Miracle-dz/UniFAR-FTUs huggingface dataset:
Longitudinal Association Between Energy Regulation and Fatigability in Mid-to-Late Life.

BACKGROUND Deficits in energy production and utilization have been linked to higher fatigue and functional decline with aging. Lesser known is whether individuals with a combination of low peak energy capacity and high energy costs for mobility (e.g., impaired energy regulation) are more likely to experience the onset and progression of high fatigability with aging. METHODS Participants in the Baltimore Longitudinal Study of Aging (n = 651, 49.0% male, mean age 71.9, range 50-94) with >2 visits who completed fatigability (Borg RPE after a 5-min 1.5mph treadmill walk), slow walking energy expenditure (VO2 ml/kg/min), and peak walking energy expenditure (VO2 ml/kg/min), testing between 2007-2018. The longitudinal association between each measure of energy expenditure, a ratio of energy cost-to-capacity, and perceived fatigability was modeled using mixed effects models adjusted for age, body composition, and comorbidities. Time to higher perceived fatigability (RPE>10) was modeled using Cox proportional hazards models. RESULTS In continuous analyses higher slow walking energy expenditure (p<.05) and a higher cost ratio (p<.001) were associated with greater perceived fatigability over time. Cox proportional hazards models using tertiles of the cost ratio suggest that, compared to those in the lowest tertile, those in the middle and highest tertiles had 1.89 (95% CI:1.57-5.16) and 2.85 (95% CI:1.05 - 3.40) times greater risk of developing higher fatigability, respectively. CONCLUSION Findings suggest that strategies to prevent fatigability should consider methods to improve energy regulation by targeting both the independent and combined effects of declining peak capacity and rising energy costs for mobility with aging.
Microfluidics Mediated Production of Foams for Biomedical Applications

Within the last decade, there has been increasing interest in liquid and solid foams for several industrial uses. In the biomedical field, liquid foams can be used as delivery systems for dermatological treatments, for example, whereas solid foams are frequently used as scaffolds for tissue engineering and drug screening. Most of the foam functionalities are largely correlated to their mechanical properties and their structure, especially bubble/pore size, shape, and interconnectivity. However, the majority of conventional foaming fabrication techniques lack pore size control which can induce important inhomogeneities in the foams and subsequently decrease their performance. In this perspective, new advanced technologies have been introduced, such as microfluidics, which offers a highly controlled production, allowing for design customization of both liquid foams and solid foams obtained through liquid-templating. This short review explores both the fabrication and the characterization of foams, with a focus on solid polymer foams, and sheds the light on how microfluidics can overcome some existing limitations, playing a crucial role in their production for biomedical applications, especially as scaffolds in tissue engineering.
Different coding strategy of sound information between GABAergic and glutamatergic neurons in the auditory midbrain

In the central nucleus of the inferior colliculus (ICC), which acts as the hub of the auditory pathways, how the sound is coded by distinct cell types is largely unknown. Large GABAergic cells are tuned broadly to pure tones and respond more strongly to frequency‐modulated sweeps than small GABAergic and glutamatergic (GLU) cells. Neurons, especially GLU cells, which share sharpness of tuning and sweep sensitivity, were spatially clustered inside the ICC. The difference in responsiveness between cell types was partially explained by the morphology of dendritic trees and the spatial distributions of excitatory and inhibitory inputs. The results suggest that each ICC cell type has a particular sound‐encoding strategy, which is partially determined by the morphological characteristics and location of cells, and contributes information coding in higher centres in different ways.
Effect of Phytase Derived from the E. coli AppA Gene on Weaned Piglet Performance, Apparent Total Tract Digestibility and Bone Mineralization

