Miracle-dz/UniFAR-FTUs huggingface dataset:
Implication of EZH2 in the Pro-Proliferative and Apoptosis-Resistant Phenotype of Pulmonary Artery Smooth Muscle Cells in PAH: A Transcriptomic and Proteomic Approach

Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by a sustained elevation of pulmonary artery (PA) pressure, right ventricular failure, and premature death. Enhanced proliferation and resistance to apoptosis (as seen in cancer cells) of PA smooth muscle cells (PASMCs) is a major pathological hallmark contributing to pulmonary vascular remodeling in PAH, for which current therapies have only limited effects. Emerging evidence points toward a critical role for Enhancer of Zeste Homolog 2 (EZH2) in cancer cell proliferation and survival. However, its role in PAH remains largely unknown. The aim of this study was to determine whether EZH2 represents a new factor critically involved in the abnormal phenotype of PAH-PASMCs. We found that EZH2 is overexpressed in human lung tissues and isolated PASMCs from PAH patients compared to controls as well as in two animal models mimicking the disease. Through loss- and gain-of-function approaches, we showed that EZH2 promotes PAH-PASMC proliferation and survival. By combining quantitative transcriptomic and proteomic approaches in PAH-PASMCs subjected or not to EZH2 knockdown, we found that inhibition of EZH2 downregulates many factors involved in cell-cycle progression, including E2F targets, and contributes to maintain energy production. Notably, we found that EZH2 promotes expression of several nuclear-encoded components of the mitochondrial translation machinery and tricarboxylic acid cycle genes. Overall, this study provides evidence that, by overexpressing EZH2, PAH-PASMCs remove the physiological breaks that normally restrain their proliferation and susceptibility to apoptosis and suggests that EZH2 or downstream factors may serve as therapeutic targets to combat pulmonary vascular remodeling.
Immunogenicity of HIV-1-Based Virus-Like Particles with Increased Incorporation and Stability of Membrane-Bound Env

An optimal prophylactic vaccine to prevent human immunodeficiency virus (HIV-1) transmission should elicit protective antibody responses against the HIV-1 envelope glycoprotein (Env). Replication-incompetent HIV-1 virus-like particles (VLPs) offer the opportunity to present virion-associated Env with a native-like structure during vaccination that closely resembles that encountered on infectious virus. Here, we optimized the incorporation of Env into previously designed mature-form VLPs (mVLPs) and assessed their immunogenicity in mice. The incorporation of Env into mVLPs was increased by replacing the Env transmembrane and cytoplasmic tail domains with those of influenza haemagglutinin (HA-TMCT). Furthermore, Env was stabilized on the VLP surface by introducing an interchain disulfide and proline substitution (SOSIP) mutations typically employed to stabilize soluble Env trimers. The resulting mVLPs efficiently presented neutralizing antibody epitopes while minimizing exposure of non-neutralizing antibody sites. Vaccination of mice with mVLPs elicited a broader range of Env-specific antibody isotypes than Env presented on immature VLPs or extracellular vesicles. The mVLPs bearing HA-TMCT-modified Env consistently induced anti-Env antibody responses that mediated modest neutralization activity. These mVLPs are potentially useful immunogens for eliciting neutralizing antibody responses that target native Env epitopes on infectious HIV-1 virions.
Biflavonoid-Induced Disruption of Hydrogen Bonds Leads to Amyloid-β Disaggregation

