Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitogen-activating protein kinase kinase kinase kinase-3, inhibited by Astragaloside IV through H3 lysine 4 monomethylation, promotes the progression of diabetic nephropathy by inducing apoptosis

ABSTRACT Astragaloside IV (AS-IV) is a bioactive saponin extracted from the Astragalus root and has been reported to exert a protective effect on diabetic nephropathy (DN). However, the underlying mechanism remains unclear. Herein, we found that AS-IV treatment alleviated DN symptoms in DN mice accompanied by reduced metabolic parameters (body weight, urine microalbumin and creatinine, creatinine clearance, and serum urea nitrogen and creatinine), pathological changes, and apoptosis. Epigenetic histone modifications are closely related to diabetes and its complications, including H3 lysine 4 monomethylation (H3K4me1, a promoter of gene transcription). A ChIP-seq assay was conducted to identify the genes regulated by H3K4me1 in DN mice after AS-IV treatment and followed by a Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. The results showed that there were 16 common genes targeted by H3K4me1 in normal and AS-IV-treated DN mice, 1148 genes were targeted by H3K4me1 only in DN mice. From the 1148 genes, we screened mitogen-activating protein kinase kinase kinase kinase-3 (MAP4K3) for the verification of gene expression and functional study. The results showed that MAP4K3 was significantly increased in DN mice and high glucose (HG)-treated NRK-52E cells, which was reversed by AS-IV. MAP4K3 silencing reduced the apoptosis of NRK-52E cells under HG condition, as evidenced by decreased cleaved caspase 3 and Bax (pro-apoptotic factors), and increased Bcl-2 and Bcl-xl (anti-apoptotic factors). Collectively, AS-IV may downregulate MAP4K3 expression by regulating H3K4me1 binding and further reducing apoptosis, which may be one of the potential mechanisms that AS-IV plays a protective effect on DN. GRAPHICAL ABSTRACT
Sleep-Specific Processing of Auditory Stimuli Is Reflected by Alpha and Sigma Oscillations

Recent research revealed a surprisingly large range of cognitive operations to be preserved during sleep in humans. The new challenge is therefore to understand functions and mechanisms of processes, which so far have been mainly investigated in awake subjects. The current study focuses on dynamic changes of brain oscillations and connectivity patterns in response to environmental stimulation during non-REM sleep. Our results indicate that aurally presented names were processed and neuronally differentiated across the wake-sleep spectrum. Simultaneously recorded EEG and MEG signals revealed two distinct clusters of oscillatory power increase in response to the stimuli: (1) vigilance state-independent θ synchronization occurring immediately after stimulus onset, followed by (2) sleep-specific α/σ synchronization peaking after stimulus offset. We discuss the possible role of θ, α, and σ oscillations during non-REM sleep, and work toward a unified theory of brain rhythms and their functions during sleep. SIGNIFICANCE STATEMENT Previous research has revealed (residual) capacity of the sleeping human brain to interact with the environment. How sensory processing is realized by the neural assemblies in different stages of sleep is however unclear. To tackle this question, we examined simultaneously recorded MEG and EEG data. We discuss the possible role of θ, α, and σ oscillations during non-REM sleep. In contrast to versatile θ band response that reflected early stimulus processing step, succeeding α and σ band activity was sensitive to the saliency of the incoming information, and contingent on the sleep stage. Our findings suggest that the specific reorganization of mechanisms involved in later stages of sensory processing takes place upon falling asleep.
Dual targeting of RdRps of SARS-CoV-2 and the mucormycosis-causing fungus: an in silico perspective