Simple Summary Plants store phosphorus mainly in a form that is indigestible to pigs: phytate. Unabsorbed minerals excreted into the environment are considered to be environmental pollutants. Our study focuses on the effects of novel types of phytase enzymes in diets deficient in external phosphorus on the performance, digestibility of crude protein, dry matter and minerals, and bone mineralization of weaned piglets. Using novel phytases, we noted a positive impact on body weight gain, feed conversion ratio, the digestibility of phosphorus and calcium, and phosphorus and calcium content in bones. There was no significant improvement in the content of dry matter or digestion of crude protein. This study reveals novel phytases to be useful additives for weaned piglet diets because of their superior performance results and phosphorus absorption. Abstract The objective of this study was to assess the effect of novel appAT1 and appAT2 phytase inclusion at 250 phytase units (FTU)/kg on weaned piglet performance, the apparent total tract digestibility of P and Ca, and bone mineralization. Piglets (48 males) were randomly divided into four treatment groups: a positive control (PC), with recommended levels of phosphorus (P) and calcium (Ca), a negative control (NC) deficient in P and Ca, and two experimental groups with NC diets supplemented with phytase derived from the appA gene of Escherichia coli. Diets fed in a mashed form were divided into prestarter (0–21 days) and starter (22–42 days) periods. During the whole period of the study, the experimental diets improved (p < 0.05) the body weight gain (BWG) and feed conversion ratio (FCR) compared to the NC diet. The apparent total tract digestibility (ATTD) of the dry matter and crude protein was not significantly different among the diets. Phytase-supplemented diets improved the ATTD of P (p < 0.05) and the ATTD of Ca (p < 0.05). Bone ash content in the third metacarpal and P and Ca content were improved among the phytase supplemented diets compared to the NC diet.
Autophagy Promotes Duck Tembusu Virus Replication by Suppressing p62/SQSTM1-Mediated Innate Immune Responses In Vitro

Duck Tembusu virus (DTMUV) has recently appeared in ducks in China and the key cellular determiners for DTMUV replication in host cells remain unknown. Autophagy is an evolutionarily conserved cellular process that has been reported to facilitate flavivirus replication. In this study, we utilized primary duck embryo fibroblast (DEF) as the cell model and found that DTMUV infection triggered LC3-II increase and polyubiquitin-binding protein sequestosome 1 (p62) decrease, confirming that complete autophagy occurred in DEF cells. The induction of autophagy by pharmacological treatment increased DTMUV replication in DEF cells, whereas the inhibition of autophagy with pharmacological treatments or RNA interference decreased DTMUV replication. Inhibiting autophagy enhanced the activation of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and interferon regulatory factor 7 (IRF7) pathways and increased the p62 protein level in DTMUV-infected cells. We further found that the overexpression of p62 decreased DTMUV replication and inhibited the activation of the NF-κB and IRF7 pathways, and changes in the NF-κB and IRF7 pathways were consistent with the level of phosphorylated TANK-binding kinase 1 (p-TBK1). Opposite results were found in p62 knockdown cells. In summary, we found that autophagy-mediated p62 degradation acted as a new strategy for DTMUV to evade host innate immunity.
Evaluation of questionnaire as an instrument to measure the level of nutritional and weight gain knowledge in pregnant women in Poland. A pilot study

Pregnancy is a period in life in which women are willing to improve their lifestyle. Providing proper information for these women is crucial for their health and the health of their offspring. Clear information about weak points in their nutritional and weight gain knowledge is the first step for proper health care assistance. There are a few previous studies evaluating the nutritional and weight gain knowledge of pregnant women. In the few studies available, different approaches were taken and there was no wider discussion on the content of the questionnaires attempting to measure level of knowledge. The aim of this study, designed in a pilot fashion, was to test the adequacy of the questionnaire as a research instrument in a group of 139 pregnant Polish women. The developed instrument is a 33-item questionnaire comprising four domains: weight gain, importance of nutrients, quality and quantity of food intake. The results of this study indicate that the questionnaire is stable and internal consistency is acceptable (Cronbach’s alpha > 0.7) for dimensions with more than four items. For dimensions with less than four items, internal consistency was poor (Cronbach’s alpha < 0.7). The cumulative explained variance for domains weight gain, importance of nutrients, quantity and quality of food intake was 54.74%, 42.74%, 54.42% and 48.99% respectively. Results from validity, reliability and factor analysis indicate that the questionnaire is adequate for its purpose.
Cellular models for discovering prion disease therapeutics: Progress and challenges

