Miracle-dz/UniFAR-FTUs huggingface dataset:
Hsa_circ_0081534 increases the proliferation and invasion of nasopharyngeal carcinoma cells through regulating the miR-508-5p/FN1 axis

Accumulating lines of evidence indicate that circular RNAs (circRNAs) are involved in the pathogenesis of human cancers, including nasopharyngeal carcinoma (NPC). However, the influences of hsa_circ_0081534 upon the pathogenesis and dynamics of NPC are undescribed. In this study, we identified a circRNA hsa_circ_0081534 was significantly upregulated in NPC tissues and cell lines. Inhibition of hsa_circ_0081534 induced a decrease in NPC cells proliferation and invasion in vitro, and repressed tumor growth in vivo. In mechanism, hsa_circ_0081534 promoted NPC progression by sponging miR-508-5p. Fibronectin 1 (FN1) is a target gene of miR-508-5p. In addition, rescue assays showed that FN1 overexpression (or miR-508-5p inhibitors) abolished the roles of hsa_circ_0081534 inhibition on NPC cells proliferation and invasion. Therefore, hsa_circ_0081534 promoted the proliferation, and invasion of NPC cells via regulating the miR-508-5p/FN1 axis. Our findings suggested that hsa_circ_0081534 could be a novel therapeutic target for the treatment of NPC patients.
Ultrastructural Changes of Blood Cells in Children with Generalized Purulent Peritonitis: A Cross-Sectional and Prospective Study

In conditions of abdominal sepsis with indications of first- or second-stage shock, blood cells undergo significant ultrastructural changes that cause impaired gas exchange, changes in reactivity, and decompensation of organs and systems functions. This paper presents a cross-sectional prospective study aimed at researching the ultrastructure of blood cells in children experiencing abdominal septic shock against the background of generalized purulent peritonitis of appendicular origin. This study was conducted with 15 children aged 6–12 who were undergoing treatment for generalized appendicular purulent peritonitis, with first- or second-stage abdominal septic shock, in emergency care. The changes in the ultrastructure of erythrocytes did not correspond to changes characteristic of eryptosis, which confirms their occurrence under the influence of such pathogenic factors as intoxication, metabolic, water–electrolyte balance, and acid–base disorders. Ultrastructural changes of granulocytes indicate their hyperactivation, which leads to the exhaustion of membrane synthetic resources, membrane destruction, ineffective expenditure of bactericidal factors on substrates that are not subject to destruction. In lymphocytes, disorganization of the nuclear membrane and intracellular membranes, uneven distribution of chromatin, the hypertrophied Golgi apparatus, and a large number of young mitochondria, lysosomes, ribosomes, vesicles manifesting the disruption of metabolism, stress and decompensation of energy supply and protein synthesis systems, have been demonstrated. In conditions of abdominal sepsis with indications of first- or second-stage shock, blood cells undergo substantial ultrastructural changes causing gas exchange disruption, changes in reactivity, as well as decompensation of organs and system functioning.
Comparison of Poly (ADP-ribose) Polymerase Inhibitors (PARPis) as Maintenance Therapy for Platinum-Sensitive Ovarian Cancer: Systematic Review and Network Meta-Analysis