Deposition of amyloid β (Aβ) fibrils in the brain is a key pathologic hallmark of Alzheimer’s disease. A class of polyphenolic biflavonoids is known to have anti-amyloidogenic effects by inhibiting aggregation of Aβ and promoting disaggregation of Aβ fibrils. In the present study, we further sought to investigate the structural basis of the Aβ disaggregating activity of biflavonoids and their interactions at the atomic level. A thioflavin T (ThT) fluorescence assay revealed that amentoflavone-type biflavonoids promote disaggregation of Aβ fibrils with varying potency due to specific structural differences. The computational analysis herein provides the first atomistic details for the mechanism of Aβ disaggregation by biflavonoids. Molecular docking analysis showed that biflavonoids preferentially bind to the aromatic-rich, partially ordered N-termini of Aβ fibril via the π–π interactions. Moreover, docking scores correlate well with the ThT EC50 values. Molecular dynamic simulations revealed that biflavonoids decrease the content of β-sheet in Aβ fibril in a structure-dependent manner. Hydrogen bond analysis further supported that the substitution of hydroxyl groups capable of hydrogen bond formation at two positions on the biflavonoid scaffold leads to significantly disaggregation of Aβ fibrils. Taken together, our data indicate that biflavonoids promote disaggregation of Aβ fibrils due to their ability to disrupt the fibril structure, suggesting biflavonoids as a lead class of compounds to develop a therapeutic agent for Alzheimer’s disease.
Effects of a Partially Perforated Flooring System on Ammonia Emissions in Broiler Housing—Conflict of Objectives between Animal Welfare and Environment?

Simple Summary Previous studies have shown positive effects of a partially perforated flooring system on animal welfare in broiler housing. Towards the end of the fattening periods, the present study showed a higher ammonia emission rate (NH3 ER) for a partially perforated flooring system compared with a littered control barn. Nevertheless, the measured NH3 concentrations were below 20 ppm, except during a mechanical litter treatment in the winter fattening period. Furthermore, the system offers the possibility of applying practical solutions that were not feasible before. By using underfloor air extraction, manure belts, or acidification systems underneath the elevated perforated area, NH3 concentrations and the resulting NH3 ER could be reduced. Thus, with some optimization, the partially perforated flooring system could be used to contribute to an increase in animal welfare and environmental protection at the same time. Abstract A partially (50%) perforated flooring system showed positive effects on health- and behavior-based welfare indicators without affecting production performance. Ammonia (NH3) is the most common air pollutant in poultry production, with effects on animal welfare and the environment. The objectives of animal welfare and environmental protection are often incompatible. Therefore, this study addresses the question of how a partially perforated flooring system affects NH3 emissions. According to German regulations, three fattening periods were carried out with 500 Ross 308 broilers per barn (final stocking density: 39 kg m−2). The experimental barn was equipped with an elevated perforated area in the supply section, accessible by perforated ramps. The remaining area in the experimental barn and the control barn were equipped with wood shavings (600 g m−2). Besides the different floor types, management was identical. Air temperature (Temp), relative air humidity (RH), NH3 concentration, and ventilation rate (VR) were measured continuously. Furthermore, dry matter (DM) content, pH, and litter quality were assessed. Towards the end of the fattening periods, the NH3 emission rate (ER) of the partially perforated flooring system was higher compared with that of the littered control barn (all p < 0.001). This effect is mainly caused by the higher NH3 concentrations, which are promoted by the lack of compaction underneath the elevated perforated area and the increase in pH value under aerobic conditions. Nevertheless, the partially perforated flooring system offers different approaches for NH3 reduction that were previously not feasible, potentially contributing equally to animal welfare and environmental protection.
CdSe Quantum Dots in Human Models Derived from ALS Patients: Characterization, Nuclear Penetration Studies and Multiplexing

CdSe quantum dots (QDs) are valuable tools for deciphering molecular mechanisms in cells. Their conjugation with antibodies offers a unique staining source with optimal characteristics, including increased photostability and narrow emission spectra, allowing for improved multiplexing capabilities using a single excitation source. In combination with pathology models derived from patients, they have great potential to contribute to quantitative molecular profiling and promote personalized medicine. However, the commercial availability of diverse CdSe QDs is still limited and characterization techniques must be performed to these materials or the conjugates developed in the lab to assure a proper function and reproducibility. Furthermore, while there is significant data of QDs experiments in cell lines, the literature with primary human cells is scarce, and QD behavior in these systems may be different. Rigorous characterization data of commercially available QDs and their conjugates with biomolecules of interest is needed in order to establish their potential for target labelling and expand their use among research labs. Here we compare the characterization and labelling performance of different QD conjugates in SH-SY5Y cell line, fibroblasts and immortalized lymphocytes derived from amyotrophic lateral sclerosis patients.
Acinetobacter baumannii Antibiotic Resistance Mechanisms