During the past few months, mucormycosis has been associated with SARS-CoV-2 infections. Molecular docking combined with molecular dynamics simulation is utilized to test nucleotide-based inhibitors against the RdRps of SARS-CoV-2 solved structure and Rhizopus oryzae RdRp model built in silico. The results reveal a comparable binding affinity of sofosbuvir, galidesivir, ribavirin and remdesivir compared with the physiological nucleotide triphosphates against R. oryzae RdRp as well as the SARS-CoV-2 RdRp as reported before. Additionally, other compounds such as setrobuvir, YAK, IDX-184 and modified GTP compounds 2, 3 and 4 show potential calculated average binding affinities against R. oryzae RdRp. The present in silico study suggests the dual inhibition potential of the recommended drugs and compounds against SARS-CoV-2 and R. oryzae RdRps.
Synchronous Disintegration of Ferroptosis Defense Axis via Engineered Exosome‐Conjugated Magnetic Nanoparticles for Glioblastoma Therapy

Glioblastoma (GBM) is one of the most fatal central nervous system tumors and lacks effective or sufficient therapies. Ferroptosis is a newly discovered method of programmed cell death and opens a new direction for GBM treatment. However, poor blood–brain barrier (BBB) penetration, reduced tumor targeting ability, and potential compensatory mechanisms hinder the effectiveness of ferroptosis agents during GBM treatment. Here, a novel composite therapeutic platform combining the magnetic targeting features and drug delivery properties of magnetic nanoparticles with the BBB penetration abilities and siRNA encapsulation properties of engineered exosomes for GBM therapy is presented. This platform can be enriched in the brain under local magnetic localization and angiopep‐2 peptide‐modified engineered exosomes can trigger transcytosis, allowing the particles to cross the BBB and target GBM cells by recognizing the LRP‐1 receptor. Synergistic ferroptosis therapy of GBM is achieved by the combined triple actions of the disintegration of dihydroorotate dehydrogenase and the glutathione peroxidase 4 ferroptosis defense axis with Fe3O4 nanoparticle‐mediated Fe2+ release. Thus, the present findings show that this system can serve as a promising platform for the treatment of glioblastoma.
Multi-View Integrative Attention-Based Deep Representation Learning for Irregular Clinical Time-Series Data

Electronic health record (EHR) data are sparse and irregular as they are recorded at irregular time intervals, and different clinical variables are measured at each observation point. In this work, to handle irregular multivariate time-series data, we consider the human knowledge of the aspects to be measured and time to measure them in different situations, known as multi-view features, which are indirectly represented in the data. We propose a scheme to realize multi-view features integration learning via a self-attention mechanism. Specifically, we devise a novel multi-integration attention module (MIAM) to extract complex information that is inherent in irregular time-series data. We explicitly learn the relationships among the observed values, missing indicators, and time interval between the consecutive observations in a simultaneous manner. In addition, we build an attention-based decoder as a missing value imputer that helps empower the representation learning of the interrelations among multi-view observations for the prediction task this decoder operates only in the training phase so that the final model is implemented in an imputation-free manner. We validated the effectiveness of our method over the public MIMIC-III and PhysioNet challenge 2012 datasets by comparing with and outperforming the state-of-the-art methods in three downstream tasks i.e., prediction of the in-hospital mortality, prediction of the length of stay, and phenotyping. Moreover, we conduct a layer-wise relevance propagation (LRP) analysis based on case studies to highlight the explainability of the trained model.
Neural-Fly enables rapid learning for agile flight in strong winds

Executing safe and precise flight maneuvers in dynamic high-speed winds is important for the ongoing commoditization of uninhabited aerial vehicles (UAVs). However, because the relationship between various wind conditions and its effect on aircraft maneuverability is not well understood, it is challenging to design effective robot controllers using traditional control design methods. We present Neural-Fly, a learning-based approach that allows rapid online adaptation by incorporating pretrained representations through deep learning. Neural-Fly builds on two key observations that aerodynamics in different wind conditions share a common representation and that the wind-specific part lies in a low-dimensional space. To that end, Neural-Fly uses a proposed learning algorithm, domain adversarially invariant meta-learning (DAIML), to learn the shared representation, only using 12 minutes of flight data. With the learned representation as a basis, Neural-Fly then uses a composite adaptation law to update a set of linear coefficients for mixing the basis elements. When evaluated under challenging wind conditions generated with the Caltech Real Weather Wind Tunnel, with wind speeds up to 43.6 kilometers/hour (12.1 meters/second), Neural-Fly achieves precise flight control with substantially smaller tracking error than stateof-the-art nonlinear and adaptive controllers. In addition to strong empirical performance, the exponential stability of Neural-Fly results in robustness guarantees. Last, our control design extrapolates to unseen wind conditions, is shown to be effective for outdoor flights with only onboard sensors, and can transfer across drones with minimal performance degradation. Description A drone adapts to dynamic wind conditions using deep neural networks in real time with stability guarantees.
Systematic review of the associations between prenatal sleep behaviours and components of energy balance for regulating weight gain