Simple Summary Poly (ADP-ribose) polymerase inhibitors (PARPis; inhibitors of a family of enzymes that are primary involved in DNA repair) are considered to be the drug of choice in maintenance therapy for platinum-sensitive ovarian cancer. However, despite the FDA approval of three such agents and their availability in clinical practice, thus far, no clinical trial investigated them in a head-to-head direct comparison. In this study, we used a statistical approach that allows comparing direct and indirect evidence (network meta-analysis) in order to compare the three FDA-approved PARPis (olaparib, niraparib and rucaparib). To this end, we used data from six randomized control trials involving a total of 2270 ovarian cancer patients. Interestingly, we found no significant differences in clinical outcomes (overall survival and progression-free survival) between the three agents. However, niraparib was found to be associated with higher risk of certain adverse events (thrombocytopenia, neutropenia, constipation, and headaches) compared to the other two PARPis. Abstract Background: Three PARPis (olaparib, niraparib and rucaparib) are currently FDA-approved as maintenance therapy in newly diagnosed and recurrent ovarian cancer. However, thus far, no trial has compared the three approved PARPis in the overall population, in patients with BRCA mutations, or in those with wild-type BRCA. Methods: A frequentist network meta-analysis was used for indirect comparisons between the different PARPis with respect to progression free survival (PFS), overall survival (OS), and adverse events. Results: Overall, six randomized clinical trials involving 2,770 patients, were included in the analysis. Results from the indirect comparisons revealed no statistically significant differences between the three PARPis with respect to PFS or OS in the entire population and in patients with mutated and wild-type BRCA, separately. Niraparib showed a statistically significant increased risk for grade 3 and 4 thrombocytopenia (risk-difference [RD] from placebo: 0.3; 95% confidence interval [CI], 0.27‒0.34) and any grade neutropenia (RD from placebo: 0.22; 95% CI, 0.18‒0.25) as compared with the other PARPis. Conclusion: No statistically significant difference was found between the three PARPis with respect to PFS or OS (overall and in subpopulations by BRCA status). There is, however, a statistical difference in toxicity as niraparib is associated with a greater risk for thrombocytopenia and neutropenia.
On Consensus of Second-Order Multiagent Systems With Actuator Saturations: A Generalized-Nyquist-Criterion-Based Approach

In this article, a frequency-domain approach is developed to deal with the global consensus problem for a class of general second-order multiagent systems (MASs) subject to actuator saturations. By employing the describing function and the generalized Nyquist criterion, the global consensus problem is thoroughly investigated for both undirected and directed topologies. First, the describing function is introduced to characterize the actuator saturations in the $s$ -plane, and the inherent representation error is quantitatively analyzed from a frequency-domain perspective. Then, by means of the Kronecker product, the addressed consensus problem of the MAS is transformed into a corresponding stability analysis problem for a certain multi-input–multi-output (MIMO) system and, consequently, the generalized Nyquist criterion for MIMO systems is exploited to derive the condition for the global consensus of the MAS where the impact from the actuator saturation is explicitly reflected. Finally, numerical simulations are provided to illustrate the validity of the proposed theoretical result.
The Protective Role of Bioactive Quinones in Stress-induced Senescence Phenotype of Endothelial Cells Exposed to Cigarette Smoke Extract

Endothelial dysfunction represents the initial stage in atherosclerotic lesion development which occurs physiologically during aging, but external factors like diet, sedentary lifestyle, smoking accelerate it. Since cigarette smoking promotes oxidative stress and cell damage, we developed an in vitro model of endothelial dysfunction using vascular cells exposed to chemicals present in cigarette smoke, to help elucidate the protective effects of anti-inflammatory and antioxidant agents, such as ubiquinol and vitamin K, that play a fundamental role in vascular health. Treatment of both young and senescent Human Umbilical Vein Endothelial Cells (HUVECs) for 24 h with cigarette smoke extract (CSE) decreased cellular viability, induced apoptosis via reactive oxygen species (ROS) imbalance and mitochondrial dysfunction and promoted an inflammatory response. Moreover, the senescence marker SA-β-galactosidase was observed in both young CSE-exposed and in senescent HUVECs suggesting that CSE exposure accelerates aging in endothelial cells. Supplementation with 10 µM ubiquinol and menaquinone-7 (MK7) counteracted oxidative stress and inflammation, resulting in improved viability, decreased apoptosis and reduced SA-β-galactosidase, but were ineffective against CSE-induced mitochondrial permeability transition pore opening. Other K vitamins tested like menaquinone-4 (MK4) and menaquinone-1 (K1) were less protective. In conclusion, CSE exposure was able to promote a stress-induced senescent phenotype in young endothelial cells likely contributing to endothelial dysfunction in vivo. Furthermore, the molecular changes encountered could be offset by ubiquinol and menaquinone-7 supplementation, the latter resulting the most bioactive K vitamin in counteracting CSE-induced damage.
Interaction of lupin and sunflower secondary plant metabolites with lactic acid- and bifidobacteria