Acinetobacter baumannii is a Gram-negative ESKAPE microorganism that poses a threat to public health by causing severe and invasive (mostly nosocomial) infections linked with high mortality rates. During the last years, this pathogen displayed multidrug resistance (MDR), mainly due to extensive antibiotic abuse and poor stewardship. MDR isolates are associated with medical history of long hospitalization stays, presence of catheters, and mechanical ventilation, while immunocompromised and severely ill hosts predispose to invasive infections. Next-generation sequencing techniques have revolutionized diagnosis of severe A. baumannii infections, contributing to timely diagnosis and personalized therapeutic regimens according to the identification of the respective resistance genes. The aim of this review is to describe in detail all current knowledge on the genetic background of A. baumannii resistance mechanisms in humans as regards beta-lactams (penicillins, cephalosporins, carbapenems, monobactams, and beta-lactamase inhibitors), aminoglycosides, tetracyclines, fluoroquinolones, macrolides, lincosamides, streptogramin antibiotics, polymyxins, and others (amphenicols, oxazolidinones, rifamycins, fosfomycin, diaminopyrimidines, sulfonamides, glycopeptide, and lipopeptide antibiotics). Mechanisms of antimicrobial resistance refer mainly to regulation of antibiotic transportation through bacterial membranes, alteration of the antibiotic target site, and enzymatic modifications resulting in antibiotic neutralization. Virulence factors that may affect antibiotic susceptibility profiles and confer drug resistance are also being discussed. Reports from cases of A. baumannii coinfection with SARS-CoV-2 during the COVID-19 pandemic in terms of resistance profiles and MDR genes have been investigated.
Sexual Interference Behaviors in Male Adult and Subadult Tibetan Macaques (Macaca thibetana)

Simple Summary Sexual interference behaviors (interruption/harassment) by male nonhuman primates can lead copulating individuals to separate and is hypothetically a form of male–male competition for access to sexually receptive females. Tibetan macaques (Macaca thibetana) provide an example of male sexual interference that can be used to discuss the sexual competition hypothesis. We found male sexual interference in this species showed significant seasonal variation. Age did not affect the proportion or type of interference behaviors that a male performed, but his social status did. Dominant males more often interrupted copulations. Subordinate males more often directed harassment behaviors toward dominant males, which reduced copulation duration, especially the post-ejaculatory phase of copulation. Our results suggest that sexual interference (interruption or harassment) may be a tactic to reduce the mating success of other males by either preventing ejaculation or reducing the duration of the post-ejaculatory phase, which is critical for sperm transport and, thus, reproductive success. Abstract Male nonhuman primate sexual interference, which includes copulation interruption and copulation harassment, has been related to reproductive success, but its significance has been challenging to test. Copulation interruption results in the termination of a copulation before ejaculation, whereas copulation harassment does not. We conducted this study using the all-occurrence behavior sampling method on sexual interference behaviors of seven adult and four subadult male Tibetan macaques (Macaca thibetana) in mating and non-mating seasons at Mt. Huangshan, China, from August 2016 to May 2017. Our results showed that males’ individual proportion of copulation interruption and harassment was higher during the mating season than during the non-mating season. In addition, dominant males more often performed interruption, whereas subordinate males more often performed harassment. We found no difference in the individual proportion of copulation interruption or harassment between adult and subadult males. Adult and subadult males both directed copulation interruption and harassment more often toward the mating male than toward the mating female. Lastly, the post-ejaculation phase of copulation was shorter when copulation harassment occurred than when it did not. Our results suggest that sexual interference may be an important mating tactic that adult and subadult males use in male–male sexual competition.
Effects of Dizocilpine, Midazolam and Their Co-Application on the Trimethyltin (TMT)-Induced Rat Model of Cognitive Deficit