This systematic review aimed to examine the magnitude and direction of the associations between prenatal sleep behaviours (i.e. nighttime sleep duration, sleep quality, night awakenings and daytime nap duration) and eating behaviours, physical activity and gestational weight gain. A systematic search was conducted using Medline/PubMed, PsychINFO, CINAHL Complete, ProQuest Dissertations and Thesis A&I, and Web of Science to identify studies with at least one sleep measure, and either eating behaviours, physical activity and/or gestational weight gain. In summary, 11 studies met the review criteria and generated 11 total effect size across 10,900 participants. The majority of the studies were conducted after 2010, which highlights the infancy of this research. Overall, the strengths of the effect size were small: sleep‐gestational weight gain (effect size = 0.29), sleep‐eating behaviours (effect size = 0.13) and sleep‐physical activity (effect size = 0.13). The only effect size that emerged as significant was for the pooled sleep behaviours‐physical activity association; good sleep behaviours were positively associated with higher levels of physical activity. These findings summarize and provide insight on how sleep behaviours are related to prenatal gestational weight gain, eating behaviours and physical activity by identifying the strength and direction of the associations that have been previously unknown. Results support the rationale for future longitudinal and randomized control trials to examine the effects of sleep behaviours on gestational weight gain, eating behaviours and physical activity over the course of pregnancy.
Investigating the role of working memory resources across aesthetic and non-aesthetic judgements

Aesthetic judgements dominate much of daily life by guiding how we evaluate objects, people, and experiences in our environment. One key question that remains unanswered is the extent to which more specialised or largely general cognitive resources support aesthetic judgements. To investigate this question in the context of working memory, we examined the extent to which a working memory load produces similar or different response time interference on aesthetic compared with non-aesthetic judgements. Across three pre-registered experiments that used Bayesian multi-level modelling approaches (N > 100 per experiment), we found clear evidence that a working memory load produces similar response time interference on aesthetic judgements relative to non-aesthetic (motion) judgements. We also showed that this similarity in processing across aesthetic versus non-aesthetic judgements holds across variations in the form of art (people vs. landscape; Experiments 1–3), medium type (artwork vs. photographs; Experiment 2), and load content (art images vs. letters; Experiments 1–3). These findings suggest that across a range of experimental contexts, as well as different processing streams in working memory (e.g., visual vs. verbal), aesthetic and motion judgements commonly rely on a domain-general cognitive system, rather than a system that is more specifically tied to aesthetic judgements. In doing so, these findings shine new light on the working memory resources that support aesthetic judgements, as well as on how domain-general cognitive systems operate more generally in cognition.
Peripheral monocyte–derived cells counter amyloid plaque pathogenesis in a mouse model of Alzheimer’s disease

Microglia, the parenchymal tissue macrophages in the brain, surround amyloid plaques in brains of individuals with Alzheimer’s disease (AD) but are ineffective at clearing amyloid to mitigate disease progression. Recent studies in mice indicate that microglia are derived exclusively from primitive yolk sac hematopoiesis and self-renew without contribution from ontogenically distinct monocytes/macrophages of definitive adult hematopoietic origin. Using a genetic fate-mapping approach to label cells of definitive hematopoietic origin throughout life span, we discovered that circulating monocytes contribute 6% of plaque-associated macrophages in aged AD mice. Moreover, peripheral monocytes contributed to a higher fraction of macrophages in the choroid plexus, meninges, and perivascular spaces of aged AD mice versus WT control mice, indicating enrichment at potential sites for entry into the brain parenchyma. Splenectomy, which markedly reduced circulating Ly6Chi monocytes, also reduced abundance of plaque-associated macrophages of definitive hematopoietic origin, resulting in increased amyloid plaque load. Together, these results indicate that peripherally derived monocytes invade the brain parenchyma, targeting amyloid plaques to reduce plaque load.
A Multilevel Approach to Investigate Relationships Between Healthcare Resources and Lung Cancer