In this work, the suitability of lupin and sunflower raw materials (flour, protein concentrate) for lactic fermentation was examined with respect to growth, persistence and metabolism of potential starter strains. Four out of five tested lactic acid- and bifidobacteria showed high fermentation performances in lupin and sunflower substrates. The secondary plant metabolites did not have a significant inhibitory effect on the selected bacteria. Depending on the fermentation strain, the concentration of antinutritives was reduced, which leads to an improved quality and enhanced nutritional value of the products.
Tyrosine in the hinge region of the pore‐forming motif regulates oligomeric β‐barrel pore formation by Vibrio cholerae cytolysin

β‐barrel pore‐forming toxins perforate cell membranes by forming oligomeric β‐barrel pores. The most crucial step is the membrane‐insertion of the pore‐forming motifs that create the transmembrane β‐barrel scaffold. Molecular mechanism that regulates structural reorganization of these pore‐forming motifs during β‐barrel pore‐formation still remains elusive. Using Vibrio cholerae cytolysin as an archetypical example of the β‐barrel pore‐forming toxin, we show that a key tyrosine residue (Y321) in the hinge region of the pore‐forming motif plays crucial role in this process. Mutation of Y321 abrogates oligomerization of the membrane‐bound toxin protomers, and blocks subsequent steps of pore‐formation. Our study suggests that the presence of Y321 in the hinge region of the pore‐forming motif is crucial for the toxin molecule to sense membrane‐binding, and to trigger essential structural rearrangements required for the subsequent oligomerization and pore‐formation process. Such a regulatory mechanism of pore‐formation by V. cholerae cytolysin has not been documented earlier in the structurally related β‐barrel pore‐forming toxins.
A Comparative Analysis of Statistical Methods to Estimate the Reproduction Number in Emerging Epidemics, With Implications for the Current Coronavirus Disease 2019 (COVID-19) Pandemic

Abstract Background As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues its rapid global spread, quantification of local transmission patterns has been, and will continue to be, critical for guiding the pandemic response. Understanding the accuracy and limitations of statistical methods to estimate the basic reproduction number, R0, in the context of emerging epidemics is therefore vital to ensure appropriate interpretation of results and the subsequent implications for control efforts. Methods Using simulated epidemic data, we assess the performance of 7 commonly used statistical methods to estimate R0 as they would be applied in a real-time outbreak analysis scenario: fitting to an increasing number of data points over time and with varying levels of random noise in the data. Method comparison was also conducted on empirical outbreak data, using Zika surveillance data from the 2015–2016 epidemic in Latin America and the Caribbean. Results We find that most methods considered here frequently overestimate R0 in the early stages of epidemic growth on simulated data, the magnitude of which decreases when fitted to an increasing number of time points. This trend of decreasing bias over time can easily lead to incorrect conclusions about the course of the epidemic or the need for control efforts. Conclusions We show that true changes in pathogen transmissibility can be difficult to disentangle from changes in methodological accuracy and precision in the early stages of epidemic growth, particularly for data with significant over-dispersion. As localized epidemics of SARS-CoV-2 take hold around the globe, awareness of this trend will be important for appropriately cautious interpretation of results and subsequent guidance for control efforts.
Non-native plants exert strong but under-studied influence on fire dynamics

Altered fire regimes are among the most destructive consequences of anthropogenic environmental change. Fires have increased in frequency in some regions, and invasion by fire-adapted non-native species has been identified as a major driver of this change, which results in a feedback cycle promoting further spread by the non-native species and diminishing occurrence of natives. We notice, however, that nonnative species are often invoked in passing as a primary cause of changing fire dynamics, but that data supporting this claim are rarely presented. We therefore performed a meta-analysis of published literature to determine whether a significant relationship exists between non-native species presence and increased fire effects and risk, examined via various fire metrics. Our analysis detected a strongly significant difference between fire metrics associated with non-native and native species, with non-native species linked to enhanced fire effects and risk. However, only 30 papers discussing this linkage provided data to support it, and those quantitative studies examined only eight regions, five biome types, and a total of 22 unique non-native taxa. It is clear that we are only beginning to understand the relationship between non-native species and fire and that results drawn from an extremely limited set of contexts have been broadly applied in the literature. It is important for ecologists to continue to investigate drivers of changing fire regimes as factors such as climate change and land use change alter native and non-native fuels alike.
Analysis of Amygdalin in Various Matrices Using Electrospray Ionization and Flowing Atmospheric-Pressure Afterglow Mass Spectrometry