Research of treatment options addressing the cognitive deficit associated with neurodegenerative disorders is of particular importance. Application of trimethyltin (TMT) to rats represents a promising model replicating multiple relevant features of such disorders. N-methyl-D-aspartate (NMDA) receptor antagonists and gamma-aminobutyric acid type A (GABAA) receptor potentiators have been reported to alleviate the TMT-induced cognitive deficit. These compounds may provide synergistic interactions in other models. The aim of this study was to investigate, whether co-application of NMDA receptor antagonist dizocilpine (MK-801) and GABAA receptor potentiator midazolam would be associated with an improved effect on the TMT-induced model of cognitive deficit. Wistar rats injected with TMT were repeatedly (12 days) treated with MK-801, midazolam, or both. Subsequently, cognitive performance was assessed. Finally, after a 17-day drug-free period, hippocampal neurodegeneration (neuronal density in CA2/3 subfield in the dorsal hippocampus, dentate gyrus morphometry) were analyzed. All three protective treatments induced similar degree of therapeutic effect in Morris water maze. The results of histological analyses were suggestive of minor protective effect of the combined treatment (MK-801 and midazolam), while these compounds alone were largely ineffective at this time point. Therefore, in terms of mitigation of cognitive deficit, the combined treatment was not associated with improved effect.
Distance Motor Learning during the COVID-19 Induced Confinement: Video Feedback with a Pedagogical Activity Improves the Snatch Technique in Young Athletes

The purpose of the present study was to investigate which of two strategies, Video Feedback with Pedagogical Activity (VF-PA) or Video Feedback (VF), would be more beneficial for the remote error correction of the snatch weightlifting technique during the confinement period. Thirty-five school aged children with at least three months of weightlifting experience were randomized to one of three training conditions: VF-PA, VF or the Control group (CONT). Subjects underwent test sessions one week before (T0) and one day after (T1) a six-session training period and a retention test session a week later (T2). During each test session, the Kinovea version 0.8. 15 software measured the kinematic parameters of the snatch performance. Following distance learning sessions (T1), the VF-PA improved various kinematic parameters (i.e., barbell horizontal displacements, maximum height, looping and symmetry) compared with T0 (p < 0.5; Cohen’s d = 0.58–1.1). Most of these improvements were maintained during the retention test (T2) (p<0.01, Cohen’s d = 1.2–1.3) when compared withT0. However, the VF group improved only twoparameters (i.e., barbell symmetry and horizontal displacement) at T1 (p < 0.05; Cohen’s d = 0.9), which were not maintained at T2. Better horizontal displacement and looping values were registered during the retention test in the VF-PA group compared with theCONT group (p < 0.05, Cohen’s d = 1.49–1.52). The present findings suggest combining video feedback with pedagogical activity during the pandemic induced online coaching or physical education to improve movement learning in school aged children.
The Gut–Brain Axis and Its Role in Controlling Eating Behavior in Intestinal Inflammation

Malnutrition represents a major problem in the clinical management of the inflammatory bowel disease (IBD). Presently, our understanding of the cross-link between eating behavior and intestinal inflammation is still in its infancy. Crohn’s disease patients with active disease exhibit strong hedonic desires for food and emotional eating patterns possibly to ameliorate feelings of low mood, anxiety, and depression. Impulsivity traits seen in IBD patients may predispose them to palatable food intake as an immediate reward rather than concerns for future health. The upregulation of enteroendocrine cells (EEC) peptide response to food intake has been described in ileal inflammation, which may lead to alterations in gut–brain signaling with implications for appetite and eating behavior. In summary, a complex interplay of gut peptides, psychological, cognitive factors, disease-related symptoms, and inflammatory burden may ultimately govern eating behavior in intestinal inflammation.
Enhancement of Mechanical and Barrier Property of Hemicellulose Film via Crosslinking with Sodium Trimetaphosphate