Background Screening for lung cancer is an evidence-based but underutilized measure to reduce the burden of lung cancer mortality. Lack of adequate data on geographic availability of lung cancer screening inhibits the ability of healthcare providers to help patients with decision-making and impedes equity-focused implementation of screening-supportive services. Objectives This analysis used data from the 2012–2016 Surveillance, Epidemiology, and End Results (SEER) Program, the Behavioral Risk Factor Surveillance System, and the county health ranking to examine (a) which cancer resources and county-level factors are associated with late-stage lung cancer at diagnosis and (b) associations between county rurality and lung cancer incidence/mortality rates. Methods Using the New York state SEER data, we identified 68,990 lung cancer patients aged 20–112 years; 48.3% had late-stage lung cancers, and the average lung cancer incidence and mortality rates were 70.7 and 46.2 per 100,000, respectively. There were 144 American College of Radiology-designated lung cancer screening centers and 376 Federally Qualified Health Centers identified in New York state. County rurality was associated with a higher proportion of late-stage lung cancers and higher lung cancer mortality rates. Discussion Visual geomapping showed the scarcity of rural counties’ healthcare resources. County rurality is a significant factor in differences in lung cancer screening resources and patient outcomes. Use of publicly available data with geospatial methods provides ways to identify areas for improvement, populations at risk, and additional infrastructure needs.
Effect of Boundary Conditions on Propagation and Morphology of Premixed Flames in Narrow Conduits

Effect of Boundary Conditions on Propagation and Morphology of Premixed Flames in Narrow Conduits Orlando J. Ugarte-Almeyda Boundary conditions play a key role in the evolution and morphology of flame fronts, especially when combustion occurs in narrow chambers. The burning intensity and the flame-generated flow can be significantly modified by the momentum and energy transferred at the walls, which are further modified by the exothermal nature of the process. In this work, the effect of the wall roughness and thermal conditions on the flame propagation is explored. Specifically, conduits with and without obstacles, having adiabatic or isothermal walls, are investigated. Wall friction constitutes one of the main reasons of spontaneous flame acceleration in narrow pipes. Although this phenomenon has been intensely studied, the researchers have focused on the mechanistic scenario of the combustion intensification, induced by the wall friction, putting less emphasis on the heat exchanged at the walls. In this study, besides the adiabatic condition, the surfaces have been kept at multiple constant temperatures in order to explore the wall thermal effects on the burning process, recognizing its potential to diminish or even quench the reaction. Moreover, the inclusion of solid obstacles at the pipe walls provides a mechanism of extremely fast flame acceleration, which is driven by an intense jet-flow generated by the delayed combustion occurring between obstacles. In this work, the flame dynamics promoted in the obstructed configuration is analyzed, comparing the attained acceleration rates to other mechanisms such as that generated by the wall friction and the so-called finger flame evolution. For this purpose, a parametric study provided by extensive fully-compressible numerical simulations of the combustion and hydrodynamic equations is performed. The geometry is primary given by 2D channels, although cylindrical ‘smooth’ tubes have been also considered. The wall conditions include non-slip walls and slip walls with obstacles; adiabatic and isothermal, with the fuel characterized by the thermal expansion coefficient. Four regimes of flame propagation in isothermal ‘smooth’ channels have been identified, for flames propagating a distance around 100-150 times the flame thickness: (i) no flame propagation or extinction; (ii) linear flame velocity; (iii) almost-constant flame propagation speed; and (iv) oscillating flame velocity. In the obstructed configuration, the developing of turbulent and laminar combustion regimes at the early stages of the process have been identified in relation to the obstacles size and spacing, including a finger flame-like limit when small enough obstacles are in place.
Effects of feeding high-energy diet on growth performance, blood parameters, and carcass traits in Hanwoo steers