Amygdalin is a natural cyanogenic compound that plants produce in the fight against insects and herbivores. Excessive amounts of amygdalin by animals and humans can potentially lead to fatal intoxication. However, studies confirm that amygdalin has antitumor properties, including the ability to inhibit the proliferation of cancer cells and to induce their apoptosis. The analysis of amygdalin in various matrices is an important analytical problem today. The publication presents the methodology of direct determination of amygdalin in water, sewage, and biological materials using electrospray ionization mass spectrometry (ESI-MS) and a new analytical method using flowing atmospheric-pressure afterglow mass spectrometry (FAPA-MS). The methods of analyte pre-concentration using a magnetic, molecularly imprinted polymer (mag-MIP) and the influence of interferents on the recorded spectra were discussed. Analytical parameters in ESI-MS and FAPA-MS methods were established. The linearity range was 4.5 µg L−1–45 mg L−1 in positive mode ESI-MS and FAPA-MS. The limit of detection (LOD) for ESI-MS was 0.101 ± 0.003 µg L−1 and the limit of quantification (LOQ) was 0.303 ± 0.009 µg L−1. In FAPA-MS, the LOD was 0.050 ± 0.002 µg L−1 and the LOQ was 0.150 ± 0.006 µg L−1. The content of amygdalin in various matrices was determined.
Tissue response to white mineral aggregate‐based cement containing barium sulfate as alternative radiopacifier: A randomized controlled animal study

The purpose of this study was to investigate the tissue reaction stimulated by BaSO4‐ and Bi2O3‐containing White MTA Angelus, in comparison with Bi2O3‐containing white Portland cement, and white ProRoot MTA. Thirty‐six adult male Wistar rats (Rattus norvegicus), weighing between 250 and 300 g, were distributed into three groups (n = 12) in accordance with the period of sacrifice (15, 30, and 60 days). Four polyethylene tubes filled with the tested cements were implanted into the dorsum of each rat. Lateral wall of the tubes served as the negative control. After the experimental periods, the animals were euthanized by overdose of pentobarbital anesthetic solution, and the specimens were prepared for microscopic analysis under ×50, ×100, and ×400 magnifications. Inflammatory scores (0–3) were used to grade the tissue reaction. Data were analyzed by the Kruskal‐Wallis test and Dunn's test for individual comparisons (p < .05). A mild to moderate inflammatory tissue reaction was observed at the 15‐day period, which decreased over the course of the periods for all cements, except for Portland cement. There was no significant difference among the tissue responses for ProRoot MTA, BaSO4‐ and Bi2O3‐containing White MTA Angelus at the 60‐day period (p > .05). The Portland group had moderate inflammatory reaction at the final period of analysis, which was statistically different when compared to the other groups (p < .05). The microscopic findings of this animal study suggest that the addition of BaSO4 to White MTA Angelus does not hampers the biocompatibility of the cement.
Gut Microbiota and Host Thermoregulation in Response to Ambient Temperature Fluctuations