Hemicellulose is a kind of biopolymer with abundant resources and excellent biodegradability. Owing to its large number of polar hydroxyls, hemicellulose has a good barrier performance to nonpolar oxygen, making this biopolymer promising as food packaging material. Hydrophilic hydroxyls also make the polymer prone to water absorption, resulting in less satisfied strength especially under humid conditions. Thus, preparation of hemicellulose film with enhanced oxygen and water vapor barrier ability, as well as mechanical strength is still sought after. Herein, sodium trimetaphosphate (STMP) was used as esterification agent to form a crosslinked structure with hemicellulose through esterification reaction to render improved barrier performance by reducing the distance between molecular chains. The thus modified hemicellulose film achieved an oxygen permeability and water vapor permeability of 3.72 cm3 × μm × m−2 × d−1 × kPa−1 and 2.85 × 10−10 × g × m−1 × s−1 × Pa−1, respectively, at the lowest esterification agent addition of 10%. The crosslinked structure also brought good mechanical and thermal properties, with the tensile strength reaching 30 MPa, which is 118% higher than that of the hemicellulose film. Preliminary test of its application in apple preservation showed that the barrier film obtained can effectively slow down the oxidation and dehydration of apples, showing the prospect of application in the field of food packaging.
Ex-Vivo Pharmacological Defatting of the Liver: A Review

The ongoing organ shortage has forced transplant teams to develop alternate sources of liver grafts. In this setting, ex-situ machine perfusion has rapidly developed as a promising tool to assess viability and improve the function of organs from extended criteria donors, including fatty liver grafts. In particular, normothermic machine perfusion represents a powerful tool to test a liver in full 37 °C metabolism and add pharmacological corrections whenever needed. In this context, many pharmacological agents and therapeutics have been tested to induce liver defatting on normothermic machine perfusion with promising results even on human organs. This systematic review makes a comprehensive synthesis on existing pharmacological therapies for liver defatting, with special focus on normothermic liver machine perfusion as an experimental ex-vivo translational model.
Regulatory Flexibility of Sustaining Daily Routines and Mental Health in Adaptation to Financial Strain: A Vignette Approach

A vignette approach was adopted to investigate flexibility of sustaining daily routines and whether and how this ability was related to mental health at different levels of financial strain. Three separate studies were conducted with community-dwelling adults (N = 1685) in the USA. In Study 1, we drafted, tested, and modified vignettes with reference to pilot data on the relevance of the scenarios and response options. In Study 2, regulatory flexibility of sustaining daily routines, as calculated in term of context sensitivity and responsiveness to feedback, was formulated correlations with self-reported instruments to demonstrate its concurrent validity, discriminant validity, and criterion-related validity. In Study 3, path analysis examined the associations of regulatory flexibility of sustaining daily routines with psychological distress and well-being, and the moderating effects of subjective financial strain on the associations. Results showed that the inverse associations of context sensitivity and responsiveness to feedback with depressive symptoms were stronger at medium/high levels relative to lower levels of perceived financial strain. The inverse association between context sensitivity and positive affect was significant only at higher levels of strain. Our findings could provide a feasible direction for developing scalable behavioral interventions for potential mental health problems, especially among those with a lower socioeconomic status.
Non-Target Effects of dsRNA Molecules in Hemipteran Insects

Insect pest control by RNA interference (RNAi)-mediated gene expression knockdown can be undermined by many factors, including small sequence differences between double-stranded RNA (dsRNA) and the target gene. It can also be compromised by effects that are independent of the dsRNA sequence on non-target organisms (known as sequence-non-specific effects). This study investigated the species-specificity of RNAi in plant sap-feeding hemipteran pests. We first demonstrated sequence-non-specific suppression of aphid feeding by dsRNA at dietary concentrations ≥0.5 µg µL−1. Then we quantified the expression of NUC (nuclease) genes in insects administered homologous dsRNA (with perfect sequence identity to the target species) or heterologous dsRNA (generated against a related gene of non-identical sequence in a different insect species). For the aphids Acyrthosiphon pisum and Myzus persicae, significantly reduced NUC expression was obtained with the homologous but not heterologous dsRNA at 0.2 µg µL−1, despite high dsNUC sequence identity. Follow-up experiments demonstrated significantly reduced expression of NUC genes in the whitefly Bemisia tabaci and mealybug Planococcus maritimus administered homologous dsNUCs, but not heterologous aphid dsNUCs. Our demonstration of inefficient expression knockdown by heterologous dsRNA in these insects suggests that maximal dsRNA sequence identity is required for RNAi targeting of related pest species, and that heterologous dsRNAs at appropriate concentrations may not be a major risk to non-target sap-feeding hemipterans.