Objective Our study aimed to investigate the effects of a 2% increase in dietary total digestible nutrients (TDN) value during the growing (7 to 12 mo of age) and fattening (13 to 30 mo of age) period of Hanwoo steers. Methods Two hundred and twenty Hanwoo steers were assigned to one of two treatments: i) a control group (basal TDN, BTDN, n = 111 steers, growing = 70.5%, early fattening = 71.0%, late fattening = 74.0%) or high TDN (HTDN, n = 109 steers, growing = 72.6%, early = 73.1%, late = 76.2%). Growth performance, carcass traits, blood parameters, and gene expression of longissimus dorsi (LD) (7, 18, and 30 mo) were quantified. Results Steers on the BTDN diets had increased (p≤0.02) DMI throughout the feeding trial compared to HTDN, but gain did not differ appreciably. A greater proportion of cattle in HTDN received Korean quality grade 1 (82%) or greater compared to BTDN (77%), while HTDN had a greater yield grade (29%) than BTDN (20%). Redness (a*) of LD muscle was improved (p = 0.021) in steers fed HTDN. Feeding the HTDN diet did not alter blood parameters. Steers fed HTDN diet increased (p = 0.015) the proportion of stearic acid and tended to alter linoleic acid. Overall, saturated, unsaturated, monounsaturated, and polyunsaturated fatty acids of LD muscle were not impacted by the HTDN treatment. A treatment by age interaction was noted for mRNA expression of myosin heavy chain (MHC) IIA, IIX, and stearoyl CoA desaturase (SCD) (p≤0.026). No treatment effect was detected on gene expression from LD muscle biopsies at 7, 18, and 30 mo of age; however, an age effect was detected for all variables measured (p≤0.001). Conclusion Our results indicated that feeding HTDN diet could improve overall quality grade while minimum effects were noted in gene expression, blood parameters, and growing performance. Cattle performance prediction in the feedlot is a critical decision-making tool for optimal planning of cattle fattening and these data provide both benchmark physiological parameters and growth performance measures for Hanwoo cattle feeding enterprises.
The Physiological Effects of Face Masks During Exercise Worn Due to COVID-19: A Systematic Review

Context: Use of face masks in sport has been a particularly complex issue during the COVID-19 pandemic. Objectives: A systematic review to examine the physiological effects the different types of masks have on healthy adults when doing physical exercise. Data sources: PubMed, SPORTDiscus, Scopus, and Litcovid were searched up to March 20, 2021, following the PRISMA model. Articles published in the last 5 years with healthy adults. Study Selection: A total of 633 studies related to the use of masks during physical exercise were found, of which 8 articles met the criteria to be included. Study Design: Systematic review. Level of Evidence: Level 2. Data Extraction: The search process and the review of the articles were carried out by independent expert researchers. The risk of bias and the methodological quality of the different studies included in the systematic review were calculated following the Cochrane criteria using an adaptation for random cross-studies. Once the information was properly structured, the results were extracted, and the findings of the study analyzed. Results: There were significant changes in the following physiological variables when engaging in physical exercise using masks: 25% in the heart rate and dyspnea, 37.5% in the rating of perceived exertion, 50% in the pulmonary variables, and 37.5% in discomfort. The oxygen saturation, blood pressure, systolic blood pressure, diastolic blood pressure, and the concentration of blood lactate did not present any significant effect in this study. Conclusion: The usage of masks by a healthy adult population during the performance of physical exercise has shown minimal effects with regard to physiological, cardiorespiratory, and perceived responses. Some symptoms can be dyspnea, effort perceived, or discomfort, among others. These findings indicate that the use of masks is not harmful to individuals’ health. It does not present any significant detrimental effect on physical performance or risk to their well-being. However, further experiments are required to corroborate the findings of this review.