Between the two L. reuteri strains, FYNLJ109L1 had a better improvement effect on blood glucose, blood lipid, liver tissue damage and other related indexes than NCIMB 30242. In particular, FYNLJ109L1 reduced weight gain, food intake and fat accumulation. Additionally, it can regulate the gut microbiota, increase IL-10, and reduce IL-6 and tumor necrosis factor-α (TNF-α), as well as liver injury, and further reduce insulin resistance and regulate lipid metabolism disorders. In addition, it could modulate the gut microbiota, particularly a decreased Romboutsia and Clostridium sensu stricto-1, and an increased Acetatifactor. The results indicated that FYNLJ109L1 could improve metabolic syndrome significantly via alleviating inflammation and gut microbiota modulation.
Housekeeping Genes for Parkinson’s Disease in Humans and Mice

A critical aspect of real-time PCR is the presence of housekeeping genes (HKGs) as an internal control for the normalization of expression data for genes of interest. It is necessary to select correct HKGs in the investigation of various pathologies. Thereby, we analyzed the stability of expression of the HKGs in Parkinson’s disease (PD). The work was carried out in the peripheral blood of patients with PD and in the brain tissues and peripheral blood of mice with MPTP-induced PD. As a result, Aars was the most stably expressed HKG in the mouse brain as a whole. However, different genes were more stably expressed in different parts of the brain. Polr2f was the most stably expressed in the cortex, Psmd6 was the most stably expressed in the cerebellum, and Psmd7 was the most stably expressed in the striatum and substantia nigra. HKGs were different in similar tissues of the studied organisms. Polr2f was the most stably expressed HKG in the peripheral blood of mice, whereas PSMD6 was the most stably expressed gene in humans. Thus, there is no universal HKG both for different brain tissues of one organism and for similar tissues of different organisms. Furthermore, the identified most stably expressed HKGs can be considered as such only under conditions in PD.
Ultrasound-Assisted Synthesis of Luminescent Micro- and Nanocrystalline Eu-Based MOFs as Luminescent Probes for Heavy Metal Ions

The luminescent coarse-, micro- and nanocrystalline europium(III) terephthalate tetrahydrate (Eu2bdc3·4H2O) metal-organic frameworks were synthesized by the ultrasound-assisted wet-chemical method. Electron micrographs show that the europium(III) terephthalate microparticles are 7 μm long leaf-like plates. According to the dynamic light scattering technique, the average size of the Eu2bdc3·4H2O nanoparticles is equal to about 8 ± 2 nm. Thereby, the reported Eu2bdc3·4H2O nanoparticles are the smallest nanosized rare-earth-based MOF crystals, to the best of our knowledge. The synthesized materials demonstrate red emission due to the 5D0–7FJ transitions of Eu3+ upon 250 nm excitation into 1ππ* state of the terephthalate ion. Size reduction results in broadened emission bands, an increase in the non-radiative rate constants and a decrease in both the quantum efficiency of the 5D0 level and Eu3+ and the luminescence quantum yields. Cu2+, Cr3+, and Fe3+ ions efficiently and selectively quench the luminescence of nanocrystalline europium(III) terephthalate, which makes it a prospective material for luminescent probes to monitor these ions in waste and drinking water.
Metformin and Dichloroacetate Suppress Proliferation of Liver Cancer Cells by Inhibiting mTOR Complex 1

The Warburg effect is important for cancer cell proliferation. This phenomenon can be flexible by interaction between glycolysis and mitochondrial oxidation for energy production. We aimed to investigate the anticancer effects of the pyruvate dehydrogenase kinase inhibitor, dichloroacetate (DCA) and the mitochondrial respiratory complex I inhibitor metformin in liver cancer cells. The anticancer effect of DCA and/or metformin on HepG2, PLC/PRF5 human liver cancer cell lines, MH-134 murine hepatoma cell lines, and primary normal hepatocytes using MTT assay. Inhibition of lactate/ATP production and intracellular reactive oxygen species generation by DCA and metformin was investigated. Inhibition of PI3K/Akt/mTOR complex I was evaluated to see whether it occurred through AMPK signaling. Anticancer effects of a combination treatment of DCA and metformin were evaluated in HCC murine model. The results showed that metformin and DCA effectively induced apoptosis in liver cancer cells. A combination treatment of metformin and DCA did not affect viability of primary normal hepatocytes. Metformin upregulated glycolysis in liver cancer cells, thereby increasing sensitivity to the DCA treatment. Metformin and DCA inhibited mTOR complex I signaling through upregulated AMPK-independent REDD1. In addition, metformin and DCA increased reactive oxygen species levels in liver cancer cells, which induced apoptosis. A combination treatment of metformin and DCA significantly suppressed the tumor growth of liver cancer cells using in vivo xenograft model. Taken together, the combined treatment of metformin and DCA suppressed the growth of liver cancer cells. This strategy may be effective for patients with advanced liver cancer.
Isolation of Persister Cells of Bacillus subtilis and Determination of Their Susceptibility to Antimicrobial Peptides