Prions, which cause fatal neurodegenerative disorders such as Creutzfeldt‐Jakob disease, are misfolded and infectious protein aggregates. Currently, there are no treatments available to halt or even delay the progression of prion disease in the brain. The infectious nature of prions has resulted in animal paradigms that accurately recapitulate all aspects of prion disease, and these have proven to be instrumental for testing the efficacy of candidate therapeutics. Nonetheless, infection of cultured cells with prions provides a much more powerful system for identifying molecules capable of interfering with prion propagation. Certain lines of cultured cells can be chronically infected with various types of mouse prions, and these models have been used to unearth candidate anti‐prion drugs that are at least partially efficacious when administered to prion‐infected rodents. However, these studies have also revealed that not all types of prions are equal, and that drugs active against mouse prions are not necessarily effective against prions from other species. Despite some recent progress, the number of cellular models available for studying non‐mouse prions remains limited. In particular, human prions have proven to be particularly challenging to propagate in cultured cells, which has severely hindered the discovery of drugs for Creutzfeldt‐Jakob disease. In this review, we summarize the cellular models that are presently available for discovering and testing drugs capable of blocking the propagation of prions and highlight challenges that remain on the path towards developing therapies for prion disease.
Engineering of Effector Domains for Targeted DNA Methylation with Reduced Off-Target Effects

Epigenome editing is a promising technology, potentially allowing the stable reprogramming of gene expression profiles without alteration of the DNA sequence. Targeted DNA methylation has been successfully documented by many groups for silencing selected genes, but recent publications have raised concerns regarding its specificity. In the current work, we developed new EpiEditors for programmable DNA methylation in cells with a high efficiency and improved specificity. First, we demonstrated that the catalytically deactivated Cas9 protein (dCas9)-SunTag scaffold, which has been used earlier for signal amplification, can be combined with the DNMT3A-DNMT3L single-chain effector domain, allowing for a strong methylation at the target genomic locus. We demonstrated that off-target activity of this system is mainly due to untargeted freely diffusing DNMT3A-DNMT3L subunits. Therefore, we generated several DNMT3A-DNMT3L variants containing mutations in the DNMT3A part, which reduced their endogenous DNA binding. We analyzed the genome-wide DNA methylation of selected variants and confirmed a striking reduction of untargeted methylation, most pronounced for the R887E mutant. For all potential applications of targeted DNA methylation, the efficiency and specificity of the treatment are the key factors. By developing highly active targeted methylation systems with strongly improved specificity, our work contributes to future applications of this approach.
Increased Colonic Epithelial Permeability and Mucosal Eosinophilia in Ulcerative Colitis in Remission Compared With Irritable Bowel Syndrome and Health

Abstract Background Barrier dysfunction is recognized as a pathogenic factor in ulcerative colitis (UC) and irritable bowel syndrome (IBS), but it is unclear to what extent the factors related to barrier dysfunction are disease-specific. The aim of this study was to compare these aspects in UC patients in remission, IBS patients, and healthy controls (HCs). Methods Colonic biopsies were collected from 13 patients with UC in remission, 15 patients with IBS-mixed, and 15 HCs. Ulcerative colitis patients had recently been treated for relapse, and biopsies were taken from earlier inflamed areas. Biopsies were mounted in Ussing chambers for measurements of intestinal paracellular permeability to 51chromium (Cr)-ethylenediaminetetraacetic acid (EDTA). In addition, biopsies were analyzed for mast cells and eosinophils by histological procedures, and plasma tumor necrosis factor (TNF)-α was assessed by ELISA. Results Ussing chamber experiments revealed an increased 51Cr-EDTA permeability in UC and IBS (P < 0.05). The 51Cr-EDTA permeability was higher in UC compared with IBS (P < 0.005). There were increased numbers of mucosal mast cells and eosinophils in UC and IBS and more eosinophils in UC compared with IBS (P < 0.05). Also, increased extracellular granule content was found in UC compared with HCs (P < 0.05). The 51Cr-EDTA permeability correlated significantly with eosinophils in all groups. Plasma TNF-α concentration was higher in UC compared with IBS and HCs (P < 0.0005). Conclusions Results indicate a more permeable intestinal epithelium in inactive UC and IBS compared with HCs. Ulcerative colitis patients, even during remission, demonstrate a leakier barrier compared with IBS. Both eosinophil numbers and activation state might be involved in the increased barrier function seen in UC patients in remission.
Semiglobal Consensus of a Class of Heterogeneous Multi-Agent Systems With Saturation