Whether gut microbiota play a role in regulating host phenotypic plasticity in small mammals living in seasonal environments has rarely been examined. The present study, through an intermittent temperature acclimation model, indicates that both gut microbiota and their host were more adaptive after repeated acclimations. It also demonstrates that dynamic gut microbiota confer host plasticity in thermoregulation in response to intermittent temperature fluctuations. Furthermore, low temperature seems to be a crucial cue in driving the symbiosis between mammals and their gut microbiota during evolution. ABSTRACT Ambient temperature (Ta) is an important factor in shaping phenotypic plasticity. Plasticity is generally beneficial for animals in adapting to their environments. Gut microbiota are crucial in regulating host physiological and behavioral processes. However, whether the gut microbiota play a role in regulating host phenotypic plasticity under the conditions of repeated fluctuations in environmental factors has rarely been examined. We used intermittent Ta acclimations to test the hypothesis that the plasticity of gut microbiota confers on the host a metabolic adaptation to Ta fluctuations. Mongolian gerbils (Meriones unguiculatus) were acclimated to intermittent 5°C to 23°C, 37°C to 23°C or 23°C to 23°C conditions for 3 cycles (totally 3 months). Intermittent Ta acclimations induced variations in resting metabolic rate (RMR), serum thyroid hormones, and core body temperature (Tb). We further identified that the β-diversity of the microbial community varied with Ta and showed diverse responses during the 3 cycles. Some specific bacteria were more sensitive to Ta and were associated with host dynamic metabolic plasticity during Ta acclimations. In addition, depletion of gut microbiota in antibiotic-treated gerbils impaired metabolic plasticity, particularly at low Ta, whereas supplementation with propionate as an energy resource improved the inhibited thermogenic capacity and increased the survival rate in the cold. These findings demonstrate that both gut microbiota and their host were more adaptive after repeated acclimations, and dynamic gut microbiota and their metabolites may confer host plasticity in thermoregulation in response to Ta fluctuations. It also implies that low Ta is a crucial cue in driving symbiosis between mammals and their gut microbiota during evolution. IMPORTANCE Whether gut microbiota play a role in regulating host phenotypic plasticity in small mammals living in seasonal environments has rarely been examined. The present study, through an intermittent temperature acclimation model, indicates that both gut microbiota and their host were more adaptive after repeated acclimations. It also demonstrates that dynamic gut microbiota confer host plasticity in thermoregulation in response to intermittent temperature fluctuations. Furthermore, low temperature seems to be a crucial cue in driving the symbiosis between mammals and their gut microbiota during evolution.
Natural polymorphism of Ym1 regulates pneumonitis through alternative activation of macrophages

Ym1 polymorphism regulates alternative activation of macrophages leading to variable susceptibility to inflammatory diseases. We have positionally cloned the Ym1 gene, with a duplication and a promoter polymorphism, as a major regulator of inflammation. Mice with the RIIIS/J haplotype, with the absence of Ym1 expression, showed reduced susceptibility to mannan-enhanced collagen antibody–induced arthritis and to chronic arthritis induced by intranasal exposure of mannan. Depletion of lung macrophages alleviated arthritis, whereas intranasal supplement of Ym1 protein to Ym1-deficient mice reversed the disease, suggesting a key role of Ym1 for inflammatory activity by lung macrophages. Ym1-deficient mice with pneumonitis had less eosinophil infiltration, reduced production of type II cytokines and IgG1, and skewing of macrophages toward alternative activation due to enhanced STAT6 activation. Proteomics analysis connected Ym1 polymorphism with changed lipid metabolism. Induced PPAR-γ and lipid metabolism in Ym1-deficient macrophages contributed to cellular polarization. In conclusion, the natural polymorphism of Ym1 regulates alternative activation of macrophages associated with pulmonary inflammation.
Could Fecal Microbiota Be a Useful Indicator of Serum Cholesterol Levels among Men?

Trepidation with blood tests among men may result in fewer routine screening and examination of their cardiovascular risk factors. Associations between fecal microbiota and serum cholesterols have not been well-established. The aim of this study was to explore such association in order to determine the potential of fecal microbiota as a non-invasive alternate predictor of serum cholesterols. Secondary data from a cross-over trial were analyzed. Associations between fecal microbiota, mainly Bifidobacterium and Clostridial group, of healthy men (n = 16) and their total cholesterols, low and high-density lipoprotein cholesterols (LDL-C and HDL-C) were assessed using generalized estimating equations, adjusted for diet intervention, diet order, frequency of defecation and flatulence level. For every two-fold increase in fecal Bifidobacterium, geometric mean of LDL-C increases by a factor of 1.23 (95% CI: 1.01, 1.49) whilst that of HDL-C increases by a factor of 1.07 (95% CI: 1.03, 1.10). For every two-fold increase in Clostridial group (C. ramosum, C. spiroforme and C. cocleatum), geometric mean of HDL-C decreases by a factor of 1.10 (95% CI: −1.16, −1.03). No association was found between total bacteria and serum cholesterols. Fecal Bifidobacterium spp. and Clostridium spp. , are potential non-invasive surrogate markers of men’s serum cholesterols.