Persister cells are growth-arrested subpopulations that can survive possible fatal environments and revert to wild types after stress removal. Clinically, persistent pathogens play a key role in antibiotic therapy failure, as well as chronic, recurrent, and antibiotic-resilient infections. In general, molecular and physiological research on persister cells formation and compounds against persister cells are much desired. In this study, we firstly demonstrated that the spore forming Gram-positive model organism Bacillus subtilis can be used to generate persister cells during exposure to antimicrobial compounds. Interestingly, instead of exhibiting a unified antibiotic tolerance profile, different number of persister cells and spores were quantified in various stress conditions. qPCR results also indicated that differential stress responses are related to persister formation in various environmental conditions. We propose, for the first time to the best of our knowledge, an effective method to isolate B. subtilis persister cells from a population using fluorescence-activated cell sorting (FACS), which makes analyzing persister populations feasible. Finally, we show that alpha-helical cationic antimicrobial peptides SAAP-148 and TC-19, derived from human cathelicidin LL-37 and human thrombocidin-1, respectively, have high efficiency against both B. subtilis vegetative cells and persisters, causing membrane permeability and fluidity alteration. In addition, we confirm that in contrast to persister cells, dormant B. subtilis spores are not susceptible to the antimicrobial peptides.
Uptake of Cell-Penetrating Peptide RL2 by Human Lung Cancer Cells: Monitoring by Electron Paramagnetic Resonance and Confocal Laser Scanning Microscopy

RL2 is a recombinant analogue of a human κ-casein fragment, capable of penetrating cells and inducing apoptosis of cancer cells with no toxicity to normal cells. The exact mechanism of RL2 penetration into cells remains unknown. In this study, we investigated the mechanism of RL2 penetration into human lung cancer A549 cells by a combination of electron paramagnetic resonance (EPR) spectroscopy and confocal laser scanning microscopy. EPR spectra of A549 cells incubated with RL2 (sRL2) spin-labeled by a highly stable 3-carboxy-2,2,5,5-tetraethylpyrrolidine-1-oxyl radical were found to contain three components, with their contributions changing with time. The combined EPR and confocal-microscopy data allowed us to assign these three forms of sRL2 to the spin-labeled protein sticking to the membrane of the cell and endosomes, to the spin-labeled protein in the cell interior, and to spin labeled short peptides formed in the cell because of protein digestion. EPR spectroscopy enabled us to follow the kinetics of transformations between different forms of the spin-labeled protein at a minimal spin concentration (3–16 μM) in the cell. The prospects of applications of spin-labeled cell-penetrating peptides to EPR imaging, DNP, and magnetic resonance imaging are discussed, as is possible research on an intrinsically disordered protein in the cell by pulsed dipolar EPR spectroscopy.
Bone Mineral Density in Patients with Hepatic Glycogen Storage Diseases

The association between bone mineral density (BMD) and hepatic glycogen storage diseases (GSDs) is still unclear. To evaluate the BMD of patients with GSD I, IIIa and IXα, a cross-sectional study was performed, including 23 patients (GSD Ia = 13, Ib = 5, IIIa = 2 and IXα = 3; median age = 11.9 years; IQ = 10.9–20.1) who underwent a dual-energy X-ray absorptiometry (DXA). Osteocalcin (OC, n = 18), procollagen type 1 N-terminal propeptide (P1NP, n = 19), collagen type 1 C-terminal telopeptide (CTX, n = 18) and 25-OH Vitamin D (n = 23) were also measured. The participants completed a 3-day food diary (n = 20). Low BMD was defined as a Z-score ≤ −2.0. All participants were receiving uncooked cornstarch (median dosage = 6.3 g/kg/day) at inclusion, and 11 (47.8%) presented good metabolic control. Three (13%) patients (GSD Ia = 1, with poor metabolic control; IIIa = 2, both with high CPK levels) had a BMD ≤ −2.0. CTX, OC and P1NP correlated negatively with body weight and age. 25-OH Vitamin D concentration was decreased in seven (30.4%) patients. Our data suggest that patients with hepatic GSDs may have low BMD, especially in the presence of muscular involvement and poor metabolic control. Systematic nutritional monitoring of these patients is essential.