This article addresses the leader-following consensus of a class of multi-agent systems (MASs) subjected to saturation. Unlike previous literature, the followers are with heterogeneous dynamics. To solve this problem, we employ the low-gain feedback technique and the parameterized algebraic Riccati equations to design the controllers. For the fixed and switching network topologies, sufficient conditions are put in place to guarantee the semiglobal stability of the consensus error system. Numerical results are also provided to validate the effectiveness of the control design.
RNA binding protein FXR1-miR301a-3p axis contributes to p21WAF1 degradation in oral cancer

RNA‐binding proteins (RBPs) associate with primary, precursor, and mature microRNAs (miRNAs), which in turn control mature miRNA levels, and post‐transcriptional gene regulation (PTR). However, the mechanistic basis of miRNA interaction and stability by RBP remains largely elusive. To understand how RBPs contribute to miRNA stability and PTR, we analyzed miRNAs that are controlled and stabilized by RBP Fragile X Mental Retardation protein‐ 1 (FXR1) in head and neck squamous cell carcinoma (HNSCC). We find that FXR1controls the expression of a subset of mature miRNAs, including a highly expressed oncogenic miR301a‐3p in HNSCC cells. We also observed that FXR1 controls the stability of miR301a‐3p by blocking 3′ to 5′ exoribonuclease activity of Polyribonucleotide Nucleotidyltransferase 1 (PNPT1). The miR301a‐3p is degraded by PNPT1 in the absence of FXR1 in oral cancer cells, and the degradation is rescued in co‐knockdown of FXR1 and PNPT1. Also, our in vitro findings show that FXR1 bound miRNA complex protects miR301a‐3p from PNPT1‐mediated miRNA degradation. This work also reveals that FXR1 knockdown destabilizes miR301a‐3p that degrades p21 mRNA, which leads to an increase in p21 accumulation, which explaining why overexpressed FXR1 and miR301a‐3p in HNSCC display p21 downregulation. Thus, our work illustrates the unique role of FXR1 that is critical for the stability of a subset of mature miRNAs or at least miR301a‐3p to target p21, thereby promoting the growth and proliferation of HNSCC.
Effects of Self-Hand Massage with Aroma Oil on Daily Cigarette Use, Smoking Craving and Depression of Female High School Student Smokers

Purpose: The purpose was to test the effects of self-hand massage with aroma oil on daily cigarette use, smoking craving, and depression of female high school student smokers who are attempting to quit smoking. Method: A convenience sampling of a non-equivalent control group time series was used. Female high school student smokers were assigned either to smoking cessation lecture only or to an intervention that involved a smoking cessation lecture and self -hand massage with aroma oil for 4 weeks. Lavender, Peppermint, and Bergamotte essence oils were used for massage. Result: There was a significant change in daily cigarette use and depression between the groups at three different times. Conclusion: It is promising that self-hand massage with aroma oil can be an effective adjunctive to decrease daily cigarette use and depression of female high school student smokers who are attempting to quit smoking.
Hof1 plays a checkpoint-related role in MMS-induced DNA damage response in Candida albicans

Cells depend on robust DNA damage recognition and repair systems to maintain genomic integrity for survival in a mutagenic environment. In the pathogenic yeast Candida albicans, a subset of genes involved in the response to DNA damage-induced genome instability and morphological changes has been found to regulate virulence. To better understand the virulence-linked DNA repair network, we screened for methyl methane sulfonate (MMS) sensitivity within the GRACE conditional expression collection and identified 56 hits. One of these potential DNA damage repair-associated genes, a HOF1 conditional mutant, unexpectedly had a previously characterized function in cytokinesis. Deletion of HOF1 resulted in MMS sensitivity and genome instability, suggesting Hof1 acts in the DNA damage response. By probing genetic interactions with distinct DNA repair pathways, we found that Hof1 is genetically linked to the Rad53 pathway. Furthermore, Hof1 is down-regulated in a Rad53-dependent manner and its importance in the MMS response is reduced when Rad53 is overexpressed or when RAD4 or RAD23 is deleted. Together, this work expands our understanding of the C. albicans DNA repair network and uncovers interplay between the cytokinesis regulator Hof1 and the Rad53-mediated checkpoint.
Seizures induce obstructive apnea in DBA/2J audiogenic seizure‐prone mice: Lifesaving impact of tracheal implants

The mechanism(s) for sudden death in epilepsy (SUDEP) remain(s) unknown, but seizure spread to brainstem areas serving autonomic and respiratory function is critical. In a rat model, we established a mechanism for SUDEP that involves seizure‐induced laryngospasm and obstructive apnea lasting until respiratory arrest. We hypothesized that DBA/2J mice, which display lethal audiogenic seizures, would be protected from death by implanting a tracheal T‐tube as a surrogate airway. In a 2 × 2 design, mice were implanted with either open or closed tracheal T‐tubes and treated with either low‐dose ketamine/xylazine to moderate thoracic spasm during the tonic seizure phase or no drug. Animals receiving both treatments had the highest survival rate, followed by animals receiving the open tube without ketamine/xylazine. The odds ratio for survival was >20 higher with an open T‐tube (odds ratio = 24.14). The impact of open tracheal tubes indicates that the mechanism of death in DBA/2J mice involves seizure‐induced upper airway obstruction until respiratory arrest. These results, our rat work, and our demonstration of inspiratory effort‐based electromyographic signals and electrocardiographic abnormalities in rats and humans suggest that seizure‐induced laryngospasm and obstructive apnea directly link seizure activity to respiratory arrest in these sudden death examples.
Phase Separation of Epstein-Barr Virus EBNA2 and Its Coactivator EBNALP Controls Gene Expression

Protein condensates can be assembled via liquid-liquid phase separation (LLPS), a process involving the concentration of molecules in a confined liquid-like compartment. LLPS allows for the compartmentalization and sequestration of materials and can be harnessed as a sensitive strategy for responding to small changes in the environment. This study identified the Epstein-Barr virus (EBV) proteins EBNA2 and EBNALP, which mediate virus and cellular gene transcription, as transcription factors that can form liquid-like condensates at superenhancer sites of MYC and Runx3. This study discovered the first identified LLPS of EBV proteins and emphasized the importance of LLPS in controlling host gene expression. ABSTRACT Biological macromolecule condensates formed by liquid-liquid phase separation (LLPS) have been discovered in recent years to be prevalent in biology. These condensates are involved in diverse processes, including the regulation of gene expression. LLPS of proteins have been found in animal, plant, and bacterial species but have scarcely been identified in viral proteins. Here, we discovered that Epstein-Barr virus (EBV) EBNA2 and EBNALP form nuclear puncta that exhibit properties of liquid-like condensates (or droplets), which are enriched in superenhancers of MYC and Runx3. EBNA2 and EBNALP are transcription factors, and the expression of their target genes is suppressed by chemicals that perturb LLPS. Intrinsically disordered regions (IDRs) of EBNA2 and EBNALP can form phase-separated droplets, and specific proline residues of EBNA2 and EBNALP contribute to droplet formation. These findings offer a foundation for understanding the mechanism by which LLPS, previously determined to be related to the organization of P bodies, membraneless organelles, nucleolus homeostasis, and cell signaling, plays a key role in EBV-host interactions and is involved in regulating host gene expression. This work suggests a novel anti-EBV strategy where developing appropriate drugs of interfering LLPS can be used to destroy the function of the EBV’s transcription factors. IMPORTANCE Protein condensates can be assembled via liquid-liquid phase separation (LLPS), a process involving the concentration of molecules in a confined liquid-like compartment. LLPS allows for the compartmentalization and sequestration of materials and can be harnessed as a sensitive strategy for responding to small changes in the environment. This study identified the Epstein-Barr virus (EBV) proteins EBNA2 and EBNALP, which mediate virus and cellular gene transcription, as transcription factors that can form liquid-like condensates at superenhancer sites of MYC and Runx3. This study discovered the first identified LLPS of EBV proteins and emphasized the importance of LLPS in controlling host gene